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For more information or to register: WhartonCEOAcademy.com | Contact Donna Gregor: +1.215.656.5348 | [email protected] Features 4 CEO LETTER Tapping the “Fountain A Doctor In Every of Youth” Career Pocket and Purse 14 6 THE LATEST THINKING Should CEOs Preach?

Precision Medicine Gets Precise 22

Medicine Goes Retail 28 8

Q&A Tony Coles, M.D., cofounder, chairman and CEO, Yumanity Therapeutics

36

Q&A Bernard J. Tyson, Chairman and CEO of Kaiser Permanente Buying Life 42 69 WORK-LIFE BALANCE Teaching Your Body to Kill Cancer 50 Pauses Really Do Refresh

Arthur L. Caplan, Ph.D. and 72 the Ethics of Compassionate Care 56 PARTING THOUGHTS Extending Human Life

From Counterculture to Mainstream: Integrative Medicine Goes Big 62 ON THE COVER: “Market-Driven Health Care” Zaitz by David 24 3 Tapping the “Fountain of Gary Burnison Chief Executive Officer Michael Distefano Youth” Career Chief Marketing Officer & President, Korn Ferry Institute Joel Kurtzman Editor-In-Chief BY GARY BURNISON

Creative Directors Robert Ross Roland K Madrid he stuff of legends has become a biotech reality. Marketing and Circulation Manager In the 16th century, Ponce de León searched for the fabled “Foun- Stacy Levyn tain of Youth” with its magical waters that supposedly could cure Project Manager illness and reverse aging. Immortal youth apparently was a perqui- Tiffany Sledzianowski site of exploration—Alexander the Great in the fourth century B.C. was said Digital Marketing Manager T Edward McLaurin to have encountered a healing “River of Paradise.” Ponce’s and Alexander’s excellent adventures, however, didn’t elongate their lives. (Ponce died at 47 and Alexander at 33.) But as we highlight in this

Contributing Editors issue of Briefings, today biologists, biotechnologists and other scientists are Chris Bergonzi hard at work cracking the code on aging. David Berreby In the early years of the 20th century, the average American lived to just Lawrence M. Fisher Hank Gilman over age 49. Since then, an additional 30 years has been tacked on, for an Victoria Griffith average life expectancy of about 80 years. Now, thanks to the biotech version Dana Landis of the Fountain of Youth, science is looking to expand longevity even further. Stephanie Mitchell Christopher R. O’Dea One day it may be possible for humans to routinely live to a healthy and vital P.J. O’Rourke 120—a feat almost accomplished by Misao Okawa of Japan, who had been the Glenn Rifkin world’s oldest person until she died recently at the venerable age of 117. Adrian Wooldridge Bioethical debates aside, the prospect of humans becoming modern-day Methuselahs has implications in every aspect of life—and will no doubt change the work paradigm. It is preposterous to consider that our idea of “retirement” Board of Advisors stems from the Social Security Act that dates to Franklin Delano Roosevelt’s Sergio Averbach Cheryl Buxton first term, becoming law in 1935. Today, AARP defines an “older worker” as Dennis Carey someone over 50. (Like every other 50-year-old in America, I have received my Joe Griesedieck share of AARP membership invitations and Social Security benefits projections.) Robert Hallagan Katie Lahey Today, people are staying in the work force longer—some by necessity, Byrne Mulrooney but many more by choice. Maybe 50 years ago it made sense to move to Sun Indranil Roy City, Ariz., bask in the warmth and play shuffleboard until dinner was served Jane Stevenson at 4 p.m. But that’s not today’s reality. In a recent Korn Ferry survey, 75 per- cent of respondents indicated that they would work past age 65. The previous century’s ideas of how long people can or should work are no longer relevant today and will be even less meaningful once life expec- tancy expands to the triple digits. One day, age 50 or 60 could very well be the midpoint of a career—or maybe even the opportune time to switch from one professional discipline to another! Sound far-fetched? It’s not! Our entire mindset must change with today’s reality: The days of the gold watch after 25 years of service are long gone! Imagine when career longevity becomes the norm and not the excep- 24 tion. Our entire ecosystem and infrastructure will need to be transformed, 4 BRIEFINGS FROM THE CEO THE FROM

from expectations of pensions to Social Security to health care. The workplace of the future will take age diversity to another level, with four and maybe even five generations working side by side, interacting and learning from each other. With more job mobility be- coming the norm, people who have eight jobs before the age of 30 might end up with 20 or more by the time they finally decide to retire (if at all). With exponentially expanded careers comes an even greater need for continuous learning in order to be relevant for a longer period of time. More and more, people will have careers that evolve with the changing needs of the global marketplace and the rapid explosion of technology. This means keeping pace by expanding one’s skills, competencies and experiences. To be adaptable means not only being able to “swipe left” and “swipe right,” but also learning and applying lessons from the past to the present— knowing what to do when you don’t know what to do. This is the essence of a leadership trait we at Korn Ferry refer to as “learning agility,” which we have found to be a perennial predictor of success. THIS ISSUE of Briefings on Talent & Leadership focuses Today’s college is yesterday’s high school. To- on the theme just outlined—the future of health care. morrow’s master’s degree will soon become, if not In it, we examine trends in health care delivery, drugs already, today’s college. Learning does not end with and pharmaceuticals, breakthroughs in cancer treat- a diploma that’s essentially a plaque on the wall, ment, medical ethics, work-life balance, digital health but should span a lifetime of new challenges, direct and integrative medicine. As you will see, the articles feedback, self-reflection and getting the job done re- are interesting and pertain to everyone. In this issue we sourcefully. At every age, learning agility taps one’s also have two interviews with giants in the field— ability to be highly self-aware, to be comfortable N. Anthony (Tony) Coles, M.D., and Bernard Tyson. with complexity, to work with and through others, Coles is a cardiologist who views medicine as if it to drive results in first-time situations and to have were a ministry and sees his role as both a servant and passion for new ideas. a leader. Coles left the daily practice of medicine to I recently asked a celebrity-type CEO (who will go work in the pharmaceutical industry, where he rose to unnamed) what he thought were a couple of the most become chairman and CEO of Onyx Pharmaceuticals, important traits of a leader. In a deep Southern drawl which specialized in developing cancer drugs. While he said, “Well, first, I was born at night, but not last CEO of Onyx, he sold it to Amgen for $10.4 billion. night.” In other words, street smarts to “read a room”— As chairman and CEO of Kaiser Permanente, one people and situations. The second, he said without of the largest health care organizations with more hesitation, was curiosity, which is the prerequisite for than 10 million members, Tyson focuses on delivering continuous learning. services to a diverse population. Efficient, affable and Those who don’t adapt to new and evolving data-driven, Tyson spent almost his entire career at demands for knowledge and skills will be as relevant Kaiser Permanente. During that time, he has over- to the work force of tomorrow as buggy-whip makers seen an organization that has always been a leader in are today. “Evolve or become professionally extinct” the field, earning it the loyalty of its membership. is the Darwinian rule of the work force—no matter In developing this issue of Briefings, we are all how long you live. grateful to the leadership of Korn Ferry’s health Looking ahead, with the reverse-aging of biotech- care practice. We appreciate the work of Thomas nology and the power of learning agility, there may be Giella, Gregory Button and Eugenie Dieck, who made few limits to what we can do and when we can do it. introductions, opened doors and helped the entire Maybe it’s not too late to become a brain surgeon Briefings team learn which issues and trends are the after all … most pressing with the widest implications. 

TALENT+LEADERSHIP 5 Should CEOs Preach?

BY HANK GILMAN

y father would never put a political bumper sticker on his car. An owner of a small M business in the 1960s—and a Kennedy Democrat—he figured there was no need to offend customers. Believe it or not, there were Republicans in Massachusetts. Massachusetts still has a few Republicans within its borders, but the days of political neutrality in commerce are long gone. Business owners and executives don’t seem shy anymore about climbing up behind the bully pulpit. Earlier this year, the CEOs at Starbucks and Salesforce.com spoke out on social issues. Companies have gotten in the middle of the marriage equality debate. And still others are in the spotlight by way of political contributions. But is such advocacy a good idea? Like all things, it depends. In the recent cases, the reaction, outside the companies, was mixed. If things go wrong, companies and their CEOs might just suffer a temporary setback or embarrassment. Sometimes customers and employees Illustrations by Illustrations don’t raise an eyebrow if the CEO is known for speaking out. But for most preachy CEOs, this is uncharted territory. To get a better grip on the subject, I turned to a few folks who know a lot more than I do. Among them: Stephen Arbogast, a former ExxonMobil executive and a finance professor at the DZIEKAN MICHAL University of North Carolina’s Kenan-Flagler Business School; Luke Lambert, CEO of public relations firm G&S Business Communications, whose clients include agribusiness giant Syngenta and General Electric; Verne Harnish, author of “Scaling Up (Rockefeller Habits 2.0)”; and Marcelo Nacht, managing partner of Praxis Research Partners, whose client roster includes UPS and MetLife.

6 BRIEFINGS Here are the experts’ rules of engagement, and some questions, for chief executives who seek the limelight:

Make sure company has always he says, it “needs to limb with them,” says there’s been transparent be questioned.” Nacht of Praxis. a real purpose. about those beliefs— Adds a C-suite Lambert agrees. In and those views have consultant for Fortune a recent G&S study, 41 “Is this well-consid- come to represent the 500 companies: percent of Americans ered advocacy?” company. “When it comes to said human rights is- asks Professor Ar- It also helps when public image, the CEO sues were “very influ- bogast. “Do most of the CEO is completely and the directors have ential” in their brand our customers and in character. “The to figure out guide- purchases. “We’ve employees like this world almost expects lines together.” been conducting this position?” If not, he (Starbucks CEO survey for several says, it doesn’t pass Howard) Schultz to Start a years,” says Lambert. muster. For example: enter the fray on is- foundation. “What it tells us is that No one, or almost no sues,” says Harnish. if an issue doesn’t tug one, would object to a Ditto for Marc Benioff Warren Buffett’s at your heartstrings, company’s campaign who was known for his family foundation has then it isn’t going to to raise awareness of public philanthropic donated to Planned affect what comes out domestic violence. efforts—such as the Parenthood. That of your purse strings.” Questioning the sci- Tibet House benefit organization may ence behind climate concert at Carnegie not be popular with, Can you avoid change? That’s a bit Hall—well before he say, the customers public backlash less clear-cut. and his company, of the individual if you run a Salesforce.com, be- Berkshire Hathaway private Do these views came stars. entities such as The company? reflect the Pampered Chef. But it company? Consult isn’t Berkshire making No. All companies, the board. those contributions, even those that are “CEOs who use their and that helps insu- privately held, have public personas to If the CEO is going late the CEO—and the constituencies—ven- effect social change to expend a lot of parent company. dors, customers and have a responsibility energy on the stump, employees. And all to do so in a way is it being done for Launch have the ability to that aligns with the the benefit of the customer disrupt your business company’s corporate company? That’s a research. if they don’t like what culture, brand, repu- good question for they hear. tation and business company directors. Learn what your cus- That’s what my dad goals,” says G&S’s “If they’re going to tomers and employees would tell you. Lambert. For example: take company time, it are thinking before A business that publi- better be for company you dive into the deep cally operates under purposes,” says Arbo- end. “They may want Hank Gilman is a former certain religious prin- gast. “It better not be to have a better feel Fortune magazine deputy ciples generally avoids ‘I’m bored and restless about whether their editor and author of the man- agement memoir “You Can’t heat from customers, and looking for new customers are willing Fire Everyone,” published by largely because the worlds.’ ” In that case, to climb out on a Portfolio/Penguin.

TALENT+LEADERSHIP 7 . ANTHONY “TONY” COLES grew up in and around the church. As Nthe son of a minister, Coles learned at an early age to think deeply regarding matters of life and death. He was taught to be comfortable speaking in front of groups and saw firsthand what service leadership looks like. His youthful experiences and his family’s teachings taught him the importance of putting others first and that, first and foremost, a leader’s job is to serve—anyone and everyone who could sup- port and enable the mission at hand. Before going to work at Merck & Co. (Merck Sharp & Dohme outside the U.S.), Coles treated Driven patients as an internist and cardiologist at Mas- sachusetts General Hospital. At Merck, he led the company’s domestic cardiovascular business. During his tenure, Coles grew the company’s To Serve cardiovascular business by 30 percent. Shortly afterward, he was recruited to Bristol-Myers Squibb, where he helped lead the launch of the blood-thinner Plavix, one of the most suc- As Many cessful cardiovascular drugs ever developed. From Bristol-Myers Squibb, Coles moved to Vertex, a biotech company headquartered in Cambridge, Mass. The scientific mission of Lives As Vertex was to discover new drugs through “ra- tional drug design,” a process used to create new molecules by designing them, one atom at a time. After Vertex, Coles moved into the corner Possible. office at NPS Pharmaceuticals and later, in 2008, he joined Onyx Pharmaceuticals. While at Onyx, An interview with Tony Coles, M.D., which specializes in developing cancer drugs, cofounder, chairman and CEO, Coles oversaw the introduction of two thera- Yumanity Therapeutics pies—one for multiple myeloma, a deadly blood cancer, and another for colon cancer. After five years at the helm as Onyx’s CEO, Coles sold the company to Amgen for $10.4 billion. Coles’s latest venture, Yumanity Therapeutics, is a start-up. It was founded based on research conducted by Susan Lindquist, a biologist at M.I.T.’s Whitehead Institute for Biomedical Re- search. Yumanity’s goal is anything but modest: It is to develop treatments for neurological diseases such as Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis (ALS). What follows is an edited discussion that took place between Coles, Yumanity’s chairman, CEO and founding investor, and Joel Kurtzman, editor-in-chief of Korn Ferry’s Briefings on Talent & Leadership, in New York City. ➜

The ministry and medicine are both about helping people and making a difference in their lives. Do you see them as related? Yes. As you say, they are both service-oriented.

Did you practice medicine before going into business? When did you know you wanted I did. I was a cardiologist. to become a doctor? Since the age of 9, it was my goal to take care of And when you went into patients. When I applied to college, I had the choice business, where did you start? between Columbia University in New York and Johns I held several jobs at Merck, but the one that was Hopkins. Accepted by both, I asked my father for advice the most formative was running the domestic cardio- about which school he thought I should go to. He wisely vascular business for Merck. It was an $800-million said, “If you want to be a doctor, choose the university business when I joined, and we grew it by more than with the best medical school and go there.” Johns Hop- 30 percent over the next two years to just under kins was one of the top-rated medical schools in the $1.2 billion. country, and on that basis, Hopkins won out. What was your experience It’s a great school. at Merck like? Yes. And it was a great place for me. I really found I thought I was the luckiest guy around. I had the best myself and learned about the power of discipline and job in industry. I had an opportunity to help physicians focus. I then went on to medical school at Duke. learn about the newest medical therapies and got a chance to help them discover the best ways to use Were either of your them for their patients. Most people would call it mar- parents doctors? keting, and I felt right at home using my education and No. My father is an accountant by training and now training to help shape new standards of medical care. a full-time minister, and my mother was an office manager for the local telephone company. Both That does sound like you are parents have always been wonderfully supportive of providing a service. all the choices I’ve made. And, when I left the practice To do what I’m describing you have to start and of medicine, they were both genuinely happy I had end with this question: “What’s in the best interest found something in the pharmaceutical industry I of the patient?” loved doing. Interestingly, in some ways, I feel what we Keep in mind, this is one of the few industries do to create new medicines is something of a ministry where your end user is not your customer. Your because my personal mission is to make a transforma- customer is the physician, or a provider group such tional difference in people’s lives. as a health maintenance organization, or the federal government, and so on. As a result, you have to develop Did you grow up watching your a way of supporting your customers so they can make dad preach to the congregation the best choices on behalf of the patient. It’s a different and ministering to its members? model of necessity, because you become partner and Absolutely. And growing up in a church meant I was collaborator with the intermediary to focus on what’s in the Easter play and recited the Christmas poem, best for the patient. But, this type of “patients first” and served as the master of ceremonies at various strategy puts the business emphasis where it should church events. It gave me the opportunity to be in be—on the end users. This service-oriented strategy is front of a congregation, in front of people, and to be how we built Merck’s cardiovascular business. at ease in front of groups. I think it helped me to find and then use my own voice and tapped into some How long did you stay at Merck? kind of latent leadership skill. Four years.

10 Q&A Tony Coles

Then what did you do? I received an invitation to join Bristol-Myers Squibb to lead the launch of a new product called Plavix. Plavix is now a very well-known and successful product. It’s a blood-thinner people take after a heart attack.

