Vaers and Veritas

The conservative legal group Judicial Watch last week issued a news release announcing that it had uncovered three deaths linked to the human papilloma virus vaccine (HPV), which has been the subject of furious debate around the country as states decide whether to require 6th grade girls to be vaccinated before admitting them to school. The release, in which Judicial Watch claimed that its perusal of adverse event reports from the vaccine also turned up cases of autoimmune disease and fetal damage in vaccinated pregnant women, produced a minor media splash, with articles in the Wall Street Journal and the Washington Times. The story didn’t get play in most other outlets, probably for this simple reason: It’s bullshit.

Journal of the Royal Society of Medicine

JRSM v. 100 (M a y 2 0 0 7)
By Michael Fitzpatrick

In his comprehensive survey of vaccination controversies
past and present, Arthur Allen quotes US vaccine chief
Walter Orenstein’s recollection that ‘for those trained in
pediatrics in the 1970s, Hib (Haemophilus influenzae type b)
was a horror.’ It was indeed. I recall a mother whose infant
died of Hib meningitis, secondary to an apparently trivial
otitis media, within minutes of arriving in hospital. Already
at an advanced stage of her second pregnancy, she promptly
went into labour and had an uncomplicated delivery. The
way her grief at the loss of one child overwhelmed her joy
at the arrival of another is my enduring memory of the
horror of Hib, which was still killing 60 children every year
in Britain in the 1980s.

Thanks to the introduction of routine Hib immunization
in 1992, this disease has now become a rarity. Yet, as
Orenstein points out, when the immunization was
introduced there was much uncertainty about its impact
on the ecology of Haemophilus and the long term
consequences. As he observes, some things are ‘only
knowable in the long run;’ in the meantime, ‘we have to
take our chances and then follow up.’ One of the themes of
Allen’s book is that this courageous and enterprising
approach to vaccination policy—vindicated by its historic
achievements in the conquest of disease—is now threatened
by the contemporary climate of risk aversion.

Allen does not ignore the history of vaccine disasters.
He includes the fiasco in the US military in 1942, when
yellow fever vaccine contaminated with hepatitis B caused
100 deaths, and the mass vaccination against smallpox in
New York in 1947 that caused six deaths (four more than
the outbreak itself). In the Cutter incident in the 1950s,
inadequately inactivated polio vaccine caused 164 cases of
paralysis and 10 deaths. While acknowledging these failures,
Allen pays tribute to immunization authorities—such as
Henry Kempe and Bob Chen—who have campaigned to
improve vaccine safety.

The great irony underlying current vaccination controversies
is that, as vaccines have become more effective
and safer than ever before, an anti-vaccine world view,
reflecting a combination of nostalgia and cultural pessimism,
has become more prevalent. Allen reports how one family
with an autistic child described ‘going down the rabbit hole’
into a ‘spooky realm of herbalists and populist mavericks
and—not to put too fine a point on it—conspiracy kooks,
who view America as a toxic hell.’ Recognizing that
parents’ anger and inclination to blame vaccines reflect
difficulties in coming to terms with their children’s
disabilities, Allen has himself bravely challenged antivaccine
campaigners who have had such a damaging impact
on the world of autism.

Allen concludes with Orenstein’s prescient warning that
a precautionary approach, reflecting corporate concerns
about a low profit, high risk area of investment and
government sensitivities to public anxieties, ‘could
paralyze’ innovation in vaccines.

Competing interests MF is the author of MMR and
Autism: What Parents Need To Know (Routledge, 2004. ISBN-
13: 978-0415321792. £18.99).
Michael Fitzpatrick
Barton House Health Centre, London N16 9JT, UK
E-mail: fitz@easynet.co.uk

The Lancet

The Lancet 2007; 369:1421-1422

Perspectives, Book
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.

The (London) Guardian

A jab in the right direction

Arthur Allen shows how inoculation's successes have led to recent concerns in Vaccine, while Robert Bud charts a very different story in Penicillin, says Mark Honigsbaum

Mark Honigsbaum
Saturday May 5, 2007

Guardian

Vaccine: The Controversial Story of Medicine's Greatest Lifesaver, by Arthur Allen. 512pp, WW Norton, £17.99
Penicillin: Triumph and Tragedy, by Robert Bud. 340pp, Oxford, £30

In March 1947, Eugene LaBar, a rug importer returning from Mexico to Maine by Greyhound bus, collapsed in Manhattan complaining of a fever, rash and headache. Within days LaBar and 11 other New Yorkers had been diagnosed with smallpox, sparking the largest mass vaccination in the city's history. During the following three weeks, six million people were inoculated with the vaccina virus, then as now the only protection. Indeed such was New Yorkers' faith in medical technology and the power of vaccination that clerks and Broadway showgirls queued through the night outside doctors' surgeries in their eagerness to join what newspapers dubbed "the Order of the Itching Arm".

