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Home , Albert Sabin, Maurice Hilleman, Sabin Vaccine Institute

SABIN REPORT the newsletter of the Albert B. at Georgetown University Volume I, Number 1, September 1998

IN THIS ISSUE Institute Announces Sabin Vaccine Institute Announces Sabin-Hilleman Fellows Program Sabin and Hilleman are the inspiration for program aimed at promoting Sabin-Hilleman Fellows Program vaccinology and . BY ERICA SEIGUER By participating in existing internships, or in projects 1 In keeping with one of its central missions, the Albert designed through a collaboration between the stu- B. Sabin Vaccine Institute has recently created the Sabin- dent and mentor, the Sabin-Hilleman Fellows will Neal Nathanson: New OAR Head Brings Diplomacy, Toughness Hilleman Fellows Program. A tribute to the pioneering work be exposed to the latest in vaccine design and imple- Renowned for his work on of two great figures in vaccinology, Albert B. Sabin and Maurice mentation. Possible projects might include intern- , Nathanson filled the vacancy left by Bill Paul in November 1997. R. Hilleman, the Fellows Program will nurture talented high ships at the Global Programme for and Im- 1 school students and undergraduates as they pursue their in- munization at the World Health Organization or in

Op/Ed terests in the health sciences, particularly in vaccinology and a laboratory at the National Institutes of Vaccines as an Instrument of immunology. Sabin Vaccine Institute Chairman H.R. Shep- Health. International Diplomacy 2 herd, a close friend of both Hilleman and the late Sabin, un- The Institute will begin the selection pro- derscores that the program is designed to encourage the next cess in February 1999, when application materials A Model of Government-Industry Collaboration, Aviron’s Intranasal generation of scientists and health professionals to dedicate are due. The first Sabin-Hilleman Fellows will be no- Flu Vaccine Paves the Way for themselves to health promotion through disease prevention. tified in April of their acceptance and the internships Needleless Protection The world’s first intranasal vaccine “The Fellows Program will provide young people with an ex- will begin shortly thereafter. Mrs. Heloisa Sabin, co- protected 93% of children against traordinary opportunity to gain unique insight into the worlds founder of the Institute, is looking forward to meet- flu in a 1997 NIH . 3 of immunology and vaccinology. The Institute is committed ing the Sabin-Hilleman Fellows: “Albert used to say to training the next generation of leaders in the health sci- to young people with ideas and interest in vaccinology Institute Awards Gala Honors Vernon Loucks, ences.” that during his thirty years in the development of Nicholas Zwick and Myron Levine The program, developed by Herbert Herscowitz, the oral , for every gratification, he had Annual benefit gala draws on Institute supporters from industry, academia, Georgetown University Professor of Microbiology and Immu- at least 100 frustrations. He told them not to give government, as well as legends in jazz. nology, the Academy for Educational Development, and Sabin up. The Fellows Program will be important in ensur- 4 Institute staff, will support Sabin-Hilleman Fellows’ participa- ing that they do not give up.” v Asia’s Other Crisis tion in activities aimed at the prevention of disease through Yale University and Sabin Institute Neal Nathanson: New OAR Head scientist is working on a the better use of vaccines. They will meet policy-makers, vac- vaccine for parasitic worms. Brings Diplomacy, Toughness 6 BY PATRICIA THOMAS

Sabin Calendar “History will judge us according to Translational Research, whether we develop a vaccine for AIDS,” Neal Symposium and more... Nathanson said, speaking from the periphery 6 of a crowded meeting room at the National In- stitutes of Health. The need for a preventive vac- Sabin Institute Bookshelf cine is urgent, he continued, and the NIH must Science for the 21st Century: preserve the clinical trials system that has been The Bush Report Revisited testing candidate vaccines for the past 10 7 years. Only two weeks into his job as the new Sabin Institute in the News director of the Office of AIDS Research (OAR) at NIH, Nathanson had come to the June 2

8 photo courtesy of L. Rosenthal Sabin-Hilleman Fellows will gather to discuss key issues in vaccine meeting of the AIDS Research Advisory Com- development and implementation. mittee expecting to listen, not talk. But that A scientist who is also a human being resolve melted by mid-afternoon, after officials cannot rest while knowledge which might cine scientists, and clinicians from academia and industry at from the Division of AIDS (DAIDS) had laid out be used to reduce suffering sits on the shelf. Institute conferences. Following their work experience, fellows their plans for changing how the NIH tests HIV vaccines and other preventive measures. Far Albert B. Sabin will stay in touch with each other and the Institute through an from rubber-stamping the DAIDS plan, mem- alumni network. It is hoped that the relationships forged will bers of this top-level advisory committee chipped away at its administrative details, es- The Albert B. Sabin Vaccine Institute is facilitate the continuous sharing of knowledge and ideas, with pecially provisions that might impinge on their a non-profit institute dedicated to the ultimate goal of accelerating the development of new vac- own roles in clinical trials. Finally the discus- continuing the work and achieving the sion bogged down in the pros and cons of al- vision of Albert B. Sabin: to fully realize cines, methods to deliver them, and strategies. lowing institutions that had not already done the enormous potential of to The Program is focused on high school students and HIV vaccine trials to compete for places in the prevent disease. new network. That brought Nathanson to his undergraduates, who are eligible to participate in internships feet. and research experiences that enhance the three-fold mission “I had the feeling that there were people Founded in 1994, the Institute strives obsessing about the process and forgetting to prevent death by promoting the of the Sabin Vaccine Institute: about the product,” he said later. “I’m not inter- development of new vaccines and ¨ stimulating progress in vaccine science; ested in open competition, I’m interested in a delivery systems. product. What the world needs is not an open ¨ advocating sound policy for the development and use competition – it needs a vaccine.” With 35 years of vaccines; of experience in , epidemiology, and pub- lic health, including leadership positions at two Dedicated to Disease Prevention ¨ educating the public about vaccines and immuniza- top medical schools, Nathanson has long had tion. continued on page 6 www.sabin.georgetown.edu SABIN VACCINE REPORT September 1998

