THE POWER OF COMMUNICATION DNA AS ANTI-AGING SOFTWARE BEATING BLOOD CANCER

THE 7TH ANNUAL WORLDVIEW SCORECARD PARTNER PROFILE RIGHT PATIENT, RIGHT MEDICINE, RIGHT NOW Addressing the Barriers to Patient Access By JONATHAN WILCOX / Policy Director, Vital Options International

By STACEY L. WORTHY, Esq. / Director of Public Policy, The Alliance for the Adoption of Innovations In Medicine t may seem obvious to proclaim that the cancer patient journey is one of crossroads moments and good news/bad news scenarios. But per- he definition of their insurance companies finally don’t have to travel to the doctor’s haps now more than ever, the oncology world is stirred by astonishing “conundrum” is agree to pay for the drug prescribed office every week, resulting in time Ibreakthroughs in lifesaving medicines simultaneous with ever-higher “a confusing and by their doctors. away from work or family. Yet, be- and more complex barriers to access for patients who need them. difficult problem One disturbing and wasteful insur- cause the co-pays can be hundreds When it comes to the science of cancer, these are definitely the best or question,”—a ance practice is what is euphemisti- or thousands of dollars per month, of times. Exciting discoveries occurring in every area of cancer research definition that clearly cally called “step therapy” or “fail studies find almost 10 percent of are producing treatments targeted to the unique molecular and genetic appliesT to the growing number of first.” In this practice, although a insured patients choose not to fill characteristics of each person’s cancer. Add the excitement over new cancer patients who are prescribed doctor may prescribe a medication their initial prescriptions for oral immunotherapies that train a patient’s immune system to destroy cancer state-of-the art cancer medicines most suitable to the patient’s indi- anti-cancer medications. and it is clear that the transformative change of precision medicine is well and yet, delay taking them or don’t vidual needs, the insurance company To save lives, the patient com- underway. take them at all. usurps the doctor’s prescribing munity, cancer advocacy groups, For some cancer patients seeking to utilize these life-saving thera- According to the latest projec- authority by requiring the patient to and public health organizations are CONTACT YOUR ELECTED pies, however, all the world’s medical innovation might as well never have tions, nearly half of Americans first fail on several inferior medica- pressing Congress and state legis- OFFICIAL to Support Patient occurred. Even as medical advances create new, potentially life-saving latures to cap co- Access to Medical Innovation medicines for patients – and more quickly than ever before – ready access pays on specialty to these life-enhancing therapies is not assured. medicines and American College of Rheumatology Why? The path is blocked in two critical ways. “We have a health insurance failure for innovative medicines. ensure equality of LEGISLATIVE ACTION CENTER: The first is governmental. What we call “new” cancer treatments are If you get cancer today, your copays can prevent you from access and insur- www.rheumatology.org/actioncenter often 8-10 years old by the time they reach patients. Why isn’t this a mat- ance coverage American Society of Hematology ter of months? The main reason is that FDA regulations were designed accessing the medicines you desperately need. That’s a failure for all anti-cancer ORAL CANCER DRUG PARITY: to evaluate the modernism of the VCR and 8-track tapes. Appropriate for of health insurance.” Tomas Philipson, Ph.D., Professor, regimens. To date, www.hematology.org/Advocacy/ their time, perhaps, but increasingly ill-equipped to co-exist with today’s 39 states and Campaigns/667.aspx speedy scientific advances. Washington D.C. Arthritis Foundation The second is access. Tens of thousands of cancer patients are custom- have enacted oral SPECIALTY TIERS/CAP THE COPAY: arily confronted with rising copays, restricted coverage and all too often, diagnosed with a chronic disease tions before it will pay for the drug chemotherapy access laws, while 15 www.arthritis.org/advocate/ insurance practices that deny access completely. This is the bitter reality take their medicine as directed that the doctor originally prescribed. states and the District of Columbia our-policy-priorities/pass-the-patients of today’s access fights – with patients and their doctors denied medica- only 50 percent to 60 percent of Equally onerous is placing new can- have either introduced or passed -access-to-treatments-act.php tions every day by a complex coverage and reimbursement insurance the time. The consequence of this cer medicines into the highest phar- bills to limit what patients pay for International Myeloma Foundation system that surely does not want to be seen as standing in the way of sick poor medication adherence is more macy (“specialty”) tier and forcing specialty medicines. ORAL ANTICANCER TREATMENT people and their disease-altering treatments. doctor visits, trips to the emergency patients to pay a large percentage of The Alliance for the Adoption of ACCESS LEGISLATION: In response, a patient revolution has ignited and touched down in 39 room, and hospitalizations, all of the drug’s price. According to a re- Innovations in Medicine supports www.cqrcengage.com/myeloma/access states and Washington, D.C. to address the problem of inequitable cover- which is estimated to cost the health cent Leukemia & Lymphoma Society these policies because adhering to Leukemia & Lymphoma Society age by requiring health plans to equalize the patients’ out-of-pocket costs care system between $100 billion report, even the new state exchange cancer medicines is a necessity. It is LEGISLATIVE ACTION CENTER: between oral and intravenous therapies. Further state-by-state reform and $300 billion annually. plans implemented under the Patient time to end the adherence conun- www.lls.org/advocate/legislative- efforts will surely follow. action-center However, for Americans fighting Protection and Affordable Care Act drum by reducing the cost-sharing As a nonprofit organization working to improve cancer care, Vital a deadly cancer, the consequences for previously uninsured patients use barriers for cancer patients, so they National Organization for Options International (VOI) believes patients should not be forced to battle can also be life-threatening and this cost containment strategy. This can fill their prescriptions and take Rare Diseases the system and their cancer at the same time. This is why VOI supports CURRENT INITIATIVES AND ISSUES thus, the conundrum: Why are can- means patients can pay up to 50 the medicines they desperately need. energetic and innovative movements underway to update the drug ap- UPDATES: cer patients skipping doses or tak- percent of the costs of new can- It’s the right thing to do for www.rarediseases.org/advocacy/ proval process using 21st century computing capabilities, genomic analysis ing less than the prescribed amount cer therapies, which leads to poor patients, the healthcare system and initiatives-updates and a new understanding of cancer on a molecular level. of their cancer medicines? The adherence. our economy. We also hope legislators and regulators will work with doctors, Patient Services, Inc. answer is simple: In the name of Then, there is the practice of LEGISLATION: patients, caregivers and payors to provide faster and easier access to the cost-containment, insurance com- shifting as much as 25 percent of the www.patientservicesinc.org/ latest medications – and do so in a way that prioritizes patient safety and panies increasingly restrict patients’ cost of oral anti-cancer medicines Advocacy/Legislation supports the integrity of new drug evaluations. access to breakthrough cancer to patients in high co-pays—even To almost countless patients, there is only one obvious move left: medicines through high copays and though these drugs are less invasive Towards a regulatory future that embraces access and accepts nothing less practices that require patients to fail than intravenous infusions, they than the right patient, the right medicine and right now. on medication after medication until carry fewer side effects, and patients COVER ILLUSTRATION by Nicholas Sutton Bell 4 LET’S GIVE ’EM SOMETHING TO TALK ABOUT… WORLDVIEW SCORECARD BY JEREMY ABBATE, MIKE MAY & YALI FRIEDMAN 36 THE 7TH ANNUAL GLOBAL SURVEY SCIENTIFIC AMERICAN WORLDVIEW IS 5 yourVIEWS: PUBLISHED BY SCIENTIFIC AMERICAN Letters, Opinions, Critiques CUSTOM MEDIA WITH PROJECT 66 PRODUCTS OF THEIR ENVIRONMENT MANAGEMENT BY BY YALI FRIEDMAN SPECIAL REPORT: THE WORLDVIEW 100 How R&D location impacts which drugs are produced. Publishing & Media Director | JEREMY ABBATE Editorial Director | MIKE MAY 68 JOELLE BOLT 8 THE WORLDVIEW 100 LAWS OF ATTRACTION Art Director | How a nation’s policies attract and discourage biopharma investment Head, Data Analytics, The visionaries who continue to reshape biotechnology YALI FRIEDMAN BY MEIR PEREZ PUGATCH, DAVID TORSTENSSON, RACHEL CHU, AMIR DAYAN & NOA WEINSTEIN Scientific American Custom Media | —and the world Copy Chief & Content Consultant | GEORGINA KEENAN BENCH TO BUSINESS WORLDVIEW EVENTS Digital Production | ZOYA LYSAK Research & Administrative | ALEXANDRA HARIRI 22 FROM EUREKA TO USEFUL 72 AN EVENING WITH TOP MEDICAL INNOVATORS BOARD OF ADVISERS Developing an idea into a productive tool demands Today’s visionaries battle cancer with cutting-edge science and the stubbornness GEORGE BAEDER experience, foresight and a persistent champion to make it work BY MIKE MAY Director, China Global Insight BY MIKE MAY JORGE BARRERO Deputy to the President, COUNTRY SPOTLIGHTS Spanish Association of Biotechnology MARY BOOTE 26 ROOM TO GROW CEO, Truth About Trade and Technology LabCentral gives start-ups the space and 76 DISPATCHES FROM: China, Germany, India, Japan, Norway, Poland, STEVEN CASPER Henry E. Riggs Professor of Management, resources to thrive BY JOHANNES FRUEHAUF Romania, Russia, Scotland, Keck Graduate Institute ANANDA CHAKRABARTY Distinguished University Professor, 28 BIOTECHNOLOGY’S WORLDVIEWPOINT University of Illinois at Chicago JOSEPH DAMOND CRUCIAL QUESTION Senior Vice President, International Affairs, BIO In this industry, what matters the most: technology 84 AGING 2.0 NINA DUDNIK or people? BY STEPHEN M. SAMMUT Founder and CEO, Seeding Labs Stem cells and digitized DNA may hold RICHARD GALLAGHER the key to high-performance longevity President and Editor-in-Chief, Annual Reviews BY ROBERT HARIRI ANITA GOEL Chairman and CEO, Nanobiosym BOB HARIRI Chairman, Celgene Cellular Therapeutics KAREN M. HAUDA Senior Director, Regulatory Policy, Novo Nordisk ROBERT KILPATRICK Cofounder and Partner, Technology Vision Group 2015 GANESH KISHORE CEO of Malaysian Life Sciences Capital Fund TOMASZ MROCZKOWSKI Professor, Department of International Business, Kogod School of Business, American University ANDREW POWELL CEO, Asia Biobusiness STEVE SAMMUT Senior Fellow, Health Care Management, Wharton School, University of Pennsylvania RAM SASISEKHARAN Alfred H. Caspary Professor of Biological Engineering and Health Sciences and Technology, Institute of Technology

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2 SCIENTIFIC AMERICAN | WORLDVIEW CONTENTS 3 YOURVIEWS yourLETTERS- / OPINIONS / CRITIQUES

marginal effects on improv- germ theory) is outdated. TRANSFORMING ing healthcare and reducing Genetic, environmental, THE FUTURE OF its costs. Specifically, the behavioral and demograph- RCT, our gold standard, ic factors regulating well- HEALTHCARE typically fails when there being have turned single n the past two decades,

SPECIAL REPORT TRACKING INNOVATION’S VALUE TO SOCIETY is multicausality for any illnesses, such as cancer, the pace of medical disease, phenotype or bio- into multidimensional Iprogress has accelerated. + LET’S GIVE ’EM SOMETHING TO TALK ABOUT… TH THE 6 ANNUAL logical feature(s) of clinical diseases for which no single The human genome has WORLDVIEW SCORECARD Confirming a drug can be successful. recovery importance. Medicine is been sequenced, hepatitis TRANSFORMING CANCER CARE Novel approaches spark a new dawn empirically, and with some Cells, tissues, organs and C can be cured, HIV has for all medicine ON THE BEAT IN BRAZIL Partnering its way to powerful solutions knowledge of mechanisms, organ systems are networks been turned into a chronic climbing multi-peaked of causal interactions, best condition and remission clinical landscapes suc- treated by smart combina- has become more common PUSHING P4 cessfully—where RCT tions of drugs, nutriments and attainable in several n our article “Trans- fails. In addition, patients and other strategies, such forms of cancer. forming Medicine: A are unique genetically and as immune therapy. Yet, Despite progress, chal- LETTER FROM THE EDITORS IManifesto” (Scientific environmentally, and hence virtually every researcher, lenges remain in translating he cornerstone of Scientific American which highlights some of the top innovators in medicine American Worldview, 2014), should not be averaged in company and regulatory basic science discover- Worldview—our annual Scorecard, evalu- and two of the patients who reaped the benefits (page 72) we challenged the founda- large populations. Rather, agency is organized around ies into medical practice. ating the life science innovation capacities of modern medical ingenuity. As in previous years, our tion of “evidence-based the personalized multi- the one drug–one disease Whereas the 20th century of countries around the globe (page 36)— “Country Spotlights” section (page 76) will take readers medicine.” We noted that dimensional data clouds of business model. saw a focus on develop- emerged from a desire to bring a much- on a tour of science-in-action, showcasing biotechnology methods used to generate each individual should be Consumers—via social ing better treatments for needed critical eye and third-party trans- success stories around the planet. this evidence, the basis for analyzed independently, networks, multi-dimen- disease, there has been far parency to the international landscape of Last but far from least, the worldVIEWpoint (page 84) less attention to preven- Tbiotechnology. We are proud to have done this for seven essay reveals a modern, data-infused approach to finding ... patients are unique genetically and environmentally, and hence should tion, early detection and years now, adding an objective, data-driven voice to an a science-based “fountain of youth.” The author, a pioneer not be averaged in large populations. interception of disease. arena with a lot of unchecked cheerleading. This year, we in stem cell therapeutics, describes his journey into this The impact of condi- add another data-led feature—albeit far less quantitative— field with an ironic story about turning what was once tions like Alzheimer’s titled The Worldview 100 (page 8), celebrating the most in- considered medical waste into cutting-edge medical treat- medical practice and reim- and then patients with sional data clouds and disease, cancer, rheuma- fluential people in biotechnology, as determined through ments. His success proves that life-changing advances can bursement—randomized similar features can be digital tools—are decipher- toid arthritis and diabetes nominations and and do materialize from highly surprising sources. clinical trials (RCT) and aggregated into related ing biological complexity to continues to burden global selections from We want to encourage readers But that’s just what we seek to uncover—the stories in comparative effectiveness groups of interest (e.g., match people to combina- healthcare systems. Patients our international to explore biotechnology from a which something unexpected makes the difference. One research—are dangerously those responding effectively tions of treatment. They affected by these diseases panel of experts. of the guiding themes of Scientific American Worldview is broken. to a drug). We are throw- are bypassing large clinical often spend years of their As with any list, broad and global perspective. that innovation and ingenuity can occur in the most un- There is a broad biparti- ing away unknown hoards trial networks to get better lives in a state of declining this one will sure- likely places. We’ve found evidence of that in every edition san effort to move towards of relevant data about both answers more quickly with health. According to the ly spawn differences of opinion about the people on it and of our Scorecard. As our ranking system shows year after personalized and precision the variability of response individualized approaches U.S. Centers for Disease those missing. Ultimately, though, driving discussion lies year, small or resource-challenged countries can dominate medicine because getting and multiplicity of causes to their disease. We should Control and Prevention, at the heart of this publication’s mission. We want to en- various aspects of biotechnology achievement, and even the right treatments to the at the genetic and pheno- enable this movement to in the United States alone, courage readers to explore biotechnology from a broad the giants can tumble on some metrics. This dynamic and right patients at the right typic level when we average accelerate personalized about half of all adults, 117 and global perspective. developing industry continues to intrigue and amaze us. time can reduce the cost of patient populations. With medicine. million people, live with at Two sections—one on turning an idea into a product And we are once again delighted to bring you the people, healthcare and save lives. the analysis of individual least one chronic condition. COLIN HILL (page 22) and another on the successes, failures and fu- places and perspectives that are moving it forward. But good policy has to be patients we can gain fun- Earlier this year, Jans- ture directions in communication about biotechnology As always, we offer our profound thanks to our sponsors guided by good science and damental new insights SUI HUANG sen Research & Develop- (page 30)—trigger fresh ways of thinking about these top- and partners: Celgene Corporation, Cure Forward, Cred- a systems-driven medicine into disease through N=1 STUART KAUFFMAN ment, one of the Janssen ics. We continue this focus on fostering new dialogue with ible Meds, and The Biotechnology Industry Organization. that is predictive, preven- experiments and appropri- —founders of Transforming Pharmaceutical Companies articles about the impact of location on drug development tive, personalized and par- ate statistical power can be Medicine: The Elizabeth of Johnson & Johnson, Kauffman Institute (page 66) and which countries excel and flounder when it Sincerely, ticipatory (P4). Marginal gained through the aggre- announced the launch comes to attracting biotechnology investment (page 68). Jeremy Abbate, Publishing Director changes to evidence-based gation of related patients. of three new research We did not, however, set out to spark debate from every Mike May, Editorial Director medicine (e.g., comput- Further, the one drug– platforms focused on element of the 2015 Scientific American Worldview. And Yali Friedman, Head, Data Analytics erizing data collection) one disease model of inno- disease prevention, disease few are likely to contest one “list” in this year’s edition, will themselves have only vation (based on Pasteur’s interception and the mi-

4 SCIENTIFIC AMERICAN | WORLDVIEW YOURVIEWS 5 crobiome. These new teams laboratories in the United being the first company to Even now, with more becoming a global threat current genetic sequencing than a solid-tumor study, will collaborate closely with States and United Kingdom develop baby products that than 10,000 people dead before we treat it like one. approaches available. These it can be quite challenging Janssen’s five therapeutic to discover solutions to allowed for “no more tears,” and 24,000 confirmed cases If we want to prevent major cells enable us to study to develop and implement areas and external partners extend people’s healthy through the Band-Aid and of Ebola in eight countries, outbreaks of diseases like diseases—Parkinson’s and successful trials. Oncolo- to propel science in an effort life span. disposable contact lenses, it is still not clear who will Ebola then we need to Alzheimer’s, ALS, muscu- gists and drug developers to change an approach from The Disease Interception medical devices and blood pay if, or when, a vaccine invest in vaccine stockpiles lar dystrophies, epilepsy, need to understand that by “disease care” to health care. Accelerator (DIA) is a new typing, to developing the becomes available. Millions and start viewing them diabetes, cardiomyopathies better addressing the treat- Our healthcare system incubator-like group based first treatment for tubercu- of doses will be needed, as the ultimate deter- and macular degeneration, ment agendas of individual is strapped with the bur- in New Jersey that seeks to losis in 40 years. It is our and not just to help end the rent—making sure they are among others—at the phe- patients, the more success geoning costs of chronic identify the root causes of responsibility as a leading current epidemic but also, there, and at the same time notypic level (i.e., how the the study will have in re- care and will ultimately disease and enable the de- healthcare company to crucially, as a stockpile to praying we never have to cell’s behavior or function cruitment and completion. seek more cost-effective velopment of interventions continue to drive innova- prevent future outbreaks use them. is affected) rather than just Unlike tumor-based approaches. As of 2006, that stop the progression tion and make a difference from getting out of control. via genotype. cancers, which are classified SETH BERKLEY patients with chronic to disease. Our first disease for people and society. The problem is that iPSC technology also based on their point of ori- CEO Induced pluripotent diseases accounted for 84% area of focus for the DIA As an industry, we have there is no market. It’s Gavi, the Vaccine Alliance offers the potential for a stem cells (iPSCs), gin in the body, hematolog- of all healthcare spending. is type 1 diabetes (T1D). accomplished great things one thing developing and Geneva, Switzerland unique approach to preci- with the potential to ical malignancies, such as By taking advantage of our Janssen scientists will work and have laid the founda- approving a vaccine, and sion medicine: personalized AML, can develop into new ability to rapidly sequence to develop new diagnostic, tion for a bright future. quite another getting it cell transplants. A first look be manufactured from cancers as they progress, The launch of ambitious, out to the people who IPSCS AND at this potential may come virtually any patient’s making them very hard to forward-thinking initiatives need it the most. With a PERSONALIZED from the National Eye blood cells, set the define. The specificity of the will further propel us into disease like Ebola, which MEDICINE Institute and its collabora- stage for research to disease also makes develop- a bold new era of research kills ferociously but occurs tion with Cellular Dynam- make enormous gains ing targeted therapies es- Our healthcare system is strapped with the and development—an era sporadically and usually in resident Obama’s ics International (CDI) in understanding how pecially critical to treating marked by the promise of remote areas, there simply Precision Medicine that ultimately may lead them. Advancing research burgeoning costs of chronic care and will to approach medical new firsts, including a day is no commercial market. PInitiative recently to a treatment for macular through genetic testing ultimately seek more cost-effective approaches. when the term “patient” is a Who would buy it? Out- pledged US$215 million to degeneration with an au- treatment. and affecting change in the historical artifact. breaks usually involve only fund research to use per- tologous (the patient’s own) regulatory process should the human genome, we therapeutic or combination a couple of hundred cases sonalized genetic informa- iPSC-derived retinal cell remain key areas of the WILLIAM N. HAIT are able to understand an approaches for T1D inter- and typically occur every tion as the starting place for transplant. This is expected initiative’s multi-pronged Global Head individual’s susceptibility ception by understanding Janssen Research & few years in poor rural understanding individual to lead to the first clinical HEMATOLOGY approach. However, clinical to disease, calculate one’s the role of potential triggers Development, LLC communities in Africa. So, response to disease and trial in the United States TRIAL NUANCES trial management can’t be risk and intervene before and initiating steps on the Raritan, New Jersey manufacturers would be treatment. While the initia- using iPSCs. forgotten. illness occurs. pathway to T1D. unlikely to see a return on tive is necessary, it fails to The convenient ouis J. DeGennaro’s Enhancing and refin- Today, early disease in- The Janssen Human that investment. address the questions that criticism of personalized “Embracing The ing our understanding of terception and prevention Microbiome Institute THE EBOLA- This means that even DNA and genetics alone medicine is the perceived LProcess” (Scientific these cancer pathologies strategies are still largely (JHMI) was designed to VACCINE if one of these candidate cannot answer, questions cost. But the price should American Worldview, 2014) can increase the number of unexplored for many of explore the relationship of FUNDING GAP Ebola vaccines receives that must be posed at the decline, just as the cost of draws much needed atten- targeted therapies to enable the illnesses that plague the organisms that inhabit clinical approval, we’ll still cellular level, where the sequencing the human ge- tion to the lack of targeted truly personalized treat- our societies. The Janssen our body in maintaining ith the number be left with a significant answers may dramatically nome rapidly declined. The treatment options available ments. Moreover, ensuring Prevention Center (JPC) health and causing disease. of new cases of funding gap. Gavi, the Vac- improve patient healthcare. time is right for the United for acute myeloid leukemia careful trial design and will focus on the preven- Ultimately, this unique WEbola appear- cine Alliance, is committed Induced pluripotent States to fully embrace (AML). I applaud the steps precise trial execution will tion of chronic, non-com- Janssen initiative will de- ing to level off, and with to purchasing necessary stem cells (iPSCs), with this rapidly developing the Leukemia & Lymphoma yield data that can inform, municable diseases such as velop new ways to maintain clinical trials for Ebola vaccines for this outbreak the potential to be manu- field with research dollars. Society is taking to address and perhaps significantly Alzheimer’s, heart disease, health and treat disease. vaccines now underway, and creating a stockpile for factured from virtually Personalized medicine has this unmet medical need impact, the greater oncol- cancer and autoimmune External collaborations for there is an almost palpable future outbreaks as well as any patient’s blood cells, arrived, and the United with the Beat AML initiative. ogy community. diseases, which increasingly this organization will be sense that the crisis is over. incentivizing next-genera- set the stage for research States needs to lead this Beat AML needs to also RAY REILLY impact aging populations fostered through anchor The reality, however, is that tion vaccine development, to make enormous gains race to the finish line. consider the impact clinical Director of Project and burden healthcare sys- research centers located in even if a safe and effective but as a public-privately in understanding how to trial management has on Management BOB PALAY tems globally. The JPC will Cambridge, Massachusetts, vaccine emerges and the funded global health orga- approach medical treat- commercial success and the Hematology Division CEO and Chairman leverage the world-class and Beerse, Belgium. epidemic is brought under nization we still have not ment. These personalized nuances surrounding prop- Novella Clinical Cellular Dynamics Morrisville, North Carolina vaccine discovery expertise During the last 120 control, we are still in many yet determined who will stem cells provide a more International (CDI) er hematological oncol- of the former Crucell Vac- years, Johnson & Johnson ways no better prepared for provide these funds. comprehensive system for Madison, Wisconsin ogy study design. Because cine Institute (The Nether- has pushed forward many future outbreaks than we We need to stop waiting understanding the behavior hematologic oncology trials Contact us at: lands) in collaboration with “firsts”—evolving from were a year ago. for evidence of a disease of particular diseases than are fundamentally different [email protected]

6 SCIENTIFIC AMERICAN | WORLDVIEW YOURVIEWS 7 t just 40 years old, biotechnology is a ing just 100 individuals, our intention is to illustrate the relatively new industry. Its starting point, range and quality of its leaders, rather than to offer a de- arguably, was the 1975 Asilomar Confer- finitive register of its “most important” contributors. Nev- ence on Recombinant DNA, at which the ertheless, the list stands scrutiny as a collection of extraor- potential benefits and hazards of DNA dinarily talented and effective people. To learn more about manipulation and the ways it should be them, we provided each with an opportunity to respond to regulated were debated and essentially a few questions—some serious and others less so—and we decided upon. Most of the seminal figures in the develop- share some of their answers. ment of biotechnology are alive today. Indeed, many of What traits do these leaders have in common? Creativity them are still working in the field that they love. and enterprise are givens. Resilience and self-sacrifice are Here, we name 100 of the industry’s leading lights in a also critical, as the complexity of the science and its regula- list we’ve dubbed “The Worldview 100.” The honorees -in tion demands they constantly strive to maintain momentum, clude researchers who provided fundamental insights into however far away their goal appears. And since risk-taking biological processes, as well as their colleagues who devel- is practically the norm in biotech, these figures have to pos- oped those insights to create the -based goods and sess the confidence to outdare the crowd, to blaze a trail and services that are the essence of biotechnology. We also recog- to maintain their nerve, sometimes against overwhelming nize the business experts who had the foresight to provide odds. Emotional intelligence is another prerequisite for financial backing in this high-risk, nascent technology The Worldview 100, who invariably have the ability to get sector, along with the entrepreneurs who constructed and along with others and the forthrightness to be constructive- implemented the business principles that made those in- ly critical when necessary. vestments pay off. Dotted throughout are several visionary One suspects that many of biotech’s key players would legislators and administrators who understood the need have stood out in whichever career they chose. So what en- to create fertile conditions enabling biotechnology to flour- ticed them into this field? Perhaps its newness, offering the ish, and a number of key media figures who have helped thrill of putting a personal stamp on a fledgling industry, to convey its potential and successes to the community at was part of the attraction. But surely the biggest draw was large. The realm of biotechnology extends so far that some the scope and potential impact of the work: re-envisioning people on our list might not even consider themselves part health and wellness, transforming agriculture, retooling of this industry. Nonetheless, these scientists and business traditional industries and providing solutions to the global builders are as complementary to the emergence of the energy crisis in a climate-friendly manner. What greater field as two parents are to a child. challenges does our world face? Advances in biotechnology are the results of the efforts We present The Worldview 100, who are facing them head-on. of many tens of thousands of people. The Worldview 100 could easily have been developed as The Worldview 500, —TheScientific American Worldview team with key contributions The Worldview 1,000, or any multiple thereof. In identify- from Alexandra Hariri and Richard Gallagher.

THE WORLDVIEW 100 SURVEY METHODS

We developed and finalized this list in several steps through a process carried out from December 2014 through March 2015. First, we invited dozens of leaders in biotechnology and biosciences to nominate their choices for the most influential people in the field. We encouraged the nominators to select living experts currently working in the sector from a range of contributing areas, including industry, academia, public policy, finance, law and beyond. That process generated a list of almost 400 nominees. We then recruited more experts—many of them from the original group of nominators—to suggest anyone on the list of nominees worthy of selection to a more refined coterie of the 100 most influential figures in today’s world of biotechnology. For the final step, we tallied the votes, and the 100 people most selected formed The Worldview 100. Here, we highlight the 10 individuals who received the highest number of votes. We present the other 90 honorees in alphabetical order.

8 SCIENTIFIC AMERICAN | WORLDVIEW THE WORLDVIEW 100 9 professor of genetics | | Boston, Massachusetts, U.S. president & cofounder | Institute for Systems Biology | Seattle, Washington, US Church started his career with sequencing, especially through the development Hood played a role in the development of five instruments that drive today’s bio- of advanced devices, and he continues to help scientists collect and analyze data logical sciences: automated DNA sequencers, DNA synthesizers, protein sequenc- about the most basic life traits. As the director of PersonalGenomes.org, he pro- ers, peptide synthesizers and an ink-jet printer for constructing DNA arrays. Today, vides open access to data that explore the foundation of human traits around the he works on integrating biology, computation and technology to build so-called P4 world. His work on next-generation sequencing and cellular and tissue engineer- medicine, which is predictive, personalized, preventative and participatory. In the 2012

ing spawned a dozen companies based on medical genomics or synthetic biology. LEE HOOD Scientific American Worldview, Hood posited that the traits of a successful entrepre- Kirkus Reviews called his book Regenesis, coauthored with science writer Ed Regis, neur are “having a clear picture of the future that is very different from what other

GEORGE GEORGE CHURCH “a valuable glimpse of science at the edge.” people have, and an ability to drive towards that future.”

director | U.S. National Institutes of Health | Bethesda, Maryland, U.S. professor of biology | MIT | Cambridge, Massachusetts, U.S. “I think my greatest contribution to biotechnology arose from the charge I was After publishing a 2005 article in Nature on the chimpanzee genome, Lander said, given to lead the international Human Genome Project,” Collins told Scientific “The goal is not just butterfly collecting or mammal collecting to simply describe American Worldview. “Through the dedicated work of 2,400 scientists in six countries, mammals. All of that comparative work across mammals is about informing the we successfully sequenced and made immediately available the 3 billion base pairs human genome for medicine. Until we actually understand all the working parts in the human genetic blueprint—ahead of schedule and under budget.” To make within our genome, we won’t really be able to practice the most informed medi- biotechnology even more effective, he said, “It is especially important to support cine.” As a core member of the Broad Institute, Lander continues to explore what the creative minds who are pursuing high-risk projects that, if successful, may ERIC LANDER genomics can tell us about human physiology and diseases—especially how to

FRANCIS COLLINS yield high rewards for expanding biological knowledge or fighting human disease.” treat them.

