Volume IV, Number 1 Sabin Vaccine June 2001 EPORT The newsletter of the Albert B. Sabin Institute —dedicatedR to disease prevention www.sabin.org Walker’s Cay Colloquium Catalyzes Work on Cancer Vaccines and Immunotherapy 3rd Annual Sabin Institute-Sponsored Meeting Convened in March at Walker’s Cay, Abaco, Bahamas Thirty of the world’s leading cancer of the colloquium, said the meeting “was notherapy to learn from each other and vaccine scientists spent three days in a great success since it provided an ex- to discuss issues that are critical for the intense, unusually open discussions of cellent opportunity for top scientists in improvement of cancer treatments.” Jef- their newest research data and ideas at the field of tumor vaccines and immu- frey Schlom, head of the Laboratory of the Sabin Vaccine Institute’s Tumor Immunology and Biology Third Annual Walker’s Cay Col- at the National Cancer Institute loquium on Cancer Vaccines in also served as co-chair. The March. Their goal was to accel- Walker’s Cay Colloquium follows erate progress toward develop- a peer review format; emphasiz- ment of vaccines to treat and pre- ing an unusually open discussion vent various forms of cancer. of ideas and data so new they have Most of the renowned scientists not yet been published. It is reported learning new informa- multidisciplinary, involving ex- tion that will speed their own re- perts in oncology, immunology, search. Several said they formed microbiology, biochemistry, he- new, multi-institution collabora- matology and several other fields. tions at the meeting. It differs from most scientific Ralph A. Reisfeld, professor at meetings of large numbers of The Scripps Research Institute in Thirty leading cancer vaccine scientists exchanged their latest ideas people in a single discipline who La Jolla, California, and co-chair and data at Walker’s Cay. A list of attendees is provided on page 11. Continued on page 11. Don L. Douglas Named President and Chief Executive of the Sabin Vaccine Institute New President Will Draw Upon Immunization Program Leadership Experience to Increase Institute’s Impact The Albert B. Sabin velopment of successful Health (PATH) where he served in sev- Vaccine Institute has immunization programs,” eral positions for 16 years, most recently named Don L. Douglas as Shepherd said. “He was as country director and Asia regional its new president and selected following an ex- Continued on page 3. chief executive. Douglas tensive search. The Board joins Sabin as the scope is confident we have cho- I nside of the Institute’s pro- sen the right person to keep Viewpoint: The Other Hainan ...... 2 grams and its influence Sabin on its upward trajec- Robbins Awarded Sabin Gold Medal ...... 4 on public progress and tory of stimulating devel- Bertrand and Rowe To Receive Sabin scientific research are opment of new vaccines Lifetime Achievement Awards ...... 6 growing. His appoint- and increasing immuniza- Report onVaccine Research Conference ...... 7 ment was announced by Don L. Douglas will serve as tion rates. His extensive in- Vaccine Diplomacy: Sabin & Smorodintsev ..8 Institute founder and Institute President and CEO. ternational experience en- Book Review: Evolution of Infectious Disease by Paul Ewald ...... 10 chairman H. R. “Shep” Shepherd. hances the Institute’s ability to catalyze Conquering Polio ...... 12 “Don Douglas brings to the Sabin global disease prevention efforts.” Sabin Institute News ...... 15 Vaccine Institute a wealth of experience Douglas comes to Sabin from the Pro- Calendar ...... 16 in organizational leadership and the de- gram for Appropriate Technology in 2 JUNE 2001 SABIN VACCINE REPORT

The Sabin Vaccine Report VIEW is published by the POINT Albert B. Sabin Vaccine Institute. The Other Hainan Subscriptions are free Please direct inquiries to: Hainan Is Home to the Highest Concentration of Endemic Tropical Diseases in China (This opinion originally appeared in The Advocate, a Stamford, Connecticut newspaper.) SABIN VACCINE REPORT 58 Pine Street The collision at the end of March be- to examine the impact of intestinal para- New Canaan, CT 06840 tween a Chinese F-8 fighter and an sites on the populations of southern phone: 203.972.7907 American Navy EP-3 electronic recon- China, especially Hainan. Our work fax: 203.966.4763 naissance plane over the tropical island there is being conducted jointly with the email: [email protected] of Hainan threatens to cast a Cold War- Institute of Parasitic Diseases of the EDITOR style shadow over diplomatic relations Chinese Academy of Preventive Medi- Veronica Korn between China and the Bush adminis- cine. In an unusually close cooperative COPY EDITOR tration. Yet most Americans may not ap- effort we are learning why some people David Bedell preciate that Hainan is also one of living in Hainan might be resistant to

PRODUCTION China’s poorest provinces and among these parasites. We are using the infor- Raymond A. MacDougall the most destitute regions in Southeast mation to design a novel vaccine in or- Asia. The province is heavily plagued der to combat parasitic worms. In at least CONTRIBUTORS Jacques-François Martin by a variety of tropical infectious dis- one instance our project took us to Edward S. Neiss, MD, PhD eases ranging from malaria to mosquito- Lingshui county—not too far away from Alexander A. Smorodintsev, MD, PhD borne viruses. Our medical parasitology where the disabled EP-3 aircraft sits on

SABIN INSTITUTE STAFF research laboratory has worked in the tarmac. The work is hard and diffi- H. R. Shepherd, Chairman Hainan since 1998 when we first real- cult; it has required lots of mutual give William R. Berkley, Co-Chairman ized that there are more intestinal para- and take on both sides. One of the many Don L. Douglas, President & CEO sites in Hainan than just about anywhere benefits of the collaboration is its re- Fran G. Sonkin, Executive Vice else on the planet. Based on diagnostic quirement for regular scientific ex- President examinations conducted on thousands of changes to each country. Over the last John M. Clymer, Vice President of Hainan residents during a medical sur- few years we have built a strong scien- External Affairs vey of the island in the early 1990s, the tific collaboration and close friendship. Philip K. Russell, MD, Senior Advisor Chinese Ministry of Health reported that Enormous good will has developed to the Chairman Peter J. Hotez, MD, PhD, Senior 94 percent of the population harbors at between the members of my laboratory Fellow & Chair, Scientific Advisory least one intestinal parasite. This in- and our Chinese friends and colleagues Council cludes more than 60 percent of the popu- during the last few years. We are driven William Muraskin, PhD, Sabin Fellow lation infected with parasitic worms, and touched by the enormous burden of Patricia Thomas, Sabin Fellow including Ascaris roundworms, Trichu- disease that the people of Hainan face Paul J. Vilk, RPh, RAC, Director of ris whipworms and Necator hookworms. on a daily basis. We also recognize that Program Management and In many cases, it is common to find resi- infectious diseases are potential threats Regulatory Affairs, Hookworm dents of Hainan who harbor all three to everyone, even in the U.S. The events Vaccine Initiative examples of this “unholy trinity.” All of the last few days should not distract Nancy Gardner Hargrave, too frequently children are the ones most us from the fact that we have much in Development Counsel Veronica Korn, Research Associate heavily infected. As a consequence they common with the Chinese, and much to Vanessa Santiago, Research Assistant suffer from malnutrition, physical gain by continued peaceful and mean- David Bedell, Executive Assistant to growth stunting, and intellectual retar- ingful cooperation. We have learned that the Chairman dation. In many cases, the children of an anti-worm vaccine makes for a ter- Gboku Lumbila, Executive Assistant, Hainan may experience life-threatening rific instrument of diplomacy. Hookworm Vaccine Initiative acute intestinal obstruction or perforation —by Peter J. Hotez, MD, PhD, FAAP Serge Valcourt, Accounting that result from the activities of large Christel Lane, Receptionist/Staff numbers of these worms. Peter J. Hotez, MD, PhD is professor and chair of the Department of Microbiology and Tropical Medi- Assistant In order to help alleviate the enormous cine, The George Washington University, and senior burden of disease in Hainan, our Na- fellow of the Albert Sabin Vaccine Institute. He is tional Institutes of Health, as well as the also visiting professor of the Institute of Parasitic March of Dimes Birth Defects Founda- Diseases of the Chinese Academy of Preventive Medi- tion is sponsoring joint research projects cine in Shanghai. dedicated to disease prevention www.sabin.org 3