Vaccines as Peace Makers THE ALBERT B. SABIN VACCINE INSTITUTE How vaccines could alter the face of conflict in Asia AT GEORGETOWN UNIVERSITY by Peter J. Hotez and H.R. Shepherd CHAIRMAN H.R. Shepherd The shadow that AIDS casts over our planet portends incomprehensible tragedy, and the shadow is growing darker. The new United Nations Report on the Global AIDS Epidemic documents a deadly disease spreading across our EXECUTIVE VICE PRESIDENT Edward Niese MD PhD planet like an eclipse. Last year, 2.3 million people died of AIDS. Thirty million people are infected with HIV, the that causes AIDS; 10 million have become infected in just the last two years. In Botswana and Zimbabwe, one in four VICE PRESIDENT adults are infected. In several other African countries, the rate is one in five. Peter J. Hotez MD PhD Although the report has focused attention on Africa, a newer and possibly more frightening HIV epidemic has BOARD OF DIRECTORS started to roll through densely populated areas of the Indian subcontinent and China. India already has more HIV- Jason S. Berman infected people — four million — than any other country. The number of HIV-infected people in China is believed to Zev Braun Kenneth L. Dretchen PhD have doubled since 1996. Conditions in Pakistan are ripe for an outbreak there. Robert E. Fuisz MD Over the last two years, new combination drug therapies have helped control the spread of HIV in developed E. Andrews Grinstead III Jerome Jacobson countries, such as the . But these therapies cost $10,000 or more per patient per year. Even with recently David J. Meiselman Esq announced discounts for developing countries where HIV is spreading most rapidly, these drugs remain utterly unaffordable Lewis A. Miller Louis Padovano SJ MD to more than 90% of the world’s HIV-infected population. Moreover, new studies indicate that patients taking the Maj. Gen. Philip K. Russell MD combination therapies can still transmit HIV, and some suffer side effects that may create serious new health problems. Heloisa Sabin Carol Ruth Shepherd The only sure way to halt the AIDS epidemic is with a vaccine. Although scientists have been trying to develop H.R. Shepherd a vaccine for over a decade and a potential vaccine just entered a large, Phase III trial, the research effort must be BOARD OF TRUSTEES intensified. More than five million people become infected each year that passes without a vaccine. Ruth Arnon PhD An AIDS vaccine has the potential to do more than conquer this deadly disease. The quest to develop a vaccine Nancy Gardner Hargrave Joseph L. Melnick PhD can resolve conflict in volatile regions such as South Asia. It can draw together scientists, advocates, and government Gustav J.V. Nossal MD PhD health officials from countries recently engaged in nuclear saber rattling, such as India, Pakistan, and China, and unite George C. St. Laurent Jr Kathryn G. Thompson them in a common cause. A joint AIDS vaccine development effort can help defuse a potential powder keg. Stephen G. Valensi Esq Vaccines are humankind’s greatest creations. They are powerful agents for changing society and for altering the James D. Watson PhD Barbara Wilson events of human history, as well as for preventing disease. Within the last thirty years, a worldwide vaccination program eradicated from our planet. Polio will be wiped out by the turn of the century, thanks to an international INTERNATIONAL COUNCIL OF SCIENTIFIC ADVISORS vaccination campaign supported by nearly every country on Earth. Two vaccines, one injected and one administered Peter J. Hotez MD PhD Chairman orally, ended the polio epidemic. Although both were created in the U.S., development of the Sabin oral polio vaccine Kenneth I. Berns MD PhD required extraordinary cooperation between the U.S. and the Soviet Union at the height of the Cold War. The safety and Fred Brown PhD FRS Robert M. Chanock MD effectiveness of the Sabin vaccine, which greatly accelerated the eradication of polio, was proved in massive field trials Stephen N. Chatworth PhD in the U.S.S.R. American and Soviet scientists put aside international political tensions between their countries to Mary Lou Clements-Mann MD MPH Jonathon M. Fine MD defeat their common viral enemy. Ian Furminger PhD Jonathan Schell writes in his new book, The Gift of Time, “Since the beginning of the nuclear age, it has been Neal A. Halsey MD Maurice R. Hilleman PhD commonplace to say that humanity’s technical achievements have outstripped its political achievements. Now the Brian R. Murphy MD situation is reversed. The world’s political achievements have raced ahead of its technical achievements. Today, we Erling Norrby MD PhD MTC Wade P. Parks MD PhD require a technical event as great as the political event that was the end of the Cold War.” Discovery of an AIDS vaccine PhD could be such an epochal event. We must commit the resources, moral and political support to accelerate development James D. Watson PhD SCIEN of an AIDS vaccine. Along the way, we may open doors to international peace. IC ADVISORY COMMITTEE A successful international effort to develop an AIDS vaccine could serve as a model for cross-cultural vaccine SCIENTIFIC ADVISORY COMMITTEE AT GEORGETOWN UNIVERSITY efforts for other diseases that are prevalent in developing countries, such as parasitic . Hookworm, for Herbert B. Herscowitz PhD instance, infects 200 million people in China and almost as many in India. One of us is working, with support from Joseph A. Bellanti MD Chinese officials, on a . A multinational effort has a far greater chance for success than when one John L. Gerin PhD A. Bennett Jenson MD country goes it alone. Our collaboration in the fight against disease tears down mistrust and leads to a spirit of Alfred A. Rabow PhD cooperation. AIDS’ visibility and enormous magnitude could make AIDS vaccine development a powerful rallying C. Richard Schlegel MD PhD Joseph G. Timpone Jr MD point for peace. v BOARD OF ADVISORS Peter Hotez, MD PhD is Associate Professor of Epidemiology and Public Health at Yale University School of Medicine and Mary Alderman Francis E. Andre MD Chairman, International Council of Scientific Advisors, Albert B. Sabin Vaccine Institute. H. R. Shepherd is Chairman of John V. Bennett MD the Albert B. Sabin Vaccine Institute at Georgetown University. Barry Bloom PhD Betty F. Bumpers Francis Cano PhD FROM THE EDITOR Ciro A. de Quadros MD MPH The Albert B. Sabin Vaccine Institute at Georgetown University is pleased to announce the publication of the Phyllis Freeman Esq inaugural issue of the Sabin Vaccine Report, the newsletter of the Sabin Vaccine Institute. The Sabin Vaccine Bruce G. Gellin MD MPH Report showcases articles and reviews on the latest in vaccine research, development, and implementation, and Lance K. Gordon PhD is meant to serve as a resource for scientists in industry, government, and academia, as well as policy makers Scott B. Halstead MD and consumers of vaccines. The views expressed are not necessarily those of the Institute, and reflect the Samuel L. Katz MD Stanley M. Lemon MD opinions of the authors. We hope that you enjoy reading the Sabin Vaccine Report and welcome any com- Sister Collette Mahoney ments or suggestions. Frederick C. Robbins MD THE SABIN VACCINE REPORT Harvery S. Sadow PhD c/o The Albert B. Sabin Vaccine Institute Ronald J. Saldarini PhD at Georgetown University Donald S. Shepard PhD Arnold Stang Building D Room 154 4000 Reservoir Road NW Patricia Thomas Washington, DC 20007-2145

