Local Researchers Take on One of Modern Science’s Most Controversial Topics
By Tom Sandborn
Two Vancouver scientists, Lucija Tomljenovic and Christopher Shaw, have recently published a paper that puts them squarely in the middle of a bitter public debate about vaccine safety. The UBC researchers argue in their paper that some components found in many vaccines may be responsible for spiking levels of autism in the western world. They also acknowledge the limitations of their study and call for wider ranging epidemiological and case controlled studies to confirm or deny their findings.
Everybody seems to have an opinion about vaccines these days, and passions run high in both lay and scientific circles. Some parents are debating whether or not to vaccinate their children, having read on the internet or heard from other anxious parents that vaccination can lead to autism or other dire diseases in the young. Some doctors are cautious advocates of vaccine skepticism, while others, who see vaccination as one of the great, transformative advances in the history of public health, say that anyone who discourages vaccination has the blood of children on their hands.
Conspiracy theories abound, on all sides of the debate, with vaccine skeptics tempted to see vaccine promotion as driven by corporate profiteering and scientific opportunism and vaccine advocates sure that anyone expressing caution or skepticism about vaccine safety are part of a lunatic or larcenous fringe more interested in wealth, notoriety and sensationalism than in saving children’s lives.
Tomljenovic and Shaw have entered this often acrimonious debate with a paper published in the November, 2011 issue of the peer reviewed Journal of Inorganic Biochemistry. (Tomljenovic is a researcher with the Shaw lab’s Neural Dynamics Research Group, Department of Ophthalmology and Visual Sciences, at UBC, and Shaw is on faculty at UBC with the Departments of Ophthalmology and Visual Sciences and Experimental Medicine and the Graduate Program in Neuroscience. Their article, “Do aluminum vaccine adjuvants contribute to the rising prevalence of autism?”(1) takes a look at the remarkable increase in childhood exposure to injected aluminum salts that has resulted across the developed world as more and more vaccinations are added to the list of treatments parents are urged to arrange for their children. (The aluminum comes into the picture because many vaccines use aluminum compounds as adjuvants, the substances that increase the impact and effectiveness of the vaccination. In an earlier paper published in Neuromolecular Medicine in 2007, Shaw and other researchers reported on neurological deficits observed in lab animals injected with the adjuvants used in anthrax vaccines during the Gulf War, including aluminum hydroxide. (2.)
Tomljenovic and Shaw say that the data they present in their paper suggest a strong possibility that today’s higher level of childhood injected aluminum salt exposure through vaccines may be a factor in increasing the prevalence of autism among children.
(It should be noted that the increase in autism and autism spectrum disorder diagnoses is itself a subject of scientific disagreement, (3.) with some authorities holding that the increase in diagnosis is a result of broader definitions of the disease -expanding “autism” to include Asbergers and other conditions on an autism spectrum- and of greater public awareness of autism, leading to increased diagnoses that may or may not reflect actual increases in the number of children who are afflicted. For example, Taylor, writing in 2006, commented:
“The recorded prevalence of autism has increased considerably in recent years. This reflects greater recognition, with changes in diagnostic practice associated with more trained diagnosticians; broadening of diagnostic criteria to include a spectrum of disorder; a greater willingness by parents and educationalists to accept the label (in part because of entitlement to services); and better recording systems, among other factors.”
Shaw told the Columbia Journal that expansion of diagnostic practice is not an adequate explanation for increases in autism diagnoses that run as high as 2000%.
“An increase of 2000% overall is not simply better diagnosis or awareness which other papers have argued accounts for about 15%,” he said in response to the Taylor argument. ”Similarly, the change in population (remember, our data are prevalence data) is about 35%. Also, re diagnostic criterion changes: the rate of ASD changes about 20% per year since 1992. Diagostic criterion changes have happened at most twice, once before the period we cover.”
The Vancouver scientists’ new paper argues that “Aluminum (Al), the most commonly used vaccine adjuvant, is a demonstrated neurotoxin and a strong immune stimulator. Hence, adjuvant Al has the potential to induce neuroimmune disorders.” They note that autism spectrum disorder is characterized by “dysfunctional immunity and impaired brain function” which they characterize as the disorder’s “core deficits.”
They note that in many jurisdictions, the number of recommended childhood vaccinations has gone up dramatically in the past decades, and with it, childhood exposure to the aluminum salts that are added to many vaccines to make them more powerful. (According to the authors, Canadian protocols call for childhood immunizations that expose children to aluminum salts as often as 18 times before school entry. The Public Health Agency of Canada web page (5.) currently lists just over forty vaccinations that it describes as routine for children in BC before the age of six. In the US, the Center for Disease Control (6.) suggests 37 routine vaccinations for children before age six.
