Winter 2017 Bulletin

A Scientist’s Work on Vaccines

Paul A. Offit

In 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 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 rotaviruses, 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 hospitalized, and 60 would die. In the developing world, about 2,000 children would die every day from rotavirus-induced dehydration. There was a desperate need for a vaccine.

During the next ten years, our team at Children’s Hospital developed a small animal model (mice) to study the disease, determined which rotavirus genes caused diarrhea, and which rotavirus genes coded for proteins that evoked protective immunity. Next, we isolated a strain of rotavirus from a calf with diarrhea that didn’t cause disease in children. Finally, we created a series of recombinant viruses between this calf strain and human rotavirus strains that didn’t include the human genes that caused diarrhea but did include the human genes that could evoke protective immune responses.

With our recombinant rotavirus strains in hand, we approached four vaccine makers hoping that one would be interested in determining whether what we thought was a rotavirus vaccine actually was a rotavirus vaccine. Merck was the first to step forward. Between 1990 and 2006, Merck Research Laboratories performed a series of studies to prove that all of the strains that were in our vaccine had to be there (proof-of-concept studies), that we didn’t have too much or too little vaccine virus in the final preparation (dose-ranging studies), that we had the right buffering and stabilizing agents (real-time stability studies), that our vaccine didn’t interfere with the safety or immunogenicity profiles of other vaccines that would be given at the same time (concomitant use studies), and that the fully liquid preparation could be easily administered to children at two, four, and six months of age. The final so-called Phase 3 study was a prospective, placebo-controlled, 11-country, 4-year, 71,000-person trial that cost about $350 million to perform and generated individual clinical reports that if stacked one on top of the other would have exceeded the height of the Sears Tower.

What I learned from all of this was how hard it was to make a vaccine.

In 1998, while we were in the midst of developing our vaccine, Andrew Wakefield and colleagues at the Royal Free Hospital in London published a paper claiming that the measles-mumps-rubella (MMR) vaccine caused autism. Wakefield reported the cases of eight children who had developed autism within one month of receiving the MMR vaccine. Because Wakefield’s “study” didn’t include a control group, the only thing he had proven was that the MMR vaccine didn’t prevent autism. Later, seventeen studies showed that children who had received MMR were at no greater risk of autism than those who hadn’t received the vaccine. Nonetheless, Wakefield’s paper touched off an international firestorm. Thousands of parents in the United Kingdom and Ireland chose not to vaccinate their children with MMR, hundreds were hospitalized, and four died from measles – died from a disease that could have been safely and easily prevented by a vaccine.

What I learned from this was while vaccines were hard to make, they were easy to damn.

In 2000, Charlotte Moser and I launched the Vaccine Education Center at Children’s Hospital of Philadelphia. The goal was to create a series of educational materials to inform the press, the public, and lawmakers about what vaccines are and how they work – to demystify vaccines. During the past sixteen years we have created tear sheets, videos, mobile apps, coloring books, online games, vaccine hero trading cards (in the same format as baseball cards), booklets, and a full-length feature film – Hilleman: The Perilous Quest to Save the World’s Children – that won the award for best documentary film at two international film festivals. In addition, I have written several books about vaccines: The Cutter Incident: How America’s First Polio Vaccine Led to the Growing Vaccine Crisis (Yale University Press, 2005), which details a biological tragedy that occurred in 1955 when one of the companies that made Jonas Salk’s polio vaccine failed to fully inactivate the virus; Vaccinated: One Man’s Quest to Defeat the World’s Deadliest Diseases (Smithsonian Books, 2007), which tells the story of Maurice Hilleman, the scientist who developed nine of the fourteen vaccines currently given to infants and young children; Autism’s 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 Movement 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 antivaccine movement. Consisting of politicians, filmmakers, celebrities, parent activists, and personal-injury lawyers, the antivaccine movement is an unholy alliance dedicated to scaring parents away from vaccines. I’ve been the victim of hate mail, death threats, and lawsuits, 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-preventable 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.

Paul Offit is Professor of Pediatrics in the Division of Infectious Diseases at the Children’s Hospital of Philadelphia and the Maurice R. Hilleman Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. He was elected a Fellow of the American Academy in 2015.

© 2017 by Paul Offit