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Alternative Vaccine Delivery Systems A model of government-industry collaboration, Aviron’s intranasal flu vaccine paves the way for needle-free protection BY ERICA SEIGUER Realizing the dream million visits to doctors and $3 to $4 billion in treatment The database that Aviron got from the NIH held costs, and accounts for untold numbers of days lost from The collaboration between Aviron, a California- the results from every clinical trial ever done with the vac- school and work. Even more important, according to physi- based biotech company, and the National Institute for Al- cine. These data, coupled with the VTEUs wealth of expe- cians, is the danger that antibiotic-resistant strains will arise lergy and Infectious Diseases (NIAID) is a remarkable chap- rience with the product, dramatically increased Aviron’s from excessive and improper use of antibiotics prescribed to ter in the annals of public-private partnerships. Instead of chances for success. Instead of reinventing the wheel, Aviron treat ear infections. galloping off in different directions as they sometimes do, could move rapidly federal agencies, academic laboratories, and industry behaved toward large field Flu in the future more like a winning relay team. Now the finish line is in studies of the vac- The vaccine sight as Aviron’s FluMist™, the world’s first vaccine that can cine. The latest ef- may be approved with be administered as a nasal spray, nears approval by the Food ficacy studies were the recommendation and Drug Administration (FDA). If FDA approval is granted, conducted at the that it be given to those the vaccine should be ready for the 1999-2000 flu season. six VTEU sites at high risk for influ- This has not been a swift race on a smooth course, sponsored by enza complications however. The story began in 1967 in the lab of epidemiolo- NIAID and four such as asthma or other gist H.F. Maassab at the University of Michigan. There, he sites funded by serious respiratory bred an unusual strain of virus that could replicate Aviron. problems. High-risk (copy itself) only in the relatively cool cells of the nose and The re- groups include elderly nasal passages, but which died in the warmer environs of the search agreement people, children, and throat and lungs where ordinary thrive and produce between Aviron those who care for the miserable symptoms of flu. Maassab’s “cold adapted” and the govern- them. Given the re- virus forms the basis of Aviron’s FluMist™, which ment has been suc- sults of study pub- vaccinologists describe as a live attenuated (weakened) vac- cessful for other rea- lished in NEJM, many cine. sons as well, accord- expect that the federal This is a departure from conventional flu shots, ing to Dominick Advisory Committee which have long relied on products made from inactivated Iacuzio, an Influ- for Immunization Practices, which is re-