Were you involved in research ‘‘My personal on Plavix? No. But I was there for the launch of the drug. In fact, mission is to I remember the day the envelope was opened and the final results of the clinical trial was delivered. When we saw the results, we suddenly knew that we had an make a extraordinary opportunity to change the practice of medicine—because the data were that compelling. I’m transformational a cardiologist, but do you know what? It was remark- able for me to see how excited other cardiologists were about even the smallest improvement in benefit difference for their patients, especially if it meant a reduction in mortality. That made a big difference because it meant in people’s lives.’’ they could do more for their patients. For physicians, it all goes back to “what’s the best I can do for my patient?” And, on that basis, I’d say improvement in the death rate after a heart attack was a big advance. And this is how we launched the drug. ➜

Tony Coles, M.D., and award winning protein folding expert Susan Lindquist, Ph.D. Yumanity is working to identify and develop new, disease-modifying therapies that address several illnesses with critical unmet medical needs. It sounds like you view that Can you create businesses that drug as a service, too. are truly service-oriented and Well it is. As I said, we all work for the patient, and our also profitable? work counts in terms of people’s lives, every day. I al- Yes, of course. And we have. We’ve created some ex- ways challenge myself and our teams to remember—to traordinary business opportunities with great returns really remember—whom we work for at the end of the for investors with that simple mantra. day. In my case, it is clear to me that I work for the employees. My job, as CEO, is to remove barriers and Will that remain your goal as you find ways to accelerate what they are doing, so they can develop new ventures? be successful on behalf of patients. Removing barriers Yes. For most of my adult and professional life, I’ve is a very important job of a leader, and it’s a great prin- been very fortunate and had some great opportunities ciple by which to abide. In essence it’s the centerpiece to help change lots of lives. There are so many ways of servant leadership. Next, I always remind myself and our employees that while I work for them, we all work for the patients. Patients who are counting on us and waiting on us to find the next cure for their diseases. That’s the reason we are here in the first place. When you think about it that way, it helps you put away your disagreements and put away those things that plague organizations, like politics. When you put away all of that, you remember that at the end of the day we often are involved in real, life-and-death problems. And it’s never really about just one person. We are there for a patient’s family, friends and loved ones, too. And The Yumanity Therapeutics team (left to right) in the Lindquist Lab at the Whitehead if you multiply the impact of this on a Institute for Biomedical Research in Cambridge, MA: Vikram Khurana, M.D., Ph.D., global scale, you begin to get a sense of vice president, discovery technologies; Susan Lindquist, Ph.D., scientific founder; Daniel Tardiff, Ph.D., associate director, yeast phenotypic screening; Chee Yeun Chung, the potential transformation that comes Ph.D., associate director, assay development; Kenneth Rhodes, Ph.D., chief scientific from what we do. It can be significant. officer; Tony Coles, M.D., chairman and chief executive officer. And it’s certainly very humbling.

If you get everyone to focus on one can do that. But if you do it by providing access to the patient, then everyone will better health care, that’s huge. I mean really huge—and line up and help remove the meaningful. Think about the number of lives that are obstacles, won’t they? broken by diseases and illness, and think about the That’s the way I think about it when I think about the fact that we don’t have cures for so many devastating architecture of leadership. If we’re doing what we’re diseases, such as Alzheimer’s and other diseases of the doing simply to make money for ourselves, then we’re brain, and many cancers. Imagine what a different ex- missing a very important and rewarding opportunity istence it would be if we could eradicate some of these in this industry to help transform people’s lives. The commonly occurring and devastating illnesses. point is, in our business we can do so much good. George Merck, a founder of Merck Sharp & Dohme, By focusing your new company, used to say if we put the patient first, then the profits Yumanity, on treating Alzheim- will follow. I concluded long ago that if we seize the op- er’s, Parkinson’s and ALS, you portunities we have to change people’s lives by giving are focusing on a number of them better health, then the returns will come. And gigantic unmet needs. That will you know, I think that’s the right relationship. I just be a huge service to humanity think it is true. If we can really help the patient, the as well as a huge financial profits will be there. opportunity.

12 Q&A Tony Coles

Absolutely. From an incidence point of view, these With Yumanity, we are at the juncture between asking diseases affect about 50 million people worldwide, at a the question and studying it, and finding clues and cost of almost $700 billion a year, if you include direct answers to get deeper understanding of the biology health care and indirect economic costs, and that cost of Alzheimer’s and Parkinson’s. We’re studying these figure is expected to triple by 2050. problems at a cellular level to try and understand the basic biology of these diseases, and at the same How do you approach solving time—and this is the beauty of it—we’re interrogating a problem that’s so big? the science and using state-of-the-art drug discovery Our new company, Yumanity Therapeutics, provides an methods to find new treatment approaches. Because opportunity to impact millions of lives. When I worked of our approach, we’re learning about the biology at in cardiovascular diseases, it was a great foundation- the same time that we’re identifying new compounds, setting exercise. I learned the industry, l learned about targets and mechanisms to find solutions to these the business of creating and developing new medicines, devastating health problems. and I learned how to create and grow value—all the while remembering that we worked for patients and Instead of doing it sequentially— their families. When I joined Onyx, the aim was the studying the biology and then attempting to remedy the problem—you are doing it all at the same time. That sounds like a new approach. Is it? ‘‘If this works, Yes. We’re in effect asking the science to show us what will make a cell better once it has been affected. We do that by creating the same problems in yeast cells and in we will have neurons that are observed in patients with the diseases we’re studying, and then we screen new compounds to changed the course try to understand what will rescue the cells after they have been affected. That’s the approach we’re taking to of history.’’ find new therapies. Where are you in the process? We are in the earliest stages of discovery. We are gaining insights about the basic cellular mechanisms same—to help change the natural course of some of of the disease. In fact, we’ve already uncovered a these diseases and improve lives by treating patients previously unknown mechanism that we think is with newly discovered medicines. At Yumanity, we involved in the development of Parkinson’s disease. It’s are focusing on some of the greatest medical needs we fascinating. And we have newly discovered compounds have, certainly as measured by the number of people that we believe interact with this target, which could affected and by the cost of those diseases over time. So one day be a new treatment. That’s why the science is you have very large problems to solve, which means you so wonderful and so exciting. We’re not just learning have significant opportunities to make an enormous about what goes wrong and causes these disorders. difference for people—which means, as George Merck We’re finding things that we hope will correct them. eloquently stated, the profits will come. And, by the way, I think we can do it. Really do it! Is this your life’s mission? Some of what attracts me to this project is the scale and Yes. If this works, we will have changed the course of significance of the problem—the sheer intractability history. The implications are that big. You can under- of treating and curing neurodegenerative diseases. stand why I’m attracted to this. I have always enjoyed a great challenge, and this one is sized just about right. At present, you and your scientific My personal mission in life is to impact as many lives as cofounder are funding Yumanity I possibly can and to productively use my time on Earth yourselves. How do you know you to do that. My goal is to always think of a bigger, more are making the right bets? challenging set of problems that would be even more We don’t. But how do you ever know anything in sci- important to the lives of people today. I believe that is ence until you actually ask the question and study it? my purpose. I also believe—with help—we can do it. 

13 14 15 digital health A Doctor in Every Pocket and Purse

By Lawrence M. Fisher

n a recent New Yorker cartoon, a harried health care administrator admonishes an incoming patient, “You can’t list your iPhone as your primary care physician.” LOL, right? But in the emerging world of digital health, that cartoon is no joke. ’Fess up. Last time you had an odd twinge in your side or an earache that wouldn’t go away, did you consult Dr. Google before phoning your flesh-and-blood physician? Then you are a consumer of digital health, or perhaps more aptly, a “prosumer,” to use fu- turist Alvin Toffler’s neologism for those who now routinely per- Iform services that we used to leave to professionals. We used to

Illustrations by Owen Gildersleeve

15 pay Kodak to process our photos; now we do it ourselves on our laptops or smartphones. Increasingly, we do the same with our health care. STICK Countless entrepreneurs now claim to have the Uber of health care in their back pocket, to which one can only say, “Good luck with that.” But somewhere amid the hope and OUT YOUR hype lurks a program that ultimately will do to health care what Uber has done to taxi service, Amazon has done to retail and Spotify has done to music. If digital health lives up to its promise, the next five to 10 years will change the way TONGUE, patients are diagnosed, what diseases are treated where, and perhaps even the definition of what it means to be a physi- cian. Coupled with precision medicine, which is the tailoring HOLD UP of pharmaceuticals to genetic profiles, digital health should be more effective, more personal and less costly. There are now more than 100,000 health apps for And- YOUR roid and iOS, but digital health encompasses far more than these bits of code that nudge you to eat less, exercise more and take your pills on time. Indeed, it can include every- thing from the Fitbit that counts your daily steps—or per- SMART- haps resides in a dresser drawer—to Foundation Medicine, which is using Big Data analytics to cross-reference cancer patients’ genetic profiles and pharmaceuticals intake with PHONE, medical outcomes, all across the country in real time. Here’s a definition from the Story of Digital Health web site: Digital health is the convergence of the digital and genetics AND SAY revolutions with health, health care, living and society. “AHH.”

IGITAL HEALTH is also the investors alike, let alone for patients. “Separating greatest gold rush the medical field the signal from the noise is a big part of my job,” said has ever seen. Investors poured Lynne Chou, who heads KPCB’s digital health group. more than $6.5 billion into digital “You have to look at each one differently, as in what is health in 2014, up from $2.9 bil- the technological innovation, the business model and lion in 2013 and $1.2 billion in the DNA of the founding team? I also would put in 2010, according to StartUp Health timing, because health care is changing so rapidly.” Insights’ report “2014: The Year One indicator of the attention being paid to digital Digital Health Broke Out.” This health is that StartUp Health, which invests in and year’s numbers will likely continue advises digital health companies, announced its June the trend, as no venture capital firm of any note now 2011 launch from the White House, with President lacks a digital health group. Kleiner, Perkins, Caufield Obama and Vice President Biden in attendance. “Our D& Byers (KPCB), the veteran Silicon Valley firm that pitch to them was we will transform health care by funded Genentech and Amazon, has half a dozen launching 1,000 companies,” said Unity Stoakes, a co- companies in a growing digital health portfolio that founder. “Today, we have a portfolio of 102 companies ranges from an Internet-connected thermometer to in 10 countries.” online dermatology. Another measure of the growth of digital health Some of these start-ups will likely be game is the rush of Silicon Valley and medical talent into changers, but identifying the credible players in such the field. Every start-up worth its seed funding seems a diverse group is difficult for payers, providers and to have a cadre of Google, Apple and Facebook senior

16 17 digital health

17 alumni on the one hand, and biopharma vets on the Sean Duffy, cofounder and chief executive of Omada

digital health other. Lyra Health, a new company tackling behavioral Health, which is developing digital therapeutics for the health issues such as anxiety, depression and substance prevention of chronic disease. “Forty percent of adults abuse, has both sides just in its founder, David Eb- will at some time in their lives find out they have type ersman, the former chief financial officer of Genentech, 2 diabetes. It’s a crisis of magnitude where it’s almost who left to take the same position at Facebook, where hard to understand how the numbers are so big.” he took the company public. Duffy has an undergraduate degree in neurosci- For decades, health care lagged behind nearly every ence, but spent the early years of his career at Google other industry in its adoption of digital technology, but and IDEO, the legendary Silicon Valley design firm. that changed with the infusion of $30 billion from the Omada reflects the application of what his former HITECH Act of 2009, or Health Information Tech- employer calls “design thinking” to health care. nology for Economic and Clinical Health, a component Omada’s first product—or service, it’s actually a bit of of the Obama administration’s stimulus package. both—is called Prevent, and it combines a full-time With that bolus of funding, hospitals and other large health coach, an online support group and an interac- providers finally adopted the electronic medical record, tive curriculum that addresses the physical, social and or EMR, much to the benefit of a little-known, privately psychological components of patients’ conditions. held company named Epic Systems, which now has All digital health companies boast about their app’s about a 70 percent share of the market. easy user interface; Omada provides patients with But digital health is about more than hospital an Internet-enabled digital bathroom scale, already enterprise systems and indeed reflects a sea change in synced to their online account, no setup required. how health care is performed and paid for. More than Prevent tackles high blood sugar, high blood pres- ever, patients have become consumers, shouldering a sure, high blood fats and obesity. Omada offers the greater share of the cost but also demanding a greater program to employers and health plans with an at- role in their care. tractive value proposition: They only pay if their em- “This is as much about the consumerization of ployees or customers show measurable improvement. health care as it is the digitalization of health care,” “People are now living lives in front of their said Kim Kraemer, a branding consultant who works screens,” said Duffy. “If you want to build a lifestyle with digital health companies. “It’s being driven by intervention program, you have to build there. It’s all well-informed patients who have found their voices incredibly dependent on peer-to-peer relationships, and are demanding access to reimbursable, prevention- accountability to their peer group, to their health oriented care. They want real-time monitoring and coach. If you are at risk for diabetes or heart disease, responsiveness from their doctors, like for irregulari- we mail you some equipment, match you to a group ties picked up on mobile heart monitors or scary high similar to you, pair you with a health coach, and we insulin levels. Providers and payers have had to adapt.” kick you off on a Sunday on a 16-week program that is all based on clinical study. Ideally you lose 5 percent or so of your body weight, and then we graduate you into a ‘Sustain’ program.” An Ounce of Prevention Behavioral health is attractive to start-ups because the barrier to entry is relatively low; there is no ERE’S A SCARY STATISTIC: Chronic requirement for clinical trials, as there is for new disease now kills more people than infectious drugs or medical devices. But that also means many disease. Indeed, three out of four Americans products are based more on hype and hope than data. will die prematurely from a disease that “In the space we’re in, there’s a lot of noise, a lot of Hstems from their own lifestyle choices, habits programs that may or may not produce outcomes,” or circumstances. This trend is most visible in the said Duffy. “You can completely empathize with the epidemic of obesity and the related surge in type 2 medical benefits manager. What you have to do, first, diabetes, an insidious disease that accounts for is build a program that works, and then you have $500 billion in annual U.S. spending. to publish the data. To date, we are one of very few “The trends are just absolutely petrifying,” said digital health companies with that strategy.”

18 19 A Very Diversified Portfolio

MADA WAS FUNDED by Andreessen Horowitz, the iconoclastic venture firm known for making a few big bets each year, and it seems to fit their slogan: Software Is Eating Othe World. But for a more inclusive view of the field, look at the portfolio of Kleiner Perkins, which has taken a more diversified approach. The firm’s investments show the sheer breadth of digital health. Kinsa Inc.’s smart thermometer is an exercise in user-friendliness. It works orally, rectally or under the arm and delivers a reading in just 10 seconds. Connected to a smartphone, it transmits that reading to your primary care physician, along with your location, which is identified by the phone’s GPS, and major symptoms, which a user provides in response to a series of simple questions. As more consumers adopt the $29.95 device, Kinsa will be able to produce epidemiological data based on its users’ geography. It’s an Internet of Things play, with an online retail option, like rapid delivery of cold and flu supplies to a family with a sick child. For patients with type 2 diabetes, Livongo Health offers a complete treatment platform that includes a dedicated wireless device for monitoring and transmitting glucose levels and other vital signs, cloud-based analysis and feedback, and a team of certified diabetes educators. Livongo “allows you to create settings and groups, for your caregiver but also for your family,” said Chou. “If your glucose is too low, it will send a message. At another level, diabetes specialists from Livongo will actually call you in that moment, and help you manage. Hopefully it doesn’t happen again and there is learning established.” Telemedicine promises to replace the office visit, and its inherent delays and high costs, with cellular or online access to qualified experts. Spruce Health, another Kleiner portfolio company, is a telemedicine dermatology provider. “See a dermatologist right from your phone; no appointment necessary,” is Spruce’s pitch. The app is free, and so is the first “visit,” with each subsequent appointment for $40. This includes a 24-hour response from a dermatolo- gist, diagnosis and personalized treatment plan, plus 30 days of post-visit messaging. The outsized success of Epic in the electronic medical record market has made the company a high-

19 the feds finally threw enough money on the table and everyone said ‘we might as well do it now,’ Epic was the best system, and it remains the best system today. That’s partly a matter of functionality, partly of breadth.” Nevertheless, Wachter’s book treats electronic medical records as a kind of necessary evil: Necessary, because a paper-based industry could not meet the demands for higher quality, accountability and trans- parency—all at lower costs—that face health care; and evil, because digital technology has led to doctors who look at their screens more than their patients, e-mail consults with radiologists replacing shared profile target. Displacing such an entrenched player perusal of X-rays, and endless beeps, buzzes and other might seem as far-fetched as was superseding Mi- alerts so frequent that staff simply ignore them. The crosoft Windows as the dominant operating system, centerpiece of “The Digital Doctor” is a detailed re- but since that is actually happening with iOS and counting of an incident in which a child was acciden- Android, why not try? Practice Fusion offers a cloud- tally given a 38-fold overdose of a powerful antibiotic. based electronic health record, or EHR, which is be- The patient survived, but the need for systems with coming the preferred term, at an attractive price: free. more human input is clear. It may take the union of Revenues come from pharmaceutical companies and Silicon Valley and the EMR to make that happen. other partners. For the time being, Practice Fusion is “The winner here will be the company that lays not targeting large hospitals, Epic’s primary turf, but the ‘Golden Spike,’ ” Wachter said. “Once the world of disruptive technologies have a history of taking over Silicon Valley style, innovation and consumer-facing markets from the low end and moving up. technology somehow links up to your health record, “Practice Fusion is not in the same space as Epic,” which will probably still live in your doctor’s office, said Chou. “Epic is in large systems, Practice Fusion is then you will get all the analytical stuff beginning to in ambulatory centers. The hospitals just spent a lot be real. In an environment where health care institu- of money on Epic.” tions are under profound pressure to deliver better care at lower cost, you want people to work at the top of their ability. The only way that works is if everyone has digital tools and they all weave together.” The Digital Doctor On the other side of the UCSF campus, the Center for Digital Health Innovation (CDHI) is working HOUGH EPIC has become the company hard to make that vision real. Part incubator, part doctors love to hate, its dominance stems from accelerator, the CDHI was formed to turn ideas into the simple reason that its systems work, said companies, whether those ideas originate at the uni- Robert Wachter, a professor at the University versity or elsewhere. CDHI is a separate entity from Tof California at San Francisco, and author of the medical school, but it receives more than $1 mil- “The Digital Doctor” (McGraw Hill, 2015). Though lion in state support and after two years in operation Wachter’s book is a largely skeptical, and sometimes is breaking even. scathing, after looking at the impact of digital tech- “We have sophisticated technology capabilities to nology on health care, he said his research left him do EHR integration, internal development and out- with a better impression of Epic. side product development, and we can scale to a level “The app developers and Silicon Valley types of a single or a couple of institutions,” said Michael almost disdain the EMR folks as old school; that’s Blum, CDHI’s director. “We develop, we pilot, we wrong,” Wachter said. “People for the foreseeable fu- prototype and we validate. Then we look for external ture will still have their health record at their doctors, partners to build them out to scale.” and Epic is the best system out there. At a time when To date, four start-ups have emerged from CDHI.