The authors suggest that all this increased exposure to aluminum via injection (which, they say, presents a much higher danger of aluminum crossing the blood brain barrier and entering the central nervous system than occurs when aluminum enters the body via food) correlates with higher levels of autism spectrum disorder in the populations of Western developed nations.
“Analysis of the relevant data shows that the number of vaccinations recommended prior to school entry increased from 10 in the late 1970s to 32 in 2010 (18 of which contain Al adjuvants) . During this same period, the prevalence of autism spectrum disorders (ASD) in the US also increased by as much as 2000%,” the Tomljenovic/Shaw paper notes.
The paper also suggests there are parallels between the immunological profile associated with exposure to aluminum and immunological phenomena associated with several other diseases, including autoimmune thyroid disease, multiple sclerosis, systemic lupus erythematosus, chronic fatigue syndrome, macrophagic myofasciitis and Gulf War Syndrome.
Tomljenovic and Shaw are persuaded that the correlations they have observed between exposure to injected aluminum in vaccines and autism diagnosis rates are more than coincidental, citing their application of Hill’s criteria (7.) a tool for testing causal relationships in epidemiology, to their data. According to the authors, the link between aluminum exposure and autism spectrum disorder meets eight of the nine criteria in the Hill system, including all four of the criteria considered most pertinent to neurological disease.
While Tomljenovic and Shaw believe their paper is the first academic research to persuasively demonstrate a correlation between aluminum exposure and autism, the literature on aluminum and neurological disorders is extensive. For example, writing in the New England Journal of Medicine in 1997, (8.) Bishop, Morley, Day and Lucas found that “ ...in preterm infants, prolonged intravenous feeding with solutions containing aluminum is associated with impaired neurologic development,” and in 2002, Becaria, Campbell, and Bondy, writing in Toxicology and Industrial Health, (http://tih.sagepub.com/content/18/7/309.abstract ) observed accumulating evidence suggests that aluminum “… can potentiate oxidative and inflammatory events, eventually leading to tissue damage.”
Two Israeli scientists, Yehuda Shoenfeld and Nancy Agmon-Levin, writing in 2010 in the Journal of Autoimmunity (9.) suggest that “ In recent years, four conditions: siliconosis, the Gulf war syndrome (GWS), the macrophagicmyofasciitis syndrome (MMF) and post-vaccination phenomena were linked with previous exposure to an adjuvant.” The Israeli scientists make clear in their paper that aluminum adjuvants are among the compounds of concern in this matter, and they add:
“Formerly, adjuvants were thought to pose little or no independent threat. Alas, studies of animal models and humans demonstrated the ability of some of them to inflict autoimmunity and autoimmune diseases by themselves.”
Still, Tomljenovic and Shaw are scrupulously careful in their paper to define the limits of their claims. While they find their comparison of aluminum exposure rates and autism diagnoses across populations, and the positive results of applying Hill’s criteria to their findings persuasive, they caution that “Clearly, we cannot draw definite conclusions regarding the link between Al adjuvants and autism based on an ecological study such as
the present one and hence the validity of our results remains to be confirmed.”
They conclude their paper with an urgent call for more comprehensive research that could validate or disprove their findings, saying “A case control study with detailed examination of vaccination records and Al body burden measurements (i.e., hair, urine, blood) in autistic and a control group of children would be one step toward this
goal.” Despite this call for intellectual caution and further research, the two scientists do argue that the case for a more thorough look at assessing the safety of aluminum adjuvants in vaccines has been made, and should guide future research and practice.
They argue that “it would seem ill advised to exclude pediatric vaccinations as a possible cause of adverse long-term neurodevelopmental outcomes, including
those associated with autism.”
In a conversation with the Columbia Journal last summer, Tomljenovic and Shaw emphasized that they are by no means univocally anti-vaccine. They cited the tetanus vaccine as one they support. Their research, they told me, makes the argument for larger scale research into possible negative impacts of aluminum salts in vaccines, not for a total retreat from immunization as a public health strategy.
“Our concerns,” said Shaw, “are safety and evidence based medicine.”
Despite all their caution about the need for more research and the limits to what their current paper proves, the recent Tomljenovic/Shaw paper places the researchers in a ferociously contested area of medical research, and some scientists have expressed deep reservations about the paper.
All of this controversy, it should be noted, takes place in the long and murky shadow of a notorious scandal involving vaccine research. The Wakefield controversy revolves around a paper by Wakefield and co-authors, (10.) since discredited amid allegations of conflict of interest and falsified data (11.) and withdrawn by the Lancet, the journal that published it. The Wakefield paper suggested a connection between MMR (measles, mumps, rubella) vaccination and autism. It has been widely cited by anti-vaccine groups, especially in the “verification free zone” of the internet, and is seen by pro-vaccine authorities as a prime example of bad science fueling public panic, leading to very unwise choices by parents to avoid vaccinating their children.
