The Lancet 2007; 369:1421-1422
Vaccines: life savers and controversy makers
By Stanley Plotkin
Vaccines occupy a peculiar place in medicine and society. That they prevent disease is incontrovertible; ample evidence for their effects is obvious in the industrialised countries and increasingly so in the developing world. Only clean water has had a greater impact on infectious diseases. Molecular biology now permits the development of more vaccines, perhaps even some against non-infectious diseases. Yet vaccination has been controversial from its inception in the primitive practice of variolation against smallpox to its latest avatar in the form of purified pseudoparticles composed of single papillomavirus proteins that prevent cervical cancer. Objections to vaccination have evolved from early theological concerns that it countered God's will to the belief in certain circles today that for a healthy immune system disease is preferable to vaccines.
This paradox is explained by two factors: first, that vaccines are usually given to healthy people, and reactions to vaccines may make some of those healthy people ill; and second, that vaccination is often made compulsory by governments because of the state's interest in protecting children and in maintaining the herd immunity provided by vaccines. On one side, society insists that refusal to be vaccinated is an act that threatens the community, whereas on the other side, libertarians insist that vaccination should be done only with consent. Thus, we live in a time when vaccines have never been more effective and when vaccine science has never been more promising, but when opposition to vaccines is, nonetheless, flourishing.
The events that brought us to this pass are described by journalist Arthur Allen, in Vaccine: The Controversial Story of Medicine's Greatest Lifesaver. Allen begins with detailed historical description of the early discoveries that led to the eventual eradication of smallpox, follows with a middle section recounting the development of vaccines that were produced in the past 150 years, and concludes with a description of the controversies regarding alleged causation of encephalopathy by whole-cell pertussis vaccine, and of autism by measles-mumps-rubella vaccine or by mercury-containing preservative.
Allen has done considerable documentary research and spoken to many people, including scientists and laypeople, which enables him to give a balanced and well referenced account. The book is a useful chronicle of the subject, and I learned a few things about old and recent history. I might have recounted some stories differently, but then personal memory is fallible and aside from a few mis-spelled names and technical errors (such as denying that pneumococcal conjugate vaccine has decreased the incidence of invasive pneumococcal disease), the book is accurate.
Both the triumphs and tragedies of vaccination are perceptively described, although emphasis is given to the latter. Allen shows how the personalities of scientists figure importantly in the choices made to follow one or the other leads in vaccine development, and how in science one can only do what current methods allow. The development of successful vaccines is, however, made to look simpler than it is, and the many failures and byways that make the process last an average 15 years from start to finish are given insufficient emphasis. Allen is clearly most interested in the controversies that surround vaccination. He gives insight into the dilemma that although vaccines give more benefit than harm, there will always be the risk of reactions, which come in three varieties: real, false, and uncertain. The real ones, such as paralysis after oral polio vaccine, are discovered after licensure and result in revised recommendations or withdrawal; the false ones, such as the claimed consequence of multiple sclerosis after hepatitis B vaccine, are disproved by studies and disappear into urban legend; but the ones that are uncertain, because of their rarity or the difficulty in designing studies, remain to agitate sincerely concerned individuals and conspiracy enthusiasts.
The problem is that each reaction to vaccines—real, false, or uncertain—needs resources to fund studies, and the results of studies do not convince everyone. Allen describes in detail the controversy over thiomersal, or ethyl mercury, which had been used for many years as a way to prevent contamination of multidose vaccine vials. After the realisation that the total quantity of mercury administered to some infants exceeded margin of safety guidelines issued by one of three US government agencies, manufacturers were pushed to eliminate thiomersal from paediatric vaccines. They had already begun to do so before the controversy, but the panic generated in paediatric organisations accelerated the removal, and now no paediatric vaccine in the USA contains more than a trace of thiomersal, with the exception of influenza (for which a thiomersal-free vaccine can be purchased).
At a recent meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, the data on thiomersal in vaccines and autism were presented by an academic investigator. Although none of the epidemiological or ecological data yet available supports an association between the two, and indeed removal of thiomersal has not changed the incidence of autism, representatives of lay organisations at the meeting refused to accept the investigator's conclusions, relying instead on extrapolation of harm from in-vitro toxicology studies. Additional controlled clinical data will be reported in the next year or two, but it is doubtful that all participants in the controversy will be satisfied by them. Allen does a good job of describing the antagonists in this controversy, with their strongly held views that sometimes run counter to the evidence.
Vaccination will never be without controversy and without risk, as Allen emphasises. An example of this was the fate of the rotavirus vaccine licensed in 1998 that rarely caused intussusception in infants, but prevented diarrhoea, dehydration, and hospital admission. Neither the USA nor any other country would accept its use, and the vaccine was withdrawn despite its benefits. It took 6 years and vaccine trials that involved 150 000 children before replacement vaccines came on the market that are not associated with a higher risk of intussusception. During those 6 years at least 2 million children died of rotavirus disease worldwide.
A contrasting example is the US government's smallpox vaccine programme, which was enacted under unrelenting pressure by Vice-President Dick Cheney, only to be halted when unexpected cases of myocarditis were seen in vaccinees. Had there been a real terrorist attack with smallpox virus, the programme would have seemed prudent and prescient, but in the absence of such events those who were vaccinated had assumed an unnecessary risk.
It is this tension between risk of disease and risk of vaccination that animates vaccine developers and vaccine objectors. Allen offers no solution to this conflict, and indeed there may be none, as rational calculation of risk is likely to remain scarce among the critics of vaccination. Nevertheless, the vaccine enterprise is alive and well, largely because technology is improving and new manufacturers from other continents are joining those in North America and Europe.
Stanley Plotkin works for the vaccine manufacturer Sanofi Pasteur and is Emeritus Professor of Pediatrics at the University of Pennsylvania.