This is truly an exciting time for the tion of new vaccines within the Ex- science of vaccine development. In the panded Programme on Immunizations A Letter from coming years, we can anticipate the in- system, and on solving logistical, eco- troduction of a number of new and im- nomic and management obstacles that the President proved vaccines that have the potential hindered the effective delivery of im- It is indeed a pleasure to be joining to further reduce the tragic and unnec- munization and other public health ser- the Albert B. Sabin Vaccine Institute. essary disease and death associated with vices. The Sabin name has had a special sig- vaccine-preventable diseases, and to I look forward to working on the nificance for me since 1964 when my dramatically improve the quality of life other end of the immunization spec- grade school in a small town in South worldwide. trum at the Sabin Institute—advanc- Florida hosted the entire community I come to the Sabin Vaccine Institute ing vaccine development, influencing to receive Dr. Sabin’s oral polio vac- having worked in public health for the vaccine-related policy, and promoting cine. School was closed that day—a past 21 years, 15 of which were in vaccine acceptance. Please join us in day dedicated to disease prevention. Southeast Asia. In Thailand, Indonesia, helping make immunization programs We have now enjoyed 45 years of Vietnam, and other countries through- more effective and widespread. If you protection against polio thanks in out the region, I witnessed firsthand the have any suggestions for how we can large part to Dr. Sabin. The world is challenges of delivering immunization better serve the vaccine community full of opportunity now for all those programs in developing countries. and general public, please do not hesi- who would have suffered the fright- My work involved technology trans- tate to contact me, or anyone on the ening and seemingly random onset fer introduction of new vaccines—ra- staff at the Sabin Institute. of polio. I vividly remember the leg bies, hepatitis B and Haemophilus braces and iron lungs that are forever influenzae B—and vaccine-related tech- associated with polio in my genera- nologies—autodestruct syringes and tion but thankfully are no longer a needles, cold-chain equipment, and vac- Don L. Douglas, President prominent part of our mental land- cine vial monitors. I also worked on Sabin Vaccine Institute scape. regulatory approvals, achieving integra- [email protected]

Don L. Douglas Named President and Chief Executive of the Sabin Vaccine Institute Board Is Confident Douglas Will Keep Institute on Upward Trajectory

Continued from page 1 ogy revolution is rapidly giving us new publishing in Hong Kong and Atlanta, he advisor, based in Jakarta, Indonesia. He tools to prevent disease. We must work shifted into public health in 1979, initially has worked 21 years in public health, with industry, government, academia and promoting health and physical education including 15 years in Southeast Asia other nongovernment organizations to in the U.S. for a Washington, D.C.- (Thailand, Indonesia and Vietnam), arm all nations with these weapons based trade association. He then joined where he managed multifaceted pro- against deadly and debilitating diseases.” the National Council for International grams including trials of hepatitis B and In 2000, the Institute embarked upon Health (now the Global Health Council) Haemophilus influenzae B vaccine, and a substantial program expansion when editing International Health News. In the evaluation, introduction and technol- it launched a program to develop a vac- 1984, he joined PATH, a nonprofit agency ogy transfer of auto-destruct syringes, cine to prevent hookworm infection, that develops and improves access to vaccine vial monitors and other immu- which afflicts more than one of every technologies to improve women’s and nization-related technologies. five people in the world. Its other pro- children’s health, primarily in developing “The Sabin Vaccine Institute has built grams accelerate cancer vaccine re- countries. a track record of accomplishment on sev- search, stimulate new ideas and policy Douglas will work in the Institute’s eral fronts, and I am excited about the proposals to make vaccines more acces- new Washington, D.C. office. The opportunity to increase our impact on sible in developing countries, and in- chairman’s office and administrative staff new vaccine development and increas- form Americans about the importance are in New Canaan, Connecticut. The ing vaccination rates in the U.S. and of immunization. Hookworm Vaccine Initiative is man- throughout the world,” Douglas said. Douglas earned a bachelor’s degree aged from the Institute’s Rockville, “Millions of people lose their lives each at Georgia State University and an MBA Maryland office, with research conducted year to diseases for which vaccines exist from The George Washington Univer- at The George Washington University or are in development. The biotechnol- sity. Following a brief stint in magazine Medical Center and other locations. 4 JUNE 2001 SABIN VACCINE REPORT Vaccine Developer John B. Robbins Receives Albert B. Sabin Gold Medal Developer of Vaccines for Meningitis and Pertussis Recognized John B. Robbins, who played central roles in the development of vaccines to prevent Haemophilus influenzae B (Hib), a leading cause of meningitis, and pertussis (whooping cough), is the ninth recipient of the Albert Sabin Gold Medal. The Albert B. Sabin Vaccine In- stitute awards the medal annually to an exemplary contributor to disease pre- vention. Robbins is chief of the Labora- tory of Developmental and Molecular Immunity at the National Institute of Child Health and Human Development in Bethesda, Maryland.

LEADING LIGHT FOR The Sabin Vaccine Institute awarded John B. Robbins the Albert B. Sabin Gold Medal on April 23, VACCINE RESEARCH 2001. Philip K. Russell applauds as Dr. Robbins is congratulated by Heloisa Sabin. “John and his colleagues have been the meningococcal C conjugate vaccine A MAN ON A MISSION the pointers of the vaccine hunt,” George introduced in the United Kingdom in “John Robbins is an extraordinary phy- R. Siber, MD, chief scientific officer of 1999 and to the pneumococcal conjugate sician, scientist and public servant,” said Wyeth Lederle Vaccines, told several which became available to all U.S. chil- H. R. Shepherd, chairman of the Sabin hundred scientists at the medal presen- dren last year and is now being intro- Vaccine Institute. “His entire career has tation ceremony. “John’s work has led duced in Europe.” been devoted to continuing directly to at least three licensed vac- Siber described the Hib Albert Sabin’s quest to con- cines: the Hib tetanus toxoid conjugate, conjugate vaccine as quer disease with vaccines the Vi-polysaccharide based typhoid vac- John B. Robbins’ “crowning ac- and immunization.” Shepherd cine and the pertussis toxoid vaccine. His complishment. Hib was Robbins— commended Robbins’ “lifelong work also contributed in a major way to the most impor- commitment to disease pre- tant cause of vention. At a time in his life bacterial menin- He is a when most people sit back and gitis with terrible man on a reflect on the past, he is charg- complications of ing ahead to develop several hearing loss, pa- mission and new vaccines. He is a man on ralysis, mental a mission and that mission is retardation and that mission to protect people all over the death. When is to protect world from deadly diseases.” many of us [physicians] be- people all PHYSICIAN, SCIENTIST, gan our training, over the it was one of the EDUCATOR most common world from Before joining the National and serious in- Institutes of Health in 1970, fections for deadly Robbins was assistant profes- which babies diseases. sor of pediatrics and microbi- were hospital- ology at the University of ized. The dis- Florida, and associate profes- ease has now sor of pediatrics at the Albert essentially disappeared in ev- Einstein College of Medicine. Between John B. Robbins with Heloisa Sabin following the Sabin Gold ery country that has introduced those faculty appointments, he did re- Medal presentation ceremony in Arlington, Virginia. the vaccine.” search at the Weizmann Institute for Sci- dedicated to disease prevention www.sabin.org Albert B. Sabin Gold Medal Presentation Former Winners Return to Recognize Latest Recipient, John B. Robbins ence in Rehovot, Israel. opment ever since. Their new Early in his career, Robbins teamed vaccine for typhoid fever re- with Rachel Schneerson in 1968. They cently achieved 92 percent effi- have worked together on vaccine devel- cacy in two-year-old children. Currently, their laboratory is de- veloping vaccines for non-typhoidal Salmonella, Shi- gella, Escheri- chia coli 0157, Clostridium difficile and an- thrax. Based on Two previous recipients of the Albert B. Sabin Gold Medal, the success of Ciro A. de Quadros (2000), of the Pan American Health their Staphylo- Organization, and Myron M. Levine (1988), of the University of Maryland School of Medicine, compare notes on vaccine coccus aureus research and development. Noted vaccinologist Lance Gordon talks with two Sabin Vaccine vaccine in pre- Institute trustees, Almedica International CEO Edward S. Neiss, and venting bacteremia in Lewis A. Miller, CEO of Intermedica, Inc., before the Sabin Gold hemodialysis patients, Medal presentation. Robbins and Schneerson’s re- search team is planning to de- velop a vaccine for opportunistic pathogens. The prestigious prize was presented to Robbins during the 4th Annual Conference on Vaccine Research on April 23 in Arlington, Vir- PREVIOUS RECIPIENTS OF THE ginia. H.R. “Shep” Shepherd with Melinda Moree of the Program for ALBERT SABIN GOLD MEDAL Appropriate