David H. Koch Institute Professor | MIT | Cambridge, Massachusetts, U.S. co-chair and trustee | Bill & Melinda Gates Foundation | Seattle, Washington, U.S. Langer described his greatest contribution to biotechnology as “discovering how Best known as the cofounder of Microsoft, Gates turned his wealth into philan- to create materials that enable the controlled release of macromolecules.” Such thropic giving through his and his wife’s foundation, which, its website states, devices can deliver drugs—even genetically engineered proteins—for long periods, works to “bring about the kinds of changes that will help people live healthier and and Langer is even working on versions that can be controlled through magnetic, more productive lives.” Clearly, innovation has always played a fundamental role ultrasonic and enzymatic methods. The best way to increase the effectiveness of in his career. He once noted, “I believe in innovation and that the way you get biotech today, he said, is to provide “more funding for basic research.” Langer’s BILL GATES innovation is you fund research and you learn the basic facts.” That thinking took LANGER BOB output—including more than 1,000 patents, which have been licensed to over 300 him a long way. companies—attests to his indefatigable drive.

co-chair and trustee | Bill & Melinda Gates Foundation | Seattle, Washington, U.S. founder | J. Institute | La Jolla, California, U.S. In her 1982 high school valedictorian address at Ursuline Academy in Dallas, In 2013, Venter told Bloomberg, “Genome design is going to be a key part of the Texas, Melinda Gates offered the following wisdom: “If you are successful, it is future. That’s why we need fast, cheap, accurate DNA synthesis so you can make because somewhere, sometime, someone gave you a life or an idea that started a lot of iterations of something and test them.” By then, he and his colleagues had you in the right direction. Remember also that you are indebted to life until you already created a bacterial genome from scratch. Now, as the CEO and cofounder help some less fortunate person, just as you were helped.” At that time, no one of Human Longevity, Inc., Venter hopes to combine information about various could even imagine the help that she would bring to the world. According to her biological features—including the genome, proteome, biome and more—with CRAIG VENTER MELINDA GATES foundation’s website, it has given grants totaling US$32.9 billion. advanced algorithms and computing to create new therapies to extend our years of high-quality life.

former commissioner | U.S. Food & Drug Administration | Silver Spring, Maryland, U.S. Born to a two-physician family, Hamburg joined the family business—but in a director | Center for Drug Evaluation & Research | U.S. Food & Drug Administration managerial capacity. Before working for the FDA, she served as commissioner Silver Spring, Maryland, U.S. of the New York City Department of Health and Mental Hygiene, where she Woodcock helped to develop a regulatory framework to accommodate future significantly slowed the spread of tuberculosis. When President Obama named advances in biotechnology. Nonetheless, the discipline’s effectiveness could be en- Hamburg the FDA commissioner in 2009, Georges Benjamin, then executive hanced even more, she said, through “greater attention to translational science.” So director of the American Public Health Association, said, “She’s all about integrity far, the biggest impact biotech has had on our daily lives is “the food revolution,” and science…. She can be tough when she needs to be, and she’s going to need to she said, adding that “forms of gene therapy may be ‘coming of age.’” And the most be real tough in that job.” How right he was. embarrassing moments of her career? “Too numerous to count!” she answered. PEGGY HAMBURG JANET WOODCOCK JANET

10 SCIENTIFIC AMERICAN | WORLDVIEW THE WORLDVIEW 100 11 NAGLAA ABDALLAH of my previous employers because SOL BARER Alliance, we have used this kind of MARY BOOTE STEVEN BURRILL head | Agricultural Genetic I refused to play politics and apple managing partner | SJ Barer Consulting model to help developing countries de- CEO | Truth About Trade and Technology CEO | Burrill LLC | Bay Engineering Research Institute polish the boss. I am who I am today Summit, New Jersey, U.S. liver vaccines to more than a half bil- Des Moines, Iowa, U.S. Area, California, U.S. Cairo University | Giza, Egypt because I left that employer. And the “We are optimistic lion additional children and prevented “Speaking specifi- Looking back on Abdallah participates two most important traits I keep out now that many fatal more than 7 million future deaths in cally about agricul- biotech’s history, in the science and of my organization are politics and diseases can indeed the 73 poorest countries in the world.” ture,” Boote said, “the Burrill opined, “On use of genetically the need to be ‘nice’ to the boss.” not only be treated ability of a farmer to balance, the science modified crops in a but potentially cured,” KAREN BERNSTEIN add a much-needed has moved far faster cofounder, chairman & editor-in-chief variety of ways. She ANTHONY ATALA said Barer, former CEO and chairman at room to his home or pay a child’s than anyone could have assumed, and is editor-in-chief of GM Crops and director | Wake Forest Institute Celgene. Biotechnology “has impacted BioCentury | Redwood City, California, U.S. school fees because of an increased the business a little slower. 1,000 years Food and the acting director of the for Regenerative Medicine entrepreneurial behavior motivating “Newspapers, mov- yield due to biotech-crop access is a from now when they write the then Egypt Biotechnology Information Winston-Salem, North Carolina, U.S. students to go into this field, motivat- ies and our culture quality-of-life success story.” 3,000 years of recorded history of Center. “Currently, there are ing entrepreneurs to create companies, in general are filled mankind, this will go down in history not enough organs to encouraging investment in the field,” with uninformed DAVID BOTSTEIN as mankind’s greatest moment—when CSO | Calico | South San Francisco, JULIAN ADAMS go around,” Atala de- he added, “and all of this leading to views about science, we truly, for the first time, understood president | research & development clared at TED2011. better therapies for patients.” business and economics that harm California, U.S. the basis of life and our ability to Infinity Pharmaceuticals He aims to solve our society’s ability to make informed With genomes avail- improve it, transforming healthcare, Cambridge, Massachusetts, U.S. that healthcare crisis by making new ROGER BEACHY decisions about everything from able for a growing list agriculture, energy and industrial With more than 30 organs with 3D printing, which could director | World Food Center | University food to medicine,” Bernstein asserts. of organisms, Bot- production.” years of experience produce an unlimited supply for the of California, Davis | Davis, California, U.S. “There is no simple fix for this, but I stein takes the next as a chemist and ex- patients who need them. This plant biologist think we must try.” step—using them to ATUL BUTTE ecutive in the phar- visionary and found- explore complete biological systems. director | Institute of Computational Health Sciences | University of Cali- maceutical industry, ing president of the SANGEETA BHATIA This includes learning to analyze and Adams played a part in delivering Robert Andrews Millikan Professor of Danforth Center director | Laboratory for Multiscale display biology’s genomic big data. fornia, San Francisco | San Francisco, many life-saving treatments. Among Biology | California Institute of Biology knows how to keep Regenerative Technologies | MIT California, U.S. Pasadena, California, U.S. Cambridge, Massachusetts, U.S. them was his role in the discovery things in perspective. “After a series BOB BRADWAY Discussing the new and development of Velcade, a block- In his Nobel Lecture, of laboratory successes that followed “We’re engineers chairman and CEO | Amgen institute, Butte notes, buster cancer drug. Baltimore said, “The the discovery of disease-resistant working in a science Thousand Oaks, California, U.S. “We hope that we study of biology is technologies, I self-assuredly ref- environment, think- Regarding a new will be successful in RICH ALDRICH partly an exercise erenced ‘being on a roll,’” he told ing about human manufacturing making discover- cofounder | Longwood Fund in natural esthetics. Worldview. “Soon thereafter I took a health,” Bhatia told plant in Singapore, ies and developing diagnostics and Boston, Massachusetts, U.S. We derive much of our pleasure as fall and a long roll down a run at the NBC News. “What engineers like to Bradway recently therapeutics. If we want to change A serial founder and biologists from the continuing real- Purgatory ski resort at a Keystone do is tinker, so we encourage that told the Pacific Coast the world of medicine, we have to builder of biotech- ization of how economical, elegant Conference. To my chagrin and spirit of tinkering in the lab.” Business Times, “This is an approach bring those discoveries into the nology companies, and intelligent are the accidents of embarrassment, a friend, Jonathan to manufacturing that we think will marketplace and closer to patients.” including Concert evolution that have been maintained Jones, from the John Innes Center, JACK BOBO enable us to reduce our cost per gram senior advisor for biotechnology Pharmaceuticals by selection.” UK, shouted, ‘Are you still on a roll, of proteins by an order of magnitude BROOK BYERS and , Aldrich Beachy?’—not just one time, but United States Department of State of about 60%.” founding member | Washington, DC, U.S. Caufield & Byers | Menlo Park, repeatedly delivers capital to promis- STÉPHANE BANCEL repeatedly in following years.” ing projects. His work, though, goes president & CEO | Therapeutics “People love in- California, U.S. Cambridge, Massachusetts, U.S. beyond biotechnology. For instance, SETH BERKLEY novation almost as “This aversion to change Byers and his family he serves on the board of the Greater After raising US$450 CEO | Gavi, the Vaccine Alliance much as they despise support innovation Boston YMCA. million for Moderna Geneva, Switzerland change,” Bobo said. has delayed the adoption so extensively at the in 2015, Bancel told On extending the “This aversion to of agricultural biotech- University of Califor- MAHALETCHUMY ARUJANAN The New York Times: global reach of change has delayed the adoption of ag- nia, San Francisco, executive director | Malaysian “We do not want to today’s cutting-edge ricultural biotechnology in some parts nology in some parts of that the school established the Byers Biotechnology Information Centre do what most biotechs do, which is medicines, Berk- of the world. To increase the effective- Family Distinguished Professor- the world.” —JACK BOBO (MABIC) | Selangor Darul Ehsan, Malaysia one drug at a time. We want to go in ley opined, “Even ness of biotechnology, we need to build ship. Moreover, Byers is especially When asked to parallel.” stronger public-private partnerships public support and trust. In order to known for developing large venture identify a career- will ensure that the products of this do this, scientists need to stop telling capital funds devoted to biotech- changing moment, revolution are made available to those people what they do and start telling nology. Arujanan replied, living in the poorest parts of the world. them why they do it. It’s only after you “I was fired by one In my current job at Gavi, the Vaccine build trust that science matters.”

12 SCIENTIFIC AMERICAN | WORLDVIEW THE WORLDVIEW 100 13 ART CAPLAN STANLEY CROOKE can’t be breakthroughs.” No won- systems to perform particular ap- MICHAEL J. FOX ANITA GOEL Drs. William F. and Virginia Connolly CEO | Isis Pharmaceuticals der he created the XPRIZE, with its plications. The scope of material I can founder | The Michael J. Fox Foundation chairman & scientific director | Nanobiosym Mitty Professor of Bioethics | New York Carlsbad, California, U.S. mission of “designing and launching work with is not limited to the set of for Parkinson’s Research | New York, Cambridge, Massachusetts, U.S. University | New York, New York, U.S. A pioneer who helped large incentive prizes to drive radical things that we inherit from nature.” New York, U.S. Goel received the 2013 As his biggest con- lead the creation of breakthroughs for the benefit of hu- Since 2000, Fox’s XPRIZE in recogni- tribution to bio- RNA-targeted drug manity.” Diamandis is also cofounder OMID FAROKHZAD foundation has con- tion of her pioneer- technology, Caplan discovery, Crooke told of Human Longevity, Inc., along with associate professor | Harvard Medical tributed over US$450 ing contributions cited: “Helping to lay Worldview that the Craig Venter and Robert Hariri. School | Boston, Massachusetts, U.S. million for research to the new field of out the ethical case “one and only time I guaranteed a new An expert in devel- on Parkinson’s nanobiophysics and her Gene-RADAR for moving advances forward while drug would work in the next clinical JENNIFER DOUDNA oping nanoparticle- disease, more than half of which went technology, which she described in protecting human subjects.” His most trial was to the SmithKline Beckman Li Ka Shing Chancellor’s Professor in based systems toward developing treatments. “We the 2014 edition of Worldview as embarrassing moment? “Applying for board when I was president of R&D Biomedical & Health Sciences | University of drug delivery, are outcomes-focused, incorporat- “a mobile diagnostic platform for a grant with Dan Callahan while at there. We had a vasopressin antagonist of California | Berkeley, California, U.S. Farokhzad said of ing milestones into every award and providing anyone, anytime, anywhere the Hastings Center in 1985 to study and it worked beautifully to increase One of the leading one of his recent studies: “This is the tying grant payments to achievements with instant access to personalized the ethics of human and animal clon- free water clearance in all animal mod- researchers who first example of a targeted nanopar- of those milestones,” the foundation information about their health.” ing and getting rejected by the NSF els. In man, it was a partial agonist and created the CRISPR- ticle technology that reduces athero- website states. and NIH on the grounds that we did actually caused water retention.” Cas9 technology for sclerosis in an animal model.” His HUGH GRANT CEO | Monsanto | St. Louis, Missouri, U.S. not understand the science and mam- genome engineer- work also explores nanomedicine’s ROBB FRALEY executive vice president and CTO malian cloning was impossible.” SUSAN DESMOND-HELLMAN ing, Doudna believes that we must potential to treat many other diseases. In discussing exciting CEO | Bill & Melinda Gates Foundation “increase connections and commu- Monsanto | St. Louis, Missouri, U.S. advances in biotech- Seattle, Washington, U.S. ISAAC CIECHANOVER nications between academic labs and NINA FEDOROFF “The ability to iden- nology, Grant said, president & CEO | Atara Biotherapeutics Desmond-Hellman companies” to help biotechnology Evan Pugh Professor of Biology tify and map every “From new areas of South San Francisco, California, U.S. told Worldview that move ahead even faster. The Huck Institutes of the Life Sciences single gene in a plant, research in agricultur- Over his 20-year she wants to “acceler- Pennsylvania State University as well as create, al biologicals to the intersection of data State College, Pennsylvania, U.S. career, Ciechanover ate a process” already NINA DUDNIK screen and identify science and precision agriculture, the has spurred numer- underway at the Gates founder & CEO | Seeding Labs | Boston, Fedoroff pioneered genetic combinations,” he said, “has seamless use of a variety of technolo- ous medical advances Foundation, which is “forging public- Massachusetts, U.S. the development of literally changed how we breed crops. gies—including biotechnology—will and driven mergers private partnerships to develop prod- “My goal, through molecular clon- Today, we are seeing record rates of transform the future of agriculture.” and licensing worth US$6.7 billion. ucts specifically for the lowest-income Seeding Labs, is to ing and analysis gains and yields in crops where these He also cycles, scuba dives and loves countries.” She added, “In recent years, ensure that as many techniques for plants advanced breeding techniques have JIM GREENWOOD Pink Floyd’s The Dark Side of the Moon. we’ve seen some very promising signs scientists as possible starting in the late 1970s, and today been applied and as technology costs president & CEO | The Biotechnology of what can happen when a nonprofit have the right tools, she would like to see governments have rapidly declined, their impact Industry Organization (BIO) Washington, DC, U.S. RON COHEN or a government agency works with a training and professional networks to “simplify their regulation and make is now reaching native and orphan founder, president & CEO | Acorda business to reduce market risks, such make impactful contributions to bio- the regulations product- and not smallholder crops.” “When I was in col- Therapeutics | Ardsley, New York, U.S. as through volume guarantees…. If I technology,” says Dudnik. “There is re- process-based.” lege I made a com- To make biotechnol- could bring about any single change markable talent around the world, and YALI FRIEDMAN mitment that I want- Head, Data Analytics, Scientific American ogy more effective, in the biotech field today, it would be developing capacity and infrastructure JAY FLATLEY ed to devote my life Cohen says, “I would to encourage all players in this sector for these individuals is a smart, mea- CEO | Illumina | San Diego, California, U.S. Custom Media | Washington, DC, U.S. to service,” Green- start a $30 billion ini- to be more imaginative and aggressive surable investment in global science.” Flatley told World- “Fresh out of wood recalls. “When I graduated, I tiative to emphasize about seeking such partnerships.” She added, “Our responsibility does view that we are graduate school I worked as a house parent with special and improve STEM education in U.S. not end in the lab, especially in the “moving into an era published Building needs children, then as a caseworker K–12 schools…. We need to ensure PETER DIAMANDIS digital age. We need to be ambassadors of greater diagnos- Biotechnology, which with abused and neglected children.” that the next generation will produce founder & chairman | XPRIZE Foundation and translators for science.” tic precision and quickly became the Later, he was elected to the Pennsylva- enough high-quality scientists and cofounder, Human Longevity, Inc. personalization of patient care,” such leading textbook on the business nia State House, the Pennsylvania State Culver City, California, U.S. industry leaders to maintain our lead- DREW ENDY as non-invasive prenatal testing for of biotechnology,” said Friedman. Senate and the U.S. Congress. “When ership, which creates not only life- In a 2012 interview associate professor chromosomal abnormalities and “Lately I have been developing a I was offered my position at BIO, I saw saving medicines, but also high-value, with Wired, Dia- Bioengineering | Stanford University liquid biopsies to detect DNA circu- novel methodology to rank patent it as an opportunity to continue that high-wage jobs.” If not for his current mandis declared, “If Stanford, California, U.S. lating in the blood from cancer cells. attorneys at PatentStat.com, build- focus on service,” he explained. career in the industry, he would have someone is always Endy, a synthetic He added, “I think one of the most ing a tech transfer search engine at been an actor in the New York theater. to blame, if every biologist, told The meaningful impacts will be allowing TechTransferWatch.com, and leading “That’s what I did in between my time something goes wrong someone Guardian, “I want us to live healthier lives longer.” data analytics for Scientific American careers in medicine and biotechnol- has to be punished, people quickly to be able to design Custom Media.” ogy,” he said. stop taking risks. Without risks, there and build biological

14 SCIENTIFIC AMERICAN | WORLDVIEW THE WORLDVIEW 100 15 “I would improve the communication of ROBERT HARIRI LUIS HERRERA-ESTRELLA CLIVE JAMES MARY-CLAIRE KING chairman & founder | Celgene Cellular chief | National Laboratory of Genomics founder & emeritus chair | International American Cancer Society Research Professor biotechnology’s enormous value proposition Therapeutics; cofounder, Human for Biodiversity | National Polytechnic Service for the Acquisition of Agri-Biotech departments of medicine & genome to society.” Longevity, Inc. | Warren, New Jersey/ Institute | Irapuato, Mexico Applications (ISAAA) | Cayman Islands sciences | University of Washington —JOHN MARAGANORE La Jolla, California, U.S. If he hadn’t gone “The contribution of Seattle, Washington, U.S. According to Hariri, into biotechnology, biotech/GM crops King applies next- RAJU KUCHERLAPATI ART LEVINSON “Biotech has been Herrera-Estrella told to the alleviation of generation sequenc- Paul C. Cabot Professor | department of founder & CEO | Calico the source of virtu- us, he might have poverty and hunger,” ing to a wide range of genetics | Harvard Medical School South San Francisco, California, U.S. ally every major new been a professional said James, is the crucial areas, includ- Boston, Massachusetts, U.S. “As a little kid,” platform of technol- dancer. Instead, he works on geneti- most impactful effect biotechnology ing breast and ovar- Kucherlapati told Levinson once said, ogy which creates new therapeutics, cally modified (GM) crops, of which has had on our lives to date. “The ian cancer, as well as the genetics of PhRMAdigital, “Per- “I was always afraid such as biologics, immunotherapy he said, “due to lack of information commercialization by Bangladesh, schizophrenia. In addition, she even sonalized medicine of getting old. On my and cellular medicine. I believe and the opposition of anti-technology one of the poorest countries in the uses sequencing to identify victims of has the potential to 7th birthday, I was cellular immunotherapy will have a groups, their full potential still has not world, of Bt brinjal (eggplant) can human rights abuse. significantly alter actually sad, because it just seemed quantum effect on the treatment of been achieved. GM crops reduce the benefit up to 150,000 small resource- the health and well-being of all of like—wow, 7 is not 6 anymore.” No cancer in the next 3 to 5 years.” cost of production and the negative poor farmers.” RACHEL KING the American population. And if our wonder he recently founded Calico, environmental impact of agriculture president & CEO | GlycoMimetics population begins to recognize what which plans to “devise interventions Gaithersburg, Maryland, U.S. DEBBIE HART by reducing the use of agrochemicals.” CALESTOUS JUMA personalized medicine is, how the that enable people to lead longer and president & CEO | BioNJ director | Science, Technology, Globaliza- In her testimony principles of personalized medicine healthier lives.” Trenton, New Jersey, U.S. tion Project | Belfar Center for Science and JAMIE HEYWOOD to the U.S. Sen- would apply to their health and well- chairman & cofounder | PatientsLikeMe International Affairs | Harvard Kennedy “My greatest contri- ate Committee on being, it would have a very significant JOHN MARAGANORE bution has been my Cambridge, Massachusetts, U.S. School | Cambridge, Massachusetts, U.S. Small Business and impact.” CEO | Alnylam Pharmaceuticals greatest blessing— When asked about Although Juma has Entrepreneurship on Cambridge, Massachusetts, U.S. my absolute passion the biggest impact more than 68,000 March 19, 2015, King eloquently dis- ANNA LAVELLE “While there’s for my life’s work,” of biotech on our followers on Twitter, tilled the relationship between science CEO | AusBiotech | South Yarra, Australia still more to do,” says Hart, who leads a biotechnology lives, Heywood said, you don’t need to and business: “Patents allow biotech In BioSpectrum, Maraganore said, his advocacy group in the biopharma “What we have seen follow his tweets long inventions of great societal value to be Lavelle recently chief contribution legacy state of New Jersey. “Out of so far is like looking at the first com- to understand his perspective. On passed or shared among parties best wrote: “High-tech to biotechnology is that has flowed an undying optimism puters and anticipating the iPhone March 21, for example, he tweeted suited to unlock their potential at any innovative industries “delivering on the promise of RNAi as for the future, an unrelenting com- and the Internet. Biotechnology is an a photo of a lion and zebra drinking given stage of development and com- generate globally a new class of innovative medicines.” mitment to work hard for our mem- information frontier that is just begin- side by side with the hashtag #peace. mercialization—each contributing its competitive economies and sustain- Regarding ways to make biotech more bers in their support of patients and ning to open and it will transform part, each sharing the risk of failure, able, high-skilled jobs and Australian effective, he said, “I would improve an unquestionable belief that what we everything about how well and how CARL JUNE each increasing the odds that a prod- biotechnology is poised to make its the communication of biotechnol- do matters.” long we live.” Richard W. Vague Professor in uct eventually reaches patients.” contribution to Australia’s growth. ogy’s enormous value proposition to Immunotherapy | Perelman School of Australia has a strong comparative society.” Medicine | University of Pennsylvania WILLIAM HASELTINE BOB HUGIN GANESH KISHORE advantage in medical research and chairman & president | ACCESS Health chairman & CEO | Celgene , Pennsylvania, U.S. CEO | Malaysian Life Sciences Capital the calibre of its researchers, and in its ANDY MARSHALL International | New York, New York, U.S. Summit, New Jersey, U.S. When we asked June Fund | St. Louis, Missouri, U.S. ability to specialize in niche manufac- chief editor | Nature Biotechnology If Haseltine could “In the last 50 years, what could drive “The greatest con- turing.” New York, New York, U.S. make one change in 50% of the economic innovative science cern I have,” Kishore Marshall described the world of biotech, growth in America is that will benefit the told Worldview, “is MARK LEVIN his greatest contribu- he would “create due to medical inno- healthcare system, he that the emotional partner | Third Rock Ventures tion to his field as virtual biotechnolo- vation…and 73% of replied, “I think now we’re at this real and geographic bar- Boston, Massachusetts, U.S. “finding the best and gy companies that outsource almost all life expectancy gain in the first decade tipping point where we can harvest riers for the adoption of products of Upon receiving the brightest to work aspects of clinical development, manu- of this century is due to medical in- many of the basic advances, and biotechnology have become glob- 2014 Leadership in with me. And helping the best and facturing and marketing of com- novation,” Hugin recently told CNBC. things previously thought impossible ally rampant. In fact, it is troubling Personalized Medi- the brightest junior faculty meet the pounds sourced from academia. I “Intellectual property is the lifeblood will be happening. I think one thing that our society fails to recognize cine Award, Levin best and the brightest in the business would work with a small staff with of innovation, and we have to make is we need to educate the public about that all food in our plant and even remarked, “The best world. Not enough is being done to little to no infrastructure.” sure as a company, as an industry, we what can happen because the public animal food chain today is ‘geneti- part of the last 40 years has been give gifted researchers the funding protect it.” will be more involved” with the new cally modified’—and even evolution is working with incredible people…to and opportunities they need. A lot of therapies. about genetic modification leading to make a difference for patients. It can- good science is falling between the adaptation.” not get any better than that!” cracks.”

16 SCIENTIFIC AMERICAN | WORLDVIEW THE WORLDVIEW 100 17 GEORGE POSTE RAM SASISEKHARAN AMY SCHULMAN Del E. Webb Chair in Health Innovation Alfred H. Caspary Professor of Biological venture partner | Polaris Partners “My philosophy has been one of differentiation. Look at biomedicine & biotechnology | Arizona Engineering and Health Sciences & Technol- Boston, Massachusetts, U.S. State University | Tempe, Arizona, U.S. ogy | department of biological engineering Not afraid to laugh what’s there and keep challenging yourself to be different.” Poste told us that he’d MIT | Cambridge, Massachusetts, U.S. at herself, Schul- like to see “radi- Sasisekharan told man told The New —KIRAN MAZUMDAR cal reform of NIH us that his biggest York Times in a 2011 funding policies for contribution to interview about the KIRAN MAZUMDAR DAVID MOTT ROGER PERLMUTTER academia,” add- biotechnology was first time she took a deposition: “I chairman & managing director general partner | New Enterprise Associates president | Merck Research Laboratories ing, “Current NIH funding policies “developing a tech- got there early, and I thought that the Biocon | Bangalore, India Timonium, Maryland, U.S. Boston, Massachusetts, U.S. are anachronistic and propagate nology platform for glycobiology that most important thing was to control In the 2011 edition After executive roles “I fairly early on individual investigator-centric silos has impacted both regulatory as well the witness. I didn’t realize…the of Scientific American in pharma, Mott established a pretty of reductionist biology, which lack as drug development in various fields.” way you control somebody is not by Worldview, Mazum- moved to healthcare simple set of guiding critical mass and are ill-suited to To enhance the effectiveness of biotech intimidating them. But I adjusted the dar told us: “My phi- venture investing principles,” Perlmut- address the complexity of unresolved today, Sasisekharan would like find chair…so that I’d be really tall, and losophy has been one in 2008, where he ter told the American disease challenges that require large ways to “speed the process of bringing could look down imposingly on the of differentiation. Look at what’s there quickly made a name for himself. Association of Immunologists in scale, multi-disciplinary, team-based much-needed medicines to patients.” witness. But I raised it so high that as and keep challenging yourself to be In fact, FierceBiotech called him the 2013, “focus on grievous illness… approaches, often involving multiple soon as I sat down, I toppled over and different: If everyone is after generic “leading life sciences venture maven,” focus on the task, not the tool…[and] institutions.” GEORGE SCANGOS fell backward.” products, how can you get into novel given the billions that he has raised. do the experiment in people.” He also won the prize for the CEO | Biogen Idec Cambridge, Massachusetts, U.S. programs? If you can do that, then best embarrassing moment: “Dur- distinguished fellow | School of Foreign you stand apart and you can do things KAREN NELSON KIM POPOVITS ing my surgery training rotation at “We’re in a very more effectively.” president | J. Craig Venter Institute chairman, CEO & president | Genomic the University of Bristol Veterinary exciting time in Service | Georgetown University Rockville, Maryland, U.S. Health | Redwood City, California, U.S. School in the UK, I quickly realized the biotechnology Washington, DC, U.S. TERRY MCGUIRE Nelson’s group pub- “The core values of that I was ill-suited for a full-time industry,” Scangos With nearly 60,000 cofounder & general partner | Polaris lished the first paper our company and career as a clinical veterinarian. Apart said in the PwC 2015 Twitter followers, Partners | Boston, Massachusetts, U.S. on the human micro- the core focus of from angry patients who bit, kicked US CEO Survey. “The stock prices Shah tweets on a “It’s not good enough biome in 2006, which our company [are] and scratched and were thoroughly of all biotechnology companies have range of topics, from to be intellectually she said, “launched centered around resentful, the nadir was reached in increased dramatically in the past few coffee to Ebola. On smart,” McGuire and invigorated an unbelievable patients,” Popovits explained in a my attempt to anesthetize a large years, so you hear talk about whether February 18th he wrote: “We have to once said, “you need awareness of the microbes in and on company video. “Each one of us who tree porcupine from the local zoo by we’re in a bubble or not. I don’t think find new ways of bringing huge pools to be clever, clever us.” For the most exciting application came here in the early days, I can say, applying the anesthetic mask to the this is a bubble. These price increases of capital to #globaldev, especially in enough to figure out new ways to of biotechnology in the past year, was personally motivated—through wrong end of what was a large, wrig- reflect actual increased value and infrastructure. Be bold & creative go- make things happen. Plus, you need Nelson pointed to “Human Longevity, professional or their own personal gling ball of spines, which prevented productivity in the higher number of ing forward.” ambition that is beyond monetary, a Inc.—bringing the genome, microbi- experience with cancer—to really any easy effort to distinguish anterior drugs coming forward.” desire to see a better world.” ome, metabolome and phenotypes of transform cancer care.” and posterior axes.” PHILLIP SHARP institute professor | David H. Koch Insti- individuals into a single vision with LEONARD SCHLEIFER founder, president & CEO | Regeneron tute for Integrative Cancer Research at MIT HENRY MILLER really major implications for how we RICHARD POPS PAM RONALD Robert Wesson Fellow in Scientific approach healthcare.” chairman & CEO | Alkermes | Dublin, Ireland director | Laboratory for Crop Genetics In- Tarrytown, New York, U.S. MIT | Cambridge, Massachusetts, U.S. Philosophy & Public Policy In 2012, Pops told novation & Scientific Literacy | University Of his early days as “My greatest contri- Hoover Institution | Stanford University of California, Davis | Davis, California, U.S. STELIOS PAPADOPOULOS Scientific American a bioentrepreneur, bution to biotechnol- Stanford, California, U.S. chairman | Biogen Idec | Cambridge, Worldview that even When Worldview Schleifer recently ogy is novel science Miller considers Massachusetts, U.S. while jogging or asked Ronald to tell told CNN, “We had and translation of his most significant In 1979, Papadopou- playing tennis he us her greatest con- this belief that the this science to help- contribution to los started collecting lets “work run in the background. tribution to biotech- world needs innovative products.” But ing people through cofounding and biotechnology to be biotech IPO data, Sometimes the solution to some nology, she pointed his career as a dealmaker began years participating on the boards of Biogen “the record-setting and he recently problem will arise after days and days. out her work with rice, in particular, before in the snow-shoveling busi- Idec (1978) and Alnylam (2002),” FDA approval of human insulin, showed that 2014 My philosophy of life is determined “isolation of the Xa21 resistance gene ness: “When you have to do a whole Sharp said. “This has benefited mil- when I headed the team that reviewed brought the industry 22% more IPOs optimism. I am always able to turn and the Sub1 submergence tolerance block’s worth of shoveling, you get a lions of people around the world as it in 1982.” He’d like to see more FDA than in 2000, the so-called bubble adversity into opportunity.” gene in collaboration with my col- lot of experience” negotiating. patients and as well in the creation of advances today, including “more year. In the age of computation and leagues.” Her pick for the most excit- new jobs.” scientific, risk-based regulation.” big data, he still gets results the old- ing application of biotech in the past fashion way—he collects it by hand. year: the HIV and Ebola vaccines.