20 21 digital health

CareWeb is an internal communications platform cians know not only are they getting the information that uses Twitter- and Facebook-like tools to facilitate about their patient’s tumor, but if there is information interchanges between doctors, nurses and patients. anywhere in the world that is relevant, we are going Tidepool is unusual first in that it is focused on dia- to spoon-feed it to them,” he said. “That’s what digital betes type 1—most digital health companies address health means for us.” type 2, which has far greater numbers—and second because it is structured as a not-for-profit. Also not- for-profit is Health eHeart, a clinical trials platform using social media, mobile technology and novel real- Health’s “Netscape Moment” time sensors to treat heart disease. Trinity Precision Team Care is a workflow application intended to aid UT DIGITAL HEALTH can mean many other multidisciplinary teams in clinical settings. things as well. Castlight Health was founded in 2008 to tackle the high cost of enterprise health care, now nearly $620 billion annually in the BU.S. alone and growing 8 percent to 10 percent Big Data vs. the Big C every year. Castlight’s products aim to make benefits more transparent, responsive and interactive. Kezzler N 2014, BIG DATA/ANALYTICS received by AS, a privately held company based in Oslo, Norway, has far the most funding ($1.46 billion) and the largest developed a proprietary process for generating billions number of deals (90) among digital health subsec- of unique encrypted codes; its first application is the tors, according to StartUp Health. Of all the Big prevention of counterfeit drugs, which IData players, the most prominent is Foundation cost pharmaceutical companies billions Medicine, whose founders and leadership team read in lost revenues and result in countless like a Who’s Who of genomics and oncology. Roche, deaths, either from untreated disease or the Swiss pharmaceutical giant, paid $1 billion in the toxicity of their bogus ingredients. January to acquire a majority stake in the company. Mango Health’s founder, Jason Oberfest, Foundation has two products so far, Founda- came from the gaming industry and has tionOne, which sequences more than 300 genes in used that background to develop an app to a sample of a solid tumor, such as a lung or breast improve compliance, ensuring that patients tumor, and FoundationOne Heme, for blood cancers take the medications they are prescribed. such as leukemia. A particular mutation may indicate Many experts believe the first killer app for that a tumor would be vulnerable to attack by a the Apple Watch will be in health. particular drug. Foundation’s platform allows oncolo- “Very soon, the concept of ‘digital health’ will gists across the country—for now, and soon around just become ‘health,’ ” said Unity Stoakes of StartUp the world—to compare their patients’ test samples to Health. “It will be merged; it will be in every concept others with the same mutation and to reference how of health and health care. This transformation, which they responded to different cancer drugs. In the past, we are very early in, is reminiscent of 1994, when this kind of information has typically been shared Netscape went public. Now think about how early informally, through e-mail or by physicians meeting Netscape was in the transformation of the Internet with colleagues at conferences. and media,” he said. “Our goal is to become the gold standard for Just as Netscape (and the World Wide Web) extracting relevant data from a patient’s tumor,” said changed the Internet from a cosseted tool of science Michael Pellini, Foundation’s chief executive. “If you and the defense industry into a public resource, send us a tissue sample, and there are tumor cells digital health will open the field of medicine to a new in there, you can count on our company to extract cohort of care providers, consumer-oriented services the relevant information from that tumor. Once we and products that blur the line between patient and extract it, we recognize that just sending that infor- customer. So are you tracking your meds or your mation to the physician doesn’t mean he or she would workouts on your smartphone? Signing into online know what to do with it. We also had to be leading- patient forums to compare symptoms? Tracking your edge in developing a database and relevant tools, so baby’s fever on the Web? Congratulations, you’re an that all the information is contextualized, so physi- early adopter of digital health. 

21 PROBLEMS WITH YOUR DNA? CHANGE IT!

ainfully, the pharma- ceutical industry has discovered that it is not immune to change. Blockbuster drugs are P fading as generics replace the current stock of remedies, and as precision medicine shifts the focus away from drugs that address large pa- tient populations to develop personalized therapies for smaller groups. The Institute of Medicine defines “precision medicine” as tailoring medical treat- PRECISION MEDICINE ment to individual (often genetic) characteristics of each patient. The preventative or therapeutic interventions can then be concentrated GETS PRECISE on those who will benefit, sparing expense and side ef- fects to those who will not. 22 BY KAREN KANE

PRECISION MEDICINE GETS PRECISE

23 FOR YEARS, the pharma busi- ness model was prosperously built around blockbuster drugs, those that treat condi- ORE than 25,000 scientists and on- tions affecting large popu- cology professionals from around the lations—high cholesterol, world gathered at the American Society infectious diseases, high of Clinical Oncologists in Chicago in blood pressure and gastro- June to learn about new developments in cancer intestinal maladies—where Mtreatment. Accounts of clinical trials documenting ex- patients receive similar, if citing breakthroughs were presented alongside reports not identical, treatments. of gnawingly difficult challenges in developing thera- A patented drug like Lipitor pies for treating stubborn cancers with therapies that contributed a record $125 bring relief to some and completely fail other patients. billion to Pfizer during its Developing drugs for rare diseases or for small subsets 12-year run, making pharma of common diseases is a risky business. There will be very profitable even if the winners and losers. Companies are placing their bets. companies had to replace an ASCO has become the place to share ground- entire book of business every breaking research, scientific developments, state-of- 10 to 12 years. the-art treatment modalities and new therapies, as well But that world is gone. Pop- as a forum to discuss controversies such as how to pay ulations are growing older; for these breakthrough drugs. more patients are living with Undoubtedly, the halcyon days of megadrugs hid more complicated diseases inefficiencies from the companies themselves. The such as cancer, rheumatoid new environment is prompting pharma companies arthritis and immune disor- to examine expenses in research and development. ders. New drugs are scruti- Like enterprises in other sectors, pharmaceutical nized more closely; clinical companies are divesting some operations to bring trials are becoming more greater focus to their core business. They are driving expensive. Trumping these cost out of their operations, becoming more agile and changes are the dynamics of taking on the bigger job of building trust with a more new regulations and require- skeptical consumer. ments of the Affordable Care Bristol-Myers Squibb was one company that Act as well as the payers, experienced the highs and lows of the conference— Medicare and Medicaid, all presenting stunning data from clinical trials that asserting a larger role in how showed Opdivo could double survival for lung cancer treatment is delivered. patients—and then a hammering of its stock when At the same time, science an analyst suggested that its competitive position for continues its dazzling trajec- Opdivo wasn’t bulletproof. tory, tapping unprecedented New CEO Giovanni Caforio sought to bring bal- computational power to slice ance. “We have successfully transformed the company,” and dice DNA genomic data he said, referring to the company’s hard slog in re- to unveil the abnormalities engineering its business, divesting its medical-imaging that create illness, explain the group, its diabetes business, wound-care division and process of aging and perhaps nutritional business to focus on the high-margin spe- unravel the secret of life itself. cialty drug group. If pharmaceutical companies “We are pioneers in immuno-oncology,” Dr. Caforio intend to grow and prosper noted. “We have a proven track record of success in in a dramatically altered 21st partnering with biotech companies, pharma, the aca- century, the business environ- demic community. That will continue to be a critical ment demands reinvention. part of our strategy. Remember, we are actively leading 24 PRECISION MEDICINE GETS PRECISE

science in the area where the medical need is very high To do that, the National Cancer Institute will work and we can bring transformative medicines to patients.” with more than 20 companies in “discovery trials” as Analysts seem to concur. According to a February 20, companies provide their drugs for study on specific mu- 2015, report by Damien Conover, who covers pharmaceu- tations. The government is paying for the trials, a huge ticals for Morningstar, Bristol-Myers Squibb “holds a wide incentive to the companies to participate. The drugs economic moat … The patent protection allows the com- included in the trial have all either been approved by the pany to price its drugs at levels that translate into superior U.S. Food and Drug Administration for another cancer returns on invested capital compared with its cost.” indication or are still being tested in other clinical trials Yet the big news at the conference was the announce- but have shown some effectiveness against tumors with ment of NCI-Molecular Analysis for Therapy Choice particular genetic alterations. program, NCI-MATCH, a clinical trial that will analyze “This is the largest and most rigorous precision patients’ tumors to determine whether they contain oncology trial that has ever been attempted,” said Dr. genetic abnormalities for which a targeted drug exists James H. Doroshow, deputy director of NCI. The trials and assign treatment based on the abnormality. NCI- promise new insight into treating tumors that have been MATCH seeks to determine whether treating cancers particularly resistant to treatment. according to their molecular abnormalities will show NCI-MATCH investigators plan to obtain tumor bi- evidence of effectiveness. opsy specimens from as many as 3,000 patients initially.

25 PRECISION MEDICINE GETS PRECISE

genomics. While the Human Genome Project was an immense international collaboration that took 13 years and cost $3.8 billion, Doroshow estimates that the genome mapping for NCI-MATCH is about $1,000 per patient. What’s exciting is the chance for NCI and the drug companies to learn quickly. “The program offers the drug companies a safe harbor,” said Doroshow. “The government will not assert any intellec- tual property rights.” It means that the participating companies will be able to study their drug’s effect on an identified mutation and proceed independently. “We’ll also test the expression levels of RNA, which will provide additional insight into why particular drugs are or are not found to be effective,” said Doroshow. Exciting innovations in biopharma The specimens will undergo DNA sequencing to identify are not limited to major drug companies or cancer those that have genetic abnormalities that may respond organizations. Instead, innovation is taking place at a to the drugs selected for the trials. Another unique as- host of smaller, greenfield companies from Cambridge pect of the trial is that there will be up to 2,400 clinical to Berkeley. sites across the U.S., which means that patients will not Two new companies—Caribou Biosciences and have to travel far to enroll. Intellia Therapeutics—will develop therapeutics and solu- Doroshow called the program a “paradigm shift,” from tions for new and improved products based on the break- treating cancer based on the organ where it originated to through work on RNA by biochemist Jennifer Doudna. zeroing in on the genetic Like DNA, RNA abnormality and matching are nucleic acids, and, it to one of the drugs being along with proteins and studied. Once enrolled, pa- carbohydrates, constitute tients will be treated with the three major mac- the targeted drug for as romolecules essential long as their tumor shrinks for all known forms of or remains stable. life. Doudna’s discovery In a sense, the trial and the development of suggests a “pay for perfor- CRISPR/Cas9 gene-ed- mance” element that could iting technology opened a be utilized when treating new frontier in biomedical cancer patients in the research. Caribou forms future. Economist Doug strategic alliances with Holtz-Eakin (see sidebar) companies in the research, envisions a future of pay- therapeutics, agriculture ment based on success. “If and industrial bio fields to a therapy is effective, you develop new and improved get continued payments,” he says. “If it’s ineffective, the products. Intellia’s goal is to develop curative medicines payments stop.” using CRISPR/Cas9 for gene editing and repair. NCI-MATCH is only possible because of the dramatic “The incredible potential of this technology for reduction in the cost of DNA sequencing. The mapping treating human genetic disease inspired a group of the human genome in 2003 jump-started medical of life science veterans to create Intellia Therapeu- 26 tics,” said Erik Sontheimer, one of the scien- tific founders of Intellia who helped unravel the mechanism of CRISPR-mediated immunity in hese drugs cost too much,” issue, which stopped the progress on bacteria. His lab at the University of Massachusetts said Dr. Leonard Saltz, chief health care policy.” With the recent studies the roles of RNA molecules in gene regula- of gastrointestinal on- Supreme Court decision in favor of the tion and genome editing. cology at Memorial Sloan law, he is now hopeful of progress. Kett“Tering Cancer Center. He managed to “The availability of therapy to treat The power of Doudna’s discovery is evident in the many awards she has received, including the rock the audience of 25,000 oncologists, conditions that were previously untreat- scientists and health care experts at the able is literally a miracle,” said Holtz-Eakin. 2014 Lurie Prize in Biomedical Sciences and elec- plenary session of the American Society “Yes there is a financing issue. But we tion to the National Academy of Sciences. Time of Clinical Oncology’s annual meeting in should not lose sight of the underlying magazine named her one of the 100 most influential Chicago in June. health policy piece of better medicine.” people in the world in 2015. The median monthly price for new Saltz notes that one Bristol-Myers “Every scientist has the dream of using their sci- cancer drugs in the U.S. had doubled, cancer drug regimen was “truly, truly re- ence to treat disease or benefit society in some way,” he said, from $4,716 in the period from markable for a disease that five years ago said Luciano Marraffini. “And I think that Intellia 2000 to 2004 to roughly $9,900 from we thought was virtually untreatable.” now has the opportunity, and I have the opportunity 2010 to 2014. Saltz noted that price The regimen, reported at the conference, by being part of Intellia.” He is a founder and leader increases haven’t corresponded to combines the drugs Yervoy and Opdivo, of Intellia, whose laboratory at Rockefeller Univer- increases in the drugs’ effectiveness. helping patients live for a median of 11.5 sity investigates the underlying molecular mecha- Saltz had seen the elephant in the months without their disease getting room, and named it. worse. Yet Saltz calculated the cost nisms of CRISPR immunity and seeks to employ this “The unsustainably high prices of at $295,000 per patient per year and natural pathway to develop new technologies. cancer drugs is a big problem, and it’s extrapolated it to $174 billion to treat all Another founder, Rodolphe Barrangou, was part our problem,” Saltz said. U.S. patients with metastatic cancer for of the team that initially established the adaptive im- While Saltz called on the industry, just one year. mune function of CRISPR systems. Yet Holtz-Eakin would hate to see the His lab at the North Carolina State government impose price controls. University focuses on the biology “As much as possible, we should and genetics of CRISPR/Cas im- let the private parties sort it out,” said mune systems in bacteria. Holtz-Eakin. Drug pricing undoubtedly “It’s the right topic and tech- will change. “Lesson No. 1 is always to engender competition wherever possible.” nology with CRISPR,” said Barr- Drug costs rose to $374 billion last angou. “It’s the right time with the year, the largest increase since 2001. But CRISPR craze. It’s the right team Holtz-Eakin urges perspective: “If we saw without a doubt. It’s the right IP physicians and insurers to work together any big pharma companies consistently strategy. It’s the right strategic partnerships. It’s the with government to address cost, beating the profit rates of the rest of the right founders’ team. It’s the right staff. It’s the right economist Doug Holtz-Eakin has also world, then you would stand up and take leadership. It’s the right investors. And when you been thinking about price concerns. Last notice. That’s not what happens—they put all of those good ingredients together, you can year, he established the Center for Health win, they lose. Pharma stocks have not expect nothing else but success.” and Economy, a think tank to serve as a beaten the market. Pharma’s ability to Yet the new and astonishing still takes time— resource to Congress, the media and the generate huge profits is limited.” such as the goal of developing drugs that could public as the health care issue is debated. There’s a bigger issue for those con- As the former director of the nonpar- cerned about the spiraling cost of health home in on a specific gene causing a disease, then tisan Congressional Budget Office and the care. “Drugs are only 10 percent of health snip it out and, if necessary, replace it with a healthy former chief economist of the President’s care,” said Holtz-Eakin. “If you want to segment of DNA. Council of Economic Advisers, Holtz-Eakin cut the nation’s health care bill, you have While CRISPR/Cas9 and other gene editing has a unique perspective, having been to go after the hospitals and doctors.” therapies offer tremendous potential for developing involved in policy, politics, academia and At the same time he endorses the new treatments for diseases caused by a mutated government. He is president of American efforts of the pharmaceutical companies gene, the drugs and trials are years away. Action Forum. to improve productivity. “Health care is a “We’ll know more,” concludes Doroshow, as a “I have always maintained that the really big part of the economy, and it has result of NCI-MATCH and other research efforts. Affordable Care Act is not the end of not been the most productive. We need “We won’t know everything. But we will build more health care reform but the beginning,” to think hard about health care policy said Holtz-Eakin. “The law is widely issues because it … has a big impact on understanding and apply that knowledge to the perceived as flawed. It became a political people’s personal lives.” —K.K. treatment patients get.”  27 BY CHRIS HODENFIELD

PHOTOGRAPHS BY DAVID ZAITZ RETAILGOES

BY CHRIS HODENFIELD

PHOTOGRAPHS BY DAVID ZAITZ

29 discussing the “health care system” in Beforethe United States, one should at least examine that word “system.” It suggests a sense of order that does not exist in the incoherent, free-jazz mambo called American medicine. The numbers are too ungainly to contemplate. We spend nearly 18 percent of our gross domestic product on health care, while major European nations do it for 10 percent to 12 percent. What we spend on health care every year in this country—$2.9 trillion—actually exceeds Britain’s entire GDP. But beyond the thousands of dollars each of us spends on health insurance, it’s the smaller numbers that sometimes cause aggravation.

30 “There’s been a tremendous explosion of interest in the urgent care model... It was because [equity firms] anticipated a migration of the way people received health care, away from primary care to urgent care. There was an immediate need to fill that gap.”

It’s the $40 painkillers at the hospital. Or the $140 “first-time patient fee” at a new doctor’s office. Given the costs, it’s no wonder that a wave of alternatives is sweeping through the market. (Or as one health executive called it, “the morass.”) Everyone from the old medical guard to the investment community is studying the swift evolution of health care options. In the past, patients went to doctors who were on a list provided by their health plan. But today’s market assures cus- tomers of more consumer-driven choices, and they’re choosing simplicity. Perhaps it shouldn’t be seen as a splintering of the old health care system but rather as a needed reconfiguration.