Technology in Health and Connie Russell at the Sabin D.A. Henderson Gold Medal reception. Johns Hopkins University Robert M. Chanock National Institutes of Health Joseph L. Melnick Baylor College of Medicine Maurice R. Hilleman Merck & Co., Inc. Myron M. Levine University of Maryland Allen C. Steere Tufts University Philip K. Russell Johns Hopkins University Ciro A. de Quadros From left, Philip K. Russell, Heloisa (Mrs. Albert B.) Sabin, George R. Siber, and John B. Robbins. Pan American Health Organization 6 JUNE 2001 SABIN VACCINE REPORT Institute to Honor Bertrand and Rowe for Humanitarianism and Leadership Awards Dinner in New York City to Benefit Sabin Research and Education Programs The Sabin Vaccine Institute will countries reporting polio cases has Mr. Bertrand committed to add manu- present its two highest non-science dropped from 125 to about 20, mostly facturing capacity for polio vaccine—a awards to Jean-Jacques Bertrand, chair- in Asia and Africa. The disease has been vaccine that the world will stop using in man and chief executive officer of eradicated from the Americas and Eu- a few years, after the global eradication Aventis Pasteur, and John W. Rowe, rope. Still, as long as the disease exists campaign is completed. Shepherd called MD, chairman, president and chief ex- and is transmitted in any country, all Bertrand’s decision “extraordinary” and ecutive officer of Aetna Inc. Bertrand countries must continue to vaccinate worthy of note by world leaders. will receive Sabin’s Humanitarian their entire populations against the eas- Senior officials from several of the Award and Rowe will receive the ily transmissible disease. countries and agencies involved in the Institute’s Lifetime Achievement Aventis Pasteur has donated approxi- polio eradication effort will attend the Award at a May 31 dinner at the Pierre mately 90 million doses of oral polio dinner in Bertrand’s honor. Hotel in New York City. vaccine (OPV) to African countries As president of the Mt. Sinai Hospi- Bertrand will be recognized for his since 1997 to support the global eradi- tal and the Mt. Sinai School of Medi- “career-long leadership to improve hu- cation effort. In October 1999, the vac- cine, Rowe steered the New York City man health,” according to Institute cine research and manufacturing com- institutions through a period of finan- Chairman H. R. Shep- pany committed to donate 50 cial distress for most academic medical herd. This leadership million doses of OPV to five centers brought on by managed care, re- is exemplified by his war-torn countries—Angola, strictions on federal medical care reim- company’s role in the Liberia, Sierra Leone, Somalia bursements and increased costs associ- global polio eradica- and South Sudan. The size of ated with research, teaching and patient tion campaign. “Mr. the donation was designed to care. He established the Mount Sinai Bertrand and Aventis cover those countries’ entire Health System, which grew to be the Pasteur have taken ex- vaccine needs for national im- largest integrated healthcare system in traordinary measures munization days during which the greater New York region. to ensure that the po- every child in a country under Rowe led the successful merger of lio vaccine reaches all Jean-Jacques Bertrand age five is vaccinated. Mount Sinai with NYU Medical Center of the people who The WHO and its global po- in 1998, becoming president and CEO need it, even the least fortunate in the far- lio eradication campaign partners set of the five-hospital organization, which thest corners of the world,” Shepherd said. 2005 as their new goal to rid the has $1.8 billion in Rowe was chosen for successfully world of the paralyzing and some- revenue and 31,000 leading Mt. Sinai NYU Health through times lethal disease. As with employees. He is a major changes in healthcare economics smallpox, which was eradicated distinguished phy- that cast many academic medical cen- in 1979, once polio is wiped out, sician, having ters into dire straits, and for bringing a vaccination is expected to be dis- founded the Divi- commitment to preventive health care continued around the globe. sion on Aging at to the helm of Aetna, which manages “For Jean-Jacques Bertrand, the Harvard Medical health and related benefits for over 19 bottom line is measured not just School and served million Americans. Rowe was president in dollars, francs or euros, but in as chief of Geron- and CEO of Mt. Sinai NYU Health prior terms of impact on humanity,” John W. Rowe tology at Beth Israel to joining Aetna in September 2000. Shepherd said. “Mr. Bertrand’s Hospital in Boston “Jack Rowe is widely regarded as a spe- company has played a vital role in the before going to Mount Sinai. He is a cial leader with a clear vision and the ongoing effort to rid the world of polio, member of the Institute of Medicine. ability to articulate it and get others to as a major producer of the vaccine for When Aetna announced Rowe’s ap- support it,” Shepherd commented. sale throughout the world and as a ma- pointment as CEO, then-chairman Wil- Before the global polio eradication jor donor of the vaccine to economi- liam H. Donaldson called Rowe, “an campaign began in 1988, about 1,000 cally-challenged countries.” But it was outstanding choice to help Aetna accom- children a day were paralyzed from po- not just the donation of tens of millions plish its strategic goal of improving its lio, according to the World Health Or- of doses that impressed the Sabin Insti- financial performance by remaking its ganization. Thanks to immunization, the tute. “At a time of intense pressure from business model to meet consumer de- number today is less than 20. Over the Wall Street for pharmaceutical mands for choice and flexibility, and en same period of time, the number of companies to limit capital outlays, Continued on page 15. dedicated to disease prevention www.sabin.org 7 Conference on Vaccine Research Features Exciting Developments Sabin Vaccine Institute, NIAID, CDC, FDA, ISV, USDA, WHO Collaborate on NFID-Sponsored Vaccine Conference Nearly 500 scientists who participated now exist. Albert Sabin understood well • Combination vaccines for infants which are in the Fourth Annual Conference on the problems with developing an effec- widely used outside of the U.S. and may be li- Vaccine Research on April 23 to 25 in tive HIV vaccine and was skeptical censed here. Arlington, Virginia heard both expected about the possibilities of developing • Protein conjugation of bacterial polysaccha- and unexpected reports. They expected one. In this regard, Gary J. Nabel, di- rides which was earlier shown to be advanta- epidemiological and clinical confirma- rector of the NIH Vaccine Research geous with the Haemophilus influenzae B tion of the lifesaving effects of both fa- Center said that Sabin “was right on.” (Hib) vaccine and is the approach used in the miliar and new vaccines and they were “He knew that the genetic variabil- effective pneumococcal and meningococcal not disappointed. They may not have ity of HIV was a huge problem and conjugated vaccines. expected the important advances re- Dr. Sabin’s words are still • Attenuated vectors which are based on the in- ported in the broad true,” Nabel said. “Fortu- sertion of genes into attenuated viruses (e.g., application of nately we now have tech- canary pox) or bacteria (e.g., attenuated sal- vaccines to di- nologies that were totally monella or shigella) results in a high stimula- verse noninfec- unavailable at his [Sabin’s] tion of B-cell response in addition to the T-cell tious diseases time and these new tools responses. such as cancer, permit us to do things in • Naked DNA has been used extensively to iden- atherosclerotic crafting novel vaccines tify protective antigens in research on new vac- cardiovascular that were only dreamed of cines. disease, inflam- at an earlier time.” • Transgenic plants which produce vaccine anti- matory autoim- In many ways the con- gens and are orally administered via a food such mune diseases such ference was summa- as banana or potato. as multiple sclerosis rized by Stanley A. and even gastric ul- Plotkin when he dis- The three-day meeting covered all of cers. They were in- cussed the 10 most im- the above developments as well as ad- formed of news as portant discoveries in vances in vaccines against malignancies different as the activa- vaccinology of the and chronic diseases (therapeutic vac- tion of dendritic cells past decade. He could have cines), vaccines for bioterrorism candi- in an anti-tumor vac- extended the list to 15 or 20 seminal date agents and other dangerous exotic cine by a glycolipid extracted from sea events and the meeting transactions re- disease and selected issues in vaccine sponges off the coast of Japan, oral vac- lated to his ten and more. Among these safety. cines from a transgenic line of potatoes, are: The Albert B. Sabin Vaccine Institute to the very successful development of a • The development of the acellular pertussis vaccine was a collaborator in presenting the con- new conjugate Meningococcus Group C which was shown to be equivalently effective to the ference, together with the Centers for vaccine by a public-private sector con- British whole cell vaccine and sparing of morbidity. Disease Control and Prevention, Na- sortium