18 SCIENTIFIC AMERICAN | WORLDVIEW THE WORLDVIEW 100 19 PATRICK SOON-SHIONG ERIC TOPOL FLORENCE WAMBUGU kids on Long Island and in New York people are in the iPSC field. The fund- chairman | Chan Soon-Shiong Family cofounder | Lysosomal Therapeutics director | Scripps Translational Science CEO | Africa Harvest Biotech Foundation City, along with tens of thousands of ing and infrastructure provided by the Foundation | Culver City, California, U.S. Cambridge, Massachusetts, U.S. Institute | La Jolla, California, U.S. International | Johannesburg, South Africa teachers, who received instruction on Japanese government is also a major “Soon-Shiong is In a 2013 article, Topol said his chief “Our mission is to teaching biotechnology-based lab units factor, as these have encouraged ex- rolling out a series of The Boston Globe contributions to improve food secu- and even entire courses. cellent scientists to enter the field.” companies that rep- called Termeer “a biotech have been rity and the welfare resent a $1 billion- life sciences legend.” the new drugs he has of African popula- MARY WOOLLEY GEORGE YANCOPOULOS plus effort to fight Termeer served as helped develop, such tions by using the president | Research!America president | Regeneron Laboratories cancer in new ways,” Forbes recently chairman, president and CEO of as tPA and abciximab (ReoPro). These tools of agronomy and agricultural Alexandria, Virginia, U.S. Tarrytown, New York, U.S. reported. “This includes buying DNA , a company that he ran for medicines, he noted, are “now ex- biotechnology,” Wambugu recently Discussing the 21st “Innovation in sci- sequencers to unravel the DNA of nearly 30 years. He sits on more than panding across all medical disciplines told the ’s Century Cures ence and technol- cancer patients, not in a clinical trial a dozen biotech boards and continues and diseases” and have “completely LSF Magazine. “We are working legislation in one of ogy is at the heart of but as standard practice, at an unprec- to mentor people entering the field. changed the landscape of effective to build healthy communities and her weekly advocacy Regeneron’s mission edented scale.” treatments.” help smallholder farmers produce messages, Woolley to discover and SHIRLEY TILGHMAN plentiful, nutritious food supplies…. wrote: “Among our priorities will be develop new treatments for serious professor | molecular biology | Princeton PAUL STOFFELS ROBERT URBAN We are working to create sustainable to ensure that basic discovery is not diseases,” Yancopoulos said while CSO | Johnson & Johnson University | Princeton, New Jersey, U.S. head | Johnson & Johnson Innovation agricultural systems.” neglected….We will continue to push discussing the 2014 Regeneron Prize New Brunswick, New Jersey, U.S. “I have been worried Boston, Massachusetts, U.S. for final bipartisan language that ef- for Creative Innovation. “Investing in “The mission of our for some time that “This moment in JUDY WANG fectively boosts the return on medical science education and the identifica- innovation centers the improvements in medicine is re- senior manager | biotech affairs & regulatory progress by accelerating discovery, tion and development of talented new is to find the best the status of women ally a very exciting DuPont Pioneer China | Beijing, China development and delivery.” researchers is critical to foster tomor- science available in our society have demonstration of “I personally have row’s medical breakthroughs.” in an early stage, slowed in recent decades, after re- how converging been engaged in TADATAKA “TACHI” YAMADA executive vice president, chief medical & and then to accelerate it in order to markable gains in the wake of the femi- talents can be leveraged,” Urban said biotech R&D and ELIAS ZERHOUNI stimulate the development of new nist movement,” Tilghman recently in a video produced by the Science & management since scientific officer | Takeda Pharmaceuticals president, global R&D healthcare solutions,” Stoffels explains told The Daily Princetonian. “It is very Technology Innovation Program at 1996,” Wang wrote Osaka, Japan Sanofi | Paris, France on a Janssen website. “By doing so, we clear that until we find better solu- the Woodrow Wilson International in a response on GMO Answers. “I If he hadn’t entered At a conference in have tracked down more than 2,700 tions for working parents—including Center for Scholars. “The biologists have seen [the China Ministry of the field of biotech- London, Zerhouni valuable opportunities in 18 months paid maternity leave and proper child who understand the molecular basis Agriculture] grant Safety Certificates nology, Yamada said, pointed out the and concluded some 80 collaboration care options—the progress is going to of disease in unprecedented ways for importing food and feed processing “I think I would still urgent need for regu- agreements.” be slow.” are beginning to work more closely material from biotech crops….In 2012 have focused on pa- latory harmoniza- with technologists and engineers to alone, China imported 58 million tons tient benefit by pursuing my career as tion, saying, “In my short experience JACK SZOSTAK LUKE TIMMERMAN [turn] that knowledge into a form of biotech soybean and became the an academic physician or as someone of five years [at Sanofi], I have not Alex A. Rich Distinguished Investigator founder & editor | Timmerman Report of know-how that can [lead] to new world’s biggest country for biotech soy- committed to global health.” Of the seen a single regulatory decision that department of molecular biology Seattle, Washington, U.S. types of products that can be used by bean importation and consumption.” past year’s biotech advances, he found was fully consistent across regulatory Massachusetts General Hospital “Many biotech physicians.” “the maturation of gene therapy and agencies.” Boston, Massachusetts, U.S. companies have microbiomics as real market opportu- chancellor emeritus “Is it easy or hard for overreached on drug MARC VAN MONTAGU nities” the most intriguing. DAPHNE ZOHAR life to emerge from pricing,” Timmer- founder & chairman Cold Spring Harbor Laboratory founder & CEO | PureTech Ventures Institute of Plant Biotechnology Outreach Cold Spring Harbor, New York, U.S. Boston, Massachusetts, U.S. the chemistry of early man asserted. “The SHINYA YAMANAKA planets?” Szostak industry could go a long way toward Ghent University | Ghent, Belgium While heading the director & professor “Our industry is very asked in an iBiology restoring public trust by lowering “I want to stress that Cold Spring Harbor Center for iPS Cell Research & Application good at pattern rec- lecture. “Unfortunately, it’s going to prices, or at least backing off on the this GM technol- Laboratory, Watson Kyoto University | Kyoto, Japan ognition,” Zohar told be a long time before we can answer relentless increases. Public reputation ogy we developed commissioned the Yamanaka received Worldview. “How- that question in the most satisfying matters for a number of reasons. Pub- in Ghent, that it’s DNA Learning Cen- the 2012 ever, creativity often way, by direct observation.” In his lab, lic funding is essential for the basic really technology ter (DNALC) in 1987 to deepen the for his invention of involves breaking those patterns, do- though, Szostak seeks to reconstruct research that helps advance industry. that we needed,” Van Montagu told public’s understanding of DNA, the ge- induced pluripotent ing things differently.” She continued, the process by which primitive cells— Biotech also needs a large pool of the audience at TEDx in 2014. “So it’s nome and related technologies. Since stem cells (iPSCs). “The ability to measure millions of that is, life—emerged from a swirl of people willing to participate in clini- a myth that is propagated that we can that time, the DNALC has provided Writing on the Knoepfler Lab Stem physiological and other health-related chemicals some 4 billion years ago. cal trials, and share their health data. do without.” hands-on training for introducing Cell Blog about the rapid pace from data points over time is one of the People are reluctant to do those things students from middle school through discovery to use of iPSCs in a clinical most intriguing areas in terms of its for people they don’t trust.” high school to molecular genetics. The trial, he said: “The rapid transition is impact on drug discovery, clinical tri- program has reached half a million because many bright and passionate als and new medical modalities.”

20 SCIENTIFIC AMERICAN | WORLDVIEW THE WORLDVIEW 100 21 Bacillus thuringiensis (Bt) that en- impossible to learn anything without a dedicated, unyielding campaigner. BENCH TO BUSINESS codes a toxin. When Ntseoane planted it.” And when gathering feedback, it He watches many of his students take these seeds on two hectares, they pro- never hurts to turn to the best and their own work down this road, and duced 7 tons of corn per hectare. That the brightest, like Robert Langer, the he says, “They are real champions of In 2009, Scientific American was more than double her previous David H. Koch Institute Professor the ideas, and having a champion is Worldview was launched to harvest of conventional corn, which, at MIT and the author of over 1,000 very important.” In fact, Langer gains bring you the stories behind at 2 to 3 tons, was kept at a low yield patents, which have been licensed to empowering feedback for himself by the numbers presented in our by stalk borers. The next year, the Bt more than 300 companies. watching his students advocate for Scorecard of biotechnology their own ideas. “Having students do innovation potential (page 36). Innovation is the creative lifeblood of every country. things that make them happy is very Since then, we have travelled important to me,” he says. the globe to discover the in- Without a champion, even an novative technologies that are corn again produced 7 tons per hect- Langer explains that determining amazing idea can fall flat. Langer of- transforming our field and the are for Ntseoane. Even in the follow- which innovations will lead to great ten cites the Apple corporation as an lives of those who reap their ing draught year, every hectare of the products “depends a lot on your goal, example. With Steve Jobs and Steve benefits. Nonetheless, inno- Bt corn yielded 5.5 tons. As Ntseoane because lots of things can be useful. I Wozniak, Apple excelled. When the vation alone cannot build an says, “Had I not used the new technol- like it to be based on breakthrough sci- board decided to replace Jobs with a industry. As Google cofounder ogy, I wouldn’t have harvested much.” ence that could be really game-chang- “professional” CEO, the organization Larry Page once said: “Invention Ntseoane’s story illustrates a fun- ing.” And when assessing the way for- stumbled through five of them while is not enough. Tesla invented damental truth in the field of bio- ward—from the discovery in the lab to its business faltered. But when Jobs the electric power we use, but technology: getting the most out of a working toward commercialization— took over again, it rose to become the ©KEITH NEGLEY ©KEITH he struggled to get it out to technical innovation requires vision, he warns against a common mistake: world’s most valuable company. The people. You have to combine courage and commitment—plus the underestimating the task. “The major lesson, Langer stresses, is that even both things: invention and inno- FROM EUREKA ability to take advantage of available thing people do is underestimate how the most astoundingly innovative vation focus, plus the company resources. long it takes, how expensive it is and ideas need the leadership of a cham- that can commercialize things TO USEFUL how many difficulties you’ll run into.” pion to succeed. and get them to people.” ACCELERATING In order to combat these issues, he Delivering cutting-edge Developing an idea into a productive tool demands experience, INNOVATION’S APPLICATION encourages biotech entrepreneurs to MAKE THE RIGHT MEASURES biotechnology to people around foresight and a persistent champion BY MIKE MAY “Innovation is the creative lifeblood of be prepared. “Surround yourself with The excitement of a eureka moment the world requires a host of every country,” wrote The Honorable great people,” he says, “and have more in the lab, however, can get some sci- capabilities apart from simply or decades, a combination of politics and peer pressure pushed Birch Bayh in the forward to Michael capital rather than less.” entists moving too fast. “If the ambi- having an innovative concept Eve Ntseoane away from farming in her native South Africa. A. Gollin’s Driving Innovation. Many Also, Langer firmly believes that tion is to commercialize an idea,” says with great potential. This sec- Although her parents both grew up on farms, they couldn’t stay would argue that the same could be any innovation with a good chance of Anders Nordström, a senior advisor at tion delves into that journey there as adults. “Black people were moved to townships, because said for the complex and promising successful commercialization requires Sweden’s Uppsala Innovation Centre, “from bench to business” by of remnants of the Land Native Act of 1913,” she explains. During field of biotechnology. meeting the researchers, men- school vacations, though, Ntseoane’s mother would take her and The question is: How can scien- In South Africa, Eve Ntseoane tors, CEOs, nonprofit leaders, her brother to a farm where her uncle worked. “As a child I hated tists turn “eureka moments” into more than doubled her yield venture capitalists and end us- Fevery first few days of the visit, but with chickens and puppies around, I would useful products and services more with genetically modified corn. ers whose lives and livelihoods start enjoying it,” she remembers. “One morning my cousin and I climbed on quickly, more effectively? In Think have been forever changed by it the wagon carrying farmworkers to the corn fields. It was fascinating to help Like a Freak, Steven D. Levitt and Ste- (see “From Eureka to Useful,” out, though we played most of the time.” phen J. Dubner write: “The modern this page). Then, a look inside Ntseoane studied agriculture during her first three years of high school, but world demands that we all think a bit LabCentral’s “launchpad” for she says, “It came with a stigma that farming was for the not-so-clever.” Eventu- more productively, more creatively, bioentrepreneurs (page 26) and ally, she succumbed to the peer pressure and her parents’ wishes, and became a more rationally; that we think from an essay by industry expert teacher. She only taught for three years before moving to the corporate world, a different angle, with a different set Stephen Sammut (page 28) where she worked in communications. of muscles, with a different set of ex- attest to the countless ways Nonetheless, her past and changing social circumstances eventually lured pectations; that we think with neither people in our field get together Ntseoane back to the corn fields. Through the South African government’s fear nor favor, with neither blind op- to nurture the evolution of ideas Land Reform Strategy, she obtained a 539-hectare farm south of Johannesburg. timism or sour skepticism.” into commercial products. As The plot is situated “near a little town called Vanderbijlpark, which is popular In addition to that new kind of these stories illustrate, this for the Vaal Dam that supplies water to most South African provinces,” she says. thinking, would-be innovators must process often takes a number She began farming corn, working with traditional varieties. But in 2011, also learn from experience. As Lev- of complicated, yet fascinating, she says, “AfricaBio, an organization in South Africa, introduced me to Bt itt and Dubner point out, “The key turns along the way. maize.” This corn gains insect resistance through a bacterial gene derived from to learning is feedback. It is nearly

22 SCIENTIFIC AMERICAN | WORLDVIEW BENCH TO BUSINESS 23 “many scientists focus too much on how to take their biotech ideas from when obstacles in its research turned « Seeding Labs sends scientific the technical science. They need to lab bench to bedside, agrees. “We now up. “We returned the money to the equipment and expertise to define what it means, the benefit, for understand that innovation in life sci- investors,” Ainsworth says, “and we developing countries. the customer.” Which is not to say ences requires two parallel paths,” he took the science back to the lab.” that potential buyers can always artic- says. “First, making the science better That experience made Ainsworth partner for HealthCap, a family of VC ulate their precise needs. “The market and useful. But second, we need to extra cautious with RetroSense—a funds investing in international life need might be there, but the custom- understand how to commercialize the company with a gene therapy that science research. In addition, Steiner ers might not know it yet,” he says. science. We never had a formal pro- repairs vision in people with retini- has served as the CEO for several Just because someone creates a cess to test whether the science could tis pigmentosa or age-related macu- small start-ups. technical solution of some sort, how- turn into a commercially successful lar degeneration. “We ensured that Although he admits his bias as ever, doesn’t mean that a market ex- product. We do now.” it wasn’t just one individual who had a partner in a VC firm, Steiner says, ists for it or can even be created. To The I-Corps/Lean LaunchPad developed and published something,” “There would be no biotech industry determine this, says Nordström, you methodology, which Blank devel- he says. “In this case, it had been done if there were no VCs.” Biased or not, “need to define the market and who oped, allows for rapid testing and with people around the world.” With few in the field would disagree with will be the customer.” learning. “People solid research in place, RetroSense Steiner’s blunt assessment, because For instance, Nordström describes hypothesize in has continued to thrive. In fact, it re- it takes money—often lots of it—to an experience that he had with Swe- The biggest the lab but rarely cently raised US$6 million to file an commercialize an innovation. den’s Mentor4Research program, mistake is think of things investigational new drug (IND) appli- How VCs invest in biotechnol- which was designed to help academic like ‘Who do cation with the U.S. Food and Drug ogy, though, depends on the overall researchers commercialize their ideas. thinking you think will Administration (FDA). economic environment, says Steiner. Olle Ericsson, then a researcher at that your pay for this?’” he When the general economy is in de- Uppsala University, had a concept for faith is fact. explains. To find SPREAD THE CAPABILITIES cline, as in 2008, financing for biotech a more efficient sample-preparation out, Blank makes Indeed, developing an innovative firms tends to dry up. This is a huge kit to be used in next generation se- scientists in the product and finding a market for it resources for research itself overshad- the life science sector grow more ef- stumbling block for fledgling inno- quencing (NGS). “Olle had no expe- program go out and talk to at least is a challenging feat under the best of ows the focus on taking the discoveries ficiently?” He answers part of his own vators. “However, even when no one rience whatsoever in business, but 100 potential customers. “The princi- circumstances. But, not surprisingly, out of the lab and into the market.” question, saying, “It mostly comes wants to invest in biotech,” he says, was extremely eager to learn,” says pal investigators must get out and see in some areas of the world it is far Helping these nations become down to innovation.” “there are always some companies Nordström, who was Ericsson’s Men- the people,” he says. “For one thing, easier than in others. As the founder biotech innovators who can get their Also, in terms of getting an in- seen as the best ones.” Those busi- tor4Research advisor. “Still, we un- you might find that the market wants and CEO of Seeding Labs in Boston, ideas or products to market also re- novation onto the market, projects nesses tend to be further along, and derstood that the NGS market was something that you have but that you Massachusetts, Nina Dudnik sees this quires a highly-skilled workforce. must cross the so-called “Valley of in troubled economic times, they’re growing tremendously.” Nordström thought no one would want.” disparity firsthand. Her organization “Being in an innovation hub like Death”—that no man’s land where the ones that get the VC. Such is the helped Ericsson structure the ap- What are the most common mis- works to bring advanced scientific in- Boston,” Dudnik says, “it’s very clear a concept is not far enough along to law of the VC jungle. proach, make important contacts and takes made in turning an innovative struments and training to developing that building human capability is ab- attract financial support but des- And while being backed by excep- build a company called Halo Genom- idea into something commercial? countries. When asked if scientists in solutely critical to making the whole perately needs it to move ahead. To tional science greatly improves the ics—which Agilent Technologies soon “The biggest mistake is thinking that developing nations suffer more from pipeline work.” (See “Biotechnology’s increase the odds of crossing that di- odds of getting funding to turn an in- acquired—that eventually turned the your faith is fact,” says Blank. The I- a lack of the tools needed to innovate Crucial Question,” page 28.) vide, Uppsala BIO created the BIO-X novation into a product, investors need innovation into a product called Halo- Corps @NIH addresses that problem or from a need for the means to com- Many groups work together to program. “Here,” says Forsberg, “we to be convinced. “Bring as much data Plex. As Nordström recalls, “We knew when it makes an innovator take an mercialize their innovations, Dudnik build human capacity in the Nor- can provide support through a net- to the table as possible,” Steiner says. we were in a very hot market.” idea to the real world. “You start with points out that the two are inextri- dic countries, which consistently work of competence—from users, Impressive data, however, won’t For most innovators, however, faith in your idea and then replace as cable linked. “There are obstacles at rank high on the Scientific American such as clinicians, and from people always be enough to ensure that one the road ahead is rarely that clear. much of that with fact as soon as pos- every point along the way,” she says. Worldview Scorecard. On this year’s with significant industrial experi- particular eureka moment leads to a Typically, says Nordström, “You have sible,” he says. “For the scientists we serve, the first list, for example, Denmark, Finland ence. In addition, BIO-X can provide groundbreaking product that’s used to start with assumptions, and then Making the right assumptions barrier is usually related to a lack of and Sweden placed second, sixth and participants with a couple hundred around the globe, or anywhere, for try to validate them through a net- about the market, however, solves access, not potential. Without access eighth, respectively. thousand dollars for a couple years.” that matter. Many other factors— work of experts. From that, you can nothing without the right science. to the tools and infrastructure needed After that, says Forsberg, “You’ll need from Ntseoane’s hard work on her see if the assumptions sound reason- Sean Ainsworth—now CEO of Retro- to make discoveries, the potential to SCANDINAVIAN SUCCESS other funders.” farm in South Africa to Langer help- able or not.” Building a community Sense Therapeutics in Ann Arbor, innovate based on that research is se- To power innovation, the Scandina- The “other funders” in Sweden, ing a student commercialize a re- of advisors helps scientists test these Michigan—learned that the hard verely diminished.” Which is exactly vian countries collaborate on many and most other countries, provide search result—come into play in mov- assumptions (see “Room to Grow,” way. “In a previous company,” he why Seeding Labs is committed to levels. For example, Sweden’s non- venture capital (VC). To gain a bet- ing biotechnology forward. The best page 26). says, “we were working on a science providing that access. For the moment, profit Uppsala BIO works to promote ter understanding of how biotechnol- results emerge when great science is Start-up expert Steve Blank, ar- that hadn’t been as fully validated as the dearth of equipment seems to be regional and national growth in the ogy VC works in Sweden, Scientific championed by an experienced team chitect of the U.S. National Institutes it needed to be.” And unfortunate- the dominant concern in developing life sciences. Uppsala BIO’s CEO, Erik American Worldview talked with Eu- that lives and breathes persistence. of Health’s I-Corps @NIH program, ly, the company was already rais- countries. As Dudnik says, “From my Forsberg, says, “We try to identify gen Steiner, CEO of Glionova Thera- Only then can biotechnology innova- which teaches scientists and clinicians ing capital and lining up customers observation, the difficulty in obtaining gaps in the system. What could make peutics in Stockholm and a venture tions change the world.

24 SCIENTIFIC AMERICAN | WORLDVIEW BENCH TO BUSINESS 25 a push-me/pull-you exchange of ideas made up a primary call ourselves a launchpad—speeding strong companies requirement in our specifications for LabCentral’s design. to take off. We accept only start-ups with the highest po- The result is an open floor plan with a very deliber- tential. In 2014 alone, our residents brought in more than ate traffic flow pattern and transparent work, lab and play $200 million in venture capital and other sources of fund- spaces that inspire collaboration and sharing. The com- ing. That’s about the same amount of venture capital raised mon corridor gently insists that LabCentral’s residents see by all of Switzerland’s biotech companies in 2014. each other multiple times per day. Labs are strategically located in the middle, with offices and amenities at either EARLY RETURNS end. A key to the flow is the café. Food and good coffee Providing biotech entrepreneurs with a fertile environ- bring people out of their workspaces, encouraging engage- ment with the best infrastructure, equipment, services ment and interaction, as do regular “lunch and learn” pro- and programming to enable their unfettered practice of grams, big-screen movie and sports-viewing parties, and science on day one is LabCentral’s raison d’être. Already, social- and business-networking events. LabCentral is at the center of the Kendall Square bioinno- vation ecosystem, which fosters collaboration and creative RAPID UPTAKE exchange of science and business ideas among our entre- We quickly learned that Peter and I were not alone in preneurs and the countless scientists, thought leaders, in- thinking that start-ups in biotech needed LabCentral. In dustry experts and potential funders who work at the aca- Case Study: 14 months, 29 early-stage companies that work in the life demic- and industry-research institutions, venture firms, sciences moved into LabCentral, and about 125 residents law practices and equipment/service suppliers nearby. work here every day. The LabCentral environment provides tremendous Upon moving in, the typical company consists of four flexibility that spurs innovation. As Michael Schrader, ROOM TO GROW people or less, most of them from academic institutions or cofounder and CEO of , explains: LabCentral gives start-ups the space and teaching hospitals. To move forward with their technol- “LabCentral has allowed us not to expend a ton of money for equipment or resources to thrive BY JOHANNES FRUEHAUF long-term leases. As n 2006, when Peter Parker and I started Cequent we look to expand, Pharmaceuticals, we needed a place to work, to do we have grown our our science. There were loads of space options for The result is an open floor plan with a very deliberate network of contacts tech companies that only needed a good computer traffic flow pattern and transparent work, lab and tenfold through the and a high-speed Internet connection to launch a play spaces that inspire collaboration and sharing. collection of compa- blockbuster, but few options for biotechnology com- nies at LabCentral, panies like ours. We needed labs with sophisticat- compared to operat- Ied—meaning expensive—equipment, and the permitting, ing on our own. We infrastructure and people to support it. Getting the right love the facility, the lab space setup took us six months and consumed precious ogy, they have already secured the rights to the underlying open floor plan and comingling with other teams who are resources, both human and financial, that we should have intellectual property through an option or a license agree- not directly competing with our science, but rather com- been spending on science. There had to be a better way. ment. Many are repeat founders or CEOs with experience plementing it— facing the same challenges in fundraising, In 2010, we started to believe that sharing could be the launching and growing life science ventures. Others are science and business development, from whom we can answer. We had just sold Cequent, and Peter and I both FILLING A VOID first-time entrepreneurs. learn and with whom we can share to the benefit of all.” started new ventures—Bio-Innovation for Peter and Cam- Biotech start-ups need lab space and resources to test out, Having started working at LabCentral, companies may Schrader’s neighbors agree. “LabCentral makes it as bridge Biolabs for me—at the Cambridge Innovation Cen- challenge and nurture early ideas. To do that, these bud- grow, adding headcount quickly. Because they have access easy to start a biotech company as it is to start a purely ter (CIC). At that facility, we thrived in the creative atmo- ding companies usually need affordable, move-in-ready to millions of dollars worth of the best lab equipment pos- IT company,” says P. Shannon Pendergrast, cofounder and sphere of the shared space, and decided to try to adapt the laboratory facilities. That’s just what LabCentral provides, sible, they can perform experiments that they could never chief science officer of Ymir Genomics. “It provides the co-working model into a shared laboratory environment and more. It gives emerging life science companies the have dreamed of if they had to do it alone. What’s more, critical infrastructure, including sophisticated scientific for biotechnology. bench space, equipment, infrastructure and services that they can spend their capital and time on advancing their equipment bio-innovators need to excel.” Most important, Cambridge Biolabs proved the concept that a biotech they need for the early-stage research that is necessary to science rather than buying equipment or building infra- he adds, it allows Pendergrast and his fellow bioentrepre- can get started on a small scale in a shared lab space. So transition into commercial-stage enterprises. structure. This gives them the flexibility to morph their neurs the freedom to focus on the work at hand: “All I have Peter and I joined forces with Tim Rowe, CIC’s founder and Nonetheless, it’s the “more” that makes up LabCen- original vision into one with greater promise, to reach to do is science.” CEO, to found a nonprofit called LabCentral. A US$5 mil- tral’s “secret sauce.” As the tech world figured out long their milestones more quickly, and makes it more likely lion grant from the Massachusetts Life Sciences Center got ago, ideas expand when they can bump, mix and mingle for them to succeed overall. Johannes Fruehauf is the president and executive director of us started, and we opened in late 2013 on Kendall Square with others; but this rarely occurs in life sciences start- Although some might call LabCentral an incubator, LabCentral. For more information, visit www..org. in Cambridge. Over time, we leveraged that funding to ups, which typically set up in traditional lab settings with we eschew that term. It suggests that biotech start-ups are bring in nearly $20 million in additional commitments of distinct and separate accommodations. Mingling hap- fragile, needing life support to survive. The opposite is true

cash, state-of-the-art equipment and in-kind services. pens every day at LabCentral, and deliberately. In fact, AVIS ©PAUL PHOTOS: / NEGLEY ©KEITH for the companies we select to take residency here. So, we

26 SCIENTIFIC AMERICAN | WORLDVIEW BENCH TO BUSINESS 27 minted or with decades of experience category. Entrepreneurial enablers Tactical planning: organize resourc- holders that the company is mindful in the industry. The production of are the experienced managers of es to achieve strategic ends. of the totality of challenges and ob- life and medical Ph.D. scientists has functional areas—such as technol- Technology assessment: manage tain needed financing. largely been addressed in most coun- ogy and information management, a team that can review scientific Impact management: marshal the tries throughout the world. Whether strategy and marketing, finance and opportunities and select those that assets and resources of the company there are an adequate number of aca- operations—who have the risk toler- justify a commercial strategy and al- towards defined needs in an ethical demic or industrial positions for these ance and drive to make something locate resources proportional to the manner that delivers the greatest good scientists is a question that is beyond new happen, but who might not in- opportunity. to the greatest number of people. the scope of this article. dependently have the vision for a Market assessment: recognize and This knowledge comes from for- new business. They know a talented measure the potential of a technology- mal training and experience. Al- Managerial & administrative. founder and leader when they see one driven product to meet unmet cus- though it is unreasonable to expect This category consists of the people and a sound idea when they examine tomer and commercial needs, com- that an intensive approach to impart- educated or experienced as strategic one, but they see themselves as team pete with alternatives, achieve a level ing the associated insights would thinkers, organizers and coordinators players and experts in their respec- of pricing that justifies the investment ever compete with disciplined study of either academic or commercial en- tive fields. Without the enablers, there over years or the terprises. In biotechnology, many of the would still be entrepreneurs, but not lessons associated people in this category were trained as many of them would be successful. Teaching can be developed to with making day- scientists and moved from the bench to to-day and strategic the boardroom. While there are some ENTREPRENEURIAL provide new entrepreneurs and choices, teaching forward-thinking academic programs EQUATIONS entrepreneurial enablers with can be developed to that combine Ph.D. studies in the life What, then, does the biotechnology a toolbox for orienting their provide new entre- sciences with MBA studies, managers industry need in the way of human preneurs and entre- in biotechnology usually emerge either resources? To answer that, we can thinking and laying a ground- preneurial enablers from the marketing side of the bio- look at the census of biotechnology work for immediate action as with a toolbox for pharma industry or from the laboratory companies. According to a 2011 well as long-term study. orienting their where they have accrued successive re- OECD (Organisation of Economic thinking and laying sponsibilities in research management. Co-operation and Development) a groundwork for These managers are necessary for the study, the United States had the immediate action success of an existing organization, but largest number of biotechnology and assures sustainability, and that as well as long-term study. Achieving insufficient to drive the “new.” firms—6,213—with the 18 reporting can be promoted with a clear, dis- that, however, requires a conscious, countries from the European Union tinct, ethical and persuasive message. deliberate effort aimed at identifying Entrepreneurial founders. having a total of 5,398. That’s about Regulatory development: define and the needs of the industry vis-à-vis Although these people make up a sub- 11,500 firms before we start counting manage the process through which the talents and experiences of people BIOTECHNOLOGY’S set of scientists, managers or a com- Japan, Australia, New Zealand or the the products must be assessed. willing to dedicate their careers to the bination of the two, it is best to break emerging markets. For round numbers, Intellectual property management: field. Those needs will change over CRUCIAL QUESTION them out into a separate category, let’s stipulate that there are 15,000 form, maintain and maximize intel- time, but like biology itself, education because the risk affinity—or toler- companies globally in the industry. lectual property assets internationally and training will adapt. What matters In this industry, what matters the most: technology or people? ance—of the entrepreneur is typically How does that census translate and domestically through a variety most in this industry is, therefore, BY STEPHEN M. SAMMUT the starting point of new venture cre- into people with entrepreneurial lean- of strategies, including licensing and its people. ation in this industry and all others. ings? It means there must be 15,000 partnering. he reflexive answer to dustry is entirely people driven and Entrepreneurs possess a combination entrepreneurial founders. If each com- Capital formation, replenishment Stephen M. Sammut is a senior fellow, this question is most enabled. The very definition and re- of native skills, education, experience pany needs, say, six entrepreneurial and stabilization: define capital re- health care management at The Wharton School of the University of Pennsylvania likely: the technology. alization of a product needs definers and personality traits that put them enablers, that would compute to a to- quirements and sources over long in Philadelphia, and developer of the Without a new meth- and builders who know how to find in a category of their own. Some are tal of 90,000 of them worldwide. So, time periods, and accumulate the fi- Biotechnology Entrepreneurship Boot Camp. od, cure, device or and marshal the necessary intellec- aware early in their careers that en- overall, the industry requires 105,000 nancial resources necessary to meet something that makes tual, managerial and financial capital trepreneurship is their career destiny. bio-entrepreneurs. the development and commercial ob- a difference in the to make things happen. Others discover their inner-entrepre- Beyond the numbers, these lead- jectives of the company. Tlives of people or communities, there The human resources biotechnology neurship tendencies after years of ers have to possess many capabilities: Communication management: en- has been no progress. As true as that demands fall into four broad categories: commercial responsibilities that build capsulate the mission and methods rings, there is at the very least a code- their confidence and hone their skills. Leadership: formulate human re- of the company into a succinct and pendence of the underlying technol- Scientific and technical. source needs and manage the hiring persuasive message in order to attract ogy and the people who turn it into This includes the Ph.D.s and other Entrepreneurial enablers. and development of teams. human resources, build internal con- reality. Some might argue—myself graduates in the life and medical The entrepreneurial academic litera- Strategic thinking: make choices sensus, drive strategy and operations

included—that the biotechnology in- sciences, whether they be recently ture implies, but seldom studies, this NEGLEY ©KEITH based on alternatives and options. in an organized fashion, assure stake-

28 SCIENTIFIC AMERICAN | WORLDVIEW BENCH TO BUSINESS 29 n a Saturday night funding. Federal and provincial and 2013. As Schwitzer reported in Steven Woloshin from the Dartmouth in November 2009, legislators pledged millions of dol- July 2014 in JAMA Internal Medicine, Institute for Health Policy and Clini- Canada’s most- lars to support clinical studies. That most of the stories overplayed ben- cal Practice in Lebanon, New Hamp- THE TRICKY SCIENCE OF COMMUNICATION watched television research, however, failed to confirm efits, minimized harms and ignored shire, analyzed the media stories writ- network, CTV, Zamboni’s hypothesis. The liberation discussions of cost. ten in response to press releases in the ran a primetime procedure proved ineffective and pos- This kind of poor reporting can mid-2000s from GlaxoSmithKline, documentary that sibly dangerous. have real-world consequences. For the company behind the first drug ap- In the field of biotechnology, the communication of ideas is often would radically example, after U.S. regulators issued proved for the syndrome. As the re- complicated by the variety of players taking part in the conversation. change the country’s healthcare land- Shortcomings of Social Media health advisories about a slightly in- searchers reported in PLoS Medicine Companies address consumers through internal mechanisms and the Oscape. The Globe and Mail—a popular The Zamboni escapade was not the creased risk of suicidal thoughts and in April 2006, most journalists un- media. The media speaks to company representatives and members of Canadian newspaper and part of the first time that a scientific claim hyped behavior in young people who take critically reported GlaxoSmithKline’s the public. Trade groups also get involved on many levels. The web of same media conglomerate—carried a in the media turned out to be wrong. antidepressants, widespread media claims, encouraging more diagnosis people talking to each other gets tangled. companion story on its front page. Thanks to the growing power of coverage spurred a dramatic decline and treatment. “Many of the stories And often much more is at stake than merely the communication The story focused on Paolo Zam- that we looked at sounded like com- of an idea. Whether a start-up sinks or swims can be determined by boni, an Italian vascular surgeon pany press releases,” says Schwartz. In its ability to clearly convey its strengths and objectives. More important, who claimed to have discovered the a 2013 article in JAMA Internal Medi- if the media gets a story wrong, the general population may face undue true cause of multiple sclerosis (MS). cine, she and Woloshin documented health risks as a result. Although physicians have long con- The Zamboni escapade was not the similar campaigning through the me- Indeed, it’s crucial to get communication right in biotechnology, tended that MS is an autoimmune first time that a scientific claim hyped dia to promote hormone-replacement and, as the following stories demonstrate, that’s not always easy to do. disorder, Zamboni theorized that therapy for low testosterone in men— it is actually a disease triggered by in the media turned out to be wrong. now a multi-billion-dollar industry. narrowing of veins in the neck. He Beyond sloppy reporting, part of asserted that this vascular constric- the problem could lie in the financial A HEALTHY DIALOGUE tion created a build-up of iron that, in ties between medical journalists and How the healthcare media impacts turn, set off the cascade of inflamma- drug companies. Wendy Lipworth, a policymakers and the public tion and nerve degeneration that are social media, public campaigns built in antidepressant use. According to a bioethicist at the University of Syd- the hallmarks of the disease. Zam- around questionable healthcare re- study published in BMJ in June 2014, ney, has studied this issue in Austra- BY ELIE DOLGIN boni advocated a treatment similar to porting might have an increasingly this had an unintended consequence: lia. She thinks that more disclosure balloon angioplasty. He even tested large influence on medical research suicide attempts increased among ado- is needed on the part of journalists the surgical intervention on his MS- and healthcare. lescents and young adults, most likely and that some kinds of monetary re- afflicted wife and, as the CTV docu- According to Roger Chafe, a health due to an under-treatment of serious lationships should be banned. But, mentary displayed, her symptoms policy expert at Memorial University mental health disorders. “The sexy sto- she concedes, it might be difficult to seemingly melted away. The treat- of Newfoundland in St. John’s, the ry isn’t ‘Be cautious and think careful- implement these remedies in an in- ment, nicknamed the “liberation pro- rise of Facebook, Twitter and other ly about medicines,’” says psychiatrist creasingly fractured media landscape. cedure,” was touted as a miracle cure. social networks reinforces the im- Steven Schlozman, associate director It’s not just journalists who are It was a powerful and emotional portance of professional healthcare of the Center for Mental Health and to blame, though. A December 2014 story, but scientifically unfounded. journalism. After all, he says, reports Media at the Massachusetts General study in BMJ from Petroc Sumner of The media coverage—based only on from the mainstream media are often Hospital in Boston. “The sexy story is Cardiff University found that press the most preliminary of Zamboni’s the ones that get passed around—and ‘These medicines might kill your chil- releases from the UK’s leading re- findings—spurred “an over-enthu- those same stories are more likely to dren.’ There’s not much of a story if you search universities often made their siastic and inadvertent promotion of influence key policymakers. “Without report it in nuanced tones.” own overblown claims and unwar- some shaky science,” André Picard, the link to traditional media,” Chafe ranted inferences about health stud- the Globe and Mail journalist who says, social media “just doesn’t seem Pushing Prescriptions ies. Scientists usually vet and approve coauthored the original newspaper to have the same kind of traction.” More often, press coverage leads con- the press releases issued by their insti- story on the procedure, wrote in BMC Yet, according to Gary Schwit- sumers toward increasing health- tutions, and thus must shoulder some Medical Ethics in February 2013. zer, founder of the watchdog website care utilization—sometimes even of the accountability for the inaccura- After the initial reports made the HealthNewsReview, traditional media for problems they might not have. cies and exaggerations that creep into rounds on the Internet, the public sources are still routinely disseminat- In a phenomenon known as “disease stories about their research. started demanding that health au- ing misleading health information. mongering,” pharmaceutical compa- In the end, everyone carries some thorities make the procedure avail- Schwitzer and a team of reviewers nies have even co-opted the media to responsibility—from the media con- able in Canada. The media coverage looked at about 1,900 health-related convince people that they are sick and sumers hungry for miraculous cures snowballed, prompting an unprec- stories about drugs, medical devices in need of medical treatment. to the companies seeking profits, and edented amount of political involve- or other interventions published by Such was the case with restless everyone in between. As Sumner says,

ment in the allocation of research NABAUM ©ALEX U.S. news organizations between 2006 legs syndrome. Lisa Schwartz and “All of us are not watchful enough.”