31 The most help a store’s business in certain seasons, Wal- noticeable Mart’s recent drive to add clinics, starting in Texas and South Carolina, appears to be with the intent of someday adding full primary care shift can be seen in the capabilities to its stores. In addition to pro- proliferation of urgent care clinics that have viding bargain-rate health care for Wal-Mart’s sprung up on every Main Street and strip mall. 1.1 million employees, it’s also nice to be able Once derided as “Doc in a Box” outlets, they are to get allergy shots at the same place you buy now an accepted part of the health scene with at your underwear and potato chips. least 9,000 to be found across the country. This With the likes of Wal-Mart poaching business model has cash-strapped hospitals customers, what do family doctors have to say moving in for a closer look. For the younger, about all this? It’s not all positive. The walk-in caffeinated generation that hasn’t formed an al- clinics are certainly convenient, but “you just legiance to a traditional doctor’s office, it’s very don’t get the continuity of care you get with a attractive to walk through a storefront door doctor who has observed you for years,” says right now, sans appointment, after work. The Dr. Robert Wergin, president of the American basic charge will be $75 to $150, and the added Academy of Family Physicians. costs for some stitches or an X-ray will still be Wergin is a family doctor at a small town a fraction of the hefty payments sought at a in Nebraska. He recalls the time a woman hospital emergency room. came into his office after two out-of-town “Recently there’s been a tremendous explo- visits to an urgent care clinic. She was suf- sion of interest in the urgent care model in the fering an aching nose. Diagnosing her with country,” says Paul Dickison, vice president sinusitis, both urgent care doctors prescribed of marketing at CareSpot, a firm with 52 antibiotics. “But I had known this woman,” such clinics. “A lot of that rush occurred in Wergin says. “I knew something wasn’t right.” 2011–2012, with a lot of funding moving into He called a neurologist he knew, got her into this category. It was because [equity firms] a CAT scan the next morning, and within 48 anticipated a migration of the way people hours she was in surgery for a brain tumor. received health care, away from primary care While urgent care clinics will freely steer to urgent care. There was an immediate need patients to a primary care physician (PCP) or to fill that gap.” a hospital, Wergin notes that the medical data On the coattails of urgent care sites are the does not always move accurately from a clinic more basic “retail medicine” clinics that have to a primary care office. sprung up in CVS pharmacies, Walgreens, But one thing that walk-in clinics do Krogers and the like. Target just made a deal provide is an easy entry portal for men in their with CVS to maintain retail clinics in 1,600 of 20s and 30s who might otherwise have avoided its stores. Why? To get shoppers in the door, going to the doctor’s office. “Psychologically, even if it’s just for a flu shot. they don’t see a need to have a primary care Retail medicine outlets are nothing fancy. physician,” notes Dickison of CareSpot. “Our According to some assessments, retail clinics studies show that 50 percent of the men who only prosper during the winter cold-and-flu come in don’t have a PCP, and neither do season. Unlike urgent care clinics, which are 38 percent of the women.” run by full MDs who can suture minor lacera- It isn’t until they age and start seeing a tions, interpret X-rays and write prescriptions, need for follow-up visits that patients begin retail clinics are staffed with physician’s as- searching for a regular family doctor. sistants or nurse practitioners. When more se- The urgent care business model has at- rious maladies arise at either location, patients tracted a lot of investors. The rush started in are steered to a primary care physician. 2011 when the probability of the Affordable While the attraction of a retail clinic might Care Act’s enactment gave rise to the notion of

32 The walk-in clinics are certainly convenient, but “you just don’t get the continuity of care you get with a doctor who has observed you for years.”

33 50 million newly insured customers storming into clinics. That was how CareSpot came into “Retail medicine” being. Originally called Solantic, it was started by Rick Scott in 2001. In 2011, just as he was clinics have becoming Florida’s governor, he sold out to the private equity firm of Welsh, Carson, Anderson sprung up in & Stowe (WCAS), which took sole ownership of the firm and renamed it CareSpot. CVS pharmacies, WCAS was not the only private equity firm to take a tidy interest in this model; dozens Walgreens, have moved into this realm. But as fascination with walk-in care rises, the private equity Krogers and the outfits now find themselves competing with hospital giants and insurance firms. like... Why? To get shoppers in the door, even if it’s just for a flu shot.

On the surface, however, it would appear surprising that hospitals are buying into urgent care clinics, given that they’re natural competi- tors. Indeed, those clinics have an advantage in being able to take on only the patients they want to take—those who are insured or who will pay right on the spot. (Not Medicaid, however, in most cases. Clinics don’t like hag- gling.) Hospitals, of course, are mandated by law CVS/MinuteClinic launched the first retail to take anyone who shows up, which can add medical clinics in the United States in 2000 financial stress. (Vermont is debating legisla- and now has more than 900 locations. tion that would force walk-in clinics to treat all patients, regardless of ability to pay.) Health insurance colossus Humana, for Maybe hospitals are dealing with a case of instance, snapped up Concentra and its 340 lo- “clinic envy.” With nonprofit hospitals now cations. Then last spring UnitedHealth Group, reporting revenue drops nationwide, it’s time the nation’s most profitable health insurance to look afield. company, raised eyebrows when it went on a There is no denying that hospitals want to shopping spree via its Optum division. Chief be part of this business, says Tom Charland among its acquisitions was the purchase of of Merchant Medicine. “They have to be. MedExpress and its 141 clinics in 11 states. Otherwise they’re going to lose this business For insurance companies, the lower costs to equity-backed start-ups or insurance com- at urgent care clinics would seem to make panies. It’s very clear that hospitals are looking a beautiful friendship. As well, there is a for alternative revenue streams and service side benefit in owning walk-in clinics: They lines to offset that.” provide a wealth of data to those who take Clearly something can be learned from the an interest. Insurance companies, of course, fast-medicine stores. Last year, when HCA, take a profound interest in data. the nation’s largest hospital group, bought up

34 CareNow, a Texas-based urgent care system, And they go and open their own clinic. There’s then–HCA President Sam Hazen fondly a significant amount of growth at the low end, noted the convenience and accessibility of the meaning the onesie-twosie operators who are walk-in clinics and told Reuters he wanted to getting into this for the first time.” “replicate that model in other markets.” This is not the first time Americans have Well, after all, what is the essential Amer- faced a shortage of doctors. During World ican paradigm? Convenience. War II, midwives and other advanced levels of The new options in retail medicine might be nurses were heavily in demand, and the con- saving the country, given our increasing shortage cept of the nurse practitioner (NP) took hold. of doctors. With boomers aging, this is no time Today, the nation’s 150,000 NPs are a funda- for doctors to be bailing out, but they are. mental part of the health scene. (NPs go past Tellingly, one new player in the urgent the regular nurse’s five-year education with care market is the burned-out doctor. “It’s the serious postgraduate work, and can participate emergency-room physicians who have made a in fields ranging from oncology to cardiology.) lot of money and have a high net worth,” says The retail clinics that one sees in a grocery or a Charland, “and decide they want a change of box store are certain to be staffed by an NP. In pace from the high-stress emergency room. rural areas, NPs are a godsend.

ut where do we go from here? margin work. (There are no heart transplants The newer, high-speed medical in strip-mall clinics.) options are, of course, perfect for The connective tissue between concierge millennials. But when it comes and urgent care is something called direct to the business of appealing to primary care, which is now being advanced B a generation that keeps its eyes welded to the by firms like MedLion, Paladina Health and smartphone, the answer might be in the higher- Qliance. These outlets offer access to doctors tech medical care promised by telemedicine. by subscription, so to speak, with monthly According to industry watchdog PwC, payments of $50 to $70. They’d like you to millennials are demanding to see “flexibility, regard it as something analogous to a gym convenience and technologies that deliver per- membership. While direct primary care is a sonalized experiences that meet their needs small niche market now, once employers seize and emphasize well-being.” Accordingly, the on it and turn it into a mainstream benefits market is preparing for advances in telemedi- plan, says Charland, “it will completely disrupt cine devices that include biosensors to monitor traditional primary care. vital signs, analyze blood and urine, and zip “And I think primary care physicians them- the information to the doctor’s office. Many selves will move into this model, because this new machines are being readied for market. is what they went to school for. They didn’t go Google and Apple are involved. And that Apple for all the paperwork and the administration Watch on your wrist must be reading your that is now a part of the traditionally run phy- pulse for a reason. sician practices.” Such changes in the market are shaking As these systems subdivide and evolve into up the offices of primary care doctors all over. other hybrid models of health care, a warning Just as the concierge-medicine model has may sound from an unlikely place: Your family proved popular among upper-end physicians doctor is hurting and could use some quick who desire a simplified office operation, the attention. Very likely, though, all the primary democratic model of the urgent care clinic has care physicians in the nation are scanning the proven attractive to a medical community that shelves for a remedy. Even doctors sometimes prefers speed and numbers—even if it is lower- have to beat “the system.” 

35 Q+A

ILLUSTRATION BY STEPHANE MANEL AN INTERVIEW WITH BERNARD J. TYSON,

CHAIRMAN AND CEO OF KAISER PERMANENTE

SERVING PATIENTS AS CONSUMERS

ERNARD J. TYSON is chairman and CEO of Kaiser Permanente, a health system with more than 10 million members and $60 billion in revenue. It is the largest nonprofit integrated health care organization of its kind, offering both care and coverage on a prepayment basis. To B take care of its members, Kaiser Permanente has 180,000 employees and 18,000 physicians. It owns 38 hospitals, has more than 600 medical offices and 500 phar- macies, and it runs its own technology innovation center near its headquarters in Oakland, Calif. It consistently is recognized for the high-quality care and services it provides to its members, patients and communities. Kaiser Permanente's origins stretch back to 1945, when the wartime health care program run by Sidney Garfield, M.D., for Henry J. Kaiser's home front workers was opened to the public. Kaiser was a major industrialist whose worldwide en- terprises included steel, dams, automobiles, building materials and housing de- velopments—but his lasting legacy was his health care plan. He believed that if his family had had access to high-quality and affordable health care for his mother, she would have had a long, healthy life instead of dying at age 52 in 1899.

37 Unlike fee-for-service models, where in- 9.1 surance companies are billed by physicians MILLION and hospitals for each of the services they MEMBERS provide, Kaiser Permanente controls the entire health care dollar within its system, and physicians make care decisions. With all of its 10 million members on Kaiser Per- manente’s electronic health record, phy- sicians, labs, pharmacies and care teams have access to patient records to elimi- There has been a lot of debate about nate duplicate tests and better coordinate Qnew drugs that appear to be very care. As a result, the “Kaiser Permanente effective but are also very costly. model” is closely aligned with the needs Some drugs, like those for cancer, cost as much as $300,000 a year. What is of its members. With its emphasis on early Kaiser Permanente’s position on the detection and prevention, Kaiser Perman- rising costs of pharmaceuticals? ente is able to focus on members’ healthy We’ve had this discussion inside life years, while also providing the best Kaiser Permanente, and I made one care possible when members are facing a thing very clear to our doctors and critical health situation. reinforced what they already know: The doctor’s job is to do the right thing at the Kaiser Permanente’s members seem to like both the care and right time to deliver the right outcomes services they receive and the organization that provides them. for the patient. I’ve said to them, “You’re Numerous studies and awards confirm this, as does the fact that not here to solve the dollar issues. Let me many members stay with Kaiser Permanente for decades. deal with that.” What I don’t want is for a Tyson has worked in nearly all parts of Kaiser Permanente physician at Kaiser Permanente to make for more than 30 years. He is a highly respected leader of the a judgment about which drug to admin- American health care community with a global reputation. ister based on price. The decision must In 2014, Modern Healthcare named him the second-most be on returning the patient to health. influential person in health care, behind President Obama. Costs are important, but we have to solve Tyson co-chairs the World Economic Forum’s Health Governors the issue of affordability as an industry. Community and is chair of its Future of “Healthy” initiative. Along with a leadership certificate from Harvard University, Tyson holds a bachelor of science degree in health service If the problem of high costs is not management and a master of business in health service your doctor’s responsibility to solve, administration, both from Golden Gate University in San how should health care administrators Francisco. Tyson sits on the board of directors and CEO think about costs? Roundtable of the American Heart Association. He served as chair of the Executive Leadership Council from 2012 to 2014. With data. You have to evaluate The NAACP Legal Defense and Educational Fund honored whether or not there’s an alternative Tyson with its 2014 National Equal Justice Award. drug, whether or not the new drug, Tyson recently discussed trends in health care with which may cost an additional $100,000, Korn Ferry’s senior client partner and managing director, cures, improves or extends quality of health care services, Thomas Giella, and with Joel Kurtzman, life. A health insurance administrator editor-in-chief of Korn Ferry’s Briefings on Talent & Leadership. should never interfere with the patient- What follows is an edited version of their discussion. physician relationship. These care deci- sions should be made by the patient and physician, not the insurance company. Q+A BERNARD J. TYSON

So it’s a matter of comparing For an expensive treatment like costs and benefits? hepatitis C, what about pricing by age or the length of time someone Yes. It may be that a new drug is a member of the system? provides only incremental changes in a patient’s life. If that’s the case, We haven’t thought through the the question raised is different. The economics of that or even how it decision is not based on the drug would work. As an industry, even costing $300,000 but because we on the pharmaceutical side, we know it will improve the quality of have been focusing on blockbusters our members’ lives and is in their where everybody gets the same best interest—with the patient medicine for the same disease. But engaged in the discussion and deci- 93,675 we’re headed for a precision medi- sion. In 2013, roughly $87 billion BABIES cine future, which will be different. was spent in this country on spe- cialty drugs like we’re talking about. DELIVERED By 2020, it’s expected to jump to Will precision medicine add to something like $400 billion. the industry’s productivity and lower its costs, or will it increase 36.5 the industry’s costs? There are That’s a huge increase in cost. MILLION people on both sides of the issue. DOCTOR It is. And the implications are Hepatitis C is going to be a good massive with regard to the afford- OFFICE VISITS case study for that. Many people are ability of health care. Affordability walking around with hepatitis C, is a major issue in our country. and they don’t even know it. What the health care industry is going to do now is to encourage people And yet it looks like the science to get checked. With hepatitis C, is moving in the direction of per- a small but significant percent of sonalized or precision medicine. But to make the economics of individuals whose disease continues Won’t that mean better and even that argument work, doesn’t it to progress experience powerful faster cures? mean you have to keep a patient negative effects. Then if they are for his or her lifetime, or at least tested, say they discover they need a If my colleagues from the a good portion of it? liver transplant. These are the kinds pharmaceutical industry were here, of complexities we’re dealing with they would say, “Bernard is only It’s difficult to know how to now. Personalized medicine will be telling you half of the story.” They’d think about the long-term benefit even more targeted in the future. say, “He’s not telling you that if he over the lifetime of an individual. If spends $100,000 on a hepatitis C you’re another health plan you’ll say, drug, it means he won’t have to “Bernard can think about the issue What’s your view on where treat that person again for the rest this way because his members stay costs are headed? of his or her life for hepatitis C and with him for 15, 18 or 20-plus years. related problems, including a liver So Kaiser Permanente can realize Let me put it this way: It’s no transplant. They’d say, “Bernard is some of those savings. But in our longer true that a dichotomy exists actually saving a lot of money with case, our members change health between costs and benefits and that that drug,” which makes sense. The plans all the time. They might be you can’t have both. It’s not true argument is much more complex with us two to five years and then that if you want to have quality than arguing that the dollars spent they roll over to another insurance health care, you have to pay more on a specialty drug will eliminate company. For insurance companies for it, and if you want affordable the need for a liver transplant and like that, they pay $100,000, and health care the quality will suffer. that A = B. the member moves on.” I don’t subscribe to the old, tired

39 theory that you have to decide on my needs. Last year we had 21 mil- What does that mean over time? cost versus quality. In fact I would lion secure e-visits! That requires a argue that Kaiser Permanente is very different infrastructure than It leads to a rebasing of our cost showing the world that the thesis is the traditional office visit. And, it structure that will drive down faulty and old logic no longer holds turns out the satisfaction rate for unit costs. The technology leads true. You can have high-quality an e visit is something like 9.7 out us to where costs stay flat. Right care that is affordable. of 10. So it is not suboptimal care now we are at, maybe, a 2 percent that people get. In fact many of cost increase a year. That’s very our members who voluntarily se- aggressive, but it is appropriate. At How would you argue it? lect e-visits are saying it is a better the same time, our quality is going form of care because they’re get- up—which is evidenced by the fact This way. Think about the ting all the information they need, that we have five stars from Medi- infrastructure required for a visit and they don’t need to drive all care in all of our plans except for to a doctor’s office. To make that the way across town to get it. They two, and we have 4.5 stars on those. happen, historically, I have to don’t need to give up a couple of We’re also at the top of the scale in build parking lots. I have to hire hours for that 15-minute visit since our Healthcare Effectiveness Data receptionists. I have to have nurses. they can communicate directly and Information Set measures— I have to have exam rooms. I have through a secure e-messaging HEDIS—as we evaluate ourselves to have physicians. In other words, system. Even though we had more against other organizations. And I have to spend a lot of money to than 50 million face-to-face visits we won the J.D. Power award for provide you with a great and worth- in 2014, these doctor visits were quality—again. So we have all kinds while 15- to 30-minute visit. requested because of the health of indicators that we use to care- Now juxtapose that against an issue or because that was the pa- fully monitor quality of care. That’s e-visit where I use technology, and tient’s choice—not because going why I would argue that you don’t I have a physician on the other end to the doctor’s office is the only have to go after affordability and who is listening and responding to way to get care. cost improvement at the expense of quality. You can do both. We are demonstrating that.

“YOU DON’T HAVE TO Bringing down costs while improving quality is a trend GO AFTER AFFORDABILITY everyone welcomes. What other trends do you see?