(killed) virus. Live attenuated vaccines generate more spe- enza Program Of- photo courtesy of Aviron cific immune responses than killed ones because they more ficer at the Child receiving the nasal spray vaccine. sponsible for recom- closely resemble viruses that make people sick. When a per- NIAID. As a start- mending how vaccines son immunized with a live vaccine encounters an actual flu up company, Aviron was able to focus on the flu vaccine and should be used, will probably suggest more widespread use. virus, both the humoral arm (which makes protective anti- to dedicate staff and funds to nurturing it. In a larger com- Although few realize it, flu causes an estimated bodies) and the cellular arm (which programs T-cells) of the pany juggling dozens of products, such as Wyeth Lederle, it 10,000 to 20,000 deaths in the United States each year. immune system are ready to attack and destroy it. might not make sense to invest so heavily in a novel vaccine Influenza “is underappreciated as an illness which can lead Like the older products, Aviron’s new vaccine still delivery system that still required so much clinical testing. to complications, ultimately resulting in more serious ill- needs to be adjusted every year, so that it will match the As determined as Aviron was to succeed, in the ness,” noted the NIAID’s Iacuzio. Clearly immunization cuts strains of virus that sci- The vaccine provided beginning “the company needed help in designing and the risk for ear infections among children, and the second entists expect to cause running the clinical trials,” Iacuzio recalled. The CRADA year of the efficacy trial may reveal other benefits as well, 98% protection against problems when the next provided assistance from the VTEUs, which already had Iacuzio said. Although no vaccine is 100% protective, otitis media, the most flu season hits. And considerable experience testing the intranasal vaccine. Since FluMist™ could have considerable public health impact in people will still need to common bacterial then, Aviron “has assembled an excellent staff and clinical the years to come. be immunized annu- infection in children. trial capability.” This will depend, of course, on how widely it is ally. The difference is Highly favorable results from the most recent clini- accepted by parents, consumers, and doctors, according to that instead of rolling cal trial of the vaccine were published in the May 14 issue of C. Jo. White, a physician and Senior Vice President for up their sleeves in doctor’s office for an intramuscular injec- the New England Journal of Medicine (NEJM 338, 20). Of Medical Affairs at Aviron. “We don’t want to give parents tion, people will sniff a measured dose of mist. Easy, painless 1,070 children who received FluMist™, 93% were pro- high expectations that every respiratory infection their child administration appeals to children, parents, and the health tected against influenza and 98% remained free of otitis may get can be prevented by the vaccine,” White explained. professionals who wield the needle. Many people will be media, a bacterial ear infection that is one of the most com- The results of the efficacy trial clearly promise fewer sleepless able to immunize themselves: in a study of 4,561 healthy mon aftereffects of flu. Only one of the vaccinated children nights and trips to the doctor. Not only that, but it doesn’t working adults, 71% of participants took the vaccine (or an developed an ear infection, compared with 20 of 532 chil- take a costly clinical trial to show that most folks – no matter inactive placebo) on their own. dren who were given a placebo, according to the study’s what their age – will avoid a shot if given a choice. authors, who represent Aviron, collaborators at several uni- A long and winding road versities across the nation, and the NIH. Note: As the SABIN VACCINE REPORT goes to press, the FDA Long before Aviron entered the picture, early ver- Anyone who’s been a parent knows the value of has requested that Aviron provide additional information sions of Maassab’s live, cold-adapted vaccine had under- preventing otitis media. This is the most common bacterial on the manufacturing processes and facilities where gone laboratory and clinical testing at NIAID and elsewhere. infection in young children; it accounts for more than 31 FluMist™ will be produced. v In the mid-1980s, Wyeth Lederle tested the safety and im- munogenicity of the vaccine through a Collaborative Re- search and Development Agreement (CRADA) with the Publications Available from the Sabin Institute University of Michigan. This is a special NIH grant that The following publications are available free of charge from the Institute, while supplies last. encourages collaborations between private companies and academic institutions. All told, nearly 10,000 people, some a few months A CRACK IN THE SHIELD: Our Unvaccinated Children old and others over 100, had received the vaccine before by Ann Fettner Wyeth Lederle, due to a shift in corporate focus, dropped Ann Fettner gives a thorough account of the December 1994 Sabin colloquium, Planning for the Next Generation of the product. When this happened, the rights to develop the Vaccines, held at the Banbury Center at Cold Spring Harbor Laboratory. This report provides an historical perspec- vaccine reverted to the NIH. If the government had lost its tive on vaccines, summarizes vaccine policy and development, analyzes the role of the public and private sectors, grip on the baton at this point, the story of the intranasal briefly examines vaccine science, and looks ahead to the Sabin Vaccine Institute’s role in advancing solutions to the vaccine would have ended in mid-race. Instead, NIH auc- obstacles facing vaccine research, development, and implementation. tioned the development rights in 1995 and Aviron was the winning bidder. From then on, the young biotechnology FORGING NEW CONNECTIONS: Vaccine Development and Delivery in the Era of Managed Care company was in a partnership with NIAID and the Univer- edited by Nancy Touchette sity of Michigan. In November 1995 a conference exploring the impact of managed care on vaccine R&D and delivery was held at the Along with the product, Aviron acquired a trea- Banbury Center at Cold Spring Harbor Laboratory. The participants in the Colloquium, including representatives sure trove of clinical trial data, some of which had been from academia, government, and the private sector, recognized the interdependence of all players in the vaccine field. collected by federally funded Vaccine and Treatment Evalu- The emergent theme was the need for greater public understanding of the importance of immunization. Touchette’s ation Units (VTEUs) located across the United States. This report identifies the role of the Sabin Institute in furthering the consensus reached at the colloquium. network of six clinical centers, which was organized in 1992, evolved from an earlier system that tested only vaccines. In THE JORDAN REPORT: Accelerated Development of Vaccines its new incarnation, the VTEU system was intended to ferry Published annually by the Division of Microbiology and Infectious Diseases (DMID) at the National Institutes of both drugs and vaccines across the gap that often divides Health, the Jordan Report is an invaluable resource to those in the field. In his introduction to the 1998 edition, Dr. laboratory research and large-scale human testing. VTEUs John R. LaMontagne, director of DMID, explains that despite recent successes in immunization campaigns, “our specialize in Phase I and II clinical trials, which for vaccines global society and economy highlight the potential effects of emerging and reemerging infectious diseases and the examine safety and the product’s ability to stimulate an im- development of antibiotic-resistant organisms. As this Report is going to press, epidemiologists and virologists are in mune response. Once these phases have been successfully investigating the occurrence of several human cases of influenza due to an avian influenza virus, and completed, companies with development know-how are more efforts are underway to develop a vaccine that could be used to control the spread of this infection.” willing to embark on Phase III trials large enough to deter- mine whether the vaccine actually protects against disease.