30 SCIENTIFIC AMERICAN | WORLDVIEW COMMUNICATION 31 BREAKING THE BAD-GUY IMAGE industry science communicators need to do more to are known to be flawed. For instance, are not what those with concerns need techniques. It will require products Johnson & Johnson’s Seema Kumar urges engage with the science press corps. Accordingly, she creating “independent” third-party to hear to address their reservations. that consumers personally benefit companies to stay transparent urges everyone in industry healthcare communications organizations to deliver the mes- Nonetheless, communications from and can control their expo- to “be more welcoming, open and transparent.” She sage—a common technique among around GM crops continue to focus sure to. Furthermore, industry must “For a long time, industry has been seen as the bad guy,” adds, “We have to spend time building relationships that agencies retained to advocate for GM on the facts. The communicators have make more concerted efforts to be says Seema Kumar, vice president of innovation, global engender trust and a sense of shared purpose.” In one crops—has been widely questioned assumed that the public just needed trustworthy, and a major part of this health and policy communication at Johnson & Johnson such collaborative relationship, for example, Johnson at high levels. In a 2013 speech, for more information, and that a better- will be to increase the perceptions of in New Brunswick, New Jersey, “but a huge gap exists in & Johnson has made its clinical trial data available for example, Margaret Chan, director- informed public would be more in- shared values and benevolence. Simi- covering the important translational research that goes research through the Yale University Open Data Access general of the World Health Organi- clined to accept biotechnology for what larly, regulators must do far more to on in industry R&D.” She points out that industry science, (YODA) Project. “When we announced this agreement,” zation, provided insight into the tac- it is. Both research and experience, safeguard the public trust, especially which involves translating basic research into practical says Kumar, “the response was unbelievably positive tics of large regulated industries—big however, fail to support this so-called in complex cases that often hinge healthcare solutions, has “a huge impact on our health inside and outside of our company.” food, big soda and big alcohol—and “deficit model” of communication. Al- around degrees of uncertainty. and well-being.” Despite what she considers a wealth of Ultimately, this type of cooperative exchange will said: “They include front groups, lob- though the first academic papers that Many factors conspire to make newsworthy science and technology stories transpiring result in a deeper understanding of the work being bies, promises of self-regulation, law- questioned the “knowledge gap” hy- the acceptance of GM crops diffi- in industry, she doesn’t see them getting covered, which done. “We absolutely can’t underestimate the impor- suits and industry-funded research pothesis were published in 1996, only cult. Nonetheless, communicators in disappoints her. “I’ve been feeling that we are not doing tance of communication in science,” says Kumar. “The that confuses the evidence and keeps recently have the critics of the deficit biotechnology, especially in North enough as a community—industry’s science communi- more we—journalists and corporate the public in doubt.” model been gaining traction. America and Australia, now accept cators and the press corps—in talking about science in science communicators—can do to Likewise, the use of so-called the need to address the cultural values business and industry,” she says. showcase how important science is credible experts, largely appointed Seeking Solutions that come into play in communicat- Improving this situation, Kumar explains, will to society, the more it will benefit all for their technical expertise, has lost Changing deficit-model approaches ing about GMOs. For example, GMO require greater efforts from all members of the com- of us in building a scientific power- much of its value, yet it remains at the will require a better understanding Answers—a U.S. industry initia- munity. Science writers have to be better educated house, an innovative country.” top of the list of approaches to com- of why people oppose the use of ge- tive—is a first effort to be responsive about how science and R&D work in the industry, and —MIKE MAY munications about GM crops. Even netically modified organisms (GMOs) to viewpoints in a direct and candid worse, some groups have tried putting from the perspective of risk and trust. way. As this initiative is duplicated in a modern twist on the tactics of big Public engagement—as a concerted other countries, cultural aspects of broader interpretations of risk, such tobacco in 1950s and ’60s, such as cre- exercise in understanding respect the communication process will need COMMUNICATION as psychological and social factors. ating fake online grassroots groups (based on shared values and inter- to be assimilated into the process. Many of the messages focused on and identities extolling the virtues of ests), uncertainties and, critically, This could well be a first step toward BREAKDOWN benefits to farmers and informing GM crops. It’s hard to imagine what vulnerabilities—will be essential. the development of a cultural cogni- a “rational” debate. In the 1970s, could do more harm to earning trust. Moving forward will require au- tion theory of risk communication Looking at the GMO controversy through the lens of communications however, Nobel laureate and Israeli- thentic communication that does not for GM crops that aims to deeply as- science BY ANDREW D. ROBERTS & ANDREW D. POWELL American psychologist Daniel Kahn- Even Facts May Fail rely on public-relations strategies, similate cultural values into a process eman and his late colleague Amos Experts, including regulators, view such as propaganda and third-party not aimed at acceptance, but aimed espite decades of global- The evolution of how people deal Tversky showed that decision making risk as measurable hazard, the product at putting people in the best possible ly expanding use of ge- with risk is a popular social concept— about risk is neither purely rational of probability and magnitude. People position to make a decision consistent netically modified (GM) dubbed the “risk society” by German nor purely “irrational.” Still, many facing the risks, however, tend to focus with their values and beliefs. crops, broad public ac- sociologist Ulrich Beck—that has biotechnology organizations employ more on what concerns them, rather Science communicators should ceptance still eludes this resulted in an environment today a strategic and tactical mandate pred- than the “technical” hazard itself. continually monitor social-science re- technology. The history where new technologies are scruti- icated on only “rational” thinking. Peter Sandman, one of risk communi- search to gain further insights into the Dof the dialogue behind these crops, nized more, and GM crops have been Some experts know that informa- cation’s pioneering practitioners, calls groups with which we are communi- however, reveals what we can learn embroiled in controversy from their tion cannot be the sole source of com- this concern “outrage,” and it’s a pow- cating. As a result, we will learn to un- from communications science. introduction. Such controversial sub- munication about GM crops to re- erful force that can escalate if not ad- derstand existing and new concerns— Over the past 20 to 30 years, the ject matter requires specific handling ally get across the point. Recently, Paul dressed. Moreover, outrage might even not just about GMOs, but also about world has changed considerably, with from a communications standpoint. Teng, chairman of the International increase in the face of sound technical all areas of innovation. When there are populations becoming aware of the The ongoing controversy shows how Service for the Acquisition of Agri- data, because the higher concerns are perceptions of risk, we should use the risks in their everyday lives. Conse- this has largely failed. biotech Applications (ISAAA), said: not addressed and these facts may con- science of communication in the com- quently, people in general have grown “Communication is key for GM prod- flict with deeply held cultural views munication of science. If we do, some more averse to risk. With health scares Following Failed Philosophies uct acceptance, but just sharing infor- and commitments. of the glaring problems with GMO in food and agriculture, like mad-cow In many cases, efforts to communi- mation alone is not sufficient. Infusing Industry often shuns this higher communication might be addressed. disease in the United Kingdom and cate about GM crops have followed a values into communication messages level of the risk debate. Instead, indus- melamine in infant formula in China, linear, educational, one-way delivery, will contribute greatly to making GM try tends to reframe the issues in terms Andrew D. Roberts and Andrew D. Powell are, people around the world have started focused mainly on technical elements products part of everyday life.” of technical expertise and experience, respectively, COO and CEO of Asia BioBusi- ness Pte Ltd. in Singapore and cofounders of losing trust in the people and organi- of the science. Likewise, these efforts Still, some groups try to get across where it is undoubtedly most comfort- the Centre for Risk Communication Asia.

zations that regulate the risks. failed to discuss, or even acknowledge, those messages with techniques that NABAUM ©ALEX able. Simply put, facts about the risk

32 SCIENTIFIC AMERICAN | WORLDVIEW COMMUNICATION 33 PARTNER PROFILE First Came Access THE MANY AUDIENCES AND VALUES OF CURE FORWARD: For Patients - Cure Forward Gene Stories will be For Clinical Trial Recruiters - Now Comes ACTIVATION Cure Forward aims to make science available to HCPs as teaching tools. Clinical research is where trans- A New Category of Innovation – Just In Time for Precision Medicine relevant, understandable and action- Additionally, through a linking formational therapies are proven. able for patients. The proprietary process in Cure Forward software, But it can take 2–3 years to fill a he irony of our new therapy or clinical trial that platform will enable patients to: patients will be able to connect with targeted trial, and more than half modern era, where might offer hope could be unseen, » Learn about diagnostic testing and their HCPs and cooperate on trial of trial sites fail to accrue a single precision medicine, unavailable or simply unknowable is clinical trials. This information will matching. 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Patients in the community ing to individualize and personalize members, the anguish of receiv- » Electronically retrieve their test For Diagnostic Test Providers – setting are simply not visible to trial treatments while revolutionizing en- ing a difficult diagnosis of a deadly results from diagnostic labs into Because patients, their families, sponsors until they apply for entry, tire categories of disease, is that all disease. Even in an era of boundless their Cure Forward account. If their and their physicians will use Cure and too often those applications of these tools and solution providers health information, digital connec- lab doesn’t make results available Forward to find tests that may be never come. Cure Forward offers a are not working as effectively and tivity and modern diagnostic tools, on the network, users will be able to relevant to their care, Cure Forward mechanism for patients to instan- efficiently as they could. 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Innova- For Health Care Providers – can result in extra work for labora- assessing large amounts of informa- ity to take advantage of every option tive new therapeutics can quickly As personalized and “precision” tories, who may not have systems in Learn More - tion and acting intelligently on it can of care available to them, activating find their beneficiaries through an medicine approaches become in- place for constructive delivery of test To learn what a Patient Activation be daunting for patients, as well as ALL parts of the health ecosystem. activated patient network. And com- creasingly available and relevant in results. Cure Forward can be a con- Company is all about, and to see other stakeholders in the system. 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Beta release begins in June 2015

34 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW PROFILE 35 10 SCIENTIFIC AMERICAN WORLDVIEW SCORECARD

Our Scorecard analyzes and interprets data on the innovation potential in biotechnology for 54 countries. Based on seven Scorecard Categories —created from 27 components—this analysis combines information from biotechnology inputs and outputs through government protection and policies and far beyond. The results reveal the dramatic range of capabilities in this dynamic POWER field, and which countries are moving ahead and which ones are falling behind. To get the most from this analysis, work your way through the introduction and Scorecard POINTS Categories on your way to the Overall Scores Which places around the globe ahead. Beyond that, finer-grain analyses add even are powering the success of more depth to our understanding of the innovation potential in biotechnology around the world. biotech today? Start exploring!

2015

SCORECARD CATEGORY #1: favor public companies because—relative to private PRODUCTIVITY firms—their reporting requirements provide trans- In overall output, no one comes close to the U.S. parency, making it easier to compare them objec- tively. Further, it stands to reason that a nation with a Our Scorecard pinpoints the countries, communities and financial sources that enable innovation to flourish Although a country’s capabilities in biotechnology favorable business climate will support the devel- depend on many factors, perhaps the most impor- opment of more public companies. In combination, LOCATION, LOCATION, LOCATION. environment to intellectual property strengths and the tant is gross productivity. Innovation is not worth these metrics assess a country’s productivity. As any real estate agent will tell you, where a piece of prop- performance of public companies. To quantify this infor- much if it cannot be commercialized, and that’s what The United States—the longstanding leader in erty lies is the key to its value. And when that property is a mation, we ranked each country’s achievement on a series of our Productivity category measures. We compute this category—remains at the top. In fact, the U.S. productivity using two metrics: “public company runs away with this metric, finishing well ahead of groundbreaking new medicine or a cutting-edge business individual components using a scale from 0 to 10, with the revenues,” and the “number of public companies” all competitors. Australia and the United Kingdom model, where it is being developed is crucial to its success. lowest-ranked nation scored as 0 and the highest-ranked as (Lawrence, S. & Lähteenmäki, R. Nat. Biotechnol. follow in second and third place, respectively, as As Scientific American Worldview enters its seventh year of 10. We then generated scores for each category—Productivity, 32, 626–632 (2014), and company disclosures). We they did last year, but far behind the front-runner. tracking international trends in biotechnology innovation, Intellectual Property (IP) Protection, Intensity, Enterprise we continue to refine our focus on which countries provide Support, Education/Workforce, Foundations, and Policy the best conditions for ensuring that that innovation will & Stability—by calculating the mean score of these com- 1.1 grow and thrive. ponents. (For detailed methods, see page 46.) .74 The 2015 Scorecard also examines the drivers of global Our analysis of gross and relative metrics provides a .58 investment. After so many years of reporting slow declines rich assessment of the biotechnology sector worldwide. .50 .31 .30 .30 in the financial position of biotech firms around the world, The results reveal a number of surprising shifts in the -in .27 .21 .14 .13 .10 .10 data from our last Scorecard presented a clear indication of dustry, as well as several unexpected players exceling in .07 .06 .06 .05 .04 .02 .02 .02 .02 economic recovery. This year, we see even more evidence certain areas. As the biotech field continues to evolve, so of bounce back, especially in one particular country. do our methods for tracking those places around the globe

As in the past, we built the Scorecard using a diverse where today’s innovators have the best chance of bringing ITALY CHINA JAPAN ISRAEL FRANCE POLAND CANADA NORWAY SWEDEN AUSTRIA IRELAND FINLAND collection of metrics—from education and political tomorrow’s innovations to the fore. —THE EDITORS BELGIUM GERMANY DENMARK INDONESIA AUSTRALIA HONG KONG SWITZERLAND TAIWAN, CHINA TAIWAN, UNITED STATES UNITED KINGDOM

36 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 37 PERCEIVED IP PROTECTION PATENT STRENGTH DENMARK 7.60 UNITED STATES 6.18 AUSTRALIA 5.24 SPAIN 3.62 SWITZERLAND 3.59 NEW ZEALAND 3.57 ISRAEL 2.90 AVERAGE

BRAZIL 2.87 IRELAND 2.85 SWEDEN 2.62 BELGIUM 2.44 UNITED KINGDOM 2.38 MEXICO 2.27 CANADA 2.21

RUSSIA 2.14 FRANCE 2.04 NORWAY 1.92 NETHERLANDS 1.91 S. KOREA 1.70 HONG KONG 1.67 S. AFRICA 1.30

POLAND 1.14 GERMANY 1.07 AUSTRIA 1.05 INDIA 1.01 JAPAN 0.91 CHINA 0.90 ITALY 0.78

SINGAPORE 0.69 FINLAND 0.64 TAIWAN, CHINA 0.59 INDONESIA 0.16 ARGENTINA 0.13 TURKEY 0.13 THAILAND 0.08

CHILE 0.07 UAE 0.07 GREECE 0.06 MALAYSIA 0.06 PHILIPPINES 0.06 PORTUGAL 0.06 SAUDI ARABIA 0.05

CZECH REP. 0.04 UKRAINE 0.03 HUNGARY 0.02 KUWAIT 0.01 QATAR 0.01 9.53 9.47 9.26 9.21 8.87 8.87 8.84 8.82 8.74 8.74 8.50 8.49 8.34 8.34 8.31 8.20 8.15 8.09 7.84 7.78 7.61 7.48 7.40 7.06 6.76 6.57 6.24 6.20 5.98 5.85 5.73 5.66 5.62 5.53 5.47 5.34 5.33 5.30 5.20 5.13 5.07 4.86 4.75 4.21 4.19 4.19 4.01 3.27 3.08 2.97 2.89 2.69 2.48 0.92 UAE

ITALY PUBLIC COMPANIES / MILLION POPULATION INDIA CHILE SPAIN CHINA QATAR JAPAN LATVIA ISRAEL BRAZIL RUSSIA MEXICO KUWAIT TURKEY GREECE PUBLIC COMPANY EMPLOYEES / CAPITA FRANCE POLAND CANADA NORWAY ESTONIA AUSTRIA SWEDEN ICELAND IRELAND FINLAND UKRAINE BELGIUM HUNGARY GERMANY MALAYSIA DENMARK THAILAND SCORECARD CATEGORY #3: PORTUGAL

LITHUANIA PUBLIC COMPANY REVENUES / US$B GDP INDONESIA AUSTRALIA SINGAPORE ARGENTINA HONG KONG PHILIPPINES

PUERTO RICO PUERTO BIOTECH PATENTS /TOTAL PATENTS FILED WITH PCT LUXEMBOURG SAUDI ARABIA SOUTH KOREA INTENSITY SWITZERLAND NEW ZEALAND SOUTH AFRICA NETHERLANDS TAIWAN, CHINA TAIWAN, UNITED STATES VALUE ADDED OF KNOWLEDGE- AND TECHNOLOGY-INTENSIVE INDUSTRIES

CZECH REPUBLIC Top marks for Denmark in UNITED KINGDOM SLOVAK REPUBLIC SLOVAK driving innovation We measure a country’s overall tion (Lawrence, S. & Lähteenmäki, U.S. National Science Foundation’s SCORECARD CATEGORY#2: medicines for domestic needs. For of protection, enforcement mecha- example, a company may be inclined nisms and restrictions (e.g., compul- efforts to boost biotech innovation R. Nat. Biotechnol. 32, 626–632 Science and Engineering Indicators IP PROTECTION to abandon a drug lead if it cannot sory licensing). Recognizing that per- by combining five characteristics (2014)). For instance, dividing each was the source for “Value added of Objective and perceived measure- find profit-enabling markets for it. ceptions also influence investment into a measurement designated country’s employee counts by its knowledge- and technology-inten- ments can diverge considerably In prior issues of Scientific American decisions, and that the perception of as Intensity. These characteristics population, as sourced from the sive industries.” “Intellectual property is the invisible Worldview, we have also shown that a country’s IP protection might not are normalized for population size U.S. Census Bureau International Last year, Denmark held its infrastructure of innovation,” writes the strength of a country’s IP protec- match objective measures, we ac- and overall economy. As a result, Database, produces the “public long lead in this category, followed Michael A. Gollin in Driving Innovation: tion correlates with its concentra- count for subjectivity with Schwab’s Intensity helps identify smaller biotechnology company employees by the United States, Australia Intellectual Property Strategies for a tion of clinical trials. Accordingly, IP “perceived IP protection” metric nations that exhibit outsized activity per capita” metric. Likewise, the and Singapore. This year the same Dynamic World (Cambridge University protection can impact whether a na- (Schwab, K. The Global Competi- in the sector. Whereas Productivity measurement of “public biotech- three countries took the top three Press, 2008). Nowhere is that state- tion’s scientists and physicians even tiveness Report, 2014–2015. World measures outputs, like commercial nology company revenues per spots. Spain advanced to fourth ment more accurate than in the field play a role in global drug develop- Economic Forum (2014)). This index products, Intensity measures GDP” is generated by dividing a place, largely due to a surge in the of biosciences. The capital and time ment, and if drugs will be developed was created using feedback from inputs—the elements that propel nation’s Productivity score by its proportion of biotech patent appli- invested in a new drug can only be for locally pervasive conditions. a global group of business leaders companies to success. Those look- GDP, as sourced from the IMF cations filed there. recouped through strong IP Protec- We measure IP protection both when asked about their perceptions ing for research partners or a place World Economic Outlook Database. tion. Without that assurance, it is objectively and subjectively. “IP of domestic IP protection. to develop biotechnology should Data for both “biotech patents per difficult to attract funding or convince strength” is drawn from a study Although the United States consider countries with high Inten- total patents” (filed with the Patent ambitious scientists and business (Park, W.G. Research Policy 37, comes in first in the objective mea- sity scores. Cooperation Treaty) and “business founders to take on the risks of pio- 761–766 (2008)) that calculates the surement, “IP strength,” Finland, The data used in the components expenditures on biotechnology neering research and development. unweighted sum of five measures: Qatar and Japan take the lead when of Intensity are gathered from vari- R&D” came from the Organisa- In addition, IP protection can patentable inventions, membership the “perceived IP protection” metric ous sources, including company tion for Economic Co-operation encourage foreign development of in international treaties, duration is added to the calculation. disclosures and published informa- and Development (OECD). And the

38 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 39 tional Database. We alsoemployed to theU.S.CensusBureau Interna- divided bythepopulationaccording using UNESCOfigures for graduates graduates percapita” iscalculated nents. “Post-secondary science category consists of five compo- tasks, suchaslaboratory processes. workers skilled invery specific overall isdependentonapoolof of disciplines,while theindustry with advanced degrees inavariety nology firms require employees and produce itsproducts. Biotech- individuals whoenvision,develop robust community ofhighly trained industry isacutely reliant onthe Without question, ahealthybiotech High-tech innovationdemandsahighlyeducatedworkforce SCORECARD CATEGORY #4: 40 40 SINGAPORE 9.20

SCIENTIFIC AMERICAN The UNITED STATES 9.00 2.82 ESTONIA

Education/Workforce UNITED STATES 6.60 HONG KONG 8.93

MALAYSIA 7.97 2.78 SPAIN

NEW ZEALAND 7.83 NEW ZEALAND 6.23 |

WORLDVIEW UAE 7.34 2.71BELGIUM

QATAR 7.33 UNITED KINGDOM 5.71

EDUCATION/WORKFORCE TAIWAN, CHINA 6.80 2.65 ITALY

ESTONIA 6.52 LUXEMBOURG 5.29 not every person whowants to stay home countries. We recognize that creating “brain drain” for their desire to stay intheUnited States, more Ph.D.graduates expressed a while a lower score meansthat United States andthenreturn home, more people earntheir Ph.D.sinthe in “talent retention” signifies that Science Foundation. Ahigherscore as reported bytheU.S.National States following graduation there, did notintend to stay inthe United a country’s doctoral recipients who tention,” we used thepercentage of employment.” To assess “talent re- “R&D personnel perthousand in thelife sciences percapita” and OECD figures for “Ph.D.graduates ISRAEL 6.49 2.65 NORWAY

SWEDEN 6.18 AUSTRALIA 4.97 FINLAND 6.12 2.61 RUSSIA

CANADA 6.07 2.48 NETHERLANDS NORWAY 6.06 CANADA 4.34

UNITED KINGDOM 6.00 2.32 TAIWAN, CHINA ICELAND 5.50 SAUDI ARABIA 4.33 THAILAND 5.44 2.27 PUERTO RICO AUSTRALIA 5.43 ISRAEL 4.28 to thefourth andseventh spots. Saudi Arabia, respectively—dropped place finisher—Luxembourg and order. Last year’s leader andsecond- cation/Workforce category, inthat take thefirst three spotsintheEdu- Zealand andtheUnited Kingdom significant amountsofbrain drain. ing DenmarkandFinland—suffer high scores inotherareas—includ- emigration rate. Even countries with repatriate, rather thantheactual to measure thesentimentto not stay; theobjective ofthismetricis ing aPh.D.findsanopportunity to in theUnited States after earn- SWITZERLAND 5.33

Overall, theUnited States, New 2.10 LITHUANIA CHILE 5.27

GERMANY 5.08 FRANCE 4.25 2.06 ARGENTINA NETHERLANDS 5.06

SOUTH AFRICA 4.99 IRELAND 4.22 2.02 MALAYSIA SAUDI ARABIA 4.92

DENMARK 4.89 1.94 GREECE GERMANY 4.20 CHINA 4.83

IRELAND 4.83 1.85 CHILE ICELAND 4.14 ENTERPRISE SUPPORT ENTERPRISE International Finance Corporation), Business 2014(World Bankandthe ment wasdrawn from Doing friendly environment” measure- of four elements. The“business- is generated usingtheaverage models—can yieldgreat returns. ating costs orto enable new business underserved market, to reduce oper- terprise supportproblems—to tap an forms. Consequently, resolving en- the availability ofcapital in various try’s business-friendly features and Support for it.TheScorecard’s Enterprise where there isnoendemicsupport No onewantsto start abusiness A triotusslesforthetopspot SCORECARD CATEGORY #5: LITHUANIA 4.77 BRAIN GAIN TALENT RETENTION R&D PERSONNELPERTHOUSANDEMPLO PHD GRADUATES INLIFESCIENCESPERMILLIONPOPULA POST-SECONDARY SCIENCEGRADUATES /CAPITA EDUCATION/WORKFORCE The Enterprise Supportmetric 1.85 TURKEY FRANCE 4.72 SINGAPORE 4.13 metric quantifiesa coun- LATVIA 4.63

(share ofglobal students studying outsidetheircountry) 1.82 UKRAINE JAPAN 4.53 THAILAND 3.90

SOUTH KOREA 4.53 (reciprocal ofbrain drain) 1.81 INDONESIA BELGIUM 4.26 DENMARK 3.79

PUERTO RICO 4.22 1.70 HUNGARY SLOVAK REPUBLIC 4.20 SOUTH KOREA 3.71 LUXEMBOURG 3.99 YMENT for thetop ranks. Last year Hong United States, withactive jockeying Hong Kong,Singapore andthe category have traditionally been Capital Access Index. comes from theMilken Institute component, “capital availability,” availability” metric.Thefourth (2014)) for the“venture capital 2014–2015. World Economic Forum The Global, Competitiveness Report international survey (Schwab,K. We employed anindex basedonan ing measurements from the OECD. capital” component wascreated us- city. The“biotechnology venture ing business inacountry’s largest size andrefers, usually, to conduct- a specific company ofaspecified tedly limited because itrelies on synthetic business case—admit- which surveyed local experts ona 1.61 BRAZIL AUSTRIA 3.97

The front-runners inthis FINLAND 3.71

PORTUGAL 3.92 1.53 HONG KONG MEXICO 3.77 JAPAN 3.46

KUWAIT 3.71 TION 1.53 LATVIA

SPAIN 3.50 SWITZERLAND 3.40 INDONESIA 3.46 1.39 MEXICO CZECH REPUBLIC 3.41 ENTERPRISE SUPPORT ENTERPRISE CAPIT VC A BIOTECH V BUSINESS-FRIENDLY ENVIRONMENT( AUSTRIA 3.36 INDIA 3.24

VAILABILITY 1.22 PHILIPPINES AL AVAILABILITY TURKEY 3.14 C, 2007(US$MM)

United States andHongKong. year Singapore leads, trailed bythe United States andSingapore. This Kong came infirst, followed bythe CZECH REPUBLIC 3.27 RUSSIA 3.12 1.06 CHINA

PHILIPPINES 3.09

WORLDVIEW SCORECARD POLAND 2.55 0.88 SOUTH AFRICA PORTUGAL 3.20

HUNGARY 2.48

ITALY 2.46 0.72 UAE SLOVAK REPUBLIC 3.14

BRAZIL 2.30 higher =better) 0.23 INDIA GREECE 2.06 SWEDEN 3.10 0.11 KUWAIT UKRAINE 1.29

41 ARGENTINA 0.40 0.04 QATAR POLAND 2.85 8.81 FINLAND 8.60 SOUTH KOREA 8.17 SWITZERLAND FINLAND 9.78 SINGAPORE 9.61 NEW ZEALAND 9.40 SWEDEN 9.39 NORWAY 9.36 SWITZERLAND 9.17 DENMARK 9.15 SCORECARD 8.14 SWEDEN

CATEGORY #6: 7.86 JAPAN FOUNDATIONS 7.62 DENMARK Finland finishes first 7.48 ISRAEL LUXEMBOURG 9.07 NETHERLANDS 9.04 CANADA 8.85 AUSTRIA 8.83 AUSTRALIA 8.79 HONG KONG 8.69 IRELAND 8.31 7.39 GERMANY

For the fourth year in a row, 7.39 AUSTRIA Finland conquers all when it comes 7.22 UNITED STATES to Foundations, those “nut and 7.03 ICELAND GERMANY 8.29 ICELAND 8.19 UNITED KINGDOM 8.08 BELGIUM 7.93 JAPAN 7.84 UNITED STATES 7.66 FRANCE 7.25 bolts” factors that allow science- 6.95 TAIWAN, CHINA based enterprises to function and 6.88 HONG KONG flourish. Moreover, Finland has 6.66 QATAR taken the top spot for five out of 6.66 SINGAPORE the seven years of the Scorecard’s CHILE 7.24 ESTONIA 7.12 TAIWAN, CHINA 7.08 QATAR 6.95 CZECH REP. 6.89 PORTUGAL 6.69 LITHUANIA 6.57 history. That’s quite a record. 6.54 NETHERLANDS The Foundations metric repre- 6.40 FRANCE sents the quality of a nation’s infra- 6.18 BELGIUM 5.92 AUSTRALIA structure as it relates to potential UAE 6.44 POLAND 6.41 SOUTH KOREA 6.22 SLOVAK REP. 6.20 LATVIA 6.18 SPAIN 6.05 HUNGARY 5.88 innovation in biotechnology. A com- 5.84 LUXEMBOURG pany can’t succeed without a stable 5.64 UNITED KINGDOM supply of electricity, efficient means 5.50 CANADA of transportation and so on. Weak- 5.47 ESTONIA MALAYSIA 5.31 ISRAEL 5.27 PUERTO RICO 5.22 ITALY 5.17 GREECE 4.48 SOUTH AFRICA 4.13 KUWAIT 3.68 nesses in the Foundations category 5.44 UAE are particularly troublesome, as 5.41 NORWAY they represent problems that cannot 5.34 IRELAND be resolved quickly. For example, it 4.97 MALAYSIA SAUDI ARABIA 3.33 TURKEY 3.02 BRAZIL 2.97 MEXICO 2.82 THAILAND 2.40 CHINA 2.16 INDONESIA 2.02 can take years to build a new power 4.90 PORTUGAL plant, port or network of highways. 4.75 SPAIN To assess a country’s Founda- 4.70 CZECH REPUBLIC tions, we use four components. PHILIPPINES 2.00 ARGENTINA 1.65 INDIA 1.61 RUSSIA 1.33 UKRAINE 0.80 4.60 NEW ZEALAND First, “R&D business expenditures 4.22 LATVIA per GDP” is generated from OECD 4.19 LITHUANIA POLITICAL STABILITY figures. For “government support & ABSENCE OF of R&D per GDP,” we rely on data 3.93 CHINA SCORECARD CATEGORY #7: Perceptions that a government VIOLENCE/TERRORISM 3.79 HUNGARY could be overthrown or destabi- GOVERNMENT from UNESCO. Our “infrastructure POLICY & STABILITY EFFECTIVENESS 3.52 ITALY quality” component comes from the Nordic nations still on top, while lized are reflected in the “political REGULATORY QUALITY World Economic Forum (Schwab, K. 3.49 SAUDI ARABIA the U.S. flounders stability and absence of violence/ RULE OF LAW The Global Competitiveness Report, 3.16 PUERTO RICO terrorism” metric. The “govern- 2014–2015. World Economic Forum 3.10 RUSSIA As in the Foundations category, ment effectiveness” component (2014))—an index based on an in- 3.04 KUWAIT Finland takes first place in Policy quantifies opinions on the quality ternational survey. The last compo- 2.93 TURKEY & Stability. The Nordic nations of a nation’s public services, of its nent, “innovation and entrepreneur- 2.84 CHILE dominate this area, holding four of civil service and the degree of its ship opportunity,” is drawn from the 2.83 SOUTH AFRICA the top seven spots, with Finland in independence from political pres- 2014 Legatum Prosperity Index. 2.79 UKRAINE first, Sweden in fourth, Norway in sures, and of its policy formulation and implementation—as well as This category includes com- 2.73 SLOVAK REPUBLIC fifth and Denmark in seventh. This the credibility of its government’s ponents based on R&D spending, 2.69 GREECE revealing section of our Scorecard which can impact future founda- demonstrates the dramatic impact commitment to such policies. 2.52 POLAND tions. Likewise, a strong showing in of policy and overall stability on a “Regulatory quality” examines im- such as enforcing contracts and 2.39 BRAZIL “innovation and entrepreneurship country’s innovation potential. pressions of the ability of a govern- property rights. 2.23 THAILAND opportunity” may yield ventures BUSINESS EXPENDITURES ON R&D Data for Policy & Stability are ment to formulate and implement Edging out most of the Nordic (% of GDP) 1.64 that fuel organic domestic growth. INDONESIA drawn from the World Bank’s 2014 sound policies and regulations countries in the Top 10 for this GOVERNMENT SUPPORT OF R&D 1.57 MEXICO Behind Finland, South Korea (% of GDP) World Governance Indicators, which that permit and promote private category, Singapore and New climbed from third to second place, INFRASTRUCTURE QUALITY 1.45 PHILIPPINES consist of “political stability and sector development. Finally, the Zealand earn the second and third pushing Switzerland down one spot (roads, ports, electricity, etc.) 1.32 ARGENTINA absence of violence/terrorism,” “rule of law” component provides slots, respectively. The United in the process. ENTREPENEURSHIP & OPPORTUNITY 1.27 INDIA “government effectiveness,” “regu- perceptions of confidence in and States continues to place poorly, latory quality” and “rule of law.” adherence to the rules of society, finishing 20th.