AND COST IMPROVEMENT AT Consumers of health care are beginning to act more like THE EXPENSE OF QUALITY. consumers and are paying more attention to cost. The reason YOU CAN DO BOTH. WE ARE they’re doing it is because they’re paying more for their own health DEMONSTRATING THAT.” care. The out-of-pocket expenses that an average American pays for health care has risen. Health care costs are second only to housing. That has gotten people’s attention. As a result, people are asking very different questions of the industry 646 than in the past when they didn’t HOSPITAL S, pay much attention to costs and the MEDICAL payer was over here and the receiver of the care was over there. It meant OFFICES everything was being paid for. But AND OTHER now for Kaiser Permanente and FACILITIES Q+A BERNARD J. TYSON the industry as a whole, people are and hospital. They believe people about what’s right for the patient, asking different questions because will get their health care needs and they are not incentivized by they have more at stake in terms of met, and it will be at a price point whether or not the physician gets what their health care is going to they can afford. While they’re at paid for providing a service and cost them and what it means from a CVS, they can also shop for other filling the bed. They are in control financial standpoint. things. You are also seeing new to make sure the patient is getting start-up businesses where physi- the right care in the right setting. cians set up their practices entirely How do you know this change on the Internet. We have our own of attitude and behavior is hap- experience with secure e-visits with Does the industry as a whole think pening? Is it anecdotal or do you members choosing to visit their the future is to become more like measure it? doctor online. The point is, with Kaiser Permanente or is it still certain illnesses people’s needs experimenting with models? I actually go to our call centers can be met with a different kind of and listen to calls from members, system—one that would have been Leaders in our industry are which helps me understand what it unheard of five or 10 years ago. playing to where the puck is going. means for working people to have They’re trying to figure that out. If to pay $30 every time they come to we are driving toward the notion Kaiser Permanente for care. So if I of a value-based system, which is have health care coverage because 54 what Kaiser Permanente is, we of the Affordable Care Act and some have to think strategically about of my costs are subsidized, I still FARMERS the best way to accommodate want to understand what the pre- MARKETS that change. Many people in our mium I’m paying is used for because industry are trying to figure that it’s a big chunk of money for me. out right now. They’re trying to If I have to pay another $30 or $40 determine how to create different each time I see a physician, I want kinds of partnerships with dif- to know what I’m paying for. It also ferent players in the industry and means I begin to ask if there are al- Are health care organizations to be more holistic with regard ternatives for how I get my care and restructuring themselves to to how they use each health care my coverage and what they cover. accommodate some of these dollar. Overall, yes, we’re still in These are real questions people changes? the experimental stage. Even so, we are asking. And beyond that there have one of the best models. It’s not are many studies and papers being The industry is trying to figure perfect, and there is a lot of evolu- written that are starting to show out how to shift in many ways. tion and change taking place in the exactly how people are responding Many organizations are trying to industry that has been prompted to changes in the cost of care. replicate the Kaiser Permanente by the cost of care. The truth is, a model. Most of the industry is still lot of people are angry. Consumers fragmented, with everybody com- are angry about how much they’re Do you think people are acting peting for the same dollars. In our paying, while businesses are angry more like the health care system is organization, however, I start with about what the care they provide market-driven? the dollar, and then it’s a matter of to their employees is costing them, what’s the best way to spend that and the government is mad about I do. And by the way, many dollar to meet the needs of the di- what it’s spending for the elderly people in our industry are betting verse population we care for around and the poor. I think all of this has that consumers of health care are the country. created momentum for change, going to act more like consumers. In practice, our model means if which is what you see happening If you look at the strategy of CVS, I have a hospital bed that’s empty everywhere in the industry. I’m for example, it is operating with here in Oakland, Calif., our physi- optimistic that we will continue to a thesis that people will be OK cians are not under any pressure see more change, and ultimately receiving medical interventions in to fill it, because an empty bed is see a transformed industry that a CVS store if they don’t need a lot not seen as lost revenue or as an will meet its obligation to provide of the high-intensity care requiring added expense. In our model, the people with higher quality and more a comprehensive medical center physician is making a decision affordable care and coverage.

41

BUYING LIFE IMAGINE YOU COULD GET A SIMPLE MEDICAL TREATMENT—A SHOT, A PILL, A COUPLE OF HOURS IN A MACHINE, A POWDER TO MIX WITH WATER AND DRINK BEFORE BREAKFAST—THAT WOULD KEEP YOU ALIVE UNTIL YOU WERE 150. OR 200. OR 250. WOULD YOU TAKE IT? •••BUYING LIFE•••

WITH THE FIRST SHOCK OF THE SUGGESTION, YOU MIGHT HAVE A GUT REACTION, SHAPED BY YOUR AGE AND HISTORY. PERHAPS YOU’VE HAD A FRIGHTENING ILLNESS OR A NEAR-DEATH EXPERIENCE TO MAKE YOU APPRECIATE THE SWEETNESS OF LIVING. THAT MIGHT INCLINE YOU TO SAY “YES.” BUT PERHAPS YOUR TROUBLES HAVE TOO OFTEN NAILED YOU TO THE EARTH WITH GRIEF AND YOU DON’T SEE THINGS GETTING BETTER. THEN THE THOUGHT OF EXTRA DECADES IN THIS WORLD MIGHT MAKE YOU SHUDDER—NOT FOR NOTHING DID THE BUDDHA SAY THAT LIFE IS SUFFERING. OR PERHAPS YOUR FAITH, LIKE MOST, TEACHES THAT HUMAN LIVES ARE LIMITED TO A FAIR SHARE OF YEARS, FOR GOOD AND ETERNAL REASONS. MANY PEOPLE, FOR MANY REASONS, WOULD SAY “NO.”

BUT DON’T BE TOO QUICK TO DECIDE. HUNCHES CAN BE WRONG. BEFORE YOU ACCEPT OR DECLINE, IT MIGHT BE WISE TO ASK A FEW CLARIFYING QUESTIONS.

STORY BY DAVID BERREBY

ILLUSTRATIONS BY TRAN NGUYEN

44 1 HOW LONG WOULD IT GIVE ME?

❋ That, for example, is the first question that occurs CEO of Genentech. The longer-term goal, as Google to John Boone, a key protagonist in Kim Stanley Rob- co-founder Larry Page made clear at the time, is to inson’s three-novel, centuries-spanning epic about extend life. the colonization of Mars. If you want to contemplate A few months after Calico’s founding, J. Craig how it might feel to choose to double your life span, Venter, the superstar biologist who raced the U.S. gov- you should turn to Robinson’s rigorous and science- ernment to map a human genome and later created based fiction. The scene he describes—a quiet chat synthetic life, founded Human Longevity Inc. with after a routine physical, offering the chance to live $70 million in venture capital backing. Human Lon- two or three times as long as you’d expected—can gevity Inc. sequences 40,000 human genomes a year, only happen in the future. looking for genetic variants associated with long life Still, it’s worth thinking about how you might and other DNA clues to the aging process—not only respond to a proposal to extend your life by tens of in human cells, but in the genomes of the bacteria, thousands more days than the 30,000 or so you can viruses and fungi that live by the trillions in a normal expect to have now. The reason is simple: The ques- human body. tion won’t be science fiction for much longer. More Then, some months after Venter’s launch, it than ever, “radical life extension” is the purview of was the turn of Leonard P. Guarente, a professor of serious scientists and serious money. And they agree biology at M.I.T. who was Sinclair’s mentor in anti- that the pleasures and pains of living to 100, 120 or aging research years ago. Earlier this year, he founded even longer are likely to face millions of people soon. Elysium Health. Guarente has spent years looking at Skeptics argue that humanity has been down this genes that affect aging—and at compounds that affect road before, and never successfully—from Ponce the rate at which those genes are active. The company de León’s search for the Fountain of Youth to the has five Nobelists in biology as advisers. operations of Serge Voronoff, a French surgeon who Nonprofit initiatives are also proliferating—like in the 1920s implanted pieces of monkey ovaries and the Palo Alto Longevity Prize, a $1 million award testicles into women and men, who—he proclaimed— that will be split evenly between the first researcher would be “rejuvenated” by the procedure. or team who can show a 50 percent increase in the What makes today’s interest in life extension dif- average life span of a mammal population and the ferent is the depth of biomedical knowledge. While team that brings the heart-rate measurements of an biologists still don’t know all the answers, they are no aging mammal back to young-adult measures. Mean- longer taking shots in the dark (or the gonads). while, the Methuselah Foundation in Springfield, Va., “We really do have the emerging technologies to be awards prizes and grants to advance “regenerative able to do this now,” David A. Sinclair, the co-director medicine.” It was founded by the philanthropist and of the Paul F. Glenn Laboratories for the Biological entrepreneur David Gobel and Aubrey de Grey, a Mechanisms of Aging at Harvard University, has said. biomedical gerontologist who is cofounder and chief This recent confidence that the mysteries of life span science officer of the SENS (Strategies for Engineered are cracking has attracted some of the best minds in Negligible Senescence) Research Foundation, an orga- biology and business. nization whose goal is to “reimagine aging.” In 2013, Google joined the movement, launching The convergence of money and talent on life the California Life Company, or Calico, a $1.5 billion extension hasn’t occurred because of a single break- research firm dedicated to finding “life-enhancing through—few researchers think they will find a therapies for people with age-related diseases,” in “magic bullet” soon. On the contrary, work is heating the words of its CEO, Art Levinson, the former up because of the many promising pathways—genes, telomeres (the structures at the end of chromosomes an issue for millions today and in the near future. that supply DNA when a cell divides to make a This is why the troubles of today’s graying world younger copy of itself), metabolic processes like are not just a medical issue for advocates of life homeostasis (the maintenance of a steady state for extension. The advances in public health in the 19th blood pressure, blood-sugar production, heart rate and 20th centuries—clean water, sewage systems, and other vital processes that deteriorate with age; it’s vaccinations, better and safer food—gave millions a one focus of the Palo Alto prize). Anti-aging research path to a life that was eight or nine decades long. But is experiencing an embarrassment of riches. the quality of those extra years has been largely disap- Indeed, an often-overlooked truth about the era of pointing. Diabetes, stroke, heart ailments, cancers life extension and all its potential benefits and prob- and dementia have contributed to an impression that lems: It is already here. life is being extended past the point of enjoyment and Until about 30,000 years ago, archaeologists be- competence. This could be a huge problem. Ponce de lieve, the average human being could expect to live no León went searching for the Fountain of Youth—if it more than 30 years. By 1800, life expectancy extended were a fountain of dementia and arthritis he would only a few years longer than the Neolithic total. In not have bothered. the 200 years since then, life expectancy in many Fearful of having that sort of long life, 56 percent nations has doubled. It continues to rise and will lead, of American adults would answer “no” if offered a demographers predict, to a much grayer population medical treatment that would slow aging and let later this century. them live to 120 or more, and 40 percent agreed with The quest for life extension includes research on the statement that medical breakthroughs in general cancer, diabetes and other ailments of older people. “often create as many problems as they solve.” But those illnesses aren’t just a hindrance to greater So, as you contemplate that question and imagine longevity; they are also a consequence of past advances. yourself extending your days, the first question you Dealing with a longer-than-expected life is and will be should ask is this: 2 WHAT KIND OF YEARS WOULD THOSE EXTRA ONES BE? OR, PUT IT THIS WAY: WHAT DO I GET BESIDES MORE TIME?

❋ Increasingly, life extension taining vitality—making 90 or 100 and writing a new chapter. advocates have an answer. They or 110 the “new 60.” And, that, for In fact, considering the mixed have become, for reasons political most of us, is a lot more appealing effects of success in lengthening the as well as medical, advocates of than more candles on our birthday human life span to 80 or beyond, better lives as well as longer ones. cakes. Even if you have found life you could argue that today’s life- Some have even dropped talk of difficult, the thought of keeping extending research is essential to the “life span,” preferring “health your wits and energy about you for our future well-being. On current span” or “youth span.” Few now 50 more years must raise the hope trends, according to estimates talk about sheer number of years. of fixing what went wrong before, by the World Health Organiza- Their emphasis instead is on main- making your peace with life’s pain tion, our planet in 2050 will have •••BUYING LIFE•••

some 2 billion people coping with the idea of research to make people As those population statistics dementia. If, as expected, the total live longer, think of it as research suggest, choices about life exten- population then will be peaking at to prevent them from living miser- sion can’t be taken in a social around 9 billion, that means that able, dependent and unproductive vacuum. Do you want to spend long nearly one person in five at mid- lives during the added years they’ve years going to funerals and finding century will be struggling with the already received from modern fewer and fewer family and friends cognitive impairments that come civilization. Those two research in the pews? If you are going to live with advanced age. If you don’t like programs are now largely the same. to 120 or more, you’ll want to ask:

47 CAN MY LOVED ONES COME ON 3 THIS TRIP TOO? WILL THEY WANT TO? ❋ The answer to that one is not as simple as it might future, it’s important to remember where you stand seem. We all hope our children and heirs will appreciate in the time line. To say “experience won’t mean as and cherish us (as most do). Yet there are many times in much in the future” is to say “experience won’t mean life when younger people need their elders to die. as much as it does to me.” But in some future that Begin with the intricate psychology of parent occurs after you have passed on, what difference does and child, which leaves many adult children feeling it make how you might have felt about it? Do we care they haven’t reached maturity until they find, as that Joan of Arc or Cotton Mather would not approve British writer John Mortimer wrote about the death of same-sex marriage, which is now legal in both their of fathers, “sudden freedom, growing up, the end of countries? We turn to the past, and to our ancestors, dependence, the step into the sunlight where no one’s for inspiration, but not approval. taller than you and you’re in no one’s shadow.” There Extended longevity could lead to extended con- is no malice in an adult offspring wanting to flower in flicts and friction between generations. If I live to be a way the older generation prevents. That is—still, for 100, I won’t be around to complain about the superfi- now at least—a part of life. Consider Virginia Woolf, cial twits of 2079. But if I live to 200, I will be around. whose father died at 71. A quarter-century later, on And I may not be pleasant company. his birthday, she noted, “he would have been 96, 96, Of course, there is more to society than your im- yes, today … but mercifully was not. His life would mediate social circle. There is also the state of your have ended mine. What would have happened? No society and the world to consider. That leads to a writing, no books—inconceivable.” Woolf was an ex- fourth essential consideration: traordinary writer, but there wasn’t anything extraor- dinary about the situation she described. In 2004, Susan Dominus of the New York Times described the case of a 73-year-old Massachusetts lawyer who wanted to retire. He could not, though—his 100-year- old father (and law partner) wouldn’t hear of it. This is why many tell pollsters they don’t want to live “too long”—they don’t wish to get in the way of the next generation. In that desire to “get out of the way” there is, of 4 course, a certain amount of fear. As we age, we can WHAT WILL feel the world passing us by—we stop listening to new music, we cease to get the point of the latest gadgets, HAPPEN IN A we don’t bother with the current slang. We know, in our bones, that those who come after us are not the WORLD WHERE same as we are. And usually our assessment is that they’re not as deep or moral or interesting as “our EVERYONE LIVES generation” was. What reason do we have to expect, if we stick around for a century and a half, that we’ll like TO 150 OR 200? what we see? Perhaps our grandchildren, taking vast life spans for granted, won’t appreciate life’s moments, ❋ One discouraging fact about this concern is that because they’ll have so many. After all, as Henry David we haven’t done a great job of managing the extended Thoreau wrote, “the price of anything is the amount lives we have won in the past century. The rapid of life you exchange for it.” If you have a lot of life, it “graying” of the global population is a source of alarm. follows that prices will fall—that neither work nor love Consider the social safety net. China, for example, nor other experiences will mean so much. now has about six workers for each retired person. On the other hand, when you deplore an imagined With current trends that ratio will be two workers per •••BUYING LIFE•••

retiree by 2050. It’s a prescription for labor shortages, advised the Japanese government earlier this decade falling production and political uproar as promised about ways to revive the nation. This is the sort of pensions and healthcare for older people become scenario Robinson presents in his novels, where a impossible to pay for. colonized Mars erupts in a revolutionary war for These new problems demand creative solutions. independence in 2061, led by some of the original Will a world full of older people have that creativity? colonists (including John Boone, in his vigorous 80s). There are reasons to wonder. It fails. Then, 66 years later, a second Martian revolu- A generation ago, the Stanford neurobiologist tion takes place. It succeeds—in no small part because Robert Sapolsky, having noticed that he didn’t like his many of the leaders of the first are still around. young research assistants’ musical tastes, did some Perhaps you find that an exhilarating prospect. So testing to see at what age and how people cease to much wisdom and experience available to later gener- be open to new experiences. He concluded that the ations! But it’s not hard to imagine a downside. With window for openness to music closed at age 35, while the Founding Founders looking over his shoulder, openness to new foods ended around 39. Lincoln might not have been free to reinvent the Imagine if such a long-lived population had ex- country he was fighting for. Rather than providing isted sooner. A 120-year old Thomas Jefferson could useful tactical insights, Napoleon might just waste have advised Abraham Lincoln about preserving the the General Staff’s time insisting that they do things Union; a 145-year-old Napoleon could have consulted the way he had 100 years earlier. Ultimately, then, the on French strategy against the kaiser on the eve of question that matters most in your attitude toward World War I; a Meiji emperor in his 160s could have life extension is an inward-looking one:

THE LAST QUESTION: HOW DO YOU THINK TIME AFFECTS PEOPLE?

❋ If you think the future is an extension of the exactly as they are today. Instead, your hunches tell present, and that people continue on the tracks they you, they’ll change, adapt and discover as much in laid early in their lives, then adding decades or their 110s as they did in their 30s. centuries to the life span will appear oppressive— This is the optimist’s view of extended “health for individuals, intimate relationships and society. span”—a world in which people have not only more “Truth never triumphs,” the physicist Max Planck raw years and more raw health, but also more of the said. “Its opponents die out. Science advances one vitality and flexibility that characterizes them at their funeral at a time.” If that’s true, and funerals wane to best. Can you live an extra 70 years and remain your- a trickle, what happens to the advances? If this out- self? Which, of course, includes all those surprising look makes sense to you, then you see human life as changes of mind and heart that keep life interesting? both a blessing and a problem. Death is usually your If you think that’s possible, you have reason to think enemy but sometimes your friend—when it removes that the personal and social problems can be solved. people who, you are certain, would only take what As for Boone, in Robinson’s Mars novels, he needs you should have and get in your way. only a short walk to mull his questions before the However, if your sense of life—your own and answer comes clear. He takes the treatment. society’s—is one of endless progress and growth, then “It’s not that hard a choice, is it?” says the doctor. you’ll see extended life as a benefit. Imagining today’s “‘No,’” Robinson writes. “He laughed with her: 60-year-olds at age 110, you don’t assume they will be ‘I mean, what have I got to lose?’” 