that has immunized the 15 mil- • The creation of sufficient community (herd) tional Institute of Allergy and Infectious lion target youthful candidates in the immunity in developed countries to permit tran- Diseases, International Society for Vac- United Kingdom with a dramatic impact sition from the oral polio vaccine (OPV) to in- cines, U.S. Department of Agriculture, on reduction of Group C meningococ- activated polio vaccine thereby avoiding the rare FDA Center for Biologics Evaluation cal disease and mortality. OPV-associated neuropathy. and Research and the World Health Or- Nonetheless, it was recognized again • Varicella-zoster (chicken pox) vaccine—the ganization. The National Foundation for that despite steady progress in the sci- first vaccine for the herpes group virus. Infectious Diseases was the Conference sponsor. ences upon which vaccinology is based, • Live influenza vaccine which uses old attenu- an effective vaccine for HIV remains un- ated strains and is 92% effective against influ- The Fifth Annual Conference on Vac- available. Progress in molecular biology enza A strains in pediatric age infections. cine Research will be held in Baltimore has been prodigious and these advances • Rotavirus which, despite the recall associated on May 6-8, 2002. have permitted new understanding with gastrointestinal intussusceptions, has which has translated into HIV vaccine —by Edward S. Neiss, MD, PhD clearly demonstrated that this major cause of clinical trials: 70 Phase I clinical stud- high global mortality can be controlled by vac- ies are now in process, five Phase II Edward S. Neiss, MD, PhD is vice chairman and CEO cination; safer rotavirus vaccines are currently clinical evaluations and two Phase III of Almedica International, Inc. He is a member of in development clinical trials with novel HIV vaccines the Sabin Vaccine Institute Board of Trustees. 8 JUNE 2001 SABIN VACCINE REPORT Anatoli Alexandrovich Smorodintsev and Albert B. Sabin —Partners in Vaccinology and Vaccine Diplomacy Smorodintsev was born in opment and its activities. For two months, “Vaccine diplomacy” is beginning to gain Birsk in the Bashkirian Repub- Smorodintsev met and exchanged infor- attention from vaccine scientists, healthcare agen- lic on April 19, 1901. The son mation with more than twenty virologists cies, academicians and diplomats. An essay on the of a physician, he earned his in the U.S. and Canada. Visiting medical degree at the Univer- Harvard, Yale, Johns Hopkins, the topic by Sabin Vaccine Institute senior fellow Peter sity of Tomsk in 1923. He Rockefeller Institute and the National J. Hotez, MD, PhD, appears in the May/June issue of served as a medical doctor in Institutes of Health, Smorodintsev cre- Foreign Policy magazine. But half a century be- the Red Army in Central Asia, ated the first bridge for future Soviet- fore the term began to gain currency, vaccine di- moved to Leningrad in 1925, American scientific exchanges in the and joined the Institute of Ob- field of virology and for the future alli- plomacy was being practiced by two giants in the stetrics where he became a di- ance in fighting against poliomyelitis in field of vaccinology: Albert B. Sabin, MD, of the rector of the Bacteriological the 1950s. United States and Anatoli Alexandrovich Department. In the early 1930s Smorodintsev organized the Ivanovski Smorodintsev, MD, PhD, of the Soviet Union. These he began to work in Institute of Virology in Moscow in 1948, Leningrad’s Pasteur Institute but soon moved to Leningrad to study physician-scientists joined forces to combat several and in the Institute of Experi- the “double-waves” of meningo-en- deadly diseases. Their efforts transcended the deep mental Medicine. He proved in cephalitis. In 1950 he isolated the virus, philosophical, political and military divides between 1933 that the influenza agent and proved that it was the cause of the the two nuclear superpowers. Most Sabin Vaccine was a virus, not bacteria. The deadly illness in Northwestern Russia. publication appeared in the Lan- He organized a laboratory at the Pas- Report readers are familiar with Sabin’s role in de- cet simultaneously veloping vaccines against polio, Japanese encepha- with the paper of litis and other diseases. But Smorodintsev’s work Smith and Laidlow and contributions to humankind may be less well from England. His early work in tick- known. Following is an account of the Russian’s borne encephalitis achievements written by his son, Alexander A. in the Far East in Smorodintsev, MD, PhD. 1937-1940 gained him a national repu- HERO OF MEDICAL SCIENCE tation in the Soviet Union. Anatoli Alexandrovich Smorodintsev He was honored with was a giant of virology, founder of “Stalin’s Prize” in 1941 and Among a group of colleagues are Anatoli Smorodintsev, standing at vaccinology in Russia, a member of the was decorated with the Gold left, and Albert B. Sabin, sitting at right in foreground (circa 1956). Russian Academy of Medical Sciences. Medal of First Degree for He was also an honorary member of the the discovery of viral agents which pro- teur Institute in Leningrad, where he American Society for Microbiology voked spring-summer tick-borne and au- began studying the isolation and attenu- (1947), honorary life member of the tumn (Japanese) encephalitis in the So- ation of measles and mumps viruses for New York Academy of Sciences (1956) viet Union. future vaccine production. and honorary member of the Royal So- Smorodintsev visited the United ciety of Medicine in Great Britain. For States more than 20 times during his life. SOVIET-AMERICAN COLLABORA- many years, Smorodintsev was a per- His first scientific visit took place in manent member of the Committee of Vi- 1944 during World War II when he was TION KEY TO CONQUERING POLIO rology in the World Health Organiza- invited as a special guest of the U.S. Ty- As a member of the Soviet Poliomy- tion in Geneva, Switzerland. His friend- phus Commission and the Rockefeller elitis Team A, Smorodintsev visited the ship with many American scientists in Foundation. It was during this period United States in January and February the field of virology helped to build a that he met Albert B. Sabin who was of 1956. Both the United States and the solid bridge between our countries dur- working on vaccines against dengue fe- Soviet Union had very large polio epi- ing World War II, and opened a hole in ver and Japanese B encephalitis at the demics in the 1950s. The mission had the Iron Curtain during the Cold War in Rockefeller Foundation Laboratories in many contacts with Jonas Salk, and for the 1950s which lasted to the end of his Princeton, New Jersey. They shared three days they visited Albert Sabin in life. many mutual interests in vaccine devel- his laboratories in Cincinnati, Ohio. dedicated to disease prevention www.sabin.org 9 Soviet-American Collaboration Was Key to Conquering Polio Effective Vaccine Effort Achieved After Visits and Exchanges on the Common Research Front Smorodintsev decided to organize the sult, by the end of the 1960s, research work with Sabin’s live polio the Sabin vaccine had be- strains, and asked Sabin for some of his come the primary medical in- newly attenuated strains of poliovirus tervention for the prevention for testing on children living in orphan- of polio in the United States, ages in Leningrad. and polio became virtually During Sabin’s visit to the Soviet non-existent in the United Union in the summer of 1956, States by 1970. The live, i.e., Smorodintsev presented him with at- oral, polio vaccine began to tenuated strains for live virus vaccines be widely used by the World against mumps and measles. Health Organization for Sabin sent all three types of attenu- complete eradication of the ated polio strains to Smorodintsev in disease from our planet. Anatoli Smorodintsev among village children in rural India. Leningrad for further human tests in November 1956. AFTER POLIO: States. The Soviet-American committee Smorodintsev then organized experi- COMBATING OTHER DISEASES of advisors gathered annually and many ments with Sabin’s strains on adult vol- researchers from around the world in- Like Sabin, Smorodintsev was not unteers, proved the stability of attenu- volved in the study of this widespread content to rest on his laurels. Fresh from ated strains and demonstrated that all infection and other respiratory viruses his success against polio, Smorodintsev three types of live vaccine were safe for visited the Institute and worked there. pressed forward to prevent other deadly the children. His granddaughter, Helena, This Institute became the initiating fa- diseases. He developed and introduced was one of the first children to be im- cility for many strains for live influenza in Russia the live vaccine against munized against polio in the Soviet vaccine production. measles by 1967. It was produced from Union by Sabin’s live vaccine. The Russian virologist published the strain “Leningrad-16.” This vaccine In 1957-1959, Smorodintsev orga- more then 700 scientific papers in vari- was safely used in Russia for 34 years nized the mass production of live polio ous journals around the world. Many of and today measles is virtually elimi- vaccine in Leningrad, and immunized his books were published in the field of nated. In 1975 he developed and