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Annual Sabin Institute Gala Honors Vernon Loucks, Nich

BY JOHN CLYMER AND TIMOTHY MAHONEY Vernon R. Loucks Jr., Chief Executive Of- earthquakes devastated that country. Loucks did not The Institute raised more than $500,000 for ficer of Baxter International, received the Institute’s hesitate to contribute those resources, Simourian said. its programs and presented awards to outstanding Lifetime Achievement Award. Shepherd praised “That tells us about the character of this man.” leaders in business, science, and philanthropy at a Loucks as “a visionary leader of a pace-setting bio- The fifth Gold Medal was gala dinner in on June 3rd. “It was an medical enterprise, and a role model for corporate awarded to vaccinologist Myron M. Levine, Director extraordinary evening for the prevention of disease, executives who want to use their acumen and influ- of the Center for Vaccine Development at the Uni- for the Sabin Vaccine Institute, and for Georgetown ence to improve the human condition.” John A. versity of Maryland School of Medicine. Shepherd University,” said Institute Chairman H. R. “Shep” Simourian, CEO of Lily Transportation Corporation applauded Levine’s career-long commitment to “so Shepherd. Three hundred people came from all parts and a longtime acquaintance of Loucks, praised his many different dimensions of vaccine development, of the United States to attend the Sabin Vaccine In- friend for dispatching Baxter employees and millions from running an internationally respected research stitute gathering. of dollars of medical equipment to Armenia when laboratory, to training the next generation of world-

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Vernon Loucks, CEO of Baxter International and Sabin Institute Chairman H.R. “Shep” Sabin Gold Medal recipient Myron “Mike” Levine a Shepherd at the VIP reception.

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Standing (l. to r.): Raymond V. Gilmartin, Chairman, President and CEO of Merck & Company Yale football alumnus Vernon Loucks is presented with the jersey, by Crimson football alum and Gala Co-Chair Georg and Gala Co-Chair; , Director of Therapeutic Research, Merck & Company; R. Gordon Douglas, Jr., President, Merck Vaccines. Seated (l. to r.): Judy Lewint, CFO, Merck & Company; Mrs. Gilmartin; Mrs. Hilleman; Mrs. Douglas.

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E. Andrew Grinstead, III (l.), a member of the Sabin Institute Board of Directors, and Vernon Albert B. Sabin Humanitarian Award honoree Nicholas Loucks of Baxter. Award recipient.

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olas Zwick and Myron Levine

class virologists and vaccinologists.” of Dialogic Corporation, received the Institute’s Hu- ist, was master of ceremonies for the dinner. The The Sabin Vaccine Institute and its gold manitarian Award. The award recognized Zwick’s gen- Lombardi Cancer Center and Sabin Vaccine Insti- medal prize are named for the inventor of the oral erosity and moral commitment, which have enabled tute are collaborating on exciting projects to develop vaccine that helped eradicate polio in the United States the Sabin Vaccine Institute to raise public awareness and promote vaccines to treat and prevent cancer, he in 1975. The medal was presented to Levine by and political support for development of an HIV vac- told the audience. Heloisa Sabin and Maj. Gen. Philip K. Russell, re- cine, promote childhood and adult vaccination, and Guests included Georgetown University tired Commander of the U.S. Army infectious dis- train a very promising young vaccinologist. Dialogic President the Reverend Leo J. O’Donovan, Medical ease research center. Both Heloisa Sabin and Russell is a Parsippany, N.J.-based manufacturer of computer Center CEO Kenneth Bloem, several University and are co-founders of the Institute and members of its telephony components. Institute board members, some of the world’s fore- Board of Directors. Marc E. Lippman, Director of Georgetown’s most vaccinologists, and many of America’s top cor- Nicholas Zwick, co-founder and Chairman Lombardi Cancer Center and a breast cancer special- porate executives. v

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nd Sabin Institute co-founder Heloisa Sabin. Standing (l. to r.): Mr. and Mrs. Nicholas Zwick, Myron Levine, and Dr. and Mrs. David Orr.

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e Sabin Lifetime Acheivement Award, and a Harvard John “Jack” Kennedy, Chair of the Board of Directors of Georgetown University and Chair, rges St. Laurent, Jr. Georgetown University Third Century Campaign, Mrs. Kennedy, Gala Co-Chair (l.), and Virginia Toulmin.

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s Zwick (l.) and Myron Levine, Sabin Gold Medal Vernon Loucks of Baxter International (l.) and Dr. Robert E. Fuisz, a member of the Sabin Institute Board of Directors and Gala Co-Chair. Photography by Battman.