49 White blood cells (green) attack a cancerous cell (blue) in a rendering of an immune response. teaching your body to kill cancer

Cure? Breakthrough? Revolution? Uncommon words to be associated with cancer, one of the scariest diagnoses a patient can receive. Yet all those headlines, and many more like them, flashed around the world from Chicago in the first days of June as journalists reported on a new class of cancer treatments that were the stars of one of the world’s largest medical meetings. It is rare that the American Society of Clinical Oncology (ASCO) annual conference generates such upbeat headlines. Disappointing trial results and incremental advances are far more common, and skepticism the prevailing sentiment. Any talk of a “cure” is usually dismissed as hype by most cancer experts. This year, though, saw a discernible shift in tone as the meeting turned into a coming- out party for an emerging group of drugs known as immunotherapies, which harness the body’s immune system to beat back malignancies. The biggest news was a clinical trial testing a combination of two immunotherapies in 945 patients with advanced melanoma, the deadliest form of skin cancer. Both drugs are made by Bristol-Myers Squibb: Yervoy, approved in 2011, and Opdivo, approved last December. The disease was kept in check in patients on the combination for 11.5 months on average, compared with 2.9 months for patients receiving Yervoy alone, a significant improvement. Plus, close to 58 percent of patients saw their cancer improve on the combination, versus 19 percent on Yervoy alone. ➜

51 ➜ Those results are part of a wave follow-up of patients with late-stage of positive data coming out for melanoma treated with Yervoy immunotherapies tested against a found that 22 percent were alive at broad variety of cancers, including the three-year mark, and 17 percent liver, colon, breast, head and neck, were still alive after seven years. and brain. One late-stage clinical It’s those kinds of results “It is trial of Opdivo against lung cancer, that prompted Dr. Roy Herbst, the biggest cancer killer, was so chief of medical oncology at Yale positive that lead researcher Dr. Cancer Center, to use the word actually Luis Paz-Ares of Madrid described “spectacular” when discussing the results as a “milestone.” immunotherapy. “I think we are There have been breakthrough seeing a paradigm shift in the way cancer treatments before, most oncology” is practiced, he told plausible notably the targeted therapies led ASCO attendees. “The potential for by Novartis’s Gleevec, approved in long-term survival is there.” that in 2001 for chronic myeloid leukemia. That’s quite a statement, given 10 years we will have cures and therapies for most, Targeted therapies pinpoint cancer that the vast majority of cancers cells without harming healthy are still treated much the way if not all, cells, so they usually carry fewer they were when President Nixon side effects than conventional declared his “war on cancer” in chemotherapies, which flood the 1971—with chemotherapy, radia- body with poison. But the immu- tion, surgery or a combination of human notherapies go a step beyond the the three. Though the survival rate targeted drugs, by holding out the for cancer patients five years after promise of lasting results. diagnosis now stands at 68 percent, cancers.” Cancer cells almost always mu- almost 20 points higher than in tate to adapt to whatever poison is 1980, cancer experts attribute most —Gary Gilliland, thrown at them, including targeted of that improvement to earlier and President, Fred Hutchinson Cancer Research Center, therapies, and the disease comes better diagnosis. Even the most Seattle roaring back. Patients typically die successful new drugs can promise not from the original cancer, but the the sickest patients only several recurrence. Immunotherapies may extra months of life on average. prevent relapses by priming the im- Immunotherapies have their mune system to “remember” cancer limitations. At this point only cells if they re-emerge. Long-term 8 percent to 40 percent of patients teaching your body to kill cancer respond to the drugs, and side to overcome the ability of prolifer- effects can be severe. Three drug- ating cancer cells to evade and mis- related deaths occurred in the trial direct the body’s immune system. combining Yervoy and Opdivo, In the 1970s scientists discov- and a third of patients receiving ered that a powerful component the combination had to drop out of the immune system, a white because of side effects. blood cell called a T cell, could be The biggest barrier to over- stimulated by proteins called in- come, however, could be the cost. terleukins. The resulting reaction Yervoy, given in four infusions destroyed malignant tumors. The three weeks apart, costs $120,000 race was on to clone interleukin for a course of treatment. Opdivo, proteins, and it was ultimately administered every two weeks, won by Chiron (now part of No- costs $150,000. Oncologists are vartis). Its interleukin drug, IL-2, alarmed that these prices will put won F.D.A. approval in 1992, first these drugs out of reach of many for kidney cancer and later for cancer patients. melanoma. IL-2 can produce re- Nevertheless, immunotherapies markable results, but it only works are the most promising cancer for about 6 percent of patients, and treatments to come along in at side effects are brutal: 2 percent of least a decade. Decision Resources patients die from the treatment. Group predicts the global market The T cells stimulated by IL-2 Allison licensed his antibody to for this class of drugs will reach act as a bludgeon against cancer; Medarex in 1999, and so started a almost $9 billion in 2022, driven immunotherapies take a more nu- 12-year journey to commercializa- by the expected approval of nine anced approach. Over the past two tion. His antibody eventually new drugs. The director of the decades scientists identified those became Yervoy, approved in 2011 Food and Drug Administration’s components of the immune system as the first of a new class of drugs oncology division, Dr. Richard that detect cancer cells, or prevent called checkpoint inhibitors. Pazdur, described immuno- T cells from detecting them, and Medarex was purchased in therapies as potentially “trans- started working on drugs that 2009 by Bristol-Myers, its develop- formative” treatments capable of would target those components. ment partner, for $2 billion. The changing the course of patients’ next year Bristol-Myers presented lives and has vowed to use the he race to cure cancer some attention-getting clinical F.D.A.’s recently launched break- is global. French trial results at ASCO: Although through-drug program to quickly researchers made one only 10 percent of advanced-stage shepherd the most promising of the most significant melanoma patients responded to candidates through the regulatory discoveries in 1987 when Yervoy, those patients who did process. “We are in the middle they found a protein survived four months longer than of a revolution,” said Dr. Louis on the T cell’s surface those receiving chemotherapy. Weiner, director of the Lombardi that acts as a brake on More remarkably, about 25 percent Comprehensive Cancer Center at Tthe immune system. The brake is of those responders were still alive Georgetown University. “I don’t called CTLA; 10 years later James two years after treatment, when think that is hyperbolic. Those Allison, then a professor at the their predicted survival had only are the kinds of observations that University of California, Berkeley, been seven months. It was the first we’ve rarely seen in our business.” and now chairman of the Depart- drug to increase survival for the “Breakthrough,” however, may be ment of Immunology at Houston’s sickest melanoma patients, and an overstatement. Researchers have M.D. Anderson Cancer Center, a review in the science journal been working on immunotherapies developed an antibody that blocks Nature concluded that Yervoy for some 50 years; make that 120 CTLA, thus freeing the immune “provides clear clinical validation years if you go back to the begin- system to attack tumors. As he for cancer immunotherapy.” nings. That’s how long scientists says, “we are treating the immune A second checkpoint inhibitor have been trying to figure out how system, not the cancer.” from Merck, named Keytruda,

53 teaching your body to kill cancer was approved by the F.D.A. in Sep- of an engineered virus, and then actually plausible that in 10 years tember 2014, followed by Bristol- injecting the modified cells back we will have cures and therapies for Myers’s Opdivo in December, both into the patient where they can most, if not all, human cancers.” for malignant melanoma. Key- eliminate cancer cells. Stunning words coming from a truda and Opdivo target a slightly Novartis formed an alliance cancer hospital president. Gilliland different T-cell brake than Yervoy, with CAR T pioneers at the Uni- also acknowledged “the costs of known as PD-1, which is why versity of Pennsylvania in 2012 oncology care are not sustainable.” Bristol-Myers decided to combine and gave the school $20 million Oncologists are not sure which Yervoy and Opdivo in a clinical to build a cell therapy center. In patients will respond to which trial. By blocking two brakes, sci- an early trial of the first drug to drug. This makes cancer difficult entists figured they would hit the come out of the UPenn/Novartis to treat, despite all of the new cancer cells with a one-two punch. drugs. Drug companies are hoping The PD-1 drugs have a higher to solve this problem by developing patient response rate than Yervoy “it’s possible companion diagnostics to better and may turn out to be effective match patients with drugs. For against a broader range of can- that we’ll be able example, one small study tested cers, especially lung cancer. The for a particular defect in the DNA American Cancer Society predicts to pinpoint, in present in about 4 to 5 percent of 221,200 new cases of lung cancer tumor types. The study found in the U.S. this year and 158,040 advance, which 60 percent of colon cancer patients deaths, more than other cancer. who tested positive for the defect Opdivo was approved this patients are the responded to Merck’s Keytruda March for squamous-cell lung – while zero patients without the cancer, which accounts for about best candidates defect responded. If diagnostic one-quarter of all cases. The tests could be paired with each clinical trial reported at ASCO for these immunotherapy, the numbers of tested Opdivo against nonsqua- patients treated and the overall mous cell lung cancer, responsible therapies.” cost to the health care system for 70 percent of cases. Patients —Dr. Lynn Schuchter could be far lower. This is a new on Opdivo lived a median of avenue being pursued. 12.2 months, compared with 9.4 alliance, 36 out of 39 children with Plenty of cancer experts are months for those receiving chemo- acute lymphocytic leukemia had optimistic that this will all work therapy, a significant improvement a complete remission, and 75 per- out. “The field of targeted immu- for patients near death. Dr. Alan cent were alive six months later. notherapy gets more exciting every Worsley, Cancer Research UK’s It’s not just big pharma chasing year,” said Dr. Lynn Schuchter, senior science information officer, CAR T. Several biotech start-ups head of the Hematology/Oncology told the BBC that “advances like are developing these drugs as well. Division at the University of these are giving real hope for lung The most notable is Seattle-based Pennsylvania’s Abramson Cancer cancer patients.” Juno Therapeutics, which raised Center. “We’re rapidly moving past Some 30 checkpoint inhibitors $265 million in its initial public the era in which immunotherapies are now in varying stages of devel- offering in December, just 16 are seen as breakthroughs for opment, and several have F.D.A. months after its founding – one of melanoma alone. Remarkably, “breakthrough” status, which the largest biotech IPOs ever. On these drugs are proving effective “fast tracks” the approval process. June 30, 2015, biotech powerhouse in other cancers where practically Also in the pipeline is a new class Celgene paid $1 billion for a devel- no treatments work. Just as im- of immunotherapies that can be opment partnership and 10 percent portant, it’s possible that we’ll be classified as highly personalized stake in Juno. Juno spun out of able to pinpoint, in advance, which medicine. Called CAR Ts, (CAR is Seattle’s Fred Hutchinson Cancer patients are the best candidates for short for “chimeric antigen recep- Research, and on the day the these therapies.” As these changes tors”) these drugs are made by Celgene deal was announced, Fred take place, oncologists might even extracting a patient’s T cells from Hutchinson’s president, Dr. Gary begin using the word “cure” and no bone marrow, attaching a piece Gilliland, told a meeting that “it is one will accuse them of hype. 

54 FACTOIDS PAGE TK Life by t h e Numbers

THE OCEAN QUAHOG IS THE LONGEST-LIVING CREATURE KNOWN... The giant clam has a life span estimated at more than 400 years. A specimen, posthumously named Ming for the dynasty during which it was “born,” was 507 years old before meeting its untimely demise when the unlucky mollusk was dredged up in Icelandic waters by marine researchers in 2006.

APOTHECARIES... Apothecaries from the Renaissance onward often displayed a preserved crocodile hanging from the ceiling (as did theologians, philosophers, alchemists and surgeon-barbers) to advertise their so-called expertise.

About FATTY ACIDS... 100 billion People with the highest concentration of DHA (a fatty acid found in many aspirin tablets fish) in their blood had nearly 50 are consumed percent lower risk of developing dementia and Alzheimer’s disease. annually throughout The American Heart Association the world. More than recommends two servings of fish, 40 million pounds such as salmon, per week. (18.14 million kilograms) are produced every year CUSTOM PRESCRIPTIONS... in the U.S. alone. First Until the 1950s, the majority of marketed in 1899 by prescription medications were German pharmaceutical custom-made from raw ingredients company Bayer, to suit individual patients. Today, the mortar and pestle used to compound aspirin is derived from medications remains an industry willow bark (Salix symbol, often appearing on drugstore alba), identified by signs along with the letters “Rx,” an Hippocrates as a pain abbreviation for the Latin word recipere, which means “Take, thou.” reliever more than

THE SOCIETY; ROYAL TUFTS UNIVERSITY, BOSTON; HISTORY CHANNEL 2,000 years ago. SOURCES: Arthur l. caplan, Ph.D.,> FOUNDING DIRECTOR OF THE DIVISION OF MEDICAL ETHICS IN N.Y.U. LANGONE MEDICAL CENTER’S DEPARTMENT OF POPULATION HEALTH. By Lawrence M. Fisher

Back in the late 1980s, when activists from Act Up were demonstrating in pharmaceuticals companies’ parking lots to demand greater access to experimental AIDS drugs, bioethicist Arthur L. Caplan, Ph.D., was chairman of amfAR, the American Foundation for AIDS Research, the arbiter of such requests. In May of this year, Professor Caplan was tapped by Johnson & Johnson to create a new panel that will decide which patients get early access to potentially life-saving medicines before they obtain regulatory approval, a process commonly known as compassionate use.

57 campaigns grew ever more sophisticated. Today nearly every disease, some of them not remotely life-threatening, has an organized patient group seeking early access to new drugs, using every tool available, from professional public relations firms nown to nearly everyone as Art, to slick social media pages. Caplan is in some ways a surprising A growing number of states passed so-called choice to head the panel, which is be- right-to-try laws allowing patients to try experi- lieved to the industry’s first. Large drug mental drugs, but Caplan said these have been companies are typically tight-lipped, and ineffectual. “I don’t like them because they give Caplan is anything but. A professor at New false hope,” he said. “They say, ‘You have a right,’ York University, Caplan is easily the most- in spite of the F.D.A., in spite of drug companies quoted bioethicist in the business; indeed he or anything. What they really are is ‘right-to-beg’ may be quoted more than all other bioethicists laws. They also don’t give you any money, so if combined. His fame, or notoriety, depending on you need a baby sitter to travel to where a trial is, your point of view, has made him a controversial you don’t get that help. A lot of these drugs are figure in his field, but he said it never entered biologic. They’re complicated to deliver, and you the conversation with Johnson & Johnson. have to get them by infusion. The main thing “J&J already knew me. They asked, ‘What I don’t like is the laws don’t do anything. They would you do if we said, how would you sound good, politicians like them. Normally if manage this differently?’ ” Caplan said. “I something is a right, then somebody has to do went back to my group at N.Y.U. and said, something. Nobody has a duty to do anything” ‘What about instead of having a under these laws, he said. medical officer at the company de- cide what to do, what if we tried a panel with many different esides, the F.D.A. grants nearly every request perspectives: patient advocacy, for early access, which typically means letting medicine, law?’ The panel patients take a drug that is still somewhere in would work anonymously, the three-phase process that leads to regulatory so you wouldn’t have social approval. Phase One trials, typically in a small media chiming in, or group of patients, assess safety, establishing first people calling their politician.” that the drug does no harm or at least that its Amrit Ray, a physician and chief medical Bside effects are tolerable in the target population. officer of Janssen Pharmaceutical Companies of Phase Two, among greater numbers of patients, Johnson & Johnson, said that Caplan’s high profile at more than one site, attempts to prove that the was not an issue for the company. “N.Y.U. has a new drug works by hitting predetermined end long history of expertise and engagement in this points such as reduced tumor size. Phase Three, area,” Ray said. “We chose to collaborate with among many more patients at multiple clinical N.Y.U. and Dr. Caplan because our assessment was settings, is intended to confirm safety and efficacy they were uniquely qualified and at the forefront of as well as the company’s ability to produce an ‘compassionate use’ thinking. Dr. Caplan will lead adequate drug while meeting F.D.A. standards. the group, but he has also elected that the panel Experimental drugs can fail at any stage. will make the decisions and he will step in if it’s not So getting early access to new drugs is no possible to reach consensus among the members.” panacea, yet desperate patients continue to ask Though the leaders of Act Up, the AIDS for it. “I was around back in the AIDS days,” said Coalition to Unleash Power, were often arrested, Caplan, referring to his time at amfAR. “We got their ultimate success in gaining early access a lot of requests, and I approved a lot of them, as to new drugs inspired other patients with life- chair. I never saw one person get better. That is not threatening illnesses to become activists. But the impression that is conveyed in things like the from Act Up’s street actions, which included a ‘Dallas Buyers Club’ movie. There were things that demonstration that closed the Food and Drug Ad- happened in terms of community that I think were ministration for a day in 1988, compassionate use good, but there’s this mythology that because of