42 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 43 COMPONENT SCORES PRODUCTIVITY(1) IP(2) INTENSITY(3) ENTERPRISE SUPPORT(4) EDUCATION / WORKFORCE(5) FOUNDATIONS(6) POLICY & STABILITY(7) OVERALL CATEGORY SCORES abcdefghijklmnopqrs tu vw x y zaa (7)(6)(5)(4)(3)(2)(1) SCORE RANK UNITED STATES 10 10 10 7.63 4.4 3.33 6.91 6.25 10 10 8.16 10 8.66 9.17 4.44 5.35 10 5.59 6.85 7.77 8.66 6.96 7.63 7.61 8.45 10.00 8.82 6.18 9.00 6.60 7.22 7.66 39.62 UNITED STATES 1 DENMARK 0.28 0.31 9.05 7.63 7.88 10 10 10 0.14 0.35 8.81 0.22 2.33 8.19 4.2 2.01 8.66 0.28 5.62 7.32 7.77 9.77 8.18 9.3 9.46 9.66 0.30 8.34 7.60 4.89 3.79 7.62 9.15 29.77 DENMARK 2 NEW ZEALAND 6.08 9.47 7.08 0.05 9.6 7 6.88 10 10 4.37 0.53 1.39 3.02 5.83 8.15 10 8.5 9.5 9.61 7.78 3.57 7.83 6.23 4.60 9.40 28.14 NEW ZEALAND 3 AUSTRALIA 0.6 1.6 6.8 8.15 10 4.4 4.63 6.25 0.92 0.04 7.78 0.25 5.33 8.37 7.06 5.82 5.19 3.44 3.36 3.4 5.84 5.83 8.59 8.43 8.07 9.42 9.23 1.10 7.48 5.24 5.43 4.97 5.92 8.79 27.80 AUSTRALIA 4 SINGAPORE 6.98 10 1.25 0.12 10 8.33 9.26 5.6 6.1 0.7 3.43 5.44 9.16 8.61 9.58 9.66 10 9.19 8.49 0.69 9.20 4.13 6.66 9.61 27.69 SINGAPORE 5 FINLAND 0 0.03 9.05 10 1.03 0.04 0.18 1.87 0.08 0.03 7.83 0.07 8.33 8.26 3.6 1.95 9.03 0.22 7.08 9.39 9.44 9.34 9.67 10 9.62 9.84 0.02 9.53 0.64 6.12 3.70 8.81 9.78 27.57 FINLAND 6 SWITZERLAND 0.23 0.31 7.52 9.47 5.44 3.05 4.15 5 0.32 0.97 6.94 0.3 5.33 8.73 3.61 3.33 6.06 0.58 6.26 7.05 10 9.37 9.72 8.71 8.89 9.36 0.27 8.50 3.59 5.33 3.40 8.17 9.17 27.44 SWITZERLAND 7 SWEDEN 0.06 0.54 8.46 8.15 7.9 1.04 1.41 2.5 0.25 0.2 7.76 0.54 8 8.41 2.46 2.31 7.26 0.37 6.68 8.36 7.5 10 8.83 9.01 9.76 9.95 0.30 8.31 2.62 6.18 3.10 8.14 9.39 27.16 SWEDEN 8 UNITED KINGDOM 0.59 0.89 8.46 9.21 1.97 0.81 2.74 5 1.36 7.86 0.81 6 9.33 7.6 6.41 5.03 3.77 5.76 3 4.15 6.38 9.02 6.51 7.52 9.34 8.94 0.74 8.84 2.38 6.00 5.71 5.64 8.08 26.70 UNITED KINGDOM 9 CANADA 0.02 0.97 9.05 8.68 3.93 0.29 0.18 5.83 0.84 0.12 7.32 0.95 6 10 6.41 5.37 3.96 1.62 2.43 4.18 7.22 8.17 8.48 8.59 9.16 9.18 0.50 8.87 2.21 6.07 4.34 5.50 8.85 25.95 CANADA 10 HONG KONG 0.07 0.03 5.18 8.94 0.54 1.31 3.16 9.03 8.33 9.42 2.78 0.27 1.71 9.72 9.2 7.95 8.45 9.88 8.47 0.05 7.06 1.67 8.93 1.53 6.88 8.69 24.85 HONG KONG 11 GERMANY 0.11 0.5 8.28 7.89 0.87 0.33 0.35 2.23 1.57 0.43 7.51 0.63 5.33 6.85 4.83 2.94 5.94 4.51 2.78 5.8 7.1 8.33 8.34 8.11 7.69 8.61 8.73 0.31 8.09 1.07 5.08 4.20 7.39 8.29 24.58 GERMANY 12 IRELAND 0.08 0.11 9.05 8.42 3.4 3 4 3.74 0.09 0.14 7.6 0.01 4 7.72 7.33 4.27 5.14 0.13 3.31 4 5.83 8.23 7.93 7.5 8.7 9.11 0.10 8.74 2.85 4.83 4.22 5.34 8.31 24.56 IRELAND 13 NETHERLANDS 0.15 0.11 9.05 8.68 0.97 1.96 2.07 4.16 0.4 0.15 6.13 0.16 5.66 8.3 2.57 0.86 5.72 0.76 3.37 4.93 9.16 8.68 8.8 8.57 9.34 9.43 0.13 8.87 1.91 5.06 2.48 6.54 9.04 24.30 NETHERLANDS 14 FRANCE 0.31 0.85 9.05 8.42 1.81 1.31 1.32 4.43 1.33 1.24 5.8 0.87 5 7.19 5.31 2.96 6.36 2.96 3.65 4.16 5.49 8.61 7.35 6.29 7.52 7.24 7.96 0.58 8.74 2.04 4.72 4.25 6.40 7.25 24.27 FRANCE 15 JAPAN 0 0.11 9.05 9.47 0.12 0 0 1.72 2.73 0.46 6.07 0.13 5.33 6.59 0.93 5.81 5.06 2.02 7.47 8.01 8.88 7.08 8.31 7.96 7.09 8 0.06 9.26 0.91 4.53 3.46 7.86 7.84 24.22 JAPAN 16 NORWAY 0.01 0.19 6.8 8.42 5.32 0.51 0.3 3.33 0.16 0.05 8.28 0.03 8.33 7.61 2.74 1.51 6.12 0.23 2.27 3.97 6.38 9.02 9.57 8.92 8.96 10 0.10 7.61 1.92 6.06 2.65 5.41 9.36 23.66 NORWAY 17 ISRAEL 0 0.42 6.62 5.78 7.71 0.78 0.15 5.73 0.13 0.14 5.03 8 6.45 4.19 9.64 3.24 0.03 9.75 9.82 3.88 6.45 0.82 6.62 7.26 6.36 0.21 6.20 2.90 6.49 4.28 7.48 5.27 23.44 ISRAEL 18 AUSTRIA 0 0.03 7.52 8.15 0.66 0.15 0.15 4.16 0.13 0.05 6.83 0.04 3 5.99 3.49 2.9 6.29 0.76 5.44 6.97 8.88 8.25 9.61 7.86 8.36 9.5 0.02 7.84 1.05 3.97 3.36 7.39 8.83 23.17 AUSTRIA 19 LUXEMBOURG 6.66 9.73 3.97 0 8 0.58 10 2.7 3.37 8.05 9.24 9.57 8.03 9.32 9.35 8.20 3.99 5.29 5.84 9.07 23.13 LUXEMBOURG 20 BELGIUM 0.04 0.23 9.05 7.63 3.14 1.06 1.11 6.66 0.24 0.24 4.99 0.22 5 6.83 2.6 1.57 6.1 0.56 4.28 5.46 7.77 7.21 8.07 7.94 7.73 7.97 0.14 8.34 2.44 4.26 2.71 6.18 7.93 22.85 BELGIUM 21 QATAR 9.47 0.01 4.66 10 0 0.08 6.66 9.16 6.1 5.86 6.69 9.47 0.01 7.33 0.04 6.66 6.95 21.76 QATAR 22 SOUTH KOREA 7.52 3.42 2.91 0.49 0.44 8.58 0.14 1.33 8.08 4.35 3.68 6.28 3.43 0.79 10 10 6.94 7.45 5.62 6.28 6.68 6.31 5.47 1.70 4.53 3.71 8.60 6.22 21.59 SOUTH KOREA 23 ICELAND 3.82 6.31 7.66 3.33 4.09 4.72 7.76 0 3.86 6.37 8.88 9.01 9.31 7.56 7.05 8.84 5.07 5.50 4.14 7.03 8.19 21.37 ICELAND 24 TAIWAN, CHINA 0 0.03 4.86 7.1 0.23 0.01 0.01 2.5 0.19 7.21 7 6.19 2.32 6.56 6.94 7.36 7.88 6.53 7.21 6.69 0.02 5.98 0.59 6.80 2.32 6.95 7.08 21.24 TAIWAN, CHINA 25 ESTONIA 6.57 0 7.25 5.33 6.97 4.5 2.77 3.99 0.01 3.49 5.79 6.11 6.5 7.38 5.79 8.19 7.12 6.57 6.52 2.82 5.47 7.12 20.35 ESTONIA 26 UAE 8.15 0.07 6.65 8.66 6.7 0.71 0.72 1.05 9.44 5.83 8.08 6.44 5.99 5.25 8.15 0.07 7.34 0.72 5.44 6.44 20.11 UAE 27 SPAIN 7.52 3.15 6.66 0.57 0.28 5.59 0.18 1.66 6.57 3.24 2.52 4.91 2.5 0.74 1.76 3.24 8.05 5.96 4.82 6.37 6.5 6.52 5.34 3.62 3.50 2.78 4.75 6.05 18.60 SPAIN 28 MALAYSIA 3.69 7.36 0.06 7.24 9.33 7.34 3.33 1.9 0.84 2.51 7.22 5.18 4.95 6.21 5.44 4.65 5.53 0.06 7.97 2.02 4.97 5.31 18.47 MALAYSIA 29 PORTUGAL 7.74 5.78 0.06 0.01 6.43 0 2.33 6.9 3.01 4.56 5.01 0.23 1.79 3.65 8.33 5.84 7.44 6.66 6.02 6.65 6.76 0.06 3.92 3.20 4.90 6.69 18.24 PORTUGAL 30 PUERTO RICO 9.21 4.77 3.66 3.03 1.5 1.05 5.27 5.69 3.59 6.21 5.38 9.21 4.22 2.27 3.16 5.22 17.19 PUERTO RICO 31 CZECH REPUBLIC 7.52 3.94 0.04 0.05 4.95 0 4.33 4.36 4.6 2.95 5.01 0.51 2.73 3.95 5.55 6.58 8.56 5.41 7.04 6.54 5.73 0.04 3.41 3.27 4.70 6.89 17.17 CZECH REPUBLIC 32 CHILE 7.29 3.94 0.07 5.03 5 5.79 1.85 0.34 0.53 6.52 0.03 0 0.88 4.72 5.77 6.11 6.72 8.37 7.74 5.62 0.07 5.27 1.85 2.84 7.24 16.35 CHILE 33 LITHUANIA 6.03 3.68 6.51 3 4.81 3.05 3.24 0.02 2.14 5.27 5.17 8.09 5.23 7.18 5.78 4.86 4.77 2.10 4.19 6.57 16.07 LITHUANIA 34 SLOVAK REPUBLIC 6.98 3.68 0 0 5.2 3.33 4.07 4.78 4.54 3.13 0.1 0.69 1.53 3.33 5.37 8.73 5.06 6.45 4.55 5.33 0.00 4.20 3.14 2.73 6.20 15.43 SLOVAK REPUBLIC 35 SOUTH AFRICA 7.16 7.63 2.5 0.09 0.02 4.98 4.66 5.32 0.92 0.77 0.94 0.75 1.73 4.16 4.67 4.56 3.84 4.73 3.4 7.40 1.30 4.99 0.88 2.83 4.13 15.37 SOUTH AFRICA 36 ITALY 0 0.11 9.05 3.42 0.26 0 0.04 2.82 0.79 0.14 4.23 0.04 0.66 4.89 2.04 2.78 4.22 3.17 1.03 1.76 2.97 4.44 4.89 6.6 3.9 5.96 4.23 0.06 6.24 0.78 2.46 2.65 3.52 5.17 14.90 ITALY 37 LATVIA 4.21 6.63 4 3.25 2.93 0.67 2.51 0.02 1.58 5.55 5.54 6.83 5.43 6.83 5.62 4.21 4.63 1.53 4.22 6.18 14.84 LATVIA 38 POLAND 0.01 0.03 6.98 3.42 0.13 0.19 0.27 5 0.13 0.02 5.71 0 1.66 2.82 5.22 3.68 2.21 0.3 0.66 1.73 2.77 4.93 8.18 4.81 6.9 5.76 0.02 5.20 1.14 2.55 2.85 2.52 6.41 14.79 POLAND 39 SAUDI ARABIA 1.44 6.57 0.05 4.67 5.33 4.76 5.04 1.67 10 0.61 0 6.11 4.36 3.29 2.52 3.61 3.9 4.01 0.05 4.92 4.33 3.49 3.33 14.38 SAUDI ARABIA 40 HUNGARY 8.28 3.42 0.02 4.32 0 1 4.58 1.95 0.89 3.73 0.22 2.24 2.89 5.55 4.49 7.58 4.59 6.36 4.97 5.85 0.02 2.48 1.70 3.79 5.88 14.08 HUNGARY 41 CHINA 0.07 0.07 6.39 4.21 0 0.03 0.09 1.66 2.71 2.51 7 4.98 1.67 0.31 1.19 4.25 4.45 3.88 3.13 2.79 2.2 2.31 1.32 0.07 5.30 0.90 4.83 1.06 3.93 2.16 13.03 CHINA 42 GREECE 7.38 3.94 0.06 3.71 0 0.33 4.18 3.54 0.6 4.02 1.1 0.43 0.39 1.51 4.44 4.41 4.05 3.89 5.44 4.52 5.66 0.06 2.06 1.94 2.69 4.48 12.05 GREECE 43 MEXICO 5.49 2.89 4.16 0.37 0.02 5.11 2.33 3.87 0.96 0.96 0.58 3.05 0.18 0.9 3.33 1.87 2.1 3.39 4.9 0.88 4.19 2.27 3.77 1.39 1.57 2.82 11.43 MEXICO 44 TURKEY 6.08 3.42 0 0.26 4.28 2.33 2.8 3 0.97 1.52 3.24 0.5 0.94 1.98 5.83 2.98 0.45 3.61 4.79 3.23 4.75 0.13 3.14 1.85 2.93 3.02 11.30 TURKEY 45 BRAZIL 4.18 2.36 5 0.73 1.17 2.66 3.07 1.18 0.44 1.08 5.15 0.18 2.87 0.27 4.04 3.76 2.02 3.57 2.52 3.27 2.87 2.30 1.61 2.39 2.97 11.00 BRAZIL 46 RUSSIA 4.59 1.57 3.75 0.52 0.04 3.69 3 2.67 4.32 0 4.72 1.69 2.33 2.27 2.56 3.05 4.5 2.06 1.02 2.1 0.14 3.08 2.14 3.12 2.61 3.10 1.33 10.98 RUSSIA 47 THAILAND 0 1.84 0.08 6.2 4 6.12 0.55 7.25 0.45 3.05 3.18 0 3.06 4.07 2.47 0.92 0.08 5.44 3.90 2.23 2.40 10.69 THAILAND 48 KUWAIT 2.89 0.01 2.66 3 5.47 0.11 0.05 3.61 5.47 5.28 2.04 3.06 4.34 2.89 0.01 3.71 0.11 3.04 3.68 9.60 KUWAIT 49 PHILIPPINES 6.84 3.42 0.06 2.36 5 1.91 0 2.44 0.1 1.94 2.3 0.94 2.51 3.11 1.42 5.13 0.06 3.09 1.22 1.45 2.00 9.24 PHILIPPINES 50 INDIA 0.05 0.03 4.95 3.42 0 0.02 0.35 4.16 0.54 0 5.66 4.07 0.29 0 0.41 1.86 1.94 0 0.48 1.63 1.74 2.6 0.04 4.19 1.01 3.24 0.23 1.27 1.61 8.28 INDIA 51 INDONESIA 0.49 4.47 0.16 1.51 7 1.87 0.69 4.67 0.08 0.02 3.33 1.58 2.96 1.46 2.68 0.96 2.48 0.16 3.46 1.81 1.64 2.02 8.27 INDONESIA 52 UKRAINE 4.59 0.78 0.03 2.2 1.66 0 3.64 2.09 0.99 0.57 1.68 3.05 3.64 2.03 0 1.18 0 2.69 0.03 1.29 1.82 2.79 0.80 6.73 UKRAINE 53 ARGENTINA 5.94 0 0.13 1.02 0 0.17 1.55 0.42 1.59 4.67 0.15 1.46 0 3.65 4.98 1.27 0 0.33 2.97 0.13 0.40 2.06 1.32 1.65 6.08 ARGENTINA 54

(A) PUBLIC COMPANY (K) BUSINESS-FRIENDLY (T) BUSINESS 2015 SCIENTIFIC age of a category’s component of a nation’s rough performance The table’s color-coding helps REVENUES (US$MM) ENVIRONMENT EXPENDITURES AMERICAN WORLDVIEW scores (e.g., “IP strength” and in each category and the oppor- to reveal the weaknesses of some (B) PUBLIC COMPANIES (HIGHER = BETTER) ON R&D (% of GDP) “perceived IP protection”) provides tunity to compare the numbers high finishers and the strengths of (C) PATENT STRENGTH (L) BIOTECH VC, 2007 (U) GOVERNMENT OVERALL SCORES the category score. A simple sum of when desired. Because the score is certain countries with lower overall (US$MM) SUPPORT OF R&D A growing lead for the United (D) PERCEIVED IP (% of GDP) the category scores generates the composed of averages of available scores. For example, fifth-place PROTECTION (M) VC AVAILABILITY (V) INFRASTRUCTURE States, with fierce competition overall innovation score. We use data, any gaps in the data, indi- Singapore performs poorly in the (E) PUBLIC COMPANIES/ (N) CAPITAL AVAILABILITY QUALITY (roads, ports, among the followers normalization techniques that give cated as blanks in the table, do not Intensity category. Conversely, MILLION POPULATION (O) POST-SECONDARY electricity, etc.) (F) PUBLIC COMPANY SCIENCE GRADUATES/ each component and each category affect the overall scores. 40th-place Saudi Arabia ranks rela- CAPITA (W) ENTREPENEURSHIP EMPLOYEES/ CAPITA & OPPORTUNITY Our 2015 Scorecard ranks the bio- equal weight. The United States remains at tively well in Education/Workplace. (P) PHD GRADUATES (G) PUBLIC COMPANY (X) POLITICAL STABILITY & This table lists all 54 countries the top, extending its lead from last As the data make clear, the REVENUES/ $USB GDP IN LIFE SCIENCES PER technology innovation potential of MILLION POPULATION ABSENCE OF VIOLENCE/ 54 countries. A nation’s aggregate in top-to-bottom order based on year over the second-place country. top finishers overall tend to score (H) BIOTECH PATENTS/ TERRORISM (Q) R&D PERSONNEL their overall innovation scores. It The next tier of finishers, however, respectably in each category. That TOTAL PATENTS FILED (Y) GOVERNMENT performance in each of the seven WITH PCT PER THOUSAND EMPLOYMENT EFFECTIVENESS categories—Productivity, IP Protec- also illustrates a nation’s rank in is rather tightly packed. Second- stands to reason, as a healthy bio- (I) VALUE ADDED OF (Z) REGULATORY QUALITY tion, Enterprise Support, Intensity, each category, showing the sub- place Denmark, for example, tech sector is dependent on so many KNOWLEDGE- AND (R) TALENT RETENTION TECHNOLOGY-INTENSIVE (RECIPROCAL OF BRAIN (AA) RULE OF LAW Education/Workforce, Foundations, score for each category color-cod- scored 13% higher than 10th-place factors—from a diverse workforce INDUSTRIES DRAIN) and Policy & Stability ed on a coarse scale in comparison Canada. And there was only a 22% skilled in both bench science and (J) BUSINESS EXPENDI- (S) BRAIN GAIN (share of —yields the final score. (For the to other countries. As a result, difference in the overall scores business to support systems includ- TURES ON BIOTECH- global students studying NOLOGY R&D outside their country) complete Methods, see page 46.) In the table offers a quick overview between the second and 20th-place ing everything from the availability brief, for each country the aver- of the final results, an indication holder, Luxembourg. of capital to the access to ports.

44 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 45 PRODUCTIVITY public company revenues Lawrence, S. & Lähteenmäki, R. Nat. Biotechnol. 32, 626–632 (2014), and company disclosures number of public companies Lawrence, S. & Lähteenmäki, R. Nat. Biotechnol. 32, 626–632 (2014), and company disclosures

IP PROTECTION IP strength Park, W.G. Research Policy 37, 761–766 (2008) perceived IP protection Schwab, K. The Global Competitiveness Report, 2014–2015. World Economic Forum (2014)

INTENSITY public companies per million population Lawrence, S. & Lähteenmäki, R. Nat. Biotechnol. 32, 626–632 (2014), company disclosures and U.S. Census Bureau International Database public biotechnology company employees Lawrence, S. & Lähteenmäki, R. Nat. Biotechnol. 32, 626–632 (2014), SCIENTIFIC AMERICAN per capita company disclosures and U.S. Census Bureau International Database WORLDVIEW SCORECARD METHODOLOGY public biotechnology company revenues Lawrence, S. & Lähteenmäki, R. Nat. Biotechnol. 32, 626–632 (2014), This Scorecard assesses 54 countries on their innovation potential in bio- per GDP company disclosures and IMF World Economic Outlook Database technology through a meta-analysis. The analysis includes 27 components biotech patents per total patents Organisation for Economic Co-operation and Development arranged in seven categories: Productivity, Intellectual Property (IP) Pro- business expenditures on biotechnology R&D Organisation for Economic Co-operation and Development tection, Intensity, Enterprise Support, Education/Workforce, Foundations, and Policy & Stability. The table shows the components of each category value added of knowledge- and technology- U.S. National Science Foundation’s Science and Engineering Indicator intensive industries and the sources of data. For each component, countries are ranked on a scale from 0 to 10, with the lowest-ranked country scored as 0 and the highest-ranked one scored ENTERPRISE SUPPORT as 10. A nation’s score in a category is derived from the average of the business-friendly environment Doing Business 2014 (World Bank and the International Finance Corporation) available component scores—any gaps in the individual components were ignored in calculating the averages for each category. biotechnology venture capital Organisation for Economic Co-operation and Development The overall innovation score is a sum of the category averages, indexed to venture capital availability Schwab, K. The Global Competitiveness Report, 2014–2015. World Economic Forum (2014) a score from 0 to 50. The normalization involved in calculating the category capital availability Milken Institute Capital Access Index and overall scores considers each component and each category on equal weighting. In short, the Scorecard gives equal importance to all components. EDUCATION/WORKFORCE Post-secondary science graduates per capita UNESCO and U.S. Census Bureau International Database Ph.D. graduates in the life sciences Organisation for Economic Co-operation and Development per capita R&D personnel per thousand employment Organisation for Economic Co-operation and Development talent retention U.S. National Science Foundation brain drain U.S. National Science Foundation

FOUNDATIONS R&D business expenditures per GDP Organisation for Economic Co-operation and Development government support of R&D per GDP UNESCO infrastructure quality Schwab, K. The Global Competitiveness Report, 2014–2015. World Economic Forum (2014) innovation & entrepreneurship opportunity 2014 Legatum Prosperity Index

POLICY & STABILITY

political stability & absence of violence/ World Bank’s 2014 World Governance Indicators terrorism government effectiveness World Bank’s 2014 World Governance Indicators regulatory quality World Bank’s 2014 World Governance Indicators rule of law World Bank’s 2014 World Governance Indicators

46 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 47 change since last year (neg. values = improvement)

COUNTRY 2009 2010 2011 2012 2013 2014 2015 AVG. UNITED STATES 1 1 1 1 1 1 1 1.0 0 DENMARK 3 5 2 2 2 3 2 2.7 -1 NEW ZEALAND 7 18 18 9 10 8 3 10.4 -5 AUSTRALIA 10 17 5 10 7 4 4 8.1 0 SINGAPORE 2 2 8 3 5 2 5 3.9 3 FINLAND 8 6 7 4 4 7 6 6.0 -1 SWITZERLAND 6 10 6 6 3 6 7 6.3 1 SWEDEN 4 4 3 5 6 5 8 5.0 3 UNITED KINGDOM 12 14 9 11 9 9 9 10.4 0 SEVEN YEARS OF CANADA 11 3 4 7 8 11 10 7.7 -1 BIOTECH TRACKING HONG KONG 17 13 20 12 11 14.6 -1 BY RANK GERMANY 16 16 16 16 14 13 12 14.7 -1 Our growing database reveals IRELAND 14 13 14 8 11 16 13 12.7 -3 ongoing competition at many levels NETHERLANDS 19 12 12 17 12 14 14 14.3 0 FRANCE 18 8 10 12 13 15 15 13.0 0 Analyzing the Scorecard data from JAPAN 13 9 11 18 18 18 16 14.7 -2 year to year uncovers certain NORWAY 17 21 21 19 22 19 17 19.4 -2 trends, such as movement or stasis ISRAEL 5 7 13 14 15 22 18 13.4 -4 in the Top and Bottom Five, but a 10 8 6 4 2 AUSTRIA 21 20 20 20 17 20 19 19.6 -1 longer perspective shows much LUXEMBOURG 25 29 25 19 10 20 21.3 10 more. The end results demonstrate BELGIUM 20 15 15 15 16 21 21 17.6 0 how each country changed relative QATAR 42 25 22 29.7 -3 to itself and others. Likewise, these SOUTH KOREA 15 19 19 22 24 23 23 20.7 0 data show the expanding list of ICELAND 9 11 22 23 23 24 24 19.4 0 countries assessed, although some TAIWAN, CHINA 21 26 17 25 22.3 8 lack data for every year. ESTONIA 27 24 38 26 26 28.2 0 Despite the fact that the United UAE 40 27 27 31.3 0 States has maintained its top spot SPAIN 30 23 23 26 21 28 28 25.6 0 throughout, it is still interesting to MALAYSIA 28 29 37 29 29 30.4 0 observe the dynamics of the other PORTUGAL 27 24 24 27 29 31 30 27.4 -1 highest-ranked countries. In early PRODUCTIVITY PUERTO RICO 52 30 31 37.7 1 IP years, for example, New Zealand CZECH REPUBLIC 23 29 32 30 25 34 32 29.3 -2 INTENSITY did not crack the Top 10, but in 2012 A SWAP AT THE TOP CHILE 26 32 28 35 33 30.8 -2 ENTERPRISE it ranked 9th and has stayed in the A familiar crew dominates SUPPORT LITHUANIA 35 33 34 32 34 33.6 2 EDUCATION/ Top 10 ever since—breaking into the Top Five SLOVAK REPUBLIC 34 22 34 28 31 40 35 32.0 -5 WORKFORCE the Top Five for the first time this FOUNDATIONS SOUTH AFRICA 24 28 36 37 30 36 36 32.4 0 Although Sweden dropped out of year. Hong Kong may be following POLICY & ITALY 26 27 33 36 33 37 37 32.7 0 this year’s Top Five and New Zealand STABILITY a similar path. Conversely, Canada LATVIA 44 50 38 38 42.5 0 moved into third, the other four coun- started below the Top 10 in 2009, POLAND 29 32 38 34 32 39 39 34.7 0 tries at the top—the United States, maintained a Top 10 ranking from SAUDI ARABIA 25 35 45 33 40 35.6 7 Denmark, Australia and Singapore— 2010 through 2013, came in 11th HUNGARY 28 26 31 31 27 41 41 32.1 0 return as this year’s leaders, al- last year, and is in 10th place this CHINA 25 31 30 43 39 42 42 36.0 0 beit jostled around a bit. There’s no STAGNANT AT THE BOTTOM year. In the future, we’ll be watch- GREECE 36 30 37 38 35 44 43 37.6 -1 change for the United States, which The same five countries struggle ing to see if Canada continues to has been the front-runner since the straddle the line, or if it can hold MEXICO 33 33 41 41 43 46 44 40.1 -2 Scientific American Worldview Score- Last year’s Bottom Five nations are back again in 2015. Argentina took onto its position in the Top 10. TURKEY 30 34 39 42 44 47 45 40.1 -2 card launched in 2009. last place, with the Ukraine right above it, just as in 2014. The news might These fluctuations in rank high- BRAZIL 32 35 42 39 36 45 46 39.3 1 Some reshuffling took place be even worse for Indonesia, which dropped from fifth from the bottom in light important considerations in in- RUSSIA 22 36 43 45 41 48 47 40.3 -1 among the other high-scorers. 2014 to third from the bottom this year. terpreting the Scorecard. First, the THAILAND 40 40 54 43 48 45.0 5 Denmark rose from third in 2014 to Other countries in this group, however, did show progress. India rose competition is fierce, and countries KUWAIT 53 49 49 50.3 0 second this year. Singapore, on the one spot, from third from last in 2014 to fourth from last this year. The that do not invest in maintaining PHILIPPINES 38 45 48 51 51 50 47.2 -1 other hand, dropped from second Philippines—now in its fourth straight year in the Bottom Five—also their positions may see others take INDIA 35 37 44 47 47 52 51 44.7 -1 in 2014 to fifth this year. Australia succeeded in moving up one place, to fifth from the bottom. their place. Second, the frequent INDONESIA 47 50 49 50 52 49.6 2 held its ground in fourth this year Perhaps 2016 will be the year the Philippines breaks free from the movement makes it important to UKRAINE 48 49 48 53 53 50.2 0 and last. Bottom Five and begins to climb the Scorecard. consider trends over time. ARGENTINA 46 46 46 54 54 49.2 0