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Asia’s Other Crisis Extent of worm infection points to vaccine as only solution hold the key for designing the vaccine: if Hotez can need it almost necessitates that the vaccine be able to BY ERICA SEIGUER isolate the antigen that leads to a protective immune survive harsh conditions and easy to administer. This The Asian financial crisis may come and go, response, he has a very good candidate for a vaccine. is a tall order in the vaccine world. Despite the inher- but the worms are here to stay. For instance, with In fact, Hotez has a few possible vaccines that ent complexities and obstacles to adequately address- more than 1.3 billion people in the world infected with he has been able to test in mice, and which have gen- ing the problems of worm infections, Hotez and his hookworm, 194 million of whom live in China, the erated the kind of immune response that, if produced colleagues are optimistic and undaunted. v parasite that causes anemia, malnutrition, and loss of in humans, could be a breakthrough in the fight against productivity has had and will continue to have a ma- the unholy trinity. In collaboration with Biomedisyn jor health impact unless its spread is stymied. Hook- Corporation of Connecticut and the Institute of Para- sabin calendar worm, roundworm (1.5 billion people infected) and sitic Diseases at the Chinese Academy of Preventive September 24, 1998 whipworm (1 billion infected) make up the “unholy Medicine in Shanghai, Hotez has used recombinant Boston, MA trinity,” as the triple threat is known in the parasite technology to create vaccine antigens based on two Albert B. Sabin Gold Medal Award world. proteins secreted by the worm larvae, ASP-1 and ASP- Presented to Allen C. Steere of the New England Medical A 1990 study estimated that 44 million preg- 2. The recombinant approach to vaccine design is an Center at Tufts University School of Medicine for his nant women carried hookworm, subjecting their un- expensive one, however, a fact which leads Hotez to discovery of the pathogenesis of , ultimately born children to retarded growth, prematurity, and conclude that hookworm control is “one of the great leading to the development of a vaccine. low birth weight. The drugs to treat worm infection challenges of the next century. We need to find inno- are relatively inexpensive, costing between $1-$2 per vative solutions, keeping in mind the fact that the October 5-9, 1998 year per person, but must be taken continuously in markets out there for worm vaccines are very poor.” New York, NY order to prevent reinfection. The spread of worm in- Week 1998 fection, like that of other chronic debilitating diseases Challenges ahead Sponsored by the Cancer Research Institute as part of its such as tuberculosis, could be drastically altered with The possibility of actually having a vaccine International Symposia Series. For more information, the development of safe, effective, and cost-effective that would alter the lives of millions of people in such email [email protected]. vaccines. a dramatic way is tempered, however, with the eco- October 21-23, 1998 nomic and practical aspects of vaccine development Bethesda, MD and implementation. Vaccine research is under-funded Mechanisms of infection 4th National Symposium on Basic Aspects of Immunology Worms enter the host through the skin, move in general, and in cases where the majority of people Sponsored by the Walter Reed Army Institute of through the bloodstream to the lungs and airways, and affected by the disease in question live in countries Research and the Office of Naval Research. For more eventually arrive in the stomach and finally the small where the annual per capita health expenditures rarely information, email [email protected]. intestine. In the small intestine, the parasites attach to make it past the $10 mark, support for vaccine R&D the intestinal walls and suck blood from the host, lead- has suffered. Developing a vaccine for worm infec- November 10, 1998 ing to anemia and malnutrition. An individual can har- tion will be difficult under these conditions, and will New Research Building, Georgetown University bor thousands of worms; in these individuals, one can require commitment from industry and governments Washington, DC actually feel the worms by placing a hand on the in- world-wide. “The challenge is to prepare a good vac- Dendritic Cell Mini-Symposium fected individuals abdomen. cine. At this point, however, there is no real interest Sponsored by Sabin Vaccine Institute and organized by Controlling the worm population in China on the part of U.S. vaccine manufacturers,” says Hotez. Sabin Scientific Advisory Council Chair Herbert has been difficult. Although the infection is treatable, “This is where the Sabin Vaccine Institute Herscowitz PhD, the one day symposium will explore individuals who are cleared of worms usually go back comes in,” he continued. According to Hotez, who the use of dendritic cells to stimulate the immune system to the same activities and environments that practi- worked on the Great Neglected Diseases (GND) of to fight cancer and HIV. cally ensure reinfection. Mankind Program at in the Date and location to be announced. 1980s, the Sabin Institute has a critical role in stimu- December 15-17, 1998 The vaccine solution lating research and directing policy on diseases, such Banbury Center, Cold Spring Harbor, NY Barring a dramatic change in the lifestyles and as hookworm, that affect disenfranchised populations. Colloquium on Translational Research livelihoods of the 700 million Chinese who are in- The GND program stimulated biomedical research An Institute colloquium dedicated to issues in transla- fected with one or more parasites, a vaccine is the in understudied human tropical diseases by providing tional research, with the ultimate goal of creating an only permanent solution to the epidemic. Yale pediat- support for young investigators in either clinical or infectious disease and vaccine translational research ric epidemiologist Peter Hotez, a world-recognized laboratory settings. In its ten years of existence, the network. For more information, contact the Institute. expert on hookworm, has been shuttling between China GND program revolutionized the field of tropical March 17-20, 1999 and New Haven, learning about the life cycle of hook- medicine and spawned a generation of highly produc- Walker’s Cay, The Bahamas worm and designing drugs that will prime the host’s tive and dedicated investigators. The Sabin Institute, Cancer Symposium immune system to prevent disease. According to Hotez, acting as a conduit between government, industry, and Co-chaired by Drew Pardoll, Director, Division of hookworm affects “the poorest of the poor in under- academia, is in a unique position to offer the kind of Immunology and Hemtopoiesis, Johns Hopkins developed countries.” In his research aimed at devel- direction and leadership needed in this arena. University School of Medicine, and James P. Allison, oping a vaccine, Hotez has looked at individuals who, Beyond the need for financial incentives to Director, the Cancer Research Laboratory at the University though at risk, for some reason do not become in- support vaccine R&D, implementing a vaccine will of California-Berkeley. fected or get mild cases. It is these individuals who be complicated. Getting the vaccine to the people who For more information, contact the Institute.

