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A Scientist's Work on Vaccines on the professions A Scientist’s Work on Vaccines Paul Offit n 1980, I began my fellowship in pediatric infectious diseases at the Children’s Hospital of Philadelphia. My mentor was Dr. Stanley Plotkin: the inventor of the ra27/3 strain of rubella vaccine–the one that by 2005 had eliminated the I disease from the United States. The year before I arrived in Philadelphia, Dr. Plotkin, along with Dr. Fred Clark, had started a program to study rotavi- ruses, a common cause of vomiting, diarrhea, fever, and dehydration in infants and young children. In the United States, every year about 3 million children would be infected, 250,000 would seek medical attention, 75,000 would be hospital- ized, and 60 would die. In the developing world, about 2,000 children would die every day from rotavirus-induced dehy- dration. There was a desperate need for a vaccine. During the next ten years, our team at Children’s Hospital de- In 1998, while we were in the midst of developing our vaccine, veloped a small animal model (mice) to study the disease, deter- Andrew Wakefield and colleagues at the Royal Free Hospital in mined which rotavirus genes caused diarrhea, and which rota- London published a paper claiming that the measles-mumps- virus genes coded for proteins that evoked protective immunity. rubella (mmr) vaccine caused autism. Wakefield reported the cas- Next, we isolated a strain of rotavirus from a calf with diarrhea that es of eight children who had developed autism within one month didn’t cause disease in children. Finally, we created a series of re- of receiving the mmr vaccine. Because Wakefield’s “study” didn’t combinant viruses between this calf strain and human rotavirus include a control group, the only thing he had proven was that strains that didn’t include the human genes that caused diarrhea the mmr vaccine didn’t prevent autism. Later, seventeen studies but did include the human genes that could evoke protective im- showed that children who had received mmr were at no greater mune responses. risk of autism than those who hadn’t received the vaccine. None- With our recombinant rotavirus strains in hand, we approached theless, Wakefield’s paper touched off an international firestorm. four vaccine makers hoping that one would be interested in deter- Thousands of parents in the United Kingdom and Ireland chose not mining whether what we thought was a rotavirus vaccine actual- to vaccinate their children with mmr, hundreds were hospitalized, ly was a rotavirus vaccine. Merck was the first to step forward. Be- and four died from measles–died from a disease that could have tween 1990 and 2006, Merck Research Laboratories performed a se- been safely and easily prevented by a vaccine. ries of studies to prove that all of the strains that were in our vaccine What I learned from this was while vaccines were hard to make, had to be there (proof-of-concept studies), that we didn’t have too they were easy to damn. much or too little vaccine virus in the final preparation (dose-rang- In 2000, Charlotte Moser and I launched the Vaccine Education ing studies), that we had the right buffering and stabilizing agents Center at Children’s Hospital of Philadelphia. The goal was to cre- (real-time stability studies), that our vaccine didn’t interfere with ate a series of educational materials to inform the press, the public, the safety or immunogenicity profiles of other vaccines that would and lawmakers about what vaccines are and how they work–to de- be given at the same time (concomitant use studies), and that mystify vaccines. During the past sixteen years we have created tear the fully liquid preparation could be easily administered to chil- sheets, videos, mobile apps, coloring books, online games, vaccine dren at two, four, and six months of age. The final so-called Phase hero trading cards (in the same format as baseball cards), booklets, 3 study was a prospective, placebo-controlled, 11-country, 4-year, and a full-length feature film–Hilleman: The Perilous Quest to Save the 71,000-person trial that cost about $350 million to perform and gen- World’s Children–that won the award for best documentary film at erated individual clinical reports that if stacked one on top of the two international film festivals. In addition, I have written several other would have exceeded the height of the Sears Tower. books about vaccines: The Cutter Incident: How America’s First Polio What I learned from all of this was how hard it was to make Vaccine Led to the Growing Vaccine Crisis (Yale University Press, 2005), a vaccine. which details a biological tragedy that occurred in 1955 when one of the companies that made Jonas Salk’s polio vaccine failed to fully Paul Offit is Professor of Pediatrics in the Division of Infectious Diseases at inactivate the virus; Vaccinated: One Man’s Quest to Defeat the World’s the Children’s Hospital of Philadelphia and the Maurice R. Hilleman Pro- Deadliest Diseases (Smithsonian Books, 2007), which tells the story fessor of Pediatrics at the Perelman School of Medicine at the University of of Maurice Hilleman, the scientist who developed nine of the four- Pennsylvania. He was elected a Fellow of the American Academy in 2015. teen vaccines currently given to infants and young children; Autism’s 80 Bulletin of the American Academy of Arts & Sciences, Winter 2017 a scientist’s work on vaccines False Prophets: Bad Science, Risky Medicine, and the Search for a Cure (Columbia University Press, 2008), which pulls back the curtain to expose some of the nefarious characters behind the vaccines-cause- autism controversy; and Deadly Choices: How the Anti-Vaccine Move- ment Threatens Us All (Basic Books, 2011), which describes the impact of antivaccine sentiment in the United States. Although performing scientific studies has in no way taught me how to deal with the media, our educational efforts at the Center and our books about vaccines have landed me on news programs such as Today, Good Morning America, CBS This Morning, NBC Nightly News, ABC World News Tonight, CBS Evening News, 60 Minutes, Stossel, MSNBC, Dateline NBC, the Jim Lehrer NewsHour, Fox News, National Public Radio, The Colbert Report (twice), and The Daily Show, as well as allowed me to participate in documentaries on NOVA, Frontline, and CNN. I’ve learned a lot along the way. One thing I have found, which I wouldn’t have predicted, was that I had inadvertently put myself in the crosshairs of the antivac- cine movement. Consisting of politicians, filmmakers, celebrities, parent activists, and personal-injury lawyers, the antivaccine move- ment is an unholy alliance dedicated to scaring parents away from vaccines. I’ve been the victim of hate mail, death threats, and law- suits, and parents have been victims of bad information. It’s been an education. But I can’t quit. Too much is at stake. Not a year goes by at our hospital without a child dying from a vaccine-prevent- able disease: most commonly influenza, but occasionally pertussis, pneumococcus, and varicella. Invariably, these parents had chosen not to vaccinate their children. As is invariably the case, it is always the children who suffer our ignorance. © 2017 by Paul Offit Bulletin of the American Academy of Arts & Sciences, Winter 2017 81 .
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