58 activism, certain people got better. I have seen one We were literally taking the drug out of medicine or two cases recently where someone got better cabinets. It extended life for a month or three.” because of an unapproved drug, but it’s rare.” Caplan is not a physician; he has a Ph.D. in the Because the F.D.A. has essentially passed history and philosophy of science from Columbia the issue of early access off to the companies University. But he said he was attracted to the developing the drugs, biopharma executives are medical field due to a childhood experience with confronted with constant requests that they lack polio. “As a 6-year-old in the hospital, I watched the time or the resources to evaluate properly, how kids were treated,” he said. “I was paralyzed Caplan said. Investors urge them not to get for a time, I had to go through rehabilitation for involved, because honoring compassionate use years, so I had this early contact with the health requests, also known as expanded access, is costly care system, and even as a little kid it raised and distracting. Small biotech firms, which often questions in my mind. Then when I was hanging around Columbia Medical School, way back in the early ’80s, I kept seeing all these issues, like newborn preemie ba- bies—how do we keep them alive? But Today nearly every I went off and got a philosophy degree and never returned to medicine, much to the continuing dismay of my 91- and disease, some of them not 94-year-old parents. Once I got into bioethics, I really liked it. There’s a new remotely life-threatening, issue every day, and sometimes I think it can really make a solid difference.” Examples where Caplan’s direct has an organized patient involvement in public policy has made a difference are many. He helped found group seeking early the National Marrow Donor Program, which created the policy of required re- quest in cadaver organ donation adopted access to new drugs. throughout the U.S. He helped create the system for distributing organs, and worked with then-Sen. Al Gore to develop the National Organ Transplant pioneer new types of therapy, often have no one Act, which included rules governing living organ on staff to manage the program. Yet the Twitter donation. He has also contributed to legislation and and Facebook onslaught is unrelenting. regulation in many other areas of health care. “I thought, you’ve got to tamp that down,” said Caplan secured the first government apology, Caplan. “Social media is not fair. People with means in 1991, for the infamous Tuskegee experiments, have an advantage. People who are photogenic have in which black patients with syphilis were left an advantage. You’re not going to see some 60-year- untreated—to test the progress of the disease— old alcoholic in one of these appeals. By having without their knowledge. He also worked with a committee trying to wrestle with anonymized William Seidelman, M.D., and others to secure requests, we’re ahead of the game already.” an apology in 2012 from the German Medical Johnson & Johnson had previously reached out Association for the role of German physicians in to Caplan for advice on a drug for ovarian cancer the Holocaust. that was already approved and on the market, but In 2000, after the death of a teenage patient in short supply due to a manufacturing problem. during a gene therapy trial at the University of “They were short, and they asked for my advice,” Pennsylvania, Caplan and several researchers he said. “I said, ‘You can’t take the drug away involved in the trial were sued by the patient’s from people who already have it, to give it to new family, who claimed the patient had not been people.’ I also said we ought to do all we can to get informed of the risks. Caplan, who had provided the drug back from people who have already died. ethical commentary, was later dropped from the

59 case. But he has also clashed with his bioethicist a big step for patients, and we want to be very peers on various topics, including a study on responsible, so we are beginning with one drug; informing parents of potential risks to premature but if this is successful, the hope is this will be babies in 2013. Public Citizen, an advocacy group, extended across J&J’s drugs and devices,” he said. criticized the study as well as Caplan’s written de- “The intent is that we will look at all of our assets fense of it, saying he was not adequately informed. and make the decision on what the right time is depending on what we learn from the pilot.” Patients will receive the treatment free if their request is approved, which is common in compas- ut Caplan is unapologetic, noting that his sionate use. But they may have to cover doctors’ opinion had appeared in the New England Journal fees and other related costs out of pocket. Insur- of Medicine, a peer-reviewed journal. “I mean, ance companies often do not cover such costs for that’s about as good an endorsement as you’re experimental drugs. going to get,” he told the New York Times. The volume of requests is not a burden for a Nor is Caplan shy about politics. He is the company J&J’s size, but the nature of the requests, author or editor of 32 books, but his layperson’s which usually come from desperate patients who guide to bioethics, “Smart Mice, Not-So-Smart have exhausted all other remedies, makes them People” (2008), has been cast by some critics as particularly difficult, said Ray. “When I think of Ba transparently anti-Republican screed. And these requests that we face from patients, their indeed, Caplan pulled few punches, highlighting families and physicians, at a personal level, every conservative hypocrisy on matters medical and single request is one of the most difficult deci- ethical, from stem cell research to right-to-die sion I face as a physician. I give every one my full laws. “Rather than shackle American scientists, attention. These are heart-wrenching requests, the U.S. should encourage cloning research,” he and everyone that tries to help with them finds wrote. “Myths should not be the basis for public themselves challenged.” policy where cures hang in the balance.” Patients seeking early access to experimental And he has no doubt that the foes of science drugs may have been excluded from clinical trials will be quick to tag his new effort with their because they did not meet criteria of the trial favorite sobriquet: death panel. “Absolutely yes, I do design, or the trial was closed after a sufficient think critics will latch onto that,” Caplan said. “But cohort was enrolled. Some patients do not wish to it’s a misunderstanding. I would say it’s a panel enter a clinical trial for fear that they will be placed that’s going to try to find a fair solution. As with in a control group, which receives a placebo rather donor organ distribution, this is about finding the than the drug that is being tested. Many do not un- best way to allocate a scarce resource. It’s great to derstand how clinical trials work. Indeed, even as theorize, but sometimes you have to sit down and some patients demand access to new drugs, many do it: try to design something that is fair.” biopharma companies struggle to enroll adequate For J&J, the creation of the panel is about numbers of patients in their clinical trials. bringing together internationally recognized The problem is particularly acute for cancer medical experts to bring a thoughtful approach patients. “Only roughly 3 percent of all cancer to complex decisions, said Ray. “For us at J&J, the patients in the United States ever agree to join collaboration with N.Y.U. comes at a time when a trial,” Stan Collender wrote in an op-ed piece innovation in science offers great potential for in the New York Times on June 19. Collender, an patients. That presents a need for compassionate executive vice president at MSLGROUP, a global use processes that are fair and patient-centric,” he communications agency, has a rare and aggressive said. “That really is the driving force.” skin cancer for which there is no approved treat- Johnson & Johnson is beginning the panel with ment. A colleague, upon hearing that Collender just one drug to consider, but Ray said he hopes was taking part in a clinical trial, said he would the effort will broaden to other therapies and to rather not be treated than be used as a “lab rat.” other drug companies. There is no exclusivity to “I am not a lab rat,” Collender wrote. “What I am J&J’s contract with Caplan, who is not being paid. is a patient who needs and is receiving treatment.” “This is new. This is innovative. This is taking One development that may aid clinical trial

60 enrollment and compassionate use alike is the drug that attacks a certain biomarker, I’m dying emergence of so-called precision medicine, which and I have that biomarker, then there is more applies new diagnostic tools to identify in advance of a rationale than 20 years ago, when we were those patients who are most likely to benefit from shooting cannons off at targets all over the place. a given drug. Precision medicine allows doctors to It makes more sense.” prescribe appropriate and optimal therapies based Yet the fact remains that while precision on a patient’s genetic makeup or other molecular or medicine may remove some level of uncertainty, cellular analysis, commonly known as biomarkers. drugs in clinical trials are unproven, so there is always the risk of raising false hopes. Adequate disclosure is critical, said Ray. “Whenever patients are in that very difficult situation, with he era of precision medicine began with no treatment option available, they are always Genentech’s breast cancer drug Herceptin, which seeking hope,” he said. “The intent is never to was approved by the F.D.A. in 1998. Herceptin only give patients false hope. Whenever patients enter works in 20 percent to 30 percent of breast cancer any preapproval avenue, there is the recognition patients. Ordinarily a drug that did not work that these are medicines under study. When a in more than 70 percent of patients would have patient enters a clinical trial, there is an under- failed to win marketing approval, but because re- standing that this is an experiment. That’s what Tsearchers at Dako, a Danish diagnostics company, informed consent is all about. In the expanded were able to devise an accompanying assay that access program, the same principle applies, that showed elevated levels of a protein called HER2 in these are medicines under study.” those patients who did respond, Genentech was While the F.D.A. hears its share of criticism, able to get Herceptin approved for that smaller from patient advocates and pharmaceutical execu- group. Because many cancers are caused by tives alike, Caplan said the agency has been very genetic mutations, oncology has been the most accommodating of compassionate use requests. fertile early ground for precision medicine, but it “They’re even more receptive than they were is applicable to other kinds of diseases as well. years ago,” he said. “The F.D.A. today has tried to “There is this revolution in treatment, with speed up its application process; you can do it in 45 more precision,” Caplan said. “If you’ve got a minutes. They have approved 99 percent. The one percent is due to error, or because something else is already approved. If a person dies when taking the unapproved drug, they don’t hold that against the drug. I don’t think they’re “the desperately ill the roadblock, but the right-to-try people do. I don’t think that’s true at all.” deserve a shot, even if it’s The F.D.A. approved 1,873 requests in fiscal 2014 from companies to grant ex- panded access, up 85 percent from the 2010 a long shot. We rescue fiscal year, when it approved 1,014 requests. Caplan said there is a growing recogni- hikers off mountaintops; tion that patients have a right to try new drugs. “As much as I don’t like right-to-try laws, they have shown that American people we scour the seas for want some resources devoted to experi- ment,” he said. “There is a notion that the missing boats. This fits desperately ill deserve a shot, even if it’s a long shot. We rescue hikers off mountain- tops; we scour the seas for missing boats. into that moral universe.” This fits into that moral universe. If you’re desperate, you deserve a chance, even if all we’re throwing you is a stick.” 

61 FROM COUNTERCULTURE TO MAINSTREAM:

BY GLENN RIFKIN

THE EMBRACE OF UNORTHODOX MEDICAL TREATMENTS IS NOTHING NEW. Today’s popularity of alternative medicine—herbal supplements, acupuncture, tai chi, yoga and meditation—is predated over the past two centuries by a raft of unusual, sometimes absurd, treatments that inevitably spawned vocal and angry pushback from conventional physicians. But rather than drawing the vitriolic reactions that past medical movements faced, the alternative, holistic treatments offered today are being embraced on a broad scale by physicians, hospitals, medical schools and clinicians in every discipline. Individuals and corporations alike are shedding decades of skepticism and integrating methods into their lives that many once shunned. Like any movement, the emergence of integrative medicine is now reaching a tipping point, and the implications are significant. Given the health care landscape, it is hardly a surprise that corporations as well as doc- tors and patients are embracing alternatives. According to a Deloitte study, the U.S. spent $3.8 trillion on health care in 2014, and that number will surpass $4 trillion in 2015. As the costs spiral upward, the outcomes continue to fall short. For Dr. Andrew Weil, director of the Center for Integrative Medicine at the University of Arizona’s College of Medicine, the steady march toward acceptance is not a surprise. 62 “A new system that emphasizes the natural healing power of human beings, treats the whole person... and makes use of all available therapies that do not cause harm and show reasonable evidence of efficacy. Integrative medicine neither rejects conventional approaches nor accepts alternative treatments uncritically.”

—DR. ANDREW WEIL

63 “The current state of medicine and health care is companies, like individuals, are seeking better, more disastrous,” said Weil, who is considered the father cost-effective ways to stay healthy. But what does it all of the field of integrative medicine. “Costs cannot mean for the average consumer? be contained, and even though we spend more per The surge of acceptance of integrative medicine, capita on health care than any people in the world, also known as complementary and alternative our health outcomes are dismal. Integrative medicine medicine (CAM), is evident in every aspect of medical can be the basis of a new, more cost-effective system. treatment and in the proliferation of wellness and It prioritizes prevention and health promotion mindfulness programs and practices in settings once above disease management. Integrative medicine is reserved exclusively for conventional medicine. Sales becoming mainstream, and along with it, alternative of natural products and herbal and homeopathic methods are much more accepted.” remedies such as fish oil, probiotics and melatonin Weil defines integrative medicine as “a new system have skyrocketed in the past decade. The number that emphasizes the natural healing power of human of Americans embracing Eastern medicines and beings, treats the whole person (body, mind and spirit), methods and doing yoga, meditation, tai chi and attends to all aspects of lifestyle that influence health, acupuncture has also increased as more consumers values the practitioner/patient relationship and makes take control of their own health needs and seek pre- use of all available therapies that do not cause harm ventative methods to incorporate into their lifestyles. and show reasonable evidence of efficacy. Integrative Rather than espouse one philosophy over another, medicine neither rejects conventional approaches nor integrative medicine is inclusive of whatever works. accepts alternative treatments uncritically.” “Western medicine is great in acute care For Weil, the outcome is clear. “One day, we will be situations,” said Dr. Mimi Guarneri, a cardiologist, able to drop the word ‘integrative,’ and it will just be president of the Academy of Integrative Health and good medicine.” Medicine and founder of the Scripps Center for Inte- For patients who simply want to become and stay grative Medicine in San Diego. “If somebody is having healthy without emptying their retirement accounts, a heart attack, a stroke, or they get hit by a truck, the debate over what constitutes “good medicine” that’s a great time to be near a major medical center. rages on. Integrative medicine has made strides as The problem is in the concept of disease prevention and how we handle chronic disease management.” Guarneri, who trained and worked as an internist and cardiologist before focusing on integrative medi- cine, believes, like many in the growing field, that patients need and want the best of both worlds. Prac- titioners tend to be physicians with medical degrees who have grown weary of the monolith that Western medicine has become: an expensive, often impersonal and ineffective system aimed at fixes and cures rather than prevention of maladies. “In the 1990s, as a cardiologist, I was putting in 700-plus stents a year,” she said. “I was doing the best that Western medicine can do, and yet my patients kept coming back. We’d stent them, they’d go home, they’d come back. We’d stent them again, and they’d come back again. Why were they coming back? Because we were doing nothing to teach them how to change their lives, how to eat differently, how to exercise, how to change the way they respond to stress and emotion.” She became disillusioned with what she calls the “ill to the pill” method—diagnose an illness, prescribe a medication—that characterizes Western medicine and is fueled by the $310-billion pharmaceutical industry. patient is missing. “They’re not so good at seeing the “One day, connections between all these things,” he concludes about old-school practitioners. “In both my training in evolutionary biology as well as my training in Chinese we will be able practices that treat the body as an ecological system that is in a dynamic balance, I got pointed in the direc- to drop the word tion of research I’m now doing.” Wayne, who happens to be a tai chi instructor, has seen a dramatic shift in bringing these two worlds ‘integrative,’ and together. Many academic medical centers, such as the Harvard Medical School hospital system, now offer it will just be acupuncture as part of their pain program or as pal- liative care for cancer patients. Most have mind/body good medicine.” courses in meditation or tai chi or yoga. “This wasn’t happening years ago. This is a culture change,” he said. “And some of this is because of the impact of strong, The road to acceptance, however, has not been compelling evidence that these methods are effective.” smooth. When Weil and his growing legion of fol- lowers began to consider an alternative philosophy in the late 1960s, the immediate reaction from conven- tional physicians was cynicism and scorn. Despite the progress, skeptics remain. OR MANY AMERICANS, Steven Salzberg, a professor of biomedical en- the turn to integrative medicine gineering at Johns Hopkins University School of comes after years of feeling frus- Medicine, is a vocal critic of what he terms “pseudo- trated, fearful, skeptical and even science.” “Whatever term is used—alternative medi- paranoid about the treatments cine or integrative medicine—this isn’t medicine,” they had been receiving for much he stated in an article in the American Association of of their lives. Patients with chronic Medical Colleges Reporter in 2012. “At best, these are health problems have grown tired of long waits for hypotheses. Over 20 years, NCCAM [the National Ffive-minute consultations with their primary care Center for Complementary and Alternative Medicine, physicians, prescription medications that have little part of the National Institutes of Health] has spent effect and a growing alienation from an overburdened more than $1 billion, and [there is] no strong evidence health care system. When they see herbal supple- that these activities work.” ments on the shelves at CVS and hear friends talking But such objections have not blocked the wave of about the benefits of yoga, large numbers are now interest and belief in the effectiveness of alternative willing to consider alternatives. methods. Health insurance companies, though still According to a report from the National Center generally reluctant to recognize alternative treatments, for Complementary and Integrative Health (NCCIH, are beginning to soften their opposition, and in some formerly NCCAM) and the National Center for cases acupuncture, chiropractic and stress-reduction Health Statistics of the U.S. Centers for Disease courses are covered. Though that battle remains Control and Prevention, since 2007, Americans have daunting, the feeling is that a new generation of health increased their use of fish oil, probiotics and mela- care providers is embracing an integrative approach. tonin, among hundreds of supplements. Sales of such Dr. Peter Wayne, assistant professor of medicine at supplements jumped 7.9 percent in 2013, reaching an Harvard Medical School and director of research for estimated $6 billion, according to the Herb Market the Osher Center for Integrative Medicine at Brigham Report published annually by the quarterly journal and Women’s Hospital in Boston, says Western HerbalGram. Among Americans ages 45 to 64, yoga medicine tends to operate in silos: A patient with joint is now practiced by 7.2 percent of the population, up pain goes to a rheumatologist; a patient with a bone from 5.2 percent in 2002. Nearly 20 million adults had problem goes to an orthopedist; a patient with heart chiropractic or osteopathic manipulation, and nearly ailments goes to a cardiologist. A holistic view of the 18 million adults practiced meditation.

65 Many medical schools are embracing the concept. the center of care and emphasize the relationship be- Dr. Brian Berman, a professor of family and commu- tween the doctor and patient, Berman explained. The nity medicine at the University of Maryland School of idea is to consider the whole person, not individual Medicine, has witnessed the metamorphosis. Having symptoms, and it is “informed by evidence, evidence studied at the Royal College of Surgeons in Ireland that is really rigorous but also relevant, and uses all in the 1970s and practiced conventional medicine in therapeutic and lifestyle approaches to emphasize the England for eight years, Berman learned how to incor- idea of optimal health and healing,” he said. porate alternative therapies such as acupuncture and With support from the NIH, academic centers and nutrition into his practice. “It was a most satisfying way hospitals, “people are voting with their feet,” Berman to practice; to be able to partner with my patients and said. “Doctors are being asked for it, and there’s not offer them more than just drugs and surgery,” he said. the outright dismissal right off the bat” as in the past. “I could offer them some ways that they could begin to The embrace of alternative treatments has help themselves with a wider medical toolbox.” spawned countless thriving practices around the But when he returned to the U.S. in the 1980s, country. Dr. Glenn Rothfeld has been practicing inte- he discovered a strong bias against these integrative grative medicine for 35 years, and his Rothfeld Center methods. He remembered what one of his mentors for Integrative Medicine, with offices in Waltham and in England, Sir James Watt, president of the Royal Plymouth, Mass., has 3,000 patients and a two-to- Society of Medicine, had said. This field, Watt told three-month waiting list. him, would never be taken seriously without solid Rothfeld holds a medical degree from the Univer- scientific evidence to support it. To that end, in 1991, sity of Buffalo Medical School and is also a licensed Berman approached the University of Maryland and acupuncturist. But even though he doesn’t accept proposed the first program for integrative medicine health insurance (and most insurance companies to be based in an academic medical center. With the wouldn’t reimburse for a lot of what he does), his university’s support, the Center for Integrative Medi- practice is thriving. “There’s a lot of disconnect be- cine opened and began the effort to influence the field tween physicians and patients,” he said. “A physician and change some minds. By the early 2000s, Berman is taught to look for a disease and either treat it or helped found the Academic Consortium for Integra- reassure the patient that they don’t have a disease. A tive Medicine and Health. He started with seven patient doesn’t care about the diagnosis most of the universities; today there are 61 member universities. time. They care about getting rid of their headache, The aim of these efforts is to place the patient in their bellyache, their disrupted sleep cycle.”