Nathanson (continued from page 1) compared with vaccines. After budgets are set, then that pays four times as much and involves one-tenth the stress, the respect and attention of his peers. Since May each institute does the complicated work of allocat- he has dedicated himself to public service for a relatively mod- 15, he has had something else as well: a direct pipe- ing funds to individual scientists. The NIAID, for ex- est salary. It’s hard to say no to somebody who sets that ex- line to NIH Director Harold Varmus and responsibility ample, is responsible for about 40% of NIH’s total AIDS ample.” for recommending how the nation’s $1.7 billion AIDS research budget and the rest is spread across about Nevertheless, friends sometimes ask Nathanson why research budget should be spent. 10 other institutes. “Each institute is naturally looking he signed up for the tsuris that goes with being OAR director. out for its own research program and trying to increase After all, he doesn’t need to prove himself to anyone. He is a OAR has a singular role and strengthen that. One of OAR’s mandates is to Harvard-educated physician who obtained his clinical training The Office of AIDS Research (OAR), which maintain an overview and try to coordinate so that there at the , then went on to work on polio at Nathanson now heads, is unique at NIH because it are neither holes nor excessive duplication,” he noted. the Centers for Disease Control. His academic career spanned can influence the scientific agendas and budgets of In addition to simply knowing who’s doing 22 years at Johns Hopkins, where he was head of infectious many separate institutes, what, Nathanson will help diseases for the department of epidemiology, and 19 years at not just one. In contrast, di- Some of us from the outside don’t shape long-range spending the University of where he chaired the microbiol- rectors of individual institutes “know what is impossible, so we on AIDS and the legislative ogy department for 15 years and finished out his stay as vice – even well-known ones and policy aspects of AIDS dean for research and research training. Nathanson had offi- such as immunologist An- just barge in and try to do it. research at the NIH. cially retired at age 70 when NIH came calling. thony Fauci, who heads the National Institute of Al- Equally important are” the vision and leadership he is “At this point in my career, when I don’t have hungry lergy and Infectious Disease (NIAID) – can exercise expected to provide. This may be easier for him – a mouths at home to feed, and where I don’t have to worry about control only over their own shop. Although the OAR newcomer to NIH campus – than for someone who’s what the next job is, it was an interesting challenge.” Nor is it a has a small staff, it wields considerable clout. In fact, been an institute scientist for years. long-term commitment, he said wryly, because the job is so Nathanson’s predecessor, immunologist William “Some of us from the outside don’t know what political that anyone who holds it is bound to succeed or fail Paul, is credited with commissioning the first com- is impossible, so we just barge in and try to do it,” within a limited number of years “and then it will be time for prehensive review of NIH AIDS research during his Nathanson said. Not only that, but he can’t be ac- someone else to pick it up.” four years on the job. cused of favoring one institute over another due to old In an interview with SABIN VACCINE REPORT, loyalties. Nathanson sees himself as one of many out- Vaccines are a top job Nathanson emphasized that the OAR’s budget rec- side scientists lured to NIH by the personal example When Varmus announced Nathanson’s appointment ommendations are broad ones – suggesting how of Harold Varmus, who became director after winning last May, he emphasized that the new OAR director was ex- much NIH should spend on blood safety, for example, a Nobel prize in 1989. “Instead of finding a cushy job pected to boost NIH’s commitment to vaccine research, even

6 SABIN VACCINE REPORT September 1998 Book shelf ALFRED RABOW, PH.D. Progress in the war against disease depends upon derstanding of government’s role in science and of Olson of the University of Washington, see private a flow of new scientific knowledge. New prod- ’s famous report, however, I would not companies more interested in cherry-picking the ge- ucts, new industries, and more jobs require con- recommend Science for the 21st Century—The Bush nome than in producing error-free results. Leaders tinuous additions to knowledge of the laws of Report Revisited. Its emphasis is often misplaced with from these private efforts, such as from , and the application of that knowledge to important textual omissions. The most glaring ex- the Institute of Genetic Research (TIGR) and Will- practical purposes. ample appears on the book’s first page, where Barfield iam Haseltine from Human Genome Sciences (HGS), identifies Bush only as “an engineer from MIT.” This take an entrepreneurial sooner-cheaper-faster approach Science can be effective in the national welfare is like calling the Empire State Building “an office and claim considerable success in sequencing the ge- only as a member of a team, whether the condi- building in New York.” A fuller account of Bush and nome. There Science for the 21st Century: tions be peace or war. But without scientific his role in shaping basic science research can be found is merit and progress no amount of achievement in other di- in G. Pascal Zachary’s new biography Endless Fron- parochialism The Bush Report Revisited rections can insure our health, prosperity, and Claude E. Barfield, ed. tier: Vannevar Bush, Engineer of the American Century to each of American Enterprise Institute, 1997. security as a nation in the modern world. (Simon and Schuster, 1997). these visions of Vannevar Bush In his early years as a professor at the Massa- how to decipher the human genetic code. What da- Science—The Endless Frontier, 1945 chusetts Institute of Technology, Bush helped create tabase of human genes will result, and who will have Vannevar Bush wrote those words at an im- the powerful Raytheon Corporation, developed an access to the information, is one of the key science portant moment in United States history. It was a important standard method for analyzing electronic policy questions today. time scarred by the upheaval and devastation of World circuits, and became Director of Graduate Studies at Recent history does instruct that government War II. The war effort had profoundly altered Ameri- MIT, soon making it the premier school for educat- funding is critical for basic research. This is clear if can society causing the intermingling of military and ing engineers. In 1930, Bush we examine the emergent in- civilian, of government and private sectors, drastically became Vice President and dustries such as computers, changing the relationship between science and gov- Dean of the MIT School of biotechnology, and the ernment. Before the war, government was only tan- Engineering and built MIT Internet. Government fund- gentially involved in U.S. science, which was carried into the most highly regarded ing has been the prime cre- out mainly by industry and universities. American engineering program of its era. ator of these fields, directly science was also the neglected stepchild to its advanced In 1939, he came to Washing- in the case of computers and European counterparts. However, the growth of ton as President of the the Internet (Department of American science and technology, through U.S. gov- Carnegie Institution, at the Defense programs) and ernment sponsored war research, fundamentally al- time a leading funder of sci- through university investiga- tered the relationships between government, academia, entific research; soon after he tors for biotechnology. De- and industry. was named director of the spite evidence that basic re- Recognizing this change, President Roosevelt White House Office of Scien- search funding leads to sci- gave Vannevar Bush the charge to examine the new tific Research and Develop- entific discovery and new technology growth, the