Fast-forward to our own MMR-challenged times, however, and it's a very different story. As the threat of smallpox, measles and other disfiguring childhood diseases has receded, so the balance of power between doctors and patients has shifted. In an era when a list of potential vaccine side-effects is just a mouse click away, few of us itch to have itching arms any longer. Nor do we automatically regard vaccination as a duty to the community, particularly if, as in the case of the HPV vaccine, the disease is sexually transmitted and thus complicated by moralising judgments about "degenerate lifestyles".

According to Arthur Allen, a former AP foreign correspondent with a decade-long interest in the subject, this state of affairs is largely a reflection of vaccination's success. Only a generation of parents that has never experienced the horrors of smallpox - a disease that Macaulay described as "the most terrible of all the ministers of death" and which was thankfully deemed to have been eradicated by the World Health Organization in 1980 - can enjoy the luxury of worrying about autism, a condition that didn't blip on to most GPs' radar screens until 1980. But it also reflects the fact that the question of whether or not to inoculate has always been as much a political as a personal question, and has always attracted zealots on either side.

One of the joys of reading Allen's well-researched but never boring 500-page history is that he pricks both camps, taking a critical look at both the anti-vaccinists' championing of pseudo-science and the medical establishment's repeated tendency to downplay the genuine dangers of vaccine side-effects.

Allen also has a keen eye for the counter-intuitive. For instance, one of the most vocal early American advocates of variolation, as the early 18th-century practice of inoculation was known, was Cotton Mather, the Bible-thumping Massachusetts Puritan and supporter of the Salem witch trials. Despite regarding the pustules of smallpox as evidence of man's innate sinfulness, Mather apparently also regarded smallpox as the "devil's work" and variolation as both a religious and a social duty. Interestingly, his opponents, starting from the same Christian premise, reached exactly the opposite conclusion: it was precisely because smallpox was "God's work" that they argued doctors should let the disease runs its course. Hence the argument of the Swedenborgians that vaccinating a child was "introducing the foul corruptions of hell into innocent life" - a position not that far removed from certain newspaper columnists' rants against the MMR programme today.

In fact, Mather's progressive attitude to vaccination was probably motivated as much by self-interest - he lost several children to smallpox and other diseases - as science. Unfortunately, these days self-interest all too often leads people to ignore the scientific evidence in support of treatment that might serve a greater good, but there was a period when the two happily coincided. Before reading Allen's book, for instance, I hadn't realised that the French superlative "c'est vache" - meaning "excellent" - dates from the early 19th-century Parisian medical practice of corralling cattle on street corners the better to extract fresh vaccine direct from the animals' lymph glands. Nor had I known that such was the enthusiasm for Edward Jenner's cowpox vaccine that Thomas Jefferson personally took charge of its distribution in America, using it to inoculate the last members of the Mohican tribe in 1801.

Present day conservative religious opponents of the HPV vaccine should also note that the reason Jenner's vaccine proved so popular was that it was a lot safer than earlier efforts at variolation in which physicians harvested smallpox directly from patients, many of them infected with syphilis and other sexual diseases. On occasion, however, people have been right to question the prevailing medical orthodoxy, as in 1901 when several children in Philadelphia and other eastern US cities were infected with tetanus as a result of contamination during a smallpox vaccination drive and died agonising deaths from lockjaw despite repeated government assurances that the vaccine was safe.

Allen subtitles his book "the controversial story of medicine's greatest lifesaver", but that is an accolade that Robert Bud, the author of Penicillin, could well dispute, for few drugs can claim to have saved as many lives as Alexander Fleming's "miracle" antibiotic.

Indeed, so closely is penicillin associated with "strong medicine" that Bud, the head of information and research at the Science Museum, argues it could almost be considered a brand, such that "the very writing of a prescription gives hope to the patient and a sense of power to the doctor".

Unfortunately, thanks to the spread of drug-resistant bacteria, the power of penicillin, like that of vaccines, is much diminished these days. The difference is that in the case of penicillin and other antibiotics, this diminution in effectiveness is the result of overuse, not underuse; hence the attempt by doctors to persuade patients to put their faith in vaccination and other medical interventions that have a greater certainty of protecting the health of all of us.

· Mark Honigsbaum's The Fever Trail: The Hunt for the Cure for Malaria is published by Pan