BY THE NUMBERS

In the early 1980s, Dr. Kenneth R. Pelletier IN THE received a call from Robert Beck, I.B.M.’s senior vice president of human resources. Beck wanted help in designing a wellness program CORPORATE for the computer giant, which would be among the first of its kind in corporate America. Pelletier, WORLD along with several colleagues at the Univer-

Health promotion programs see a % 32 percent reduction in workers’ compensation -32 and disability claims. Though most of his patients are those who have 91 percent reduction in chest pain; patients lost become dissatisfied with conventional approaches to weight; their blood sugars got better,” Guarneri said. their illnesses or cannot tolerate treatments such as “The data was so compelling that for every dollar we chemotherapy, Rothfeld sees many who are “alterna- spent on such treatments, we saved $6.60 per patient.” tive in their thinking and wouldn’t even think about According to Weil, the payoff is simple yet potent. going to a conventional physician.” Some of those Integrative medicine “is producing better outcomes patients, he said, have to be persuaded to take antibi- at lower cost in the management of common disease,” otics when they have an infection or prodded to ac- Weil said, “and through its emphasis on prevention cept medicine for high blood pressure. “Remember, an and lifestyle, can greatly reduce the incidence of many integrative approach doesn’t rule out using standard of these chronic conditions.” conventional treatments,” Rothfeld said. For those who believe in alternative options, this is “commonsense medicine,” Guarneri said. Ultimately, the conversation comes down to money. “What do in- surance companies pay for?” she asked. “They pay for us to do things to people. Do a test. Put in a stent. Put in a pacemaker. They don’t pay for us to teach people AN how to eat or how to keep people well.” But that is changing. Health insurers are beginning to offer INTEGRATIVE more extensive coverage for alternative treatments such as chiropractic and acupuncture. Medicare is RESULT now covering heart health programs such as the one Guarneri established with Ornish. But for most current integrative medicine, patients the end, nothing succeeds like success. are paying out-of-pocket dollars, and this means that Guarneri, working with Dr. Dean Or- people who lack the means—minorities and other nish in the late 1990s, participated in a underserved populations—are far less likely to have IN research study in which severely ill heart access. “When the insurance companies turn around patients were taught how to eat better foods, do yoga and say, ‘You know what; we’re going to pay you to and meditation, join support groups and increase keep this guy well,’ that would be a game changer,” physical exercise. “What we found was there was a Guarneri said. “We’re not there yet.” 

sity of California, San Francisco, School of money to Pelletier to investigate the effec- Medicine designed a program for I.B.M. that tiveness of such wellness programs. In 1985, focused on addressing the known risk factors armed with those funds, Pelletier created the for heart disease, cancer, pain management Corporate Health Improvement Program and other conventional health concerns. (CHIP), aimed specifically at developing and When Beck left I.B.M. and took a similar job evaluating innovative preventive health and at Bank of America in 1985, he offered grant medical interventions at big companies. % % 26 percent overall reduction -26 in health care costs, and a -57 57 percent reduction in the use of pain medications. % “There was no such thing as stress on the job and an increased integrative medicine 30 years ago,” -27 appreciation of life as opposed to said Pelletier, director of the CHIP Health promotion work. Dow Chemical has incor- program and clinical professor of programs see a porated the program into other medicine at the University of Ari- 27 percent reduction executive programs throughout the zona College of Medicine. But over in sick leave-related company’s global offices. time, as the advent of alternative absenteeism. The difficulty in measuring medicines and treatments began outcomes is tied to the variety of to have an impact, he grew more wellness programs. Some compa- convinced that these innovative nies make serious investments; practices could find support in the others pay little more than lip unlikeliest of places: corporations. service to the concept. But those Today, Pelletier oversees a CHIP that do make the commitment are membership of 15 Fortune 500 seeing trends such as lower ab- companies, including senteeism, higher job satisfaction For every Prudential Insurance, and productivity, higher employee Oracle, PepsiCo, Lock- retention and lower health care dollar heed Martin, IBM, Dow costs. A 2012 report from the invested in Chemical and Ford. American Journal of Health Promo- wellness, The group, including tion analyzed 56 published studies employers medical directors on workplace health promotion saw an or human resources programs. The findings were average of executives from each significant. Employers with health $5.81 due to company, meets twice a promotion programs saw a 27 per- improved year to develop research cent reduction in sick-leave absen- projects that are put in teeism, a 26 percent reduction in employee place inside the compa- 58 percent reduction in the use of health care costs and a 32 percent health and nies and then evaluated opioid pain medications. decrease in workers’ compensation reduced for both the clinical and “That’s important to Ford,” and disability claims. medical cost outcomes. Over Pelletier said, “because when a The return on investment claims. the past decade, “we’ve worker is on opioid medications, was impressive. For every dollar moved into doing they cannot be actively employed; invested in wellness, employers genuinely integrative medicine,” so in effect, they are on short-term saw an average of $5.81 due to Pelletier said. disability. So a 58 percent reduction improved employee health and In 2010 at Ford Motor Co., for in medication is a savings on medi- reduced medical claims. example, Pelletier’s team helped cation costs but also an enormous “The good thing about the cor- create the Integrative Medicine savings in getting workers back porate sector is it is very practical,” Intervention for Back Pain pro- onto the assembly line.” Ford has Pelletier said. “Their business is gram. A control group was offered adopted the basic integrative model not medicine; it’s making rocket conventional care for lower-back for managing back pain throughout ships or cars or tires. They are not pain, which is a serious and costly its corporate clinics. doctrinaire, and their objective issue for companies such as Ford, In another recent study, CHIP is not about conventional versus while the second group was given initiated a telemedicine program at alternative medicine. Their objec- conventional care plus integrative Dow Chemical. Using computers, tive is to produce a healthy, high- medical treatments, including phones and coaches, a mindfulness performing, productive, happy, acupuncture, chiropractic and meditation program was created for retained work force. We take their mindfulness meditation. The Dow’s executives at the corporate employees, which is a high cost results were dramatic. Employees headquarters. The results showed area for them, and demonstrate in the integrative medicine group “extraordinary improvements” that there is a less expensive, more experienced faster return to work, in measures of performance and clinically effective way to take care less recurrence of problems and a productivity, the ability to manage of this.” —G.R. WORK-LIFE BALANCE

Pauses Really Do Refresh

BY KEVIN CASHMAN

N OUR HECTIC 24-7 GLOBAL LIVES, are like a full-out sprint that rapidly becomes a is it any wonder that we go on vacation and triathlon of meetings, metrics and mania. I find ourselves envying the guy running the If leadership means crossing boundaries and scuba shop on the beach? We’ve all been there: helping others to go beyond what is typical or checking out the real estate in a resort spot and average, then how can we, as leaders, transcend the wondering, “Maybe I could slow down the pace a conventional notions of career-life balance to create bit and live here. …” It is not surprising that this a new way of living and leading? This is no easy idea frequently surfaces. Our hyper-performance task. A new way requires a new mind-set, a new and hyper-connectedness push us, and those approach and new multidimensional behaviors. around us, to the limit physiologically, mentally, Is it possible that our pushing and pressure have emotionally and spiritually. We persist, through become counterproductive, especially when com- alternating doses of heavy caffeine and light plexity and importance escalate? Take a moment to cabana time. Unfortunately, the low dosage of consider a fresh, counterintuitive way of leading: to down time rarely restores us for the unrelenting step back, to pause in order to refresh ourselves, inspire and escalating demands. others and catalyze new possibilities. Try these Trans- As a result, for most leaders, the work-life formative Pauses to energize yourself, your team balance ideal has become increasingly more im- and your organization to move from transactive portant and more difficult to achieve. Our days management to transformative leadership.

Illustrations by KATIE EDWARDS

TALENT+LEADERSHIP 696969 Transformative we are equipped to face volatility, illustrate values, purpose and ap- Pause One: unpredictability, complexity and preciation is a crucial language for Pause to Push the Boundaries. ambiguity because our vitality and multiplying sustainable energy and ow often does our vision resilience are bigger than the chal- drive in an organization. Hnarrow to the immediacies of lenges we confront. Energized leaders I was recently conducting a key- the moment, nearly forgetting our “flip” the turmoil, transforming vola- note in Europe with the chairman longer-term strategy and compel- tility to vision, unpredictability to and CEO of Bayer CropScience, Liam ling purpose? The next time you understanding, complexity to clarity Condon, and his top 100. Practicing WORK-LIFE BALANCE WORK-LIFE feel the restrictive pull of managing and ambiguity to agility. “Stories as the Language of Leader- the short term, take a deep indi- A hard-charging CEO with ship,” Condon told his life/career vidual and collective breath and whom we worked nearly did not story and explained how it aligned pause to consider: survive the personal and organiza- so precisely with the purpose-driven tional chaos he was facing. A series story of the organization: “Science • What is important to our customers? of health, relational and business for a Better Life.” You could have • How can we see this from crises captured his attention and heard a pin drop in the room. The a new perspective? awakened a new commitment to authenticity and relevance of the • What would be the optimal energy management. He first at- stories—personal and organiza- long-term approaches? tended to his own vitality by drop- tional—energized and inspired an Stepping back from the imme- ping 25 pounds, getting fit, taking experienced senior team. Take a diate situation to address the bigger real vacations and restoring his re- pause and consider the power of the context of self, others and innova- silience. After this was established, language of leadership: authentic, tion may be the key to inspiring he provided incentives to employees relevant, purpose-driven stories. yourself and others to realize new who joined their newly built fitness potentials. center. He ensured his top people Transformative Steven Baert, head of human took vacations or got docked on Pause Four: resources at Novartis, the global their bonuses. He established a cul- See Purpose as Elevating life-sciences company, shared an ture of healthier off-sites and began Performance to New Heights. aligned way of looking at this: “As to have walking meetings rather s leaders, we rise or fall results-driven leaders, we must than keeping participants confined Ain relation to our sense have something to counterbal- to their chairs. Commenting on of purpose-fueled energy, that ance all this nonstop action and this three- to four-year journey, unshakable awareness that in the striving. Developing an inquisitive, he said, “I honestly do not know midst of crazy difficult challenges, thoughtful approach to complex, where my energy came from before. we will prevail and make a lasting important issues harnesses our Clearly, I was running on fumes difference. While even great leaders drive by consciously serving our until my vehicle, my body, crashed.” like Mandela or Gandhi experi- people and patients in a more Sustainable leadership becomes enced moments of low energy, purposeful manner. As strange as more possible when we proactively what they sought to contribute was it sounds, slowing down helps us to build up our own energy and then stimulated and magnified by the speed up to what is significant and multiply it in others. same crises and challenges that let go of what is not.” threatened to destroy them. Transformative What is the purpose that would Transformative Pause Three: most energize and inspire you and Pause Two: Generate Energy by Sharing your organization to elevate together Multiply Energy to Generate Compelling Stories. and serve something bigger now? Sustainable, Differentiated Value. hen our energy is calm, Ludwig Hantson, CEO of Baxalta, ineteenth-century philosopher- Wfocused and above the fray, the bioscience and pharmaceutical Npoet Ralph Waldo Emerson we are more on top of the challenges spinoff of Baxter, has rallied himself, understood this dynamic when he and “the game” slows down, as it his team and his organization around posited, “The world belongs to the does when a great athlete is fully “in the customer-centric theme of energetic.” Leaders multiply energy to the zone.” When our energy is low or “Sparking Life.” Nearly everything fuel strategy, awaken mission and in- manic, everything seems on top of us in the organization is part of this spire followers to create unique value. and “the game” speeds up and starts purpose to foster and extend life. The Interestingly, when we are multi- to slip away. energy in the corporation has risen to plying our energy and that of others, Using inspiring stories to new heights because the new reality

70 BRIEFINGS is vitalizing and worthy of individual and collective dedication. Employees are excited to step up and contribute their own “spark” to impacting the lives of people, inside and outside the firm. They now have a purpose bigger than product or performance, a purpose that will likely drive per- formance to new levels. Transformative Pause Five: Focus on Coaching and Authenticity. anagers seek to be “right,” Mbut leaders need to be “real.” The evolution from critic to coach and from accuracy to authenticity is fundamental to transformative leadership. Last year, a new CEO came to me for help in activating his vision. He is brilliant, strategic and creative—not a bad profile for Transformative one of the most underdeveloped the rigors of corporate leadership Pause Six: competencies in leaders today. today. However, his precise, critical, Use Questions to Innovate. The next time you are in a discerning intellect and his need to uestions are the language of meeting with a complex and impor- be “right” in nearly every situation Qinnovation and transforma- tant topic and you think you have was squeezing the life and collabora- tion. The right question at the right it figured out, take a pause and ask tive potential out of his team. After moment can stop us in our tracks, yourself, “What question would take some very important and tough work force deeper insight and allow us this discussion to a deeper, broader together, he began to see himself and to examine new perspectives. From or more significant level?” Keep the his impact more clearly. Commenting our research, we know that innova- collaborative inquiry going a bit on his insights, he reflected, “I was tive leaders ask questions at four longer and see where your questions always trained to be right. Little did I times the rate of asserting their ex- lead you. You may be amazed to see know that one of the most important pertise. This constant inquiry, even yourself, and the group, generating aspects of senior leadership is to be when innovators think they know more innovative potential. real. Letting go of my need to control the subject matter well enough, the outcomes, I now see that the engages deeper, broader, fresher n Pausing to energize transfor- collaborative, innovative results are and more integrative outcomes. A mative leadership is a complex, actually better. The more I coach, colleague at Korn Ferry, Andrew multidimensional journey. Con- facilitate and support my people, Pek, an author and thought leader sider purpose, stories, questions, the more they rise up to the tough in innovation, postulates that a coaching and authenticity as initial demands we face with greater energy new type of acumen is required practices to begin building the en- and impact. I thought the team was nowadays; he calls it “integrative ergy required to face the complexity not stepping up to activate the vision, intelligence,” and it is precisely the and demands in our lives. And, if but I discovered that I was the one “connecting the dots, as well as cre- these principles turn out to be less who needed to re-envision my own ating new dots” skill required in to- than helpful to you, then you just leadership for them to step up. I day’s marketplace. Becoming adept might want to take a different kind step back, I support, and then they at the language of integrative intel- of pause and go buy that scuba shop step up. It is counterintuitive and ligence—compelling questions—is in the Caribbean!  amazing to experience. Don’t get me wrong; I can always step in, if neces- sary. But it is no longer my first and Kevin Cashman is a senior partner at Korn Ferry. He focuses on CEO and executive development only response.” and is the best-selling author of “Leadership From the Inside Out” and “The Pause Principle.”

TALENT+LEADERSHIP 71 / 1900 Avenue of the Stars, Suite 2600 Suite AvenueStars, 1900 the / of Briefings Additional copies:Additional BY JOEL KURTZMAN [email protected] Extending Human Life 90067 CA Angeles, Los

PARTING THOUGHTS PARTING Those of us lucky enough to have worked on this issue of Korn Ferry’s Briefings on Talent & Leadership have learned that humanity is about to give itself a gift of staggering generosity. We are about to give ourselves the gift of longer lives. This gift is likely to be measured in years, not weeks or months. And, we are giving it to ourselves not Circulation Customer Service:Customer Circulation because we are better or more deserving than previous generations, Reprints: Advertising:LevynStacy but because science, building upon the findings of those previous generations, is accelerating at a pace never before known. TiffanySledzianowski ow much is an extra five or 10 years with other people. As the pie chart here shows, H worth? You can calculate it the old- even when it comes to what makes us happy, fashioned way, which is the way I was taught. it’s all about who you know. Relationships Multiply those extra years times the amount matter more than anything else. +1 (310) 556-8502 (310) +1 you expect to earn and reduce that number by The more you are engaged in activities you

the rate of inflation in each year. enjoy with other people, the more life matters. 556-8502 (310) +1 +1 (310) 226-6336 (310) +1 If you look at it that way, this priceless gift Relationships take the sting out of mortality. receives a price tag—and it’s not all that big. Even the people who always seem to be com- Don’t get me wrong, a gift of $233,000 for the plaining are complaining about other people. average American for five more years isn’t That might not be the best kind of relationship nothing. But, it turns out, it’s not really what to have, but it’s a relationship nevertheless. people most value. Decades ago, I wrote a book about the scientific assault on the aging process and the quest to prolong the healthy part of our life spans. Back then, a number of people were Nice Place Hea 8% 4% lth to Live 2 researching this subject, and I learned two things: First, for reasons unknown, there are Money/ 7% Financial people all around the world who lie about their with with PRINTED IN THE U.S.A. ages, and when their lies are corrected, they fully environmentally responsible manner.

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Think about what matters more to you— search about what enables people to live long, five years of earning power or five more years healthy lives. It’s not bulging muscles, nor is it © Copyright 2015, KornFerry Copyright2015, © 1 949 ISSN to spend with the people you love? We know adherence to a diet rich in yogurt, exotic teas from research on happiness that the most and certain types of nuts and fruits. The secret important thing in people’s lives—the part of to a long, healthy life seems to be having people -8365 life that makes them happiest—isn’t money or in your life you really enjoy, even if they tell the titles or bright shiny objects or a storage locker same stories over and over. The secret to a long filled with Bon Jovi tapes. It’s relationships life is having lots of friends! 

72 BRIEFINGS