48 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 49 40

AUSTRALIA CANADA DENMARK FINLAND HONG KONG NEW ZEALAND SINGAPORE SWEDEN SWITZERLAND UNITED KINGDOM 36 UNITED STATES TOP 10 BY SCORE TOP 10 BY RANK

32

10

9

28 8 7

6

5

4

3

2

1 2009 2015 2009 2015

LESS ROCKING IN card—placing second four out of 7th in 2009, then dropped to 18th MOST LEADERS LACK in first place, its overall score 10 finishers have jumped up and THE RANKING seven years. Sweden also earned for two years, before getting back CONSISTENT SCORES does fluctuate, even though it was down and back over the years. For The order of the Top 10 countries relatively steady ranks over the in the Top 10 in 2012 and staying years, always in the Top 10 and in there—moving all the way to 3rd in Ongoing ups and downs plague nearly the same this year and last. example, Denmark’s scores for varies less than the scores the Top Five six of our seven years. 2015. Hong Kong’s ranking leaps many countries at the top Compared to the others in the Top 2009–2015 were 31.6, 27.3, 31.9, 10, the United States earned fairly 37.2, 35.7, 29.7 and 29.8. New Zea- Likewise, Singapore has secured around as well: 17th in 2011, 13th steady scores for 2009–2015: 37.1, land’s scores move all over as well In comparison to the overall a Top 10 ranking throughout the in 2012, then 20th, 12th and 11th in Some of the fiercest competition 36.6, 39.0, 38.0, 37.6, 39.6 and 39.6. in that time: 30.0, 23.3, 24.9, 32.7, scores, the ranking at the top looks Scorecard’s history, never dropping 2013, 2014 and 2015, respectively. on the Scorecard is seen among That’s a seven-year average of 38.2, 28.6, 27.5 and 28.1. relatively stable. It starts with the lower than 8th place, and otherwise Like any industry, biotechnol- the Top 10 countries. This graphic with the annual scores remaining So far, our growing database United States earning a steady always reaching the Top Five. ogy demands ongoing efforts to shows the volatility of their fin- fairly close to that number. does not show any conclusive first place across all years. Next, Not every top-placing country, maintain a nation’s standing on the ishes by overall scores. Although Going down the list, however, trends in scores at the top for any Denmark grabs the second-highest however, was so constant. New world stage. the United States is consistently we see that all of the other Top country except the United States. ranking over the life of the Score- Zealand, for example, started in

50 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 51 52 52

SCIENTIFIC AMERICAN world excel around the Countries |

WORLDVIEW venture capital availability.” Andin takes thegoldmedalin“greatest Hawaii andNew Mexico. Even so,it tween theGross State Products of lion people, anditsGDPisbe- it ishometo just alittle over 2mil- the sizeofstate ofConnecticut, Take Qatar, for example. Notquite players withinacertain category. in size. globe, andthey vary dramatically shown here hailfrom allaround the ers inthewiderange ofcategories centralized. Nonetheless, thelead- parts oftheindustry remain bigand and domesticated. Thus far, many tion ofbiotechnology to call itsmall Maybe it’s alittle early intheevolu- rather thanbig andcentralized.” becoming smallanddomesticated that von Neumann failed to foresee, of thecomputer industry, thepath industry when itfollows thepath bright future for thebiotechnology ton, New Jersey, once said,“Iseea tute for Advanced StudyinPrince- his work asaphysicist at theInsti- Freeman Dyson,now retired from in theircategory Countries ofallsizescanbegiants LOSERS AND WINNERS, SMALL AND LARGE Small countries can bebig of “smallanddomesticated.” more andmore like Dyson’s vision goes on,amaplike thiswilllook es where itexcels. Perhaps astime tools thatitrequires andtheplac- of biotechnology today, bothinthe Ph.D. studies abroad. rather notreturn homeafter their tion oftheirstudents whowould they lead theworld inthepropor- drain” category, whichmeansthat prefer notto winthe“worst brain Ukraine, for example, would surely ways desirable. India,Chinaandthe undersized, nation. ing itasahighly educated, albeit per total employment,” designat- lion—won “most R&Dpersonnel mil a population ofonly abouthalf than RhodeIsland,andwitha instance, Luxembourg—smaller ones, sizedoesn’teven matter. For some categories, suchasrelative This mapillustrates thestate Ranking first, though,isnotal- - CAPITALIZATION: MARKET COMPANY PUBLIC GREATEST Canada Australia, States, COMPANIES: PUBLIC MOST United Kingdom Australia, States, United REVENUES: COMPANY PUBLIC GREATEST United States PATENT PROTECTION: STRONGEST MEASURED States zerland/United Swit- Kingdom, United EMPLOYEE: COMPANY PUBLIC PER REVENUE GREATEST Denmark States, United Netherlands, COMPANY: PUBLIC PER REVENUE GREATEST France Australia, States, EMPLOYEES: COMPANY PUBLIC MOST United Kingdom Australia, States, United UNITED STATES

AUSTRALIA

UNITED KINGDOM

Finland, Finland, United United United United CANADA

NETHERLANDS

FRANCE

DENMARK BIOTECHNOLOGY: PATENTS OF IN PERCENTAGE GREATEST Finland/Singapore PATENT STRENGTH: GREATEST PERCEIVED CAPITA: PER SCIENCES LIFE IN GRADUATES PH.D. MOST Arab Emirates Qatar, United States/United CAPITAL AVAILABILITY: GREATEST VENTURE United States, HongKong Israel, Finland MENT: TOTALPER EMPLOY- PERSONNEL R&D MOST Germany Kingdom, United States, United SCIENCES: LIFE THE IN GRADUATES PH.D. MOST Kingdom Canada/United SUPPORT: GREATEST ENTERPRISE Belgium Singapore, Denmark, SWITZERLAND

FINLAND Luxembourg,

SINGAPORE New Zealand, Zealand, New S

ingapore, BELGIUM

QATAR

HONG KONG

UNITED ARAB EMIRATES New Zealand

NEW ZEALAND grabs two golds BEST TALENT RETENTION BEST home) to return intending graduates ( R&D (% GDP): of R&D ON EXPENDITURES BUSINESS GREATEST France Kingdom, United students): graduate (share global of GAIN BRAIN BEST Ukraine China, India, States): United the in stay to intending ate graduates doctor- (most U.S.-trained WORST BRAIN DRAIN BRAIN WORST Chile Thailand, QUALITY: INFRASTRUCTURE BEST Korea, Israel, Finland Emirates/Finland Arab United Kong, Hong OF R&D(%ofGDP): GOVERNMENT SUPPORT Japan Israel, Korea, most U.S.-trained doctorate doctorate U.S.-trained most GERMANY LUXEMBOURG : Saudi Arabia, Arabia, Saudi

United States, States, United ISRAEL

Switzerland, Switzerland, SAUDI ARABIA

South South THAILAND

2 3 1 South nd rd CHILE st PLACE PLACE PLACE

INDIA

CHINA WORLDVIEW SCORECARD States, Brazil, Argentina CROP PLANTINGS:United TOP BIOTECHNOLOGY Australia MARKETS: United States, BIOTECHNOLOGY PUBLIC BEST GROWTH IN Australia, United Kingdom NOLOGY: United States, MARKETS FOR BIOTECH- LARGEST PUBLIC Norway, Sweden, Finland QUALITY: REGULATORY GREATEST Singapore, Denmark EFFECTIVENESS: Finland, GREATEST GOVERNMENT Finland Switzerland, STABILITY: POLITICAL BEST Denmark, Switzerland CLIMATE: Sweden, ENTREPRENEURSHIP STRONGEST PERCEIVED BEST RULEOFLAW: Sweden Kong, Hong UKRAINE

SOUTH KOREA

Singapore, Singapore, JAPAN New Zealand, Zealand, New SWEDEN

NORWAY

BRAZIL

53 ARGENTINA 40,000

AN AUSPICIOUS UPTICK CAPITAL GAINS The U.S. sees an increase in The United States takes its The U.S. industry’s value is higher than ever public biotechs biggest lead yet in public- 800,000 company market capitalization

Information from public compa- UNITED STATES 35,000 nies—those whose shares are One of the most telling metrics traded on public stock exchanges— we use to chart the global biotech 600,000 provides a strong objective mea- landscape is public-company mar- 250 surement of a country’s economic ket capitalization, or the market performance. Because they are value of a business’s outstanding 400,000 publicly traded, public companies shares. When considered in com- have greater transparency than bination with the number of public 30,000 private firms, and offer a clearer companies in each country, this UNITED STATES picture of a nation’s business land- information provides a broad inter- EX-US 200,000 scape. We collect this information national comparison of the industry. from a published study (Lawrence, Our data on market capitalization S. & Lähteenmäki, R. Nat. Biotechnol. was gathered from a published 32, 626–632 (2014)) and company study (Lawrence, S., Lähteenmäki, 200 PUBLIC COMPANY MARKET CAPITALIZATION disclosures. R. Nat. Biotechnol. 32, 626–632 For most of Scientific American (2014)) and company disclosures. (US$ MM) 25,000 Worldview’s history, the number of The United States has histori- AUSTRALIA public companies has been falling cally led the world in biotech market AUSTRIA around the world. As we’ve noted capitalization, and continues to do BELGIUM in the past, a decrease in public so this year. But what’s striking is CANADA CHINA businesses should be considered how much that lead has increased. A DENMARK in the context of other factors, such year ago, the U.S. market capitaliza- FINLAND as employee counts, revenues or tion was close to four times that of FRANCE 150 GERMANY 20,000 market capitalization. Increases the non-U.S. global total—and this HONG KONG in these other factors as company year it ballooned to nearly six times ICELAND INDIA counts drop could indicate that the that total. Australia had the second- IRELAND industry is consolidating, which can largest growth, adding nearly US$ ISRAEL be a positive sign. 5 billion in market capitalization, or ITALY NUMBER OF PUBLIC JAPAN This year, the tally of U.S. public roughly the sum of all of Sweden’s COMPANIES NETHERLANDS biotechnology companies increased public biotechnology companies. (Worldview 2009–2015) NORWAY for the first time in the history POLAND 15,000 While most of the Top 10 countries RUSSIA of Scientific American Worldview. saw progress in this area, Ireland SWEDEN Most other countries have seen a was the lone standout, continuing its SWITZERLAND 100 TAIWAN, CHINA decrease in the number of public two-year drop. 2009 UK firms, although France has demon- The strong U.S. gains in both the 2010 2011 strated a positive trend in this area number of public companies and 2012 since we started measuring in 2009. public-company market capitaliza- 2013 Understanding the complete story, 2014 tion indicate the likelihood of further 2015 10,000 however, also requires an analysis growth ahead. In other nations, of the market capitalization. decreases in the number of firms, paired with increases in market capitalization, point to consolidation, which may help to support slower- 50

AUSTRALIA growing domestic industries. CANADA 5,000 UNITED KINGDOM FRANCE SWEDEN GERMANY ISRAEL SWITZERLAND DENMARK BELGIUM NETHERLANDS NORWAY JAPAN CHINA ITALY IRELAND AUSTRIA FINLAND POLAND INDIA ICELAND HONG KONG TAIWAN, CHINA TAIWAN, RUSSIA

2009 2015

54 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 55 SUM OF R&D US$ MM POLAND AUSTRIA TAIWAN, CHINA CHINA INDIA FINLAND ITALY JAPAN NORWAY ISRAEL 25

NETHERLANDS MAKING R&D RELATIVE Considering biotech spending in proportion to overall R&D reshuffles the rankings CANADA In addition to assessing the simple sum of a nation’s R&D, we use the same sources to determine what pro- SWEDEN portion of its commercial R&D spending is dedicated to biotechnology. We report this as biotech R&D as a GERMANY percentage of the business enterprise R&D expendi- all green tubes: 20 ture, a metric that alters the country rankings derived spent on R&D in the U.S. from the simple sums. IRELAND In this relative measurement, Switzerland and Denmark take the lead, which is not surprising as they are comparatively small countries with strong biotech BELGIUM industries. Ireland’s position in third place, in the context of its relatively lower level of revenues, signifies that it is a desirable location for taking companies offshore. WHERE R&D IS DONE DENMARK A clear win for the U.S., and then 15 it’s a tighter race R&D US$ MM As we’ve noted in the past, countries promote domestic biotechnology SWITZERLAND industries for, among other things, the financial benefits of bringing in high-wage jobs associated with research and development. Accord- ingly, we take a look at where that Russia lags R&D predominantly occurs. 10 the field in FRANCE Using data from a published relative biotech study (Lawrence, S. & Lähteenmäki, investing R. Nat. Biotechnol. 32, 626–632 (2014)) and company disclosures, we present the simple sum of R&D expenditures in 23 nations. Here, AUSTRALIA the United States is the world leader—spending nearly 22 times as much as the United Kingdom, in second place. Then there is a 5 near-tie between Australia, France, Switzerland and Denmark. Not surprisingly, these counties also rank high on market capitalization. UNITED KINGDOM This indicates that for many compa- nies the bulk of their research and development is located in the same country as their headquarters. AUSTRALIA AUSTRIA BELGIUM CANADA CZECH REPUBLIC DENMARK ESTONIA FINLAND FRANCE GERMANY IRELAND ISRAEL ITALY JAPAN KOREA MEXICO NETHERLANDS NORWAY POLAND PORTUGAL RUSSIA REPUBLIC SLOVAK SLOVENIA SOUTH AFRICA SPAIN SWEDEN SWITZERLAND UNITED STATES

US

56 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 57 100 ITALY ITALY SPAIN SPAIN KOREA KOREA ISRAEL ISRAEL MEXICO MEXICO FRANCE POLAND POLAND CANADA CANADA NORWAY ESTONIA ESTONIA AUSTRIA AUSTRIA SWEDEN IRELAND FINLAND BELGIUM BELGIUM SLOVENIA SLOVENIA GERMANY GERMANY DENMARK PORTUGAL PORTUGAL AUSTRALIA SWITZERLAND NEW ZEALAND SOUTH AFRICA SOUTH AFRICA NETHERLANDS UNITED STATES UNITED STATES CZECH REPUBLIC UNITED KINGDOM SLOVAK REPUBLIC SLOVAK PERCENTAGE OF DEDICATED 80 BIOTECHNOLOGY FIRMS BY APPLICATION, PERCENTAGE OF BIOTECHNOLOGY (latest available year) R&D EXPENDITURE PERFORMED

BY SMALL BIOTECHNOLOGY R&D FIRMS (fewer than 50 employees) HEALTH BY MEDIUM & LARGE BIOTECHNOLOGY R&D AGRICULTURE FOOD AND BEVERAGES 60 NATURAL RESOURCES ENVIRONMENT INDUSTRIAL PROCESSING BIOINFORMATICS

40

20 SOURCE: OECD, Key Biotechnology Indicators, http://oe.cd/kbi, October 2014. October http://oe.cd/kbi, Indicators, Biotechnology SOURCE: OECD, Key

THE SPENDING These data consist of public Of all of the countries on this THE SPENDING categories: health, agriculture, food rate—only about 13%—went to SPREAD BY SIZE and private companies, mak- list, Israel was the only one in SPREAD BY and beverages, natural resources, industrial processing. Big businesses outspend small ing this analysis more inclusive which small companies invested APPLICATION environment, industrial processing, In some nations, biotechnol- than the public company figures more in biotechnology R&D than and bioinformatics. ogy spending is spread a bit more ones in biotech R&D While biotechnology encom- presented earlier. For the majority medium and large ones. There, In most countries there is equally.For instance, New Zealand passes many sectors, the most Is Dyson’s vision about the future of of the countries considered here, small companies supplied 67.1% of significantly more R&D spending dedicated about 31% of its R&D investment is in healthcare biotechnology—that it may be head- large businesses accounted for the spending. on health applications than on expenditures to health applications, ing toward an industry composed of most of the spending on biotech Clearly, the numbers suggest In addition to knowing the size of the any other category. The second and roughly 20% each to food and small companies—taking shape? R&D. That was especially true in that it will take some time before companies engaged in biotech R&D highest amounts spent were on beverages, agriculture and indus- Our data may hold the answer. Us- Denmark, the Netherlands and the biotech industry reaches Dy- spending, understanding the indus- industrial processing and agri- trial processing. ing the OECD’s “Key Biotechnology Switzerland, where large compa- son’s predicted point. try also requires an assessment of culture. In the majority of cases, Somewhat surprisingly, bioin- Indicators” for October 2014, we nies provided 94.6%, 92.1% and where the money goes. To find out, however, these areas received far formatics receives very little of the collected information for 25 coun- 90.9% of biotech R&D expendi- we turned once more to the OECD’s less funding than healthcare. For funding. In a field that is already tries on the percentage of biotech tures, respectively. The United “Key Biotechnology Indicators” for example, in the United Kingdom very data-focused, one might R&D spent by small firms (meaning States and South Korea were not October 2014, where we gathered 84% of R&D investment was on expect more support of this area. they have less than 50 employees) far behind, with large firms mak- data for 18 nations. Spending on bio- health applications. The United It will be interesting to see if that versus medium and large ones. ing up 88.4% and 87.7%. technology R&D is divided into seven Kingdom’s next highest spending trend changes over time.

58 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 59 to thehost country, enhancing and capital andeven expertise can flow FDI for Qatar. Inthisway,foreign Qatar, thatwould beconsidered for example, owns abusiness in other. Soifsomeone from France, a company inonenationisfrom an- person ororganization controlling direct investment (FDI),orwhena environment isthrough foreign improve itsbiotechnology business One ofthemanywaysacountry can foreign directinvestment How hostnationsprosperfrom EXCHANGEFOREIGN NEW TECHNOLOGY BROUGHT INBY FOREIGN INVESTMENT BUSINESS IMPACT OFRULESONFDI FOREIGN OWNERSHIP 60 60 ARGENTINA ALBANIA ARGENTINA

SCIENTIFIC AMERICAN ANGOLA AUSTRALIA AUSTRALIA ARGENTINA AUSTRIA AUSTRALIA AUSTRIA AUSTRIA BAHRAIN BARBADOS BAHRAIN BARBADOS BELGIUM BARBADOS BELGIUM BELGIUM BRAZIL BHUTAN BOTSWANA |

CANADA WORLDVIEW BOLIVIA BRAZIL CHILE BRAZIL CAMEROON BULGARIA CHINA CANADA CANADA CZECH REPUBLIC CHINA CHILE COLOMBIA CHINA DENMARK CROATIA

on FDIassesses to whatdegree a the lowest, 3.0,to Kuwait. to Luxembourg, went 6.3, and score, tries received a4orhigher. Thetop prevalent (7)—most ofthecoun- from extremely rare (1)to highly ownership metric—whichisscored and FDItechnology transfer. business impactofrules onFDI, prevalence offoreign ownership, (2014)) andanalyzed three metrics: 2014–2015. World Economic Forum Global, Competitiveness Report published study (Schwab,K.The FDI onvarious nations,we useda industry. To examine theimpactof expanding itsdomestic biotech COSTA RICA ESTONIA CYPRUS CZECH REPUBLIC CROATIA The business impactofrules For theprevalence offoreign FINLAND DENMARK CZECH REPUBLIC FRANCE EGYPT ESTONIA DENMARK GERMANY ETHIOPIA ESTONIA GREECE FINLAND FINLAND FRANCE GUATEMALA GABON FRANCE HONDURAS GEORGIA GABON GERMANY HONG KONG GERMANY GHANA GREECE HUNGARY GREECE GUATEMALA GUATEMALA ICELAND GUYANA HONG KONG INDIA HONG KONG HUNGARY INDONESIA ICELAND INDIA ICELAND IRELAND INDONESIA INDIA ISRAEL IRELAND INDONESIA and technology foreign investment Irelands attracts ISRAEL ITALY ITALY IRELAND JAPAN JAMAICA ISRAEL JAPAN ITALY JORDAN KENYA JAMAICA KUWAIT KUWAIT LATVIA JAPAN LATVIA LITHUANIA KUWAIT LITHUANIA LUXEMBOURG LATVIA MADAGASCAR LUXEMBOURG MALAWI LESOTHO MALAYSIA MALAYSIA LITHUANIA

investment. the only factors influencing foreign that rules andregulations are not the prevalence ofFDI,suggesting still received areasonable grade for the most discouraging score, 1.8, it though Zimbabwe wassaddled with son itenjoys somuchFDI.Andeven 6.6, whichexplains partoftherea- most encouraging, withascore of encourage FDI.Ireland wasranked and regulations inmost countries According to ourdata, therules ages (1)to strongly encourages (7). is scaled from strongly discour- or discourages FDI.Thismetric rules andregulations—encourages nation’s business environment—its 1 2 3 4 5 6 7 1 2 3 4 5 6 7 1 2 3 4 5 6 7 Without adoubt, thesemetrics MALTA MALTA LUXEMBOURG MAURITIUS MEXICO MEXICO MALAYSIA MONGOLIA MEXICO MOROCCO MOROCCO MOROCCO NETHERLANDS MOZAMBIQUE NAMIBIA NAMIBIA NEW ZEALAND NETHERLANDS NETHERLANDS NORWAY NEW ZEALAND NEW ZEALAND NICARAGUA PANAMA NIGERIA NORWAY PERU OMAN NORWAY PHILIPPINES PANAMA PANAMA PERU PERU POLAND PHILIPPINES great extent) to each country. Not it brought innew technology to a in new technology) to 7(signifying ing FDIhadnoimpactonbringing we assigned scores from 1(mean- Using thesameinformation source, brought inbyforeign investment. at thelevels ofnew technology increase itscapabilities, we looked op anation’s biotech industry and explore. location for foreign businesses to Ireland’s position asadesirable on FDI.Thatcombination cements and leads business impactofrules nology R&D,”tiesfor second inFDI “business expenditures onbiotech- add to Ireland’s appeal.Itleads in PHILIPPINES PORTUGAL POLAND To measure how FDIcan devel- PORTUGAL POLAND PUERTO RICO PUERTO RICO PORTUGAL QATAR QATAR ROMANIA PUERTO RICO ROMANIA RUSSIA ROMANIA RUSSIA RWANDA RUSSIA SAUDI ARABIA RWANDA SAUDI ARABIA SENEGAL SAUDI ARABIA SEYCHELLES SERBIA SINGAPORE SINGAPORE SINGAPORE SLOVAK REPUBLIC SLOVAK REPUBLIC SLOVAK REPUBLIC SOUTH AFRICA SOUTH KOREA SOUTH AFRICA SOUTH AFRICA SPAIN SOUTH KOREA SOUTH KOREA SWEDEN SPAIN homegrown tech-based companies. often seedsanew generation of prises, thistransfer ofcapabilities employment indomestic enter- FDI. Inadditionto theincreased gy flows gainasecond benefit from went to Argentina. through FDI.Thelowest score, 3.1, amount oftechnology introduced countries alsosawasignificant highest score, 6.4.Most oftheother surprisingly, Ireland secured the SPAIN SWITZERLAND TAIWAN, CHINA SWEDEN Countries withstrong technolo- SWEDEN TAJIKISTAN SWITZERLAND SWITZERLAND THAILAND TAIWAN, CHINA

WORLDVIEW SCORECARD TIMOR-LESTE THAILAND TAIWAN, CHINA TURKEY THAILAND UAE TURKEY UGANDA UAE TURKEY UKRAINE UGANDA UAE UNITED KINGDOM UNITED STATES UKRAINE UKRAINE URUGUAY UNITED KINGDOM VIETNAM UNITED KINGDOM UNITED STATES YEMEN UNITED STATES URUGUAY

ZAMBIA 61 URUGUAY ZIMBABWE ZAMBIA 0–400 400–800 801–1,200 1,201–1,600 1,600–2,000 2,001–6,000 6,000+

NUMBER OF PATENTS

MOTHERLAND OF INVENTION Mapping the source of patents to track innovation around the world

Our Scorecard relies heavily on economic indicators, such as public company revenues, to measure biotechnology innovation. But while revenues reflect the final output of commercialization, to get a full picture of the state of the industry worldwide it is critical to consider the inputs as well—especially inventions. Inventions are notoriously difficult to measure. Academic 0–400 institutions, which tradition- 400–800 801–1200 ally focus on research and do not 1,201–1,600 “develop” products, might tally the 1,600–2,000 output of research papers or inven- 2,001–6,000 tion submissions to gauge their 6,000+ participation in innovation. Other metrics use patent applications as a surrogate. These methods share a NUMBER OF PATENTS common flaw: they lack an objec- BORN IN THE U.S.A. tive performance bar. Just as most Which states generate the most biotech patents? research papers or invention sub- missions never become commercial credit for one patent, regardless To measure biotechnology inven- inventorship was assigned as the products, most patent applica- of the number of inventors. In torship in the United States, we proportional representation of each tions do not become patents. This cases where a patent’s inventors employed a similar approach to our state. If, for instance, a patent had section calculates biotechnology came from multiple locations, global patent data (overleaf). This three Californian inventors and one patents by country—which also has we assigned inventorship as the allowed us to pinpoint the centers from Connecticut, then California a substantial weakness, because proportional representation of each of innovation in the country that received 75% of the credit for the most patents never become com- country. For example, if a patent produced—far and away—the most patent, and Connecticut 25%. mercial products—but it does had two French inventors and one patents from 2004 to 2014. The results, available at provide an objective measurement German one, then France would be For this metric, we counted the InventorWatch.com, show Califor- of substantial commitment to de- given 66% credit for the patent, and number of patents from each state, nia generated the most patents, veloping a product. Germany would receive 33%. based on the WIPO categories for 6,017—about 18% of the nation’s To count the number of patents The results, from Inventor- biotechnology. Echoing the methods total. Massachusetts came in a dis- in each nation, we identified patents Watch.com, show that the United used in the analysis by country, for tant second with 1,711, accounting aligning with the World Intellec- States leads with 34,159 patents U.S. patents with inventors in a sin- for about 9%. Interestingly, every tual Property Organization (WIPO) for 2004–2014. Japan, Germany gle state, we gave that state credit state in the union produced some categories for biotechnology. When and South Korea come in 2nd, 3rd for one patent, regardless of the patents, although North Dakota a patent’s inventors were from the and 4th with 6,236, 3,084 and 1,715 number of inventors. For patents only obtained three in a decade. same place, that country received patents, respectively. with inventors in multiple states,

62 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 63 AUTHOR! AUTHOR! COMPARING COLLABORATIONS The highest-ranked nations publish the most Leading countries team up the least As a meta-analysis, the Scientific American fractional count (WFC), which indicates the Information from the Nature Index, a new Worldview Scorecard is created from a broad percentage of authorship from a country (and database that tracks affiliations of high-quality collection of data comparisons. This year we includes an adjustment that addresses an imbal- US scientific articles, enables us to generate an added a new resource to this mix, the Nature ance in some of the journals being tracked). SCIENTIFIC AMERICAN WORLDVIEW SCORE informal “collaboration metric” in peer-review Index (http://www.natureindex.com/), which For each country, we compare the Nature 100% publishing. Here, we present that metric for life tracks scientific publications. In past issues Index 2014 WFC for life sciences articles to sciences articles. The results show that coun- we’ve examined the connection between a the overall Scorecard ranking (excluding Hong tries ranking higher overall on the Scientific nation’s rank on the Scorecard and its publish- Kong and Puerto Rico, which are not in the Na- American Worldview Scorecard tend to collabo- ing output, and the Index allows us to revisit ture Index). Not surprisingly, the results show rate less in terms of article authorship. that concept—but with data from a far greater considerable scatter, especially since some To make this calculation, we started with number of countries. Our results show that sev- segments of the life sciences do not relate to the Nature Index’s 2014 article count (AC) and eral nations in particular generate many more biotechnology. Likewise, other categories of weighted fractional count (WFC) for the life publications than might be expected. the Nature Index, such as chemistry, include sciences category. Then we computed each The Nature Index not only provides a data- articles that would impact aspects of biotech- nation’s percentage of collaboration, or how base of scientific publications but it also keeps nology. Nonetheless, the graph shows that a many of its articles included authors from track of the institutional and country affiliations higher overall Scorecard finish is associated other countries. (We calculated this metric as: of each author. It divides articles in four main with a higher article output. In fact, the findings [(AC – WFC)/AC] 100.) categories: chemistry, earth and environmental suggest a potentially exponential correlation. * Much like the comparison of life sciences sciences, life sciences and physical sciences. Certain countries score much higher than AC versus the overall Scorecard results, the data Data for each country are collected by article expected. For example, the U.S. WFC lands show considerable scatter. In general, though, count (AC), with each nation receiving a credit nearly off the chart—more than four times an increase in the overall Scorecard ranking for any article in which it can claim one of the greater than predicted by the correlation equa- correlates with a lower rate of collaboration authors. The database also calculates a weighted tion that best fits the data. China also exceeded with foreign authors for life sciences articles. expectations, publishing far more articles than Also like the previous comparison, some other nations finishing as low as it does on the countries take the trend to an extreme. The United Scorecard. As we’ve noted in the past, however, States, for example, earned a collaboration score publishing lots of articles is not the same as of about 22%, while the trend would predict that publishing lots of valuable articles. number should be about 40%. This means that scientists in the United States collaborate with foreign authors far less than expected. The same can be said for India. Although it received a col- NATURE INDEX’S WEIGHTED laboration score of about 45%, according to the FRACTIONAL COUNT FOR trend its score should be closer to 80%. Japan’s LIFE SCIENCE ARTICLES VS. 2,000 collaboration rate is also considerably lower SC OVERALL SCORE than expected. INDIA The take-home message seems to be that

countries with less potential in biotechnology

tend to collaborate more on articles. That could ON LIFE SCIENCES ARTICLES (%) INDEX COLLABORATION NATURE be a pragmatic result: they have no choice. How- ever, keeping in mind Dyson’s vision for the future of biotechnology—as small and domesticated rather than big and centralized—it’s possible this 1,000 trend may very well shift in the years ahead. In any case, comparisons like these reveal the JAPAN vast potential of combining the power of two rich databases. The articles that follow—“Products CHINA of Their Environment” (see page 66) and “Laws of Attraction” (see page 68)—offer additional examples of how pooling more data sources helps NATURE INDEX WFC: LIFE SCIENCE ARTICLES INDEX WFC: NATURE us to dig ever deeper into the complexities of this industry. (See more at www.natureindex.com.) US