intro- three million children in various regions virology and antiviral immunity. He was duced the live vaccine against mumps of the Soviet Union. As a result, polio- the director of the Leningrad Scientific from the strain “Leningrad-3.” This vac- myelitis disappeared from these huge School of Virology in Russia. More than cine is also successfully used in Russia. territories. From January 1959, the pro- half of the vaccines widely used in Rus- In 1967, Smorodintsev established the duction of live polio vaccine started in sia and in the countries of the former Research Institute of Influenza in Mikhail Chumakov’s Institute of Polio- Soviet Union were developed and intro- Leningrad and was its director until myelitis in Moscow and during that duced by Smorodintsev and his schol- 1983. During this period, the Institute year, Smorodintsev and Chumakov im- ars. Under his scientific supervision became a world center for many foreign munized nearly 10 million children by more then 120 researchers received their researchers, especially from the United live oral polio vaccine prepared from MD and PhD degrees. Sabin’s strains. —by Alexander A. Smorodintsev, MD, PhD Chumakov and Smorodintsev Alexander A. Smorodintsev, MD, PhD, is director were awarded the “Lenin Prize” general and CEO of Antivirus Smorodintsev, a joint- and a Gold Medal in 1963 (the venture company in St. Petersburg, Russia. As labo- highest awards in the USSR) for ratory chief at the Soviet State Influenza Research the organization of mass pro- Institute from 1967-76, he was Russia’s official co- duction of polio vaccine and ordinator of Soviet-American collaborative research eradication of child paralysis on influenza, concerned with interferon develop- from the Soviet Union. Their ment and application of interferon-inducers during victory was also a victory for influenza epidemics. From 1976-85, he coordinated Sabin who in 1962 received a Russian-Finnish collaborative studies on human license for industrial production interferon. He earned his MD from the Medical Uni- and sale of the live oral polio H.R. Shepherd and Alexander A. Smorodintsev at the Sabin versity of Leningrad, 1954, and his PhD in virology, Gold Medal Reception in April 2001. vaccine he developed. As a re- immunology and vaccinology in 1970. 10 JUNE 2001 SABIN VACCINE REPORT BOOK that evolution and then us- ing that knowledge in prac- REVIEW tical situations that our most effective defense against Evolution of Infectious Disease emerging diseases lies. —by Paul Ewald What are some of those evolutionary rules that Paul Ewald’s book Evolution of In- lately been alerted to the dan- Ewald sees as vital to under- fectious Disease is a seminal work that ger of “emerging diseases.” stand? A key one is that convincingly makes the case for the ur- Stephen Morse, one of the pathogens carried directly gent need to integrate a modern under- most effective people in rais- from one person to another standing of evolutionary processes into ing public awareness of the tend to be less lethal than both medical education and patient care. problem, has closely linked new dis- those transmitted by non-human carri- He maintains that despite superficial ap- eases to what he calls “viral traffic.” This ers. The logic of the situation is quite pearances this has not been adequately idea attributes the appearance of new simple: if the microbe is spread by a done, and as a result our society acts in diseases primarily to trade, exploration, mobile person, then incapacitating that ways that undermines rather than pro- new settlements and civil disturbances, host will lower the likelihood that its off- motes long-term health prospects of our where the movement of people, goods spring will be successfully passed on to population. Ewald also contends that to or animals create physical contact be- a new host. For example, if a cold virus the limited extent that evolutionary ideas tween groups that had previously been is to be effectively spread, it is best that have influenced medical thinking, they geographical isolated. Morse indicts a it not force the victim prematurely into have involved outmoded concepts large variety of social activities as the bed. Virulent cold viruses that tended which have fostered an unjustified con- chief causes of increased human vulner- to immobilize people would face selec- fidence in our future prospects. ability, especially those that result in tive pressure that favored less virulent For example, Ewald dismisses as a ecological disruption. As a result, Morse strains which allow people to carry on dangerous myth the widespread belief argues that “the essential first line of their daily lives. that there is a natural tendency for mi- defense” against such threats is the cre- On the other hand, if a mobile human crobes over time to adapt to humans by ation of a series of early warning sur- is not necessary (for example in a vec- becoming less virulent. He says that less veillance systems, many of them aimed tor-borne disease such as yellow fever), pathogenic microbes will replace more at distant and exotic places, where viral then the virus can be considerably more pathogenic ones, only if conditions traffic (i.e., exposure to novel viruses) virulent without paying any cost in its make it more likely that their offspring might originate through ecologically ability to successfully pass on its genes. (and thus their genes) successfully in- unsound human activities. Morse further It is not only insect-carried diseases fect new hosts. If conditions make it maintains that the emergence of new that are more likely to be deadly. Water more likely that increasing virulence diseases from human activity has one often acts as a vector for disease trans- will produce that favorable result, then significant positive aspect because it mission. Cholera incapacitates its host evolutionary processes will select for makes counter measures possible; if new but because of the infected bodily dis- such an outcome. In other words, patho- diseases resulted simply from random charges that the disease induces, even gens can become more as well as less genetic mutation of microbes, then there the immobilized individual can contami- dangerous over time depending on the would be little humans could do to pro- nate the ground water and through it environment that they experience. tect themselves except sit and wait for spread the bacteria to new victims. Thus, According to Ewald, human beings misfortune. the host can quickly die with little or no often create conditions through their On the other hand, Ewald contends impediment to the pathogen passing its cultural, economic, and medical activi- that emphasizing evolutionary processes virulent genes on. ties that favor the evolution of more rather than “viral traffic” is a far more In the same way, other forms of wa- rather than less dangerous microbes. He productive way of looking at the prob- ter-borne dysentery have evolved to- believes that only the use of modern lem. For him, the key to understanding ward more virulent forms because there evolutionary concepts can reverse this the emergence of virulent pathogens is is little or no price to be paid if it immo- destructive tendency. If evolutionary not the existence of mutations per se, bilizes or kills its host. Ewald says that ideas are not used, or if they are only but rather the forces that select which the existence of vectors encourages the given lip service while alternative, and mutations are successfully passed on, selection of strains that reproduce faster inferior theoretical perspectives are em- and which are not. According to Ewald, over those that reproduce slower — and phasized, the results could be dire. the range of human activities that unin- those strains tend to be more virulent Ewald believes that just such a dan- tentionally affect microbial evolution is and destructive. gerous misconception of where the dan- far wider than simple disruption of the Ewald also points out that society by ger to humanity lies has recently oc- natural environment, and it is in speci- its practices can artificially create a “cul curred. The scientific community has fying the basic principles that govern Continued on page 14. dedicated to disease prevention www.sabin.org 11 Walker’s Cay Colloquium Puts Spotlight on Cancer Vaccines and Immunotherapies Ideas and Data So New They Have Not Yet Been Published