landscape and to delineate what the “Government ment. By the time he wrote photo courtesy of the National Research Council [can] do now and in the future to aid research activi- Science—The Endless Frontier, Vannevar Bush United States lags behind ties by public and private organizations.” Bush was Vannevar Bush was the leading figure in U.S. science many countries in per capita research funding. also asked to determine whether “an effective pro- policy. For all the difficulties in assessing the eco- gram [can] be proposed for discovering and develop- Fifty years later nomic returns on basic science and the role govern- ing scientific talent in American youth so that the Today Bush’s vision of American science ment should play in fostering research, one fact is continuing future of scientific research in this coun- policy in general, and medical research in particular certain: there is no clearly defined role for the partici- try may be assured.” We are still struggling with an- still affects how the U.S. Government funds basic re- pation of the “non-elites,” individuals not in govern- swers to these crucial questions today and Vannevar search. The policy questions arising from the Human ment, the scientific establishment, or in high-tech Bush’s vision still speaks to Americans who want to Genome Project (HGP) clearly illustrate many of the companies. Recent studies, including the Institute renew U.S. commitment to scientific progress. issues discussed in the Bush Report more than fifty of Medicine’s examination of how the NIH sets re- In 1995, on the 50th anniversary of Science— years earlier. Based in the National Center for Hu- search priorities, call for a greater involvement of all the Endless Frontier, Claude Barfield of the American man Genome Research (NCHGR) at the National of society. Individuals who want their children to grow Enterprise Institute assembled a group of policy ana- Institutes of Health, the HGP is well on its way to up free of disease, who want to live long and healthy lysts to reflect on the importance of Bush’s blueprint revolutionizing biomedical research. The HGP is the lives, who want a clean environment, who care about for the future of American scientific endeavors. These best illustration of the tensions and payoffs inherent the health and well-being of individuals all around scholars examined the role of the Bush report in shap- in government funding of basic research. The sup- the world– all have a role to play in fostering the kind ing U.S. science and the mechanisms and payoffs of porters of the government-funded sequencing project, of science we need in society, a science in line with government-funded scientific research. To gain an un- such as HGP Director Francis S. Collins,and Maynard Vannevar Bush’s vision of an endless frontier. v though his own research has not concerned vaccines per se. virus are so variable that results from different labora- the Food and Drug Administration’s approval process. Nathanson’s laboratory at Penn has studied HIV since 1987, tories may be impossible to compare. Earlier the Bal- In the meantime, he thinks vaccine advocates should focusing mainly on the molecular mechanisms that HIV uses timore committee urged primate researchers to stan- stop “beating up on companies.” to damage the human brain. dardize their models; now Nathanson is encouraging Since early 1997, however, Nathanson has acquired a NIH’s efforts to accomplish this. He also wants pri- The bigger picture first-class education in HIV vaccine mate researchers to inject monkeys with HIV vaccines Due to his close association with the Balti- research from experts who have ap- that have already been tested in humans, challenge more committee, Nathanson said that some people peared before the AIDS Vaccine the monkeys with virus, and see how their immune mistakenly labeled him “a one theme director” who Research Committee (AVRC). He responses compare with those seen in people. An could care only about vaccines. Writing in the August is one of 10 members picked by animal model that matches human responses could issue of Nature Medicine, he makes it clear that vac- , Nobel laureate and ultimately be used to decide which candidate vaccines cine development is only one of his top priorities for recently appointed president of the should move forward in clinical trials. tax-supported AIDS research. In addition, he empha- California Institute of Technology. Once a vaccine is approved for clinical test- sized the need to control mother-to-child transmission Nathanson’s experiences with this photo courtesy of NIH ing, “we’ve got a very powerful system that works ter- of HIV, to develop a microbicide that will reduce the Neal Nathanson group will surely affect his view of rifically well to test candidate vaccines in humans. NIH risk of sexual transmission, and to help make the blood NIH vaccine research. has done many trials with many products. The fact supply in other countries as safe as it is in the United Finding a vaccine against AIDS will require “a coher- that the products weren’t very promising is a different States. Less costly, easier to use drugs are also ent program that leads from the light bulb phase to human issue from whether we have a process for testing,” needed so that more people in developing countries trials.” When Nathanson surveys what various institutes are Nathanson said. In the wake of the AIDS Research can have access to treatment. doing, it is clear that some parts of this continuum are stronger Advisory Committee meeting in June, he has been As OAR director, Nathanson will pursue these than others. “The NIH is best at watering the research environ- assured by DAIDS that the clinical trials system won’t goals with a mix of diplomacy and toughness. “Part of ment and letting 100 flowers bloom,” he said. “I’m much less be compromised by reorganization. being a success at this job is working with the insti- concerned about this than about what happens at the next In the future, he expects the vaccine pipeline tutes and their directors. You couldn’t accomplish much step. How are we going to harvest those flowers and bring them to be filled with candidates from academic laborato- if you got everybody’s back up. On the other hand, forward?” ries or possibly from the NIH itself. Only after an HIV leadership is about developing a vision and promoting For starters, he believes that the use of primate mod- vaccine looks promising in humans does he expect a it – and getting other people to buy into it and work els in HIV vaccine research should be revamped. Right now, private company to license the vaccine, figure out how together to accomplish it.” v protocols for immunizing animals and challenging them with to manufacture large quantities, and take it through

7 In the News...

Q&A/H.R. Shepherd Inspiration, Sabin; Mission, Vaccines Copyright (c) 1998 by Co. Reprinted by permission. Times Copyright (c) 1998 by The New York

v ON THE WEB AT WWW.SABIN.GEORGETOWN.EDU How to subscribe to the SABIN V ACCINE REPORT: SABIN VACCINE REPORT The Sabin Vaccine Report is published by the Erica Seiguer Albert B. Sabin Vaccine Institute at Georgetown University. EDITOR Subscriptions are provided free of charge. Please direct inquiries to: Patricia Thomas CONSULTANT SABIN VACCINE REPORT Building D, Room 154 4000 Reservoir Road, NW WRITERS/STAFF CONTRIBUTORS Washington, DC 20007-2145 phone: 202.687.9145 J. Clymer T. Mahoney Peter J. Hotez, MD PhD facsimile: 202.687.9242 D. Medrano A.R. Rabow, PhD H.R. Shepherd email: [email protected] A.V. Kasten, PhD E. Seiguer Patricia Thomas