SOURCE: http://www.natureindex.com/country-outputs; Not in NI: Hong Kong & Puerto Rico Not in NI: Hong Kong & Puerto SOURCE: http://www.natureindex.com/country-outputs; 20% 0 SCIENTIFIC AMERICAN WORLDVIEW SCORE 40

64 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 65 serendipitous tangents), the location, or context, of the re- defined list of patents covering the product and method of CHALLENGING CHINA’S ROLE PRODUCTS search activities can influence which tangents are pursued. use of each of their drugs. The lack of drug inventors in China and India challenges For example, offshoring R&D to emerging economies By consulting the DrugPatentWatch.com database and the emergence of domestic innovative capacity. With OF THEIR can lead to knowledge spillovers that seed an innovative following this logical chain, I assembled a list of patent virtually no existing inventors in these countries, who will industry, and the new enterprises would naturally target inventor locations from 2000 through 2014. To ensure that seed growth? ENVIRONMENT domestic needs. every patent was counted on par, each nation was attrib- But, perhaps it is wrong to measure Asian innova- So, simply offshoring research to new locations might uted proportional ownership of each patent. For example, tion using the same metrics as for Western innovation. How R&D location impacts which drugs are produce novel outputs. Accordingly, a shift of R&D away if a patent’s inventors are all from a single country, that Innovation can differ substantially even among Western produced. By Yali Friedman from Western countries may result in fewer drugs being country would get credit for one patent. For a hypothetical countries. For example, the MIT Production in the Inno- developed for Western conditions, and more drugs being patent with two Swiss inventors and one German inventor, vation Economy (http://web.mit.edu/pie/) research group here are drugs currently invented, developed for previously neglected conditions. Switzerland would receive two-thirds credit and Germany observed that innovative companies in the United States and where will future drugs come one-third credit. tend to emerge from from? A key question facing drug de- WHERE ARE DRUGS INVENTED? In the global continental distribution of drug patent new entities, but in velopers and policymakers is whether This study extends prior investigations (Friedman, Y. Nat. inventors, North America—largely the United States—has The continued Germany they are drug development will shift locations, Rev. Drug Discov. 9, 835–836 (2010) and Friedman, Y. maintained a roughly 50% representation, Europe about dominance of often built on lega- in much the same way that manufac- Nat. Biotechnol. 32, 523–524 (2014)) and goes further to 30% and Asia approximately 10% (Figure 1). For all of established cies. So, using new Wturing jobs and business administrative jobs have moved examine patents covering marketed pharmaceuticals by the drug manufacturing occurring in Asia, there is little company formation from industrialized to emerging economies. leveraging objective drug-patent linkages. The logic is as measurable innovation. The continued dominance of pharmaceutical (i.e., the U.S. model) Although the location of innovation might initially follows: 1) The United States is the world’s largest phar- established pharmaceutical innovation hubs suggests that innovation hubs as a metric for seem to affect primarily the economics of healthcare— maceutical market, so most—if not all—globally valuable pharmaceutical innovation is very difficult to relocate. Just innovation would reducing drug prices or increasing throughput of new drugs should have U.S. patents. (The primary purpose of as Hollywood has maintained its position as the global suggests that create an unfair bias drugs—it can also have qualitative implications. For this study is to compare innovation outside the United hub of the television and movie industries, so too have the pharmaceutical against Germany. knowledge-based activities, such as drug development, States, so any potential bias emerging from focusing United States and Western European countries maintained innovation is very The MIT group also the scope of the research projects constrains the outputs. on U.S. patents must be weighed against the benefits of their leadership in pharmaceuticals (data not shown). noted that, contrary For example, strong research funding in Western coun- leveraging rigid U.S. patent inventor listing rules and the When asked which nations in Asia are responsible difficult to relocate. to popular opinion, tries directed at locally endemic diseases results in the objective drug-patent linkages provided by the U.S. Food for its drug inventorship, many propose that India or Chinese firms excel development of drugs directed at those diseases. Likewise, and Drug Administration (FDA).); 2) For U.S. patents, all China might be the regional leader. A closer look at Asian in mass manufac- if tropical countries, for instance, participated more in of the individuals who had “intellectual domination” of the countries demonstrates otherwise (Figure 2). Japan is the turing “not because of low-cost labor, but because of their biopharmaceutical research, then more new drugs directed research must be listed as inventors, along with their loca- source of more than 90% of Asia’s drug patent inventors. ability to move complex advanced product designs into at tropical diseases would be expected. tions, and listing too many or too few inventors can yield a Japan’s dominance in Asia further proves the permanence production and commercialization.” While the precise outputs of innovative research proj- patent that is either unenforceable or invalid; 3) The FDA of pharmaceutical innovation hubs. Innovation has not Accordingly, if Chinese innovation is based on process ects cannot be predicted (many successful drugs emerge as requires pharmaceutical manufacturers to submit a strictly moved in decades. improvement, rather than low-cost labor or develop- ment of novel drugs, then one must ask: Why are China’s FIGURE 1. FIGURE 2. policies directed at Western objectives? Through directed INVENTORSHIP BY REGION incentives, China has established itself as a world leader in scientific publishing and in patent filings (as shown in previous issues of Scientific American Worldview). Low citation rates of scientific papers and low patent-grant rates JAPAN 779 demonstrate that these policies are not producing effective NORTH AMERICA SOUTH KOREA 28 inputs for innovation. EUROPE CHINA 12 ASIA INDIA 9 In other words, China’s current strategy promotes OCEANIA Western-style outputs to anachronistically build founda- SOUTH AMERICA tions, rather than supporting its substantial capabilities MIDDLE EAST already in place. A better development path would be to ASIAN DRUG PATENT INVENTORS leverage China’s unique strengths in advanced manufac- (2000–2014) turing and design to improve on existing drugs and to develop global leadership in research in areas that other countries cannot address.

Yali Friedman is publisher of DrugPatentWatch.com, a competitive intelligence database focused on pharmaceutical patents. 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

66 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 67 ASK THE EXPERTS spondents’ answers are translated into a policy mix that attracts biomedical IP’S IMPACT lenging environment, scoring in the LAWS OF One way of measuring the impor- a quantitative score, which is used to investment. Rather, nations that have Quantitative measures of actual bottom half of the countries sampled tance of policy inputs to investment, benchmark countries’ performance introduced heavy-handed localization levels of investment also confirm in the GIPC Index. Concurrently, ATTRACTION and identifying which are most and overall attractiveness for invest- policies in the past few years, on top of the maxim that policies matter. One China hosts a very small number of important, is to poll those actually ment. The first edition covered 11 not prioritizing policies that are also area where this is remarkably clear is clinical trials in per capita terms—less How a nation’s policies attract making investment decisions—for developed and emerging markets. necessary conditions for biomedical in- intellectual property (IP) protection than 1 trial per million population and discourage biopharma instance, local biopharmaceutical The second edition of the BCI, novation, tend to score poorly relative and the effect of a country’s IP envi- in a given year—which is among the investment executives. Indeed, country managers carried out in 2014, covers 16 nations. to other countries. ronment on the number of clinical lowest globally. By Meir Perez Pugatch, and their teams often have a candid Among other insights, the 2014 BCI To illustrate, Russia has implement- trials hosted in that country—used as In general, policies that run David Torstensson, Rachel Chu, and accurate understanding of how reveals a clear link between policy ac- ed top-down policies, such as preferen- a proxy for biomedical foreign direct contrary to the conditions needed Amir Dayan & Noa Weinstein different aspects of the local policy tions and levels of investment. Those tial treatment for domestic manufactur- investment. We found that nations for biomedical innovation are likely environment factor in when discuss- countries with market-based, pro- ers, to meet its Pharma 2020 goals of with weak IP environments, as mea- to translate into reduced biopharma ing whether to allocate further re- innovation policies in place—such as increasing locally produced medicines sured by the U.S. Chamber of Com- investment. In addition, low costs, iven the inherent sources in the nation. This is precisely the United States, United Kingdom and growing export markets. Yet, these merce’s GIPC International IP Index demand and market potential are not challenges involved what the Biopharmaceutical Com- and Switzerland—score at the top of policies came prior to adequately ad- (GIPC Index), tend to host three to sufficient prerequisites for invest- in the policymak- petiveness and Investment Survey the sample (Figure 1). In contrast, dressing areas like quality of manufac- five times fewer clinical trials than ment; rather, the policy environment ing process, not (BCI)—a global survey-based index even considering their high levels of turing and scientific capabilities and the countries scoring in the upper half is an equally, if not more, important least when it comes of countries’ biomedical-investment demand and future market potential, soundness of its regulatory and legal (Figure 3). In fact, regression analysis determinant. Finally, the outputs to healthcare and attractiveness—aims to understand. those markets that do not yet provide frameworks. Not surprisingly, Russia of the data suggests that the strength themselves, or the lack thereof, actu- biomedicalG innovation, the question is First presented in the 2012 Scien- wide-ranging support for biomedical scores below 60% of the total possible of IP protection can explain over 40% ally shed light on which policy inputs often asked whether policies actually tific American Worldview (“Does your innovation—such as Brazil, Russia, BCI score, and is categorized as “strug- of clinical trial intensity, which is sig- are necessary to promote investment. matter. At the end of the day, does the country deserve investment from India and China, the BRICs—still tend gling to compete.” Moreover, Russia nificant given that a number of other Ultimately, looking at the policies state of the policy environment really biopharma?”), the BCI ranks nations’ to place at the bottom of the group. is ranked lowest in the exact areas in factors—such as adequate capabilities of countries that secure biopharma translate into more or less investment biopharma investment environments Take, for example, countries which it seeks to be competitive, such and infrastructure—are also typically investment might provide a roadmap and innovative activities in the bio- based on the perspectives of local using protectionist-type policies as in manufacturing, where it scores considered important for attracting for all nations seeking the same success. medical sector? The answer is yes. executives. The BCI is composed of or requirements to stimulate local well below the rest of the group at just clinical trials. A growing body of data shows 50 questions that capture the entire biomedical manufacturing or R&D. 54% (Figure 2). China makes an interesting exam- Meir Perez Pugatch is managing director that there is a positive link between biopharmaceutical ecosystem, from The BCI results suggest that these and ple. By some measurements China’s of Pugatch Consilium and IPKM profes- sor at the University of Maastricht. David a country’s policy inputs—all of the scientific capabilities to market condi- similar policies that seek to coerce IP laws and their enforcement are Torstensson and Rachel Chu are partners, laws, regulations and initiatives in tions. Using statistical analysis, re- localization do not constitute part of gradually making strides, but overall Amir Dayan is CTO, and Noa Weinstein is a place affecting biopharmaceuticals— BCI it continues to represent a very chal- statistician at Pugatch Consilium. RESULTS BY and its outputs, such as biomedical BCI CATEGORY R&D and the production of new OVERALL health technologies. In other words, SCORES & whether or not a nation provides, for RANKING THE IP POLICY ENVIRONMENT IMPACTS INVESTMENT: instance, support for basic research, ASSOCIATION BETWEEN THE LEVEL OF IP PROTECTION & CLINICAL strong biopharmaceutical-related TRIAL ACTIVITY (as measured by the annual rate of new clinical trials, 2009–2013) intellectual property rights, robust SCIENTIFIC CAPABILITIES CLINICAL ENVIRONMENT MANUFACTURING & LOGISTICS REGULATORY FRAMEWORK HEALTHCARE FINANCING EFFECTIVE IP PROTECTIONS MARKET OVERALL CONDITIONS GENERAL CONCLUSIONS OVERALL SCORE OVERALL COMPETITIVENESS RELATIVE COMPETITIVE STRONGLY COMPETITIVE REASONABLY COMPETE LIMITED ABILITY TO COMPETE STRUGGLING TO regulatory standards, streamlined FIGURE 1: FIGURE 2: FIGURE 3: USA 13.38 11.13 12.00 11.56 10.94 13.38 12.63 1.88 86.88 USA processes and a fair price does in fact GIPC International IP index score as % or total score, life sciences UK 11.90 10.70 12.60 12.90 11.10 11.20 11.40 1.40 83.20 UK indicators, 2014 Clinical trial activity (standard /million population), impact its competitiveness for bio- SWITZERLAND 11.06 9.89 13.00 11.83 9.78 12.22 12.06 1.72 81.56 SWITZERLAND average rate 2009-2013 Expon. * 25 medical investment much more than IRELAND 10.25 9.50 13.17 12.67 10.08 11.17 12.58 1.92 81.33 IRELAND 80 might initially be expected. SINGAPORE 10.71 11.21 12.29 10.43 9.07 11.43 11.71 1.29 78.14 SINGAPORE Source: Pugatch Consilium, 2014; Clinicaltrials.gov; GIPC International IP Index (2014) Such findings not only suggest JAPAN 9.40 10.26 11.76 11.20 8.88 12.16 11.42 1.72 76.80 JAPAN 20 that putting policies in place that CANADA 10.32 11.07 11.54 11.21 8.86 10.74 11.18 1.64 76.56 CANADA 60 support biomedical innovation is im- ISRAEL 10.21 10.64 11.29 9.39 9.39 9.79 10.50 1.64 72.86 ISRAEL MEXICO portant if countries want to actually MEXICO 7.50 10.21 9.64 8.64 8.71 10.07 9.86 1.57 66.21 SOUTH AFRICA 7.21 10.00 10.50 8.86 6.64 10.71 9.57 1.50 65.00 SOUTH AFRICA 40 15 attract investment and improve the ARGENTINA 8.29 9.36 8.50 8.14 9.29 7.50 7.86 1.36 60.29 ARGENTINA competitiveness of the local sector, INDIA 6.94 9.17 10.00 8.56 6.61 8.00 9.11 1.56 59.94 INDIA but they also shed light on which TURKEY 6.11 10.11 10.18 8.14 7.14 8.46 8.43 1.36 59.93 TURKEY areas nations might want to focus on RUSSIA 6.58 9.67 7.58 7.63 7.38 9.42 8.96 1.42 58.63 RUSSIA in order to enhance their chances of CHINA 7.73 7.92 8.62 6.69 7.42 8.19 9.38 1.65 57.60 CHINA CLINICAL TRIAL ACTIVITY CLINICAL NIGERIA INDONESIA INDIA VIETNAM CHINA UAE CHINA BRAZIL MEXICO COLOMBIA TURKEY RUSSIA THAILAND MALAYSIA JAPAN UKRAINE SOUTH AFRICA ARGENTINA UNITED KINGDOM FRANCE UNITED STATES AUSTRALIA SINGAPORE securing investment. BRAZIL 4.93 7.86 8.79 7.93 7.57 9.00 9.00 1.50 56.57 BRAZIL IP INDEX SCORE GIPC INTERNATIONAL

68 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW SCORECARD 69 PARTNER PROFILE because his doctor, a well-trained PRESCRIBING WITH A MEDICATION SAFETY AUTO-PILOT: Food and Drug Administration’s and extremely capable physician, Critical Path Initiative—an effort to did not know that the heartburn An actionable, attainable step towards truly personalized medicine is accelerate the drug development medicine he had prescribed had the the “Auto-Pilot” system envisioned by Dr. Raymond Woosley and being and regulatory process. ability to cause sudden death.” developed under AZCERT’s contract with the FDA’s Safe Use Initiative. The C-Path’s mission entails reach- In 2000, Dr. Woosley moved his Auto-Pilot considers multiple factors in real time and provides the doctor ing across the boundaries separat- CERT from Georgetown University and other healthcare providers with the most pertinent data needed to ing drug companies, academia, to the University of Arizona, where guide prescription therapy. researchers, and regulatory agencies it became AZCERT and eventually to facilitate unique cross-disciplinary CredibleMeds. Through its web por- PHYSICIAN: AUTO-PILOT: collaborations, which take place in tal, CredibleMeds gives clinicians, » Makes the diagnosis for a » Accesses patient data, including neutral, pre-competitive space. In researchers and patients access to a patient’s illness and chooses a current prescription medications its ten-year existence, C-Path has robust and continuously updated list prescription medication and their risk, allergies, other helped to improve the efficiency and of drugs that are categorized by their medicines and existing conditions efficacy of drug development by Safe risks for causing torsades de pointes » Cross-references patient data discovering and receiving regula- (TdP), the heart arrhythmia that can against the continuously updated tory endorsement for standardized Use lead to sudden cardiac death. CredibleMeds list of drugs biomarkers (tools to help speed Pioneer Currently, Dr. Woosley is working » Determines potential drug-drug drug development) for Alzheimer’s under a contract with the U.S. Food interactions or side effects that disease, Parkinson’s disease, skeletal Below is an illustration of how and Drug Administration to establish could harm the patient and dis- muscle injury, kidney injury, and For more than 3 decades, the Auto-Pilot would guide collaborations that can incorporate plays the findings more. C-Path was also the first orga- life science innovator decisions for a prescription for the potentially life-saving informa- » Confirms physician’s prescribed nization to effectively pool patient- Dr. Raymond Woosley Azithromycin: has revolutionized patient tion created by CredibleMeds into medication, or recommends moni- level data from multiple clinical trials care by harnessing the the systems that support healthcare toring or safe alternative(s) shared by several major pharmaceu- power of collaboration. decision-making. This work is also tical companies in order to better supported by grants from the Bert PHYSICIAN: understand the course of Alzheimer’s ©BALFOUR WALKER ©BALFOUR W. Martin Foundation and Oracle Prescription for » Directs therapy and provides disease. This database is now being Health Sciences and made possible Azithromycin learning on how information re- used to design and simulate new rescription drug use in CredibleMeds began as part of a by a new partnership between Credi- ceived can be made more useful clinical trials with greater likelihood America continues to national network of Centers for Edu- bleMeds, Banner Health Systems or improved of success in testing new treatments rise, and while properly cation and Research on Therapeutics and the University of Arizona Col- for this and other diseases. prescribed medications (CERTs) launched by the federal lege of Medicine – Phoenix. yes no “Today, digital and cloud tech- can have a markedly Agency for Healthcare Research and “We have developed a system to nologies allow us the ability to ana- Accepted Medical positive impact on pa- Quality in 1999 following a ten-year analyze drug safety evidence that can Indication lyze and communicate vast amounts Ptients’ well-being, incorrect or inap- campaign by Dr. Woosley to obtain fuel a ‘behind-the-scenes’ software of information in an instant,” Dr. yes propriate use of medicines can also Congressional legislation and fund- program that we call the ‘Auto-Pilot,’” no Woosley concludes from his office in have devastating consequences for ing for such programs. Dr. Woosley explains. “When a medi- TdP Risk Score Positive Oro Valley, Arizona, where he works patients. Assessing and communi- “There was a critical need for cine is prescribed, all of the medical closely with scientists in the local cating those benefits and risks has research that drug companies would evidence about the safety of that no yes Sanofi and Roche-Ventana facilities. been the life’s work of Dr. Raymond medicine is com- “I feel like the tools and infrastruc- Woosley. Over the past thirty years, “AZCERT’s concept for ‘Auto-Pilots’ is a bined with in- ECG Concomitant ture now exist to enable research Screen TdP Risk Drug Dr. Woosley has matched his keen novel integration of innovative technologies formation found and healthcare delivery systems to scientific acumen, vision and orga- in the patient’s fully utilize the enormous amount of nizational skills, carving out new that furthers the FDA’s mission to reduce electronic medi- data and knowledge our scientists areas of consensus science capable preventable harm from medicines.“ cal record. From QT yes are generating. But, partnerships of tackling the complexities in both —Ali Mohamadi, M.D. that analysis, the such as those created by Credi- the efficient development and safe system provides bleMeds and C-Path will continue use of life-saving medications. He normally not perform,” he explains, valuable guidance to the patient’s to be essential for patients to reap has made the greatest impact on “and that the National Institutes of healthcare team.” (See sidebar.) no maximum benefit from this invest- medical progress as the founder of Health just doesn’t fund.” Of particu- Parallel to the development ment in science. Future advances the Critical Path Institute and Credi- lar concern to Dr. Woosley was the of CredibleMeds is the continued will require collaborations among bleMeds—both of which are guided potential for certain medications to growth of the Clinical Path Insti- translational scientists, those who by the concepts of collaboration induce sudden cardiac death (SCD). tute (C-Path), which Dr. Woosley Dispense Dispense Azithromycin Suggest Safe deliver healthcare and those who and data sharing. “My brother died of SCD in 1996 founded in 2005 in response to the Azithromycin with QT monitoring Alternative train healthcare practitioners.”

70 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW PROFILE 71 WORLDVIEW EVENTS

SUPER SIMULATIONS For decades healthcare ex- NATURAL HEALING As Abbate noted earlier, the perts predicted that computers would transform the field, “tweaking” of natural processes can lead to innovative dis- but until Colin Hill came along we did not know precisely coveries, which was the case for Bob Hariri. “We realized Today’s visionaries battle cancer with cutting-edge Indeed, when a researcher’s discovery yields a revolution- how. Hill is combining computational physics, systems bi- probably 20 years ago that for cellular medicine to have a science and the stubbornness to make it work ary new medicine, that tweaking can change lives. “Innova- ology and personalized medicine to completely rewrite the meaningful impact on patients’ lives we were going to have to BY MIKE MAY | Illustrations by MEEN CHOI tion is inventiveness put to good use,” Bob Goldberg, one of way that clinical trials are done. Instead of running them identify a reliable, renewable source that could be turned into the cofounders of CMPI, told the audience. “Inventiveness in people, he plans to simulate them in computers. a product and put into the hands of physicians—sort of the urviving cancer requires teamwork. On the springs from the imagination of our honorees this evening.” That night in California, I asked Wuest: “Why test a same way we provide them with pharmaceuticals,” he said. evening of Monday December 8, 2014, a small As I took the podium, I started to call up four of the drug in a computer?” While working as a neurosurgeon, he realized that army of some of the best “soldiers” in the battle innovators who joined us that night: Patricia Ernst of the “You can gain a lot of insights,” she answered, “and stem cells would be particularly useful in treating head against blood cancer mingled with patients and University of Colorado Denver–Anschutz Medical Cam- there are more opportunities to study disease on a ho- and spinal cord injuries, but he needed a source of them. members of the press in “The Swamp” at the pus; Bob Hariri of Celgene Cellular Therapeutics; Carl listic level in ways that are cheaper and in ways that are So he turned to what he called “the leftovers of full-term CaliforniaS Academy of Sciences in San Francisco. Just feet June of the University of Pennsylvania’s Perelman School faster because we can take in data that’s already being healthy pregnancies, namely, the placenta.” He added, away, Claude—an albino alligator—laid still, but deadly, of Medicine; and Diane Wuest, representing Colin Hill of collected in the healthcare system.” That information can “This organ is nature’s stem-cell factory.” much like an undiagnosed cancer waiting to unleash itself GNS Healthcare. I felt awed to be there as I invited Carl then be used to find just the right treatment for each in- At Celgene Cellular Therapeutics, Hariri and his col- on an unsuspecting victim. The crowd gathered there that June to the panel. dividual patient. leagues convert stem cells into new therapies for diseases night to learn how sophisticated research from dedicated CHANGING THE ODDS June’s groundbreaking ap- MINING NEW TARGETS Genetic solutions to cancer including cancer. and driven scientists promises to—and in some cases al- proach to combating leukemia begins with the immune-sys- have been anticipated since the sequencing of the human NEVER GIVE UP! When I asked the panel how we can ready does—cure cancer. tem cells from a particular patient, genetically re-engineers genome more than a decade ago, and some of today’s treat- be sure to keep innovation moving forward, June replied This Top Medical Innovators forum was organized those cells to kill that person’s specific cancer and then injects ments do target changes in genes. But Patricia Ernst be- that scientists must be stubborn. “Basically, I tell people through a partnership between Scientific American World- them back into that individual. He first used this protocol lieves that examining other cellular alterations will unveil when they start in my lab that you have to expect 90% of view and The Center for Medicine in the Public Interest in 2010 to treat an adult with the disease—which typically even more targets. She looks at so-called epigenetics. the time—at least—you are going to fail, so if you’re play- (CMPI). The event recognized eight experts for their work kills 80–90% of its victims—and the injected cells destroyed “Most people are familiar with the concept that when ing baseball, that means you bat 100,” he said. “You have to in the fight against blood cancer, from diagnosis to treat- seven pounds of tumor. The man is alive and well today. you get cancer one of your genes has suffered a mutation get used to that, but when you do get something that works ment (see “Innovator Alley”). Gaining ground in this dif- In addition, June had recently completed a study in and that’s why the cells grow uncontrollably,” Ernst ex- it’s an amazing thing.” ficult battle demands crusaders like these to continue the which 39 children with leukemia—for whom several tra- plained, “but there are a lot of other things that can happen The things that work change lives (see “Marathon mission of developing innovative new treatments. ditional treatments had failed—received their own re- to a cell.” For example, the molecules that control genes— Man” and “Saving Dolphins Despite Disease”). As Hariri As Jeremy A. Abbate—publishing director of Scientific engineered immune cells. Of these children, 35 went into known as regulators—may also cause or affect the growth said, “I am moved and compelled by each story where the American Worldview and global vice president for global complete remission. That translates into a response rate of of cancer. This is an example of epigenetics, and such investment and the time of creating a new drug, a new media alliances at Scientific American—said in his intro- 92%! As June said, “It’s a heartwarming story, because you changes can impact the onset and severity of leukemia. therapeutic, has transformed those individuals’ lives.” duction, “One of the most defining characteristics of the see kids who have gone through all the kinds of things that “There are many new drugs that are being developed As I thought over what the panel had said that night enterprise of innovating is taking nature and making it a chemotherapy can do, or radiation, and most of them al- that not only influence heritable changes in gene expres- and looked over the crowd, I felt moved, too, and optimis- little bit better, using what nature gives us and tweaking it ready relapsed after a bone marrow transplant—but after sion,” she continued, “but also directly target epigenetic tic about a more powerful today and an even more innova- just a little bit.” immunotherapy, these kids have returned to a normal life.” regulators that are mutated in particular leukemias.” tive tomorrow.

72 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW EVENTS 73 INNOVATOR ALLEY IANNIS AIFANTIS SUSAN DESMOND- BOB HARIRI CARL JUNE CHRISTOF VON KALLE Professor and Chair Chairman Richard W. Vague Director of Translational Oncology Scientific American Worldview HELLMANN Department of Pathology CEO Celgene Cellular Therapeutics Professor in Immunotherapy National Center for Tumor and The Center for Medicine in New York University Bill & Melinda Gates Foundation Warren, New Jersey Department of Pathology Diseases and German Cancer School of Medicine and Laboratory Medicine Research Center the Public Interest recognized Seattle, Washington Hariri discovered pluripotent eight “Top Medical Innovators.” New York, New York Director of the Translational Heidelberg, Germany When Desmond-Hellmann was stem cells, which are capable of Research Program Each of them works on life science Aifantis uses blood stem cells to president of product development developing into any kind of cell, University of Pennsylvania’s Von Kalle researches techniques or medical research that is already study cellular development and at , she contributed to within the placenta and pioneered Perelman School of Medicine in therapeutic genetics, such as changing lives, and is sure to how cells turn into leukemia and the development of Avastin and their use in regenerative medi- Philadelphia, Pennsylvania using a virus to deliver a drug. lymphoma. He also studies the This process could lead to treat- affect many more in the future. Herceptin, which were two of the cine. He and his colleagues work He developed CTL019 immuno- immediate environment around a ments for certain cancers and Here are our innovators: first gene-targeted therapies for with these cells to fight inflamma- therapy for B-cell cancers, includ- tumor in hopes of creating more the prevention of others. He also cancer. tory diseases, cancer and other ing acute lymphoblastic leukemia targeted drugs. works with colleagues on new conditions. (ALL), non-Hodgkin lymphoma PATRICIA ERNST ways to diagnose cancer sooner JAMES ALLISON and chronic lymphocytic leukemia. and more accurately. Professor COLIN HILL The US Food and Drug Admin- Professor University of Colorado CEO and Cofounder Department of Immunology istration gave CTL019 “break- Denver–Anschutz Medical Campus GNS Healthcare through therapy” status in 2014 Executive Director of the Aurora, Colorado Cambridge, Massachusetts Immunotherapy Platform for the treatment of relapsed and University of Texas Ernst studies the epigenetic— Hill uses advanced computing, so- refractory adult and pediatric ALL. MD Anderson Cancer Center traits that can be inherited but are phisticated algorithms and large Recently, he reported on a study Houston, Texas not in the genes—mechanisms datasets to assess the impact of in which this treatment put 35 out Allison showed that blocking that impact the development of drugs on patients. In this way, of 39 children with leukemia into CTLA-4 on T cells can cause them healthy blood and the changes he is redesigning the manner in complete remission. to fight cancer more effectively, that lead to leukemia. This basic which we test drugs: instead of and this work led to the drug ipili- research uncovers a vast collec- running clinical trials in humans, mumab, which is FDA-approved to tion of new drug targets. he runs clinical trials on computers. treat metastatic melanoma.

PATIENT CASE STUDIES: Innovation In Action MARATHON MAN SAVING DOLPHINS

n February, several weeks before he planned to run his 72-year-old Don Wright—a multiple myeloma DESPITE DISEASE 86th marathon, Don Wright made time to talk with survivor—takes aim at his 100th marathon Hardy Jones fights to protect marine Scientific American Worldview. A few years earlier, in life even as he battles cancer IDecember 2012, he had achieved his goal of finishing one marathon in each of the 50 states. Now, he wants to raise n 2000, life couldn’t have been better for life-long diver and filmmaker his marathon count to 100, a feat he hopes to reach by Hardy Jones. Teaming up with actor Ted Danson, Jones founded BlueVoice. the end of 2016. But without a doubt, his greatest accom- org to protect whales and dolphins. But in 2003, he was diagnosed with plishment is staying healthy despite being diagnosed with Imultiple myeloma. His treatment started with an oral cancer medication and multiple myeloma just after his first marathon, in 2003. a steroid, which stops the growth of cancer cells in the bone marrow. “My Then, instead of giving in to the cancer, he decided to myeloma burden was reduced by 97%,” Jones says. “It was very fast.” take on the Boston Marathon, followed by one race after He started on high doses of the medications, but his oncologist brought them another. His wife and daughter often come along and down over time. Eventually, Jones got 16 months off without any treatment run the half marathon at the events he attends. Wright at all. “In that 16 months,” he says, “I was quite stable, but then the myeloma can keep running in spite of his myeloma because of a began to creep up.” So he tried another drug and experienced a similar cycle— once-a-day pill. He has been on the therapy for seven treatment, quick cancer-killing response, eventual treatment vacation, followed years—starting with a clinical trial five years before it was by cancer recurrence, which led to a new treatment. approved—without any major side effects. Well, except for At 71 years old, Jones continues to receive treatment and pursue his work. one, he laughs: “The big side effect is that it makes me want When he spoke with Scientific American Worldview, he was deep in a project to to go run marathons!” save dolphins being killed in Peru for use as shark bait. “We’re making a film on Jokes aside, Wright deeply appreciates his treatment it now,” he says. “If we don’t stop this dreadful practice, they will wipe out the as well as his health. And of his current cancer-fighting dolphins and sharks.” medication, he says, “It’s helped me live long enough to While Jones saves the world’s marine life, advanced drugs—with ongoing meet my grandchildren, and that’s extremely important in innovations keeping his options coming—save him. There is no better team- my life.” work than that.