Continued from page 1 believed that creating a venue where the could supplement or even replace con- make prepared presentations, one after an- world’s leading cancer vaccine scientists ventional cancer treatments such as che- other, with little time for serious discussion. could candidly exchange their latest motherapy, radiation, and surgery. The “The format resulted in all attendees ideas and data could speed scientific vaccines have the potential to attack tu- presenting their latest data, and some of progress in this field. In 1999 the Sabin mors themselves, without the collateral it was absolutely striking,” according to Vaccine Institute held its first Walker’s damage to other cells and parts of the Philip O. Livingston of Memorial Sloan Cay Colloquium on Cancer Vaccines body caused by the conventional treat- Kettering Cancer Center in New York. and Immunotherapy. According to the ments. He described revelations of cellular re- scientists, Shepherd and Abplanalp’s “It was particularly helpful for can- sponses to particular cancer vaccines hunch was correct. cer researchers such as myself who are with high correlations in experimental W. Martin Kast, director of the Can- beginning to translate their laboratory treatments of humans as “revolution- cer Immunology Program at Loyola findings into clinical trials to be able to ary.” According to Livingston, this University Chicago’s Cardinal Bernadin get input from investigators who have should result in rapid progress in the de- Cancer Center, found “the challenging already done this,” said Yvonne Pater- velopment of more effective cancer discussions and information flow far ex- son, professor of microbiology at the vaccines. It will immediately change the ceed that of any normal scientific meet- University of Pennsylvania School of focus of immunogenicity monitoring ing.” Medicine in Philadelphia. “I always among the colloquium attendees and, “The size of the meeting and the venue come away from this meeting with new very quickly, the biomedical research were very conducive to excellent dis- ideas for my own research,” she added. field. cussions, both inside and outside the conference room, and to cross-fertiliza- CATALYST FOR COLLABORATION A NEW CHAPTER IN THE tion between disciplines in the field,” Another colloquium goal is to encour- WAR ON CANCER said Jay A. Berzofsky, chief of the Mo- age development of new collaborations lecular Immunogenetics and Vac- The colloquium was conceived by between researchers at multiple institu- cine Research Section at the National Sabin Vaccine Institute chairman H. R. tions. Cancer Institute. “This kind of inter- “Shep” Shepherd and his friend, Robert Jeffrey B. Ulmer, senior director of change and cross-fertilization has been H. Abplanalp, CEO of Precision Valve Vaccine Research at Chiron Corporation seen historically over and over again to Corporation. Abplanalp in Emeryville, California, said that at be critical for many ma- owns Walker’s Cay, a last year’s colloquium, he “set up sev- jor advances in science.” small island in the north- eral collaborations to test our gene de- Colloquium Attendees Esteban Celis of the ern Bahamas that his livery technologies in cancer models. Jay A. Berzofsky, Claudine Mayo Clinic in Roches- close friend, former This year’s meeting allowed me to build Bruck, Esteban Celis, Richard ter, Minnesota, put it suc- President Richard Nixon, on those collaborations and several oth- B. Ciccarelli, Edgar G. cinctly: “This setting fa- visited frequently to re- ers are being contemplated.” Engleman, Olivera J. Finn, Eli cilitated strong scientific lax and contemplate ma- Reisfeld reported, “I started two sci- Gilboa, Allan L. Goldstein, interactions between jor issues. It was during entific collaborations at the meeting and Lance K. Gordon, John groups which are certain a stay at Walker’s Cay I am certain that I was not the only one Gutheil, Jane C.I. Hirsh, W. to translate into cancer that Nixon decided to de- to do this.” Kast said he “will literally em- Martin Kast, Larry W. Kwak, therapy breakthroughs.” bark on three research collaborations that clare “war on cancer,” Philip O. Livingston, Albert F. and make the search for otherwise would not have been possible.” LoBuglio, Grant D. MacLean, ACCELERATING Albert LoBuglio, director of the Com- a cure a national priority. Lewis A. Miller, Malcolm S. Nixon increased funding PROGRESS FROM prehensive Cancer Center at the Univer- Mitchell, Dennis Panicali, for basic research at the sity of Alabama at Bingham, summed Yvonne Paterson, Ralph A. BENCH TO BEDSIDE National Institutes of up a sentiment expressed by most of the Reisfeld, Philip K. Russell, The colloquium mis- Health that paved the colloquium participants. “I had heard Jeffrey Schlom, Steve sion is to speed up the way for today’s experi- very good things about it and the meet- Schoenberger, Allessandro conversion of scientific ments with vaccines to ing surpassed my expectations.” Sette, Walter J. Storkus, knowledge into therapies shrink and even prevent —by John M. Clymer James Tartaglia, and Jeffrey B. that are available to treat cancerous tumors. Ulmer patients. A new class of John M. Clymer is the Sabin Institute’s Vice Presi- Shepherd and Abplanalp therapeutic vaccines dent of External Affairs ([email protected]). 12 JUNE 2001 SABIN VACCINE REPORT Realizing the Dream: Closing In on the Conquest of Polio A Hard-fought Battle Against the Disease That Crippled Millions over the Course of 3,000 Years Polio. Ask an older American about it and they will guess it began in the first part of the 1900s: a fair assumption since it had hardly ever been documented. By the second decade of the 20th century it gained a national reputation, because future president Franklin Delano Roosevelt had it. As the century turned 40 and 50, there was nowhere left to run from it and few people’s lives would re- main untouched in some way. Those growing up in the last few decades of the second millennium knew little about it and probably never even saw it first- hand. But ask medical and social histo- rians about it and they will point to an- cient Egyptian stone engravings and ref- erence 16th century paintings by artist Pieter Brueghel. They will explain, in- World Health Organization map depicts the recent progress in the conquest of polio terestingly enough, im- proved hygiene and sani- ets of contagion. The dream foothold. Most important is the tation throughout the of a polio-free world is being fact that polio is preventable, years only encouraged it brought to fruition. Now is the but there is no cure. by eliminating the crucial time before that dream —by Veronica Korn chance for children to is fully realized and it necessi- Veronica Korn is a research associate acquire immunity. And tates extra vigilance and com- at the Sabin Vaccine Institute they will also tell you, mitment. Because of its high rate ([email protected]). with guarded excite- of infection and conta- ment, its days—polio’s gion, any amount of re- days—are numbered. maining poliovirus is It has been exactly 40 still a threat and could years since the Sabin potentially regain a oral polio vaccine (OPV) was licensed in the United States and many other coun- Images that reflect the human tries. In other words, since the Sabin impact of poliomyelitis. vaccine became available in 1961 and an intravenous vaccine was licensed be- fore that, polio has been preventable for more than 40 years! It is hard to believe then, in some respects, that it has taken that long for poliomyelitis, the disease that has crippled millions for at least 3,000 years, to be on the verge of global eradi- cation. Part of the reason is that although incidences of polio have been declining since 1988 (see map), as the disease it- self dwindles so does the momentum on the part of governments and ordinary citi- zens to combat the remaining pock Photos courtesy of Roosevelt Warm Springs Institute for Rehabilitation. dedicated to disease prevention www.sabin.org 135

In Memoriam—Three Research Champions in the Conquest of Polio Joseph L. Melnick, PhD, DSc (1914-2001) the first woman professor at Yale, but in 1969 also became the first woman 1966 Sabin Gold Medal Awardee there to receive an endowed chair which was named after her mentor and On January 7, 2001, the modern virology world lost one if its principal renowned polio expert, Dr. John R. Paul. founders, Dr. Joseph L. Melnick, who died in Houston, Texas at age 86. In Among Horstmann’s many contributions in the fields of epidemiology and 1996, Dr. Melnick was awarded the Albert B. Sabin Gold Medal for his many infectious diseases, her major scientific achievement in polio was one which contributions to the study of polio and vaccines to prevent the disease that upset scientific dogma in the middle part of the last century. She disproved the affected as many as 57,000 people a year in the 1950s in the United States widely held belief that the poliovirus grew only in nerve cells by showing that alone. For more than 30 years, he served on the World in fact the virus reached the brain by way of the blood. Scientists of the time Health Organization Expert Panel on Virus Diseases and thought that because their efforts to isolate the virus from the blood of para- was active in WHO programs concerned with poliomyeli- lyzed patients failed, the virus directly attacked the nervous system. Horstmann’s tis. team rationalized this failure when they detected polio in the blood of infected Dr. Melnick was founding chairman of the Department apes—before paralysis occurred. The team found that by the time the apes of Virology and Epidemiology at the Baylor College of were paralyzed, antibodies had already eliminated the poliovirus from the Medicine from 1968 until 1991, when he was named dean blood. What was at first viewed as a scientific upset, later became to be viewed emeritus. During this time, he was also Dean of Graduate as somewhat of a relief that indeed poliomyelitis acted like other infectious Joseph L. Melnick Sciences. He wrote the virology section of a standard text- diseases. book on microbiology, now updated and in its 22nd edi- These findings and contributions led to the licensing of the Sabin oral tion, and was chief editor of three scientific textbooks. He polio vaccine (OPV). While the OPV was being tested on millions in the former was formerly the chief biologist at the Division of Biological Standards at the Soviet Union, other countries, including the United States, were not wholly National Institutes of Health. convinced of it effectiveness. Horstmann was asked by the World Health Or- Dr. Melnick proved himself to be an international leader in identification ganization to study polio incidences in vaccinated areas; concluding that the and control of virus diseases, especially polio. His work on the poliomyeli- Sabin vaccine was safe. It was subsequently licensed in the United States. tis virus included his demonstration that the poliovirus usually invades the Other honors during her career include election to the National Academy intestines of the host rather than the long-held belief that it invaded the host of Sciences. In the mid-1990s, when she was in her eighties, Horstmann was through the central nervous system. In 1960, Dr. Melnick demonstrated a member of the International Commission of the Certification of Poliomyeli- that the Sabin oral polio vaccine (OPV) produced less damage to the tis Eradication. nervous system than the competing intravenous vaccine. In addition, he headed the team that developed thermostabilized live vaccines. By adding Charles Mérieux (1907-2001) magnesium chloride to vaccines, such as the Sabin OPV, the need for deep- Jacques-François Martin Remembers a Mentor Committed to the freeze storage facilities was eliminated which enabled the immunization of Health of the Poor millions of people worldwide. This had, and continues to have, an Charles Mérieux, vaccinologist, born January 9, 1907, died January 19, invaluable and far-reaching effect on those living in the least developed 2001. Strongly influenced by Louis Pasteur’s approach (his father had been countries. assistant to Emile Roux and to Pasteur), Charles Upon Dr. Melnick’s death, Sabin Vaccine Institute Chairman, H.R. Mérieux gave his whole life to preventive medicine: it Shepherd said, “Joseph Melnick was an extraordinary scientist, mentor was he, together with Jonas Salk, who coined the term and colleague who will never be forgotten.” “vaccinology.” Charles Mérieux, who liked to say that there is no Dorothy Horstmann, MD (1911-2001) boundary between the two branches of medicine, in- Made Significant Contributions to the Sabin Oral Polio Vaccine dustrialized modern virology in veterinary medicine. The death of Dorothy Horstmann, MD came only four days after the death By culturing cells in-vitro, he enabled the large-scale of her colleague and collaborator, Joseph L. Melnick, PhD, DSc. They worked production of a vaccine for foot-and-mouth disease. together at Yale University, co-authoring scholarly papers and conducting He then applied this approach to the development of Charles Mérieux research during the polio epidemics in New Haven, Connecticut throughout human vaccines against polio and measles. the 1940s and 50s. In the 1970s he developed the first vaccine against meningococcal menin- Horstmann was an epide- gitis, which found an unexpected application in Brazil when the entire popu- miologist, virologist, and lation was immunized in 1975. That campaign was a precursor to the Na- at mid-career became a tional Immunization Days which were introduced, again by Brazil, for polio, pediatrician. During a po- paving the way for eradication of the disease. lio outbreak in 1943 in His family life was not unmarked by hardship, but he never failed to dem- New Haven, she joined the onstrate the strength that sprang from hope. Resolutely turned towards the Yale Poliomyelitis Study future, he taught us to believe in the impossible because in his case, the Unit and decided at that impossible was no match for his determination. time to devote much of (First published in the March 2001 Immunization Focus: the her research to infectious newsletter of GAVI: Global Alliance for Vaccines and Immunization.) diseases. She was not only Dorothy Horstmann and Albert B. Sabin. 14 JUNE 2001 SABIN VACCINE REPORT BOOK ventions to put pressure on microbes to evolve in ways that are better for us, or REVIEW we can ignore such principles and inad- vertently help select for more virulent Evolution of Infectious Disease and deadly pathogens. In the case of an- tibiotic resistance, our Continued from page 10 The countries that first health practices have been tural vector.” A striking example of this experienced this phe- disastrous working against is found in hospitals where doctors and nomenon tended to be our long-term interest and nurses ignore good hygiene practices the ones that had made threatening to return us to and carry pathogens between immobi- improvements in their the pre-antibiotic age. lized patients. In this situation the patho- drinking water. Most While Ewald argues the gen is free to evolve into more lethal observers have not importance of using evolu- forms since its ability to spread is not been able to adequately tionary theory, it is never- dependent on leaving its victims mobile. explain this replace- theless full of provocative ment situation. How- The implications of this situation are The author, Paul Ewald. practical interventions that rather striking because it casts light on ever, if one looks at the may make healthcare better. why hospital-acquired infections tend to question of changing cholera strains For example, one of the more important be more lethal than community-acquired from an evolutionary perspective, one ideas in the book is that the symptoms a ones. Ewald hypothesizes that the grow- can understand both why the El Tor type pathogen produces in the body may ei- ing problem of deadly infections in hos- made little progress in replacing the ther be a “defense” by the host or a “ma- pitals may have less to do with the fact classical strain in the 50 years before nipulation” by the microbe. In the case that patients are very sick and have weak 1960, and then almost completely sub- of diarrhea, the symptom is often the immune systems than that healthcare stituted for it within a single decade. The way that the body tries to rid itself of a workers can and do spread pathogens classical strain of cholera bacteria pos- pathogen. Other times, the diarrhea is a between bedridden hosts. Thus, accord- sesses a toxin-producing gene that way for the pathogen to contaminate the ing to Ewald, tighter enforcement of hy- makes it a more efficient pathogen than environment and be successfully spread gienic standards should work as an “evo- the El Tor strain which lacks it, in places to other victims. It is important for us to lutionary” pressure to lower the viru- where contaminated water is abundant. recognize this distinction. lence of hospital-acquired infections. If But where water supplies become If the symptom is a defense of the health professionals don’t carry mi- cleaner, the El Tor strain, which can be body, then we do not want to take medi- crobes between non-mobile patients passed directly from person to person cine that will prematurely stop the diar- then the more lethal ones will die out, without using water as a vector, has a rhea; to do so may be dangerous or even and those that require direct contact be- selective advantage over its more lethal lethal because it keeps the pathogen in- tween ambulatory patients will be fa- competitor. side the intestines. On the other hand, if vored. Ewald argues that a similar situation the diarrhea is a “manipulation” by the In the same way, according to Ewald, potentially exists in the case of malaria, pathogen, it may be necessary to counter if water acts as a vector to increase mi- and it should be exploited. The fact that the symptom to protect other people. crobial virulence, cleaning up the water the disease is carried by mosquitoes The same situation holds in the case supply and protecting it against contami- means that different strains of it can of “fever” — sometimes it is a defense nation should put evolutionary pressure evolve into more virulent forms despite by the body and sometimes it is a ma- on microbes to be less lethal. Many immobilizing its victims. Thus, cultural nipulation by the pathogen that allows people believe that cleaner water totally patterns which expose bedridden people it to thrive better. According to Ewald, eliminates pathogens, but actually it acts to mosquitoes help spread the most viru- knowing the difference between a de- as a selective agent in producing more lent forms of the disease. This implies, fense and a manipulation will aid in the benign strains of existing microbes. This however, that a health intervention that treatment of illnesses that are now fre- has been the case in the United States makes it impossible for mosquitoes to quently mishandled. where deadly forms of dysentery have bite severely ill people ( e.g., screens on Ewald’s use of evolutionary theory been replaced by more benign strains as houses, or bednets) would favor the also has a major application in the area the water system has been upgraded over spread of less severe strains that leave of emerging diseases. One of the key the years. infected people healthy enough to move questions that he asks is how can we Ewald