74 SCIENTIFIC AMERICAN | WORLDVIEW WORLDVIEW EVENTS 75 and 21% higher yields, while using 37% fewer pesticides, as compared to farmers utilizing non-GM seeds. Hoping to quell fears about in- dustry funding and publication bias, Qaim also incorporated data from studies not published in journals, such as working papers, conference presentations and reports in institu- tional series. Over 90% of the studies included were funded by public- sector sources. “A typical allegation COUNTRY SPOTLIGHTS is that a study showing benefits must ILLUSTRATIONS BY NICOLET SCHENCK have been funded by industry, so results may be influenced by private- sector interests,” says Qaim. “But the GREAT STALL process. And in addition to these enormous increase in the registration SEEDS OF results don’t support that argument.” THE MODI global firms, says Cho, “The domestic of innovative medicines. “Now they Another widely cited concern is that OF CHINA companies who are focusing on their have their own R&D pipeline from CONTROVERSY journals would only publish studies OPERANDI Regulatory paperwork further own R&D products are facing the China and around the world,” Cho German research provides clarity with significant benefits. “We didn’t Tackling India’s social same challenges.” says. “They need to be able to cope in the ongoing crop debate find any evidence of such publication problems with IT slows drug approval RDPAC is working hard for with the advancement of the pharma bias,” he notes. BY REBECCA KANTHOR change, but has had limited success R&D here. That is a very huge chal- BY KEREN SOOKNE In addition, some GM-crop BY ZACH GOLDBERG so far. The real challenge is getting the lenge.” skeptics fear that the economic and atience is a necessity for ear of the right high-level decision Last year, the CFDA announced espite numerous scientific agronomic benefits they provide are y 2001, the Western pharmaceutical companies makers. “Policy making in China is so the recruitment of 20 new Center for studies demonstrating only short-term. “This is often men- Indian state of Gujarat— seeking to bring drugs to fragmented, so we are facing different Drug Evaluation employees, adding the benefits and risks of tioned in connection with resistance known locally as the market in China. Last year, ministries and to its existing staff of 80 overworked genetically modified (GM) development in insect pests or weeds,” “Jewel of the West”—was the six-to-eight-year drug sometimes they reviewers, and earlier this year they crops, they continue to be Qaim says. But resistance develop- deep in the doldrums. Last year, Plag these firms have had to contend come up with announced the addition of 53 review- Dthe subject of vehement debate. Low ment is not an issue that is specific BYears of political instability, misman- the six-to- with was lengthened another two different ideas ers. In May, CFDA deputy head Yin levels of public trust regarding GM to GM crops. “This can also occur agement and corruption had frittered eight-year years. “A lot of products were asked about how things Li announced plans to outsource crop safety present a major problem with conventional and biological pest away precious resources. The public drug lag to queue in the line again to get the should be done,” some of the reviewing to third-party for experts and governments, as the control technologies, and it hap- cried out for a savior. Instead, they these firms approval for clinical trial stage,” says says Cho. At organizations. Even so, its capabilities demand for technological advances pens faster when good agricultural got an earthquake that killed 20,000 have had Joseph Cho, who heads RDPAC, an RDPAC’s March don’t compare to the FDAs in other focused on food security has never practices aren’t followed,” he says. The residents, destroyed nearly 400,000 to contend association of 40 multinational R&D- 2014 meeting countries like the United States. been more pressing. Seeing a need for bottom line: farmers cannot substitute homes and caused over US$5.5 bil- with was based pharmaceutical companies with China’s As the agency struggles to get an objective breakdown of the facts, GM seeds for recommended agrono- lion in damages. From the fallout, lengthened working in China. The extension was State Food and through the backlog of approvals and Matin Qaim, an agricultural econo- my techniques, such as crop rotation. Narendra Modi, a former tea peddler another unexpected. “We say it is a shock, not Drug Adminis- pick up the pace, Cho says foreign mist at the University of Goettingen, As Qaim puts it, GM seeds “are not and science enthusiast, was catapulted two years. a surprise,” he relates. tration (CFDA), pharma is increasingly frustrated. “I Germany, and his colleague Wilhelm magic bullets.” into power. Since being recognized in 2005 as officials revealed think the sudden change of prac- Klümper conducted a meta-analysis As European consumer polls call Gujarat’s unpopular government a nonprofit by the Chinese govern- the government’s tice is making the lives of our R&D on the effects of GM crops on pesti- for more public information, Qaim intended for him to be the deputy ment, RDPAC has developed into a rationale for the people and regulatory people on the cide use, crop yields and farmer prof- continues to participate in the GM chief minister. But Modi refused: “I’m lobbying voice for improving China’s added two years. ground and at headquarters frustrat- its. Their report, based on 147 studies, debate by addressing public con- either going to be fully responsible pharmaceutical R&D environment. “They think ing. A lot of investments are being was published on November 3, 2014. cerns through his research. He notes for Gujarat, or not at all.” Some called According to its website, the orga- they have been making mistakes in affected by these uncertainties here in “Many people in Europe believe that even in the face of clear scien- him arrogant, if not authoritarian. In nization is “committed to securing the past, and they just want to do the China.” GM crops do more harm than good,” tific data, it may take some time to truth, Modi simply understood sci- patients timely access to innovative right things,” he explains. explains Qaim. “We felt that a publicly overcome public distrust, as has been ence and technology’s ability to solve drugs”—a formidable task, particu- Indeed, the CFDA is playing funded analysis of studies carried out the case with countless other scien- the seemingly unsolvable. larly in China. As of early January catch-up with the pharmaceutical worldwide would be a useful contri- tific advances in history. Still, Qaim His model is simple: Lay the infra- 2015, the group reports that at least R&D industry. Whereas in the past it bution to the public debate.” The re- remains hopeful: “I’m optimistic that structure—electricity, roads, schools, 34 applications from multinational reviewed mainly generics, since China sults indicate that farmers employing more evidence about the benefits of public transportation, broadband and drug companies have been delayed joined the World Trade Organiza- insect-resistant or herbicide-tolerant GM crops will contribute to wider so on—and harness information tech- by a new step in the drug-approval tion in 2001 the agency has seen an GM seeds earned 69% higher profits public acceptance in the future.” nology (IT) to streamline governance

76 SCIENTIFIC AMERICAN | WORLDVIEW COUNTRY SPOTLIGHTS 77 and achieve synergy between public that rapidly tests for many diseases at drugs and vaccines to treat malaria, chemical compound libraries, which Now, a coalition of forest indus- ZERO, a Norway-based nonprofit officials and grassroots society. Such a cost of just a few dollars—has been tuberculosis and neglected tropical have not yet been screened for their try representatives, environmental that promotes cuts in greenhouse-gas a model calls for far-flung flows of discussing plans with Modi “to place diseases. These conditions affect over potential to tackle the diseases that organizations and aviation companies emissions, and which helped organize critical, often scientific, knowledge this mobile device in every village a billion people—most of them living the program addresses. hope to make air travel in Norway the flights. Among the passengers to empower individuals. This means throughout the country.” in poor conditions in Africa—but Slingsby says the fund’s model of greener by laying the groundwork traveling from Bergen to Oslo was linking agro-scientists and technolog- India faces an arduous road limited financial returns prevent most driving open innovation with good for aviation biofuels. In November Tine Sundtoft, Norway’s Minister of ical engineers with local farmers and ahead, but the significance of Modi’s major pharmaceutical companies from governance is changing the Japanese 2014, two jets operated by Norway’s Climate and Environment. While she entrepreneurs, digitally educating the undertaking cannot be overstated. investing in research to treat them. culture of innovation. To avoid any two major airlines, was impressed with the flight, she under-educated and creating respon- Modi, says Goel, “wants to turn India “The GHIT Fund addresses an conflict of interest, for example, SAS and Norwe- said that the government would be sive and transparent civil institutions into a technological wellspring. But important market failure,” says BT representatives of pharmaceutical gian, flew between reluctant to unilaterally require Nor- that can be accessed and monitored most of all, he wants to inspire hope Slingsby, the fund’s CEO. “The de- companies are excluded from GHIT’s “When domestic airports way’s airlines to use a biofuel blend, from one’s home. in hearts around the globe.” mand is there, but the global society selection committee and advisory God with a 48–52 blend because it is at least double the price The “Modi model” worked won- panel, which includes some of the created of biofuel and of conventional jet fuel. ders in Gujarat, now India’s premier world’s leading authorities on infec- Norway, conventional A-1 In spite of the costs, the Lufthansa e-governed state. Today, all 18,000 of tious disease. he was jet fuel. The blend Group, SAS and KLM have signed an its villages enjoy nationally unparal- Experts outside Japan also agree thinking cuts carbon dioxide agreement to purchase biofuel from leled 24-hour electricity and Internet that GHIT is already having an about emissions by 40% the Oslo Airport refueling facil- access, 95% of its electronically sub- impact. For instance, Medicines for aviation.” compared to regular ity. Avinor, the government-owned mitted public complaints have been Malaria Venture (MMV)—a nonprofit jet fuel. In addition, company that runs 46 of Norway’s 52 addressed and its GDP and agricul- research organization in Switzer- Oslo Airport is the airports, will subsidize the cost of the tural sector have grown at 10% and land—has formed 10 partnerships world’s first biofuel biofuel, says Olav Mosvold Larsen, 9%, respectively, over the past decade. with Japanese pharmaceutical com- “hub,” where biofuel senior executive advisor at Avinor. Having been elected, overwhelm- panies, including one with Takeda to will be supplied through the fuel Biofuel users will also avoid Norway’s ingly, as India’s Prime Minister in test a new drug for malaria. pipelines and hydrants. US$0.13 per liter carbon tax on do- May 2014, Modi is poised to work his MMV’s CEO David Reddy Norway’s first two biofuel flights mestic jet fuels, he says. magic at the national level. Challeng- says the fund is effectively helping “were important to show people that One potential source of biofuels is es—including Japanese pharmaceutical compa- this was possible, because there are wood, says Erik Lahnstein, execu- India faces limited funds, nies, which are “looking to globalize a lot of myths about biofuels,” says tive director of the Norwegian Forest an arduous infrastructural themselves, deep-seated in social re- Kåre Gunnar Fløystad, an adviser at Owners Federation, which represents road ahead, shortcomings NEUTRALIZING still doesn’t have the right tools. That sponsibility and hold a rich chemical 36,000 landowners and roughly 70% but the and stifling regu- is where and why we focus our work.” library.” He adds, “We share the same of the country’s forest production. As significance latory environ- NEGLECT The project was originally con- sense of responsibility and strong demand for paper products drops, of Modi’s ments—abound. Japanese experts collaborate ceived by Tachi Yamada, who previ- willingness to work together.” the industry has closed mills and undertaking Nonetheless, ously led the Bill & Melinda Gates factories. with bullet locally and internationally to Foundation’s Global Health Program Two recent initiatives are intended cannot be fight neglected diseases overstated. trains, “smart and is now chief medical and scien- GREEN SKIES to pave the way for Norway’s do- cities,” new solar BY ICHIKO FUYUNO tific officer at Takeda Pharmaceuti- mestic production of wood-derived projects and sci- cals, Japan’s biggest pharma company. AHEAD biofuels. The renewable-energy com- entific research lthough Japan ranks third Five pharmaceutical firms, including pany Statkraft and the Swedish forest hubs in the pipeline, Modi has faith worldwide in develop- Takeda and Eisai, helped jumpstart Norwegian wood may power company Södra are exploring biofuel in the force-multiplying effects of sci- ing new pharmaceutical the fund by persuading Japan’s foreign tomorrow’s air travel production at a former cellulose fac- ence and technology. products, its contribu- and health ministries to finance half tory in Hurum, while Avinor has BY NANCY BAZILCHUK Consider Modi’s “Digital India” tion to global health lags of it. The remainder is currently pledged roughly US$12 million over campaign: by expanding broadband Afar behind. That imbalance may be backed by six Japanese pharmas, the the next decade for biofuel projects. A and mobile Internet coverage across shifting, however, with the launch of Gates Foundation and the United Na- ith more than 2013 study commissioned by Avinor the country, virtual medical technolo- the Global Health Innovative Technol- tions Development Programme. 2,500 kilometers of and the Norwegian airline industry gies can then be used to ameliorate a ogy (GHIT) Fund, the world’s first Although the GHIT doesn’t seek coastline rumpled concluded that Norway could sustain- health crisis compounded by the 700 public-private partnership dedicated financial returns, awarded developers by deep fjords and ably produce up to 230 million liters million Indians who live isolated from to supporting global health R&D. must show that their potential products rugged mountains, of biofuel from wood products at the nearest hospitals. Since its establishment in 2013, the are innovative, feasible, cost-effective WNorway seems tailor-made for the competitive prices by 2025. On this front Anita Goel, CEO Tokyo-based, US$100 million initiative and accessible to the poorest of the airline industry. In fact, industry ex- “There is a need and space for of Nanobiosym and developer of has funded 30 partnerships between poor. The fund’s investment covers perts are known to joke that “When aviation in the future world,” Larsen the Gene-RADAR technology—a Japanese and non-Japanese companies drug discovery to clinical testing, and God created Norway, he was think- says. “We just have to make sure it is wireless iPad-sized diagnostic tool and public institutes aiming to develop it opens the door to access Japan’s vast ing about aviation.” as sustainable as possible.”

78 SCIENTIFIC AMERICAN | WORLDVIEW COUNTRY SPOTLIGHTS 79 sterile, single-use disposable fermen- those honored with the 1923 Nobel REVOLUTION- tation bags. The single-use bags are Prize for the discovery of insulin, incinerated onsite, says Martin, and experts have since contended that IZING RUSSIA even help generate electricity at the Paulescu was robbed. Some say that To embrace its economic future, Gdansk plant, further reducing costs. his accomplishment stayed hidden Production can be scaled up quickly while World War I ravaged his coun- Russia must let go of its past by operating fermenters in parallel. try. Whatever the reason, it remains BY KARYN HEDE He adds that very few pharmaceutical clear that the Romanian scientist was companies have bothered to re-engi- not sufficiently recognized for his any experts wonder neer their cell lines to achieve higher contributions to the field. And today, what will emerge from Looking to capture the biosimilars productivity with existing biologic as Romania makes significant strides Russia’s economic turn BETTING ON market in Eastern Europe, Polphar- drugs, because doing so would entail toward building a dynamic biotech away from the West. BIOSIMILARS ma, Poland’s largest manufacturer of new rounds of expensive clinical trials industry in the region, its efforts have Is its standing among generic pharmaceuticals, has invested to show biosimilarity to their earlier gone similarly unnoticed by the rest Mthe so-called BRIC nations—the A Polish pharmaceutical in an R&D laboratory and facility production lines. of the world. up-and-coming economic powers of company scales up to meet the capable of manufacturing clinical- In addition, lower upfront costs In a concerted effort between Brazil, Russia, India and China—in demand in a burgeoning market grade biosimilar drugs. Located in allow Polpharma to produce these government agencies, academia and jeopardy? In the future, will we be the Gdansk Science and Technology medicines at a reduced price, which private companies, Romania has grown discussing the rise of the BICS nations BY KARYN HEDE Park, Polpharma’s biologic unit hopes should offer further financial relief its biotechnology sector with research Neamt Iaşi. In addition, bioROne col- instead, replacing Russia with South to register four or five biosimilar for patients and healthcare providers centers in Bucharest, Cluj-Napoca, laborates with international advisors, Africa, whose growing momentum ust as generic versions of drugs with the EMA in the next few worldwide. Brasov and other cities. But the first including the U.S.-based nonprofit can’t be ignored? And how will small-molecule drugs have years, according to Klaus Martin, dedicated biotechnology cluster in Center for Integration of Medicine Russia’s past, with its complicated at- helped to reduce health- the company’s head of biologics. Romania—and southeastern Europe for and Innovative Technology. titudes toward business and capital- care costs, biosimilars offer “Like generics, that matter—is bioROne in Iaşi, located Eventually, scientists at bioROne ization, affect the country’s present an alternative to the class biosimilars are in the northeastern part of the country. hope to commercialize their laborato- ability to cultivate aspiring entrepre- Jof medications known as biologics. Over the very important Researchers at bioROne focus on ry discoveries. In order to develop its neurs from within? Unlike small-molecule drugs, which next decade, to rein in health- biomedicine, including bioinformat- own pharmaceutical products, how- In Lonely Ideas: Can Russia Com- are derived from chemicals, biolog- biosimilar care spending ics and biopharmaceuticals, genetic ever, the cluster will need far more pete? (The MIT Press, 2013), Loren ics are produced from living cells. drugs may and allow wider testing and gene therapy. In the past funding. As it stands its entire annual Graham chronicles the brilliance of Generic-like versions of biologics well provide access to drugs,” five years, scientists there have been budget would barely pay for a small Russian inventiveness, as well as the are called biosimilars because they substantial he says. Cur- granted 100 patents, and the center’s fraction of the cost of developing a work like their patented counterparts, price and rently, the firm cumulative budget during that period single drug. Alternatively, bioROne And how will Russia’s but—unlike generics—can have small market has a proprietary was about US$56 million. is looking to attract clinical trials or past, with its complicated structural differences. Over the next competition portfolio, but Truly a collaborative venture, start-ups to the region. To do this, attitudes toward business decade, biosimilar drugs may well for biologics. Martin says at the cluster was launched by a group the Romanian government is taking and capitalization, affect provide substantial price and market least some are representing the country’s leading steps to improve its infrastructure, the country’s present competition for biologics, which monoclonal antibody drugs that will universities, research centers, industry for example, by joining forces with ability to cultivate aspiring made up a US$170 billion industry in soon be coming off patent. “I’m quite members and other key organizations. the European Union and the Grigore entrepreneurs from within? 2013 and ranked among the world’s confident that Polpharma can deliver Among the 12 founding partners T. Popa University of Medicine and most profitable drugs. quite a cost-competitive set-up,” he REDEFINING are the Grigore T. Popa University Pharmacy Iaşi to raise about US$11 Many biologic drugs will soon says. “If you look at originator drugs, of Medicine and Pharmacy Iaşi, the million for a research facility in nation’s continued failure to sustain lose patent protection in Europe many of these use technologies that ROMANIA Institute of Macromolecular Chem- northeastern Romania to be used for and build upon its scientific achieve- and the United States, opening the were available 10, 15, 20 years ago. Generating the infrastructure istry “Petru Poni” Iaşi, the Institutul preclinical and clinical studies. ments. A leading U.S. scholar on door to manufacturers poised to The cell lines they used years ago Naţional de Cercetare-Dezvoltare Despite Romania’s underappreci- Russian science and technology and a bring biosimilar versions to market. were nowhere near as productive as and financing to establish a pentru Fizică Tehnică Iaşi, the clinical ated status in the biotech field, some foreign member of the Russian Acad- Europe has been at the forefront of modern systems.” vital biotech presence hospitals Spitalul Clinic Judetean de metrics do attest to its impact. For emy of Sciences, Graham goes on to the biosimilar industry, adopting a The first biologics manufacturing BY BACHIR ABI SALLOUM Urgente Sf. Spiridon Iaşi, Spitalul example, a search of PubMed revealed question whether Russia can reverse regulatory framework in 2005. The facilities relied on large, dedicated Clinic de Recuperare Iaşi and Insti- more than 500 scientific publications in its centuries-old pattern of stifling European Medicines Agency (EMA) fermenters and fixed stainless steel n 1916, Romanian physiologist tutul Regional de Oncologie Iaşi, SC 2014 based on work carried out in Iaşi. domestic technological progress. has approved 20 biosimilars, and the pipes that required time-consuming Nicolae Constantin Paulescu Antibiotice SA, which is the largest To move from research to commercial “[Russians] have made the U.S. Food and Drug Administration and expensive work stoppages to developed a pancreatic extract Romanian-owned pharmaceutical results, however, Romania must ensure mistake again and again and again approved its first biosimilar product, a clean and maintain. In contrast, that was an early version of the company, and the public agencies that the world sees its discoveries—and of thinking that modernization is version of the white blood cell–boost- modern cell-line technology uses life-saving insulin used to treat Institutul de Medicina Legala Iaşi continue to build an industry that will the same thing as obtaining technol- ing filgrastim, in March 2015. smaller-batch, flexible systems with Idiabetes. Although he was not among and Directia de Sanatate Publica generate more of them. ogy,” says Graham, who is a research

80 SCIENTIFIC AMERICAN | WORLDVIEW COUNTRY SPOTLIGHTS 81 scholar in Russian studies at Harvard “The ocean currents are very favor- Not surprisingly, Fowler points University. “They’ve got to come to able to us, and there are industrial- out, deriving products from na- the realization that a high-tech coun- scale quantities of seaweed.” The ture fosters collaboration between try possesses those ingredients in the currents bring a large brown algae academia and industry. Research society that make the development species that is of particular interest, partners include the University of of high technology self-sustaining. Fowler says, called Laminaria hyper- the Highlands and Islands’s Scottish It doesn’t have to be ordered from borea—8 to 11 million tons of it, with Association for Marine Science, the above. If you get the right ingredients sustainable annual yields of 100,000 Industrial Biotechnology Innova- together, it will take off on its own.” to 200,000 tons. This bounty of sea- tion Centre and large companies like Graham characterizes Russia’s weed is not only used in its raw form Unilever, Croda, DSM and BASF as failure to achieve success commensu- as organic fertilizer and an animal well as more specialized ones, such rate with its intellectual firepower as, feed supplement, but also provides a as GlycoMar, which screens marine in part, an attitudinal problem that gelling agent called alginate, made up organisms for useful polysaccharide stems from its distain for business as of acids from its cell walls, which can compounds and supplements. a “disreputable activity.” Even today, be used in food processing. In fact, Brown says the research-business with the rise of Russia’s middle class it was the Scottish chemist E.C.C. crosspollination is beginning to division of Charles River Laboratories, That blue Until Charles and its burgeoning business commu- Stanford who discovered alginates in pay off. At his first Natural Product a US$1 billion-plus global contract blood is River pioneered nity, Russian scholars maintain nega- the 1880s. Biotechnology meeting in 2009, 50 research organization with head- remarkable the test in the tive attitudes about commercializing Fowler and Brown support people showed up, mostly academ- quarters in Wilmington, Massachu- at detecting 1970s, labs tested their inventions, he says. Graham increasing seaweed harvests through ics. “We thought we were doing quite setts—is remarkable at detecting harmful for pyrogens by does concede that there are calls for the development of sustainable and well,” he says. But when the group met harmful impurities in pharmaceuti- impurities in exposing rabbits commercialization of technology “extensive farms for biorefining of last fall, the gathering had swelled to cals and medical devices. pharmaceuti- to the substance among Russia’s growing business class alginates and other high-value chemi- more than 300 attendees, including Charles River has built its endo- cals and in question and and in its schools of management. cals with byproducts for biofuels,” 80 businesses—many of them casting toxin and microbial detection busi- medical then checking Still, he finds that the attitudes of Fowler says. Brown notes a “potential an eye toward Scotland’s seaweed, ness by harnessing the crab’s natural devices. them for fever. many innovators remain mired in a for a virtuous cycle” if these seaweed its most abundant and undulating of defense against infection: at the first The LAL is much distain for the “bourgeoisie.” farms can be located near Scotland’s natural resources. sign of a toxin, the blood clots to less cumbersome, Nonetheless, Graham sees some sprawling fish farms—salmon alone block further spread. The company’s much more hopeful signs for Russia’s economic is a US$2 billion industry—to “tie in Limulus amebocyte lysate (LAL) test sensitive and is future, such as systemic changes in the SEA OF GREEN with environmental remediation.” detects this clotting reaction and is now the standard worldwide. What’s way it invests in science and technol- That is, to sop up nitrogen from fish FROM CRAB “the most sensitive in the world for more, the horseshoe crab is a renew- ogy. New institutions like the Russian Seaweed may be the solution excrement. “There’s a real synergy TO LAB bacterial endotoxins,” says Dubczak, able resource. Technicians can remove Foundation for Basic Research (akin to for Scotland’s natural-products there,” Fowler says, with “fish farm who is based in South Carolina, up to a quarter of the crab’s blood the U.S. National Science Foundation) industry and seaweed side by side [and] with Fighting infections the natural way where he supervises the capture, without harming the animal, which is and such venture capital funds as Max- other species grazing on the seaweed blood collection and safe return of held for less than 24 hours. Dubczak BY BILL CANNON BY BILL CANNON well Biotech have been established, that have a harvestable value as well— crabs to the sea. meets annually with a state natural making it possible for individuals and sea urchins, sea cucumbers.” Endotoxins or “pyrogens”—from resources official, crab suppliers and small groups to seek funding outside ynonymous with golf and Researchers at Scottish companies ore spider than crus- the Greek for “fire” because they cause handlers to discuss best practices for of state control and direction. In ad- whiskey, Scotland brims have been investigating seaweed and tacean, the horseshoe fever—reside in cell wall membranes minimizing loss as crabs are shuttled dition, foreign technology companies with something else that its microscopic cousin, microalgae, crab resembles a ta- of E. coli and other so-called gram- between the ocean and lab and have made inroads and forged col- might one day help define for a variety of uses, Fowler explains, rantula wearing an old negative bacteria that can induce back. In the early 1990s, alarmed by laborations with Russian scientists and this nation: seaweed. At least including nutritional supplements, army helmet. It’s a liv- lethal bloodstream infections. These dwindling crab populations, Charles nascent entrepreneurs. Sthat’s the hope of biotechnology boost- anti-aging creams and other “cos- Ming fossil, its basic design unchanged “dead bug parts,” as Dubczak calls River found itself in an unusual Yet foreigners with available cash ers Donald Fowler and Jim Brown. meceuticals,” or pharmaceutical- in 440 million years. And the Atlan- them, in a concentration of 70 parts position for industry—lobbying for don’t feel legally secure investing in Fowler, based in Argyll, is senior cosmetics hybrids. In addition, tic horseshoe crab, Limulus poly- per billion, “will make a person sick.” more regulation. South Carolina now Russian science, according to Graham. development manager for life sciences Scottish biotechnologists see other phemus, can survive out of water for Limulus blood clots when it encoun- limits times and places where crabs Reforming Russian laws to provide busi- with the Highlands and Islands (HIE), natural-product targets that fit today’s weeks, on beaches from Maine to the ters an endotoxin concentration of can be collected and bans their use as nesses with greater intellectual property a government economic and commu- going-green philosophy. For example, Yucatan. Moreover, royal bluebloods just 1 part per trillion. bait. Consequently, crab populations protections, he says, would go a long nity development agency for the north the Scottish firm CelluComp converts have nothing on the horseshoe crab. “You’ve seen an IV bag?” Dubczak rebounded. way toward improving the country’s and west of Scotland. Brown directs the vegetable processing waste from car- Its blood really is blue, enlisting asks. “The solution in that bag has In recent years, Charles River economic prospects. Otherwise, Russia annual Natural Product Biotechnology rots and beetroot and other naturally copper, rather than iron, to transport to be tested for the absence of these invented a cartridge that requires will likely maintain the status quo, or conference in Inverness. derived waste products into pigments, oxygen. That blue blood—says John pyrogens using our LAL reagent.” So 20 times less blood than its original as Graham describes it, its “consistent “There’s a huge resource of kelp specialty celluloses, coatings and Dubczak, general manager of the do the tubes and needles connecting assay. That’s good for business and record, both brilliant and dismal.” forest off the west coast,” Brown says. rheology products. endotoxin and microbial detection the bag to the patient. horseshoe crabs.

82 SCIENTIFIC AMERICAN | WORLDVIEW COUNTRY SPOTLIGHTS 83 WORLDVIEWPOINT Fundamentally, this work depends repair and renew itself. What’s fuel- knowledge into treatments for disease BY ROBERT HARIRI on making the most of tools that our ing that ability? Stem cells. and to fight ordinary aging. In short, bodies already possess, and I started These same cells keep us healthy we must find ways to replenish the thinking about these tools years ago. in our youth. Over the years, though, regenerative engine, and we do that this regenerative “engine” runs lean by replenishing the reservoir of stem AGING 2.0 FROM TRASH TO TREATMENT on fuel, the stem cells. As that hap- cells that provide synthetic versatility. Early in my medical career, I special- pens, the defects of age start to accu- With this knowledge, we can iden- Stem cells and digitized DNA ized in the treatment of head and mulate. In addition, stem cells orches- tify defective products—cells or tissues may hold the key to high- spinal cord injuries. With one patient, trate our response to injury, making or organs—and then use stem cell– performance longevity a defect in the tissue that surrounds them perhaps our best defense against driven synthesis to restore the function the brain, the dura mater, needed to disease. The susceptibility to disease of those parts. Doing this, though, lthough we can’t live for- be repaired after a serious head injury. thus increases as we age. depends on a deep understanding of ever, we can aspire to live I realized, from my ob/gyn rotation, how the biological software, a stem much longer and health- that the amnion—this amazing, clear REPOSITORY OF REPAIR cell’s DNA, drives repair in its youth ier lives. In fact, living plastic-like tissue that surrounds an How can stem cells fix things? It’s in and loses that ability with age. So by well into our 90s lies just embryo—looked a lot like the tissue their DNA, which forms a repository better understanding aging and the Aahead, if we keep fine-tuning the right around the brain that I needed to of synthetic repair. Every stem cell molecular changes that drive it, we can tools. We start by understanding that replace. That moment spawned other contains information, in its DNA, that learn to slow it down or work around it aging arises from an accumulation of ideas about biological tissues being codes for the production of molecules in places. We can find ways to use stem defects in our biology, and this causes used in new ways. In particular, I that guide the signaling and synthe- cells—maybe our own, those from joint decay, decreased muscle mass, started thinking that the placenta— sis behind all of the steps that make someone else or from a placenta—to Alzheimer’s and so forth. With digital the leftovers of birth—could be used tissues and organs. In this process, control certain diseases or to restore health—basically, using high-perfor- as a source of stem cells. Instead of a primordial stem cell undergoes a functionality as we age. mance computational tools to study just throwing away the placenta after series of cellular divisions that make The future of stem cells and the complex biological processes—we can future of cellular medicine will benefit interrogate the cellular and molecu- from this analogy with computers and lar events that occur during human Living well into our 90s lies just ahead, digital processing. Your software, your aging, and identify those that can if we keep fine-tuning the right tools. biological software, that is, resides in be controlled or modified to slow or the nucleus. It’s not that different than arrest those that degrade or degener- having binary code that resides in the ate our bodies over time. To make the birth, we could make use of it. My it more specialized at every step. We memory access of a computer. This most of digital biology, I joined forces personal “eureka moment” led me can watch such a change under a thinking leads us to the concept of re- with my friends and colleagues— to form Anthrogenesis, which later microscope, as this primordial cell programming the biological software Craig Venter and Peter Diamandis— became Celgene Cellular Therapeu- turns into a heart cell or a neuron—all of stem cells, which is already hap- to form Human Longevity, Inc. (HLI). tics, where we mined the placenta as a depending on its surrounding envi- pening in activities to create induced At HLI, we combine knowledge source of stem cells that can be turned ronmental cues that drive the DNA to pluripotent stem cells. These tools from many areas of biology—the into treatments. create different things. provide a platform for controlling fate genome, proteome, biome and A stem cell carries the remark- This DNA makes up a sort of and function, and they have broad more—with advanced approaches able capacity to participate in biological software. Like lines of biomedical applications. The most to computing and informatics, all to renovation or repair at any place in digital code, the genes in the DNA exciting one to me is prolonging and create sophisticated cellular therapies. the body. Moreover, we can get these can be processed to drive an action, extending the quality of life. To build these treatments, we are col- cells from many places beyond the like generating a protein. As a stem lecting data on genomes and health placenta, including bone marrow cell develops into a specialist like a Robert Hariri is the founder and chairman of outcomes from people around the and even fat tissue. Stem cells all neuron, though, it loses the ability Celgene Cellular Therapeutics, where he turns stem cells into therapies for many diseases, world. All of that information will be “think” they are still in a fetus, and to be anything else. That neuron, for cofounder and vice chairman of Human combined to build powerful cellular that is perhaps the most regenerative example, can’t turn on the genes that Longevity, Inc., and founder and chairman therapies—actually developed from environment of all. In fetal surgery, make a heart cell. And this is what of Myos Corporation, a company developing enhanced human cells—that will for instance, you can open the uterus happens as our cells age—they lose products that improve the health of muscle. He battle cancer, diabetes, obesity, heart early in a pregnancy, perform sur- their versatility. At some point, we trained as a neurosurgeon, is an avid jet and high-performance aviator and has produced disease, dementia and more. Further, gery on the fetus, close up and let the lose the ability to rejuvenate. several feature films and documentaries. these treatments will keep our bodies baby come to term—and you won’t As we gather data on human and minds performing as if they were see a scar. You won’t see any evidence genes and the outcomes that they cre- Opinions expressed in worldVIEWpoint do not necessarily reflect those of the editors.

younger and for a longer time. NABAUM ©ALEX of the surgery at all. So a fetus can ate, healthcare experts can turn that

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