says that it is not only dysen- around. In this case both screens and bed know which types of new diseases are tery that has been positively affected by nets would function as an “evolution- most dangerous to us? He believes that changes in water quality. The same thing ary device” not just as direct protection illnesses like Ebola, Marburg, and Lassa has happened in the case of Vibrio for uninfected individuals as most pub- Fever which cause the most public and Cholerae. The milder “El Tor” strain re- lic health workers assume. governmental anxiety because of their placed the more virulent classical form The theme of the book is that we can Continued on page 16. throughout the world during the 1960s. use evolutionary principles and inter- dedicated to disease prevention www.sabin.org 15 INSTITUTE NEWS New Staff Member Has Personal Link to Sabin Institute Honors Sabin Vaccine Institute Mission The new executive assistant to the the full strength of an average adult, Continued from page 6 chairman, David Bedell, has a close certain specific actions were difficult family connection to the Sabin for him, and I always knew I could hancing relationships with doctors and Vaccine Institute’s mission. His outrun him. He enjoyed hiking and hospitals.” father, George Bedell, contracted biking, but only in his dreams could Shepherd praised Rowe as “a leader polio in 1954, before the Salk and he run or jump hurdles as he had on with the experience, skill, vision and Sabin vaccines became available. his high school track team. For him, passion to lead his company through a During the polio epidemics that the lasting effects of polio were only major set of challenges. He is the right struck North American cities in the minor inconveniences, not really person at the right time for Aetna. And 1940s and early 50s, George Bedell disabilities. He was far luckier than he is helping Aetna share his commit- was in Mexico and Korea, somewhat some of his contemporaries who ment to preventive healthcare, includ- removed from the industrialized ended up in iron lungs or bed-ridden ing disease prevention.” Shepherd epicenters and the media scares for life.” noted, “The Sabin Vaccine Institute had surrounding the “summer plague.” In recent years, George Bedell has important affiliations and dealings with However, he came down with polio felt the effects of post-polio syn- various academic medical centers dur- at the age of 27 while traveling in drome, where his muscles, especially ing all of the upheaval in the ‘90s. We rural Mexico. He was diagnosed and for walking or climbing stairs, tire saw research scaled back and hospitals admitted to the polio ward at the easily. David Bedell, like others of sold from positions of weakness, so I American British Cowdray Hospital his generation, was given the Sabin know that Jack did an extraordinary job in Mexico City, where he received oral vaccine as a child, and he took a to forge a combination of strength and therapy that led to a full recovery, booster dose before a trip to China in excellence with Mount Sinai and NYU.” but only after three months confined 1992. He knows that polio still The awards dinner is a benefit for the to bed and wheelchair. His recovery exists “only a plane ride away,” and Sabin Vaccine Institute. Co-chairs of the coincided with his wedding to he looks forward to the final eradica- event are E. John Rosenwald, vice chair- David’s mother—he depended on his tion of the disease. man of Bear Stearns, and David Low, best man to support him as he walked David Bedell comes to the Institute managing director of JPMorgan Chase. to the altar of the hospital chapel. after many years of teaching English, The 2000 event raised nearly $600,000 David Bedell recalls: “As a child, first in China and then with interna- to support the Institute’s research and I remember my father showing me tional students in the United States. education programs, and this year’s din- the wasted flesh between his left He has also worked with various ner already has surpassed that bench- thumb and forefinger and letting me nonprofit organizations on issues mark. Tickets are available by contact- compare the unequal grip of his two related to the environment, public ing the Sabin Vaccine Institute at (914) hands. Although he had, in general, health, and social justice. 244-0910.

In February, the In- Eugene Andrews Grinstead, III he served in various stitute lost our valued operational and ex- colleague, E. Andrews August 10, 1945-February 28, 2001 ecutive positions at Grinstead, III. Andy Eli Lilly, Drexel was a founding member of the Albert B. Sabin Burnham Lambert, Kidder Peabody, and Institute’s Board of Trustees. He will be Paine Webber. Andy was a member of the missed for the guidance and insight he so gen- President’s Circle of the National Academy erously provided to the Institute since its be- of Science and the Institute of Medicine and ginnings, but most of all he will be missed for served on numerous boards. his friendship and kindness. Andy was chair- —by H. R. Shepherd man of the board and chief executive officer H.R. Shepherd is co-founder and chairman of the Albert E. Andrews Grinstead, III of Hybridon, Inc. Prior to joining Hybridon, B. Sabin Vaccine Institute. 16 JUNE 2001 SABIN VACCINE REPORT

BOOK REVIEW SABIN JULY 2001 Continued from page 14 July 9-11, 2001 2001 AMERICAN IMMUNIZATION REGISTRY extreme lethality, are the least likely CALENDAR ASSOCIATION CONFERENCE to pose a threat to mankind. Why? Be- www.cdc.gov/nip/registry/2001broc.pdf cause they are spread by human-to-hu- MAY 2001 May 27-31, 2001 E-mail: [email protected] man contact and they are so virulent that Little Rock, Arkansas they quickly burn themselves out. The 7TH CONFERENCE OF THE INTERNATIONAL SOCIETY OF TRAVEL MEDICINE (CISTM7) truly dangerous viruses are not these, but AUGUST 2001 www.istm.org rather those that are carried by vectors August 13-14, 2001 Innsbruck, Austria where the spread is not arrested by the 7TH INTERNATIONAL DENGUE COURSE immobilization and death of the host or May 29-June 1, 2001 Instituto Pedro Kouri Havana, Cuba by those that are carried silently within 35TH NATIONAL IMMUNIZATION CONFERENCE infected people and spread over long www.cdc.gov/nip/NIC [email protected] periods of time before symptoms appear Atlanta,Georgia SEPTEMBER 2001 —such as in the case of HIV infection. May 31, 2001 September 10-12, 2001 Even in cases such as AIDS, however, 4TH A LBERT SABIN VACCINE INSTITUTE BRITISH SOCIETY OF PARASITOLOGY 12TH evolutionary thinking can offer help. It AWARDS CELEBRATION MALARIA MEETING is Ewald’s contention that we can un- Honoring: www.abdn.ac.uk/bsp derstand why HIV type I suddenly be- Jean-Jacques Bertrand, Aventis-Pasteur University of Leeds, UK came such a virulent plague, and why Chairman and CEO September 12-14, 2001 HIV type 2 gives rise to a much milder Albert B. Sabin Humanitarian Award VACCINES FOR ENTERIC DISEASES form of the disease. Experiments have and Tampere, Finland shown that pathogens that are quickly John W. Rowe, M.D., Aetna Inc. Chair- [email protected] spread between animals tend to become man and CEO more virulent. Lifetime Achievement Award September 26-29, 2001 A possible reason for this is that rapid www.sabin.org WORLD MELIODOSIS CONGRESS passage from host to host selects for the The Pierre Hotel, New York, New York www.e-tiology.com/ Perth, Western Australia fastest growing strains which are more JUNE 2001 likely to be more harmful. In areas June 8-10, 2001 September 30-October 4, 2001 RD where HIV type 1 predominate, multi- NEW AND REEMERGING INFECTIOUS 53 MEETING OF THE GERMAN SOCIETY FOR partner sex leads to exceptionally rapid DISEASES: A CLINICAL COURSE HYGIENE & MICROBIOLOGY passage of the virus from person to per- Nat’l. Foundation for Infectious Diseases www.dghm-2001.de son, making the resulting disease far www.nfid.org/conferences/june01/ Aachen, Germany more lethal. In areas where HIV type 2 Atlanta, Georgia OCTOBER 2001 predominates, passage is far slower be- June 13-16, 2001 October 9-11, 2001 cause of sex practices that favor having TH 5TH INTERNATIONAL SYMPOSIUM ON 8 ANNUAL SABIN VACCINE COLLOQUIUM fewer sexual partners—which selects Accessing & Evaluating New Technologies for HEMORRHAGIC FEVER for slower growing strains. According to www.fond-merieux.org/eng/colloque/ Vaccines for the Developing World Ewald , anything that slows down infec- Hantavirus.html Sponsored by Sabin Vaccine Institute tion—for example, the use of condoms— Veyrier-du-Lac, France E-mail: [email protected] act as a selective pressure favoring the Cold Spring Harbor, NY evolution of less virulent strains of the disease.

Needless to say, many of Ewald’s NON-PROFIT ORG. ideas are highly speculative because the U.S. POSTAGE research necessary to prove them has PAID yet to be done. Nevertheless, his argu- WASHINGTON, DC ment is a very powerful and persuasive PERMIT NO. 2235 one, and he successfully highlights both 58 Pine Street the price paid for not integrating evolu- New Canaan, CT 06840 tionary perspectives into our understand- U.S.A. ing and treatment of infectious diseases and the potential benefits from rectify- ing this omission. —by William Muraskin, PhD William Muraskin, PhD is a Sabin fellow and profes- sor of urban studies, Queens College, New York.