More recently, Wakefield has taken legal steps in early 2012 to contest negative views of his research, filing a defamation suit against Brian Deer, the investigative reporter at the centre of criticism of the Wakefield research, and the editors of the British Medical Journal based on material Deer published in the BMJ last year.
The debate about vaccine safety is a high stakes matter on several counts. Lives are at stake, and immense fortunes in drug company profits. According to a January 2011 article on the pharmaceutical industry website Drug Discovery and Development (12.)
“Human vaccines, earlier considered as a low profit yielding business, have transformed into cash cows for global pharmaceutical giants. Patents for human and animal vaccines accepted by European and US patent authorities totaled nearly 250 in 2007.”
In 2010, vaccine sales soared (13.) to $ 28 billion as compared to $26 billion in 2009, $24 billion in 2008 and $18.5 billion in 2007.
Paul Offit, of the University of Pennsylvania, is the developer of a very lucrative rotavirus vaccine patent that has made him a millionaire (14.)
and, as the author of Deadly Choices How the Anti-Vaccine Movement Threatens Us All, one of the leading pro-vaccine voices in the current debate. (The academic chair Offit holds at Penn is named after vaccine pioneer Maurice J. Hilleman, and funded in part by a foundation created by the pharmaceutical giant Merck.) (15.)
Offit is critical of the research reported in the Tomljenovic/Shaw paper. He said in an early October phone interview that the anti vaccine movement, with its “appeals to fear” was “worse than scientific illiteracy.” Prior to the interview, Dr. Offit reviewed a copy of the Vancouver paper provided to him, and concluded that it “should never have been published.” Offit said that ecological studies such as the one authored by Tomljenovic and Shaw were not helpful.
In epidemiology, ecological studies, which investigate whole populations rather than individuals or cohorts which have been matched for key variables, are commonly viewed as weaker evidence than the gold standard of case control studies.
“What we need,” Offit said, “is more epidemiological and case controlled studies.” He seemed unimpressed by the fact that Tomljenovic and Shaw also call for exactly the same sorts of further research and more rigorous studies.
Offit believes that vaccination has been the target of irrational opposition since it was first developed and popularized by Jenner. (16.) at the end of the 18th century. But he blames the controversial Wakefield research for sparking a new and very dangerous trend of vaccine skepticism, which he says has been amplified by irresponsible media and internet commentary, all leading to decisions by a significant number of parents not to vaccinate their children. He is particularly scathing about the role played by Barbara Loe Fisher, who he characterizes as the founder of the modern US anti-vaccine movement and of her National Vaccine Information Center. (17.)
While he believes the anti-vaccine movement is weaker now that the Wakefield research has been discredited, Offit says that anti-vaccine statements lead to lower levels of vaccination and subsequent breakdowns in “herd immunity” (the phenomenon that sees the spread of contagious diseases contained once a certain percentage of a population has been vaccinated.) He points to outbreaks of Hib, measles and pertussis (whooping cough) among unvaccinated children in the developed world, and charges that the Wakefield paper “killed children.”
Offit also questions Tomljenovic and Shw’s concerns about aluminum adjuvants in vaccines, sayng that “All the evidence, biological and epidemiological, shows that aluminum is safe.” He does grant that aluminum can cause some harm, but points out that it is the most common of all light metals, and insists that the half life of aluminum in the body is 24 hours. He argues that children get far more aluminum from food than they do from vaccinations, without any observable harm.
“The choice not to take aluminum adjuvanted vaccines is not risk free,” he insisted.
One of the physicians responsible for public health in BC, Dr. Monica Naus, is also skeptical about the Tomljenovic/Shaw paper. Naus, Associate Medical Director, Epidemiology, Medical Director, Immunization Programs, BCCDC, and Associate Professor, School of Population & Public Health, UBC, said in November that a choice not to vaccinate a child would be drastic, and said that research like Shaw and Tomljenovic’s “…can have a bad effect.”
Naus believes that, while the etiology of autism has not yet been fully elucidated, genetic factors are clearly involved. She told the Columbia Journal that some cases of autism occur well before children are vaccinated, and that there is some evidence for autism already manifesting in utero, all of which, in her view, undermines any suggestion of a link between vaccination and autism. Like Offit, she maintains that ecological studies are not very useful, and called for more case controlled and cohort studies to determine whether there is a link between exposure to aluminum in vaccines and rates of autism diagnosis.
Naus was scornful of the journal in which Shaw and Tomljenovic published their research, saying that the Journal of Inorganic Biochemistry is not a magazine that pediatricians read. She added that vaccine safety is studied globally and that vaccines are among safest medical treatments available.
Dr. Christopher Exley is an internationally recognized expert on aluminum and was the guest editor of the issue of the Journal of Inorganic Biochemistry that carried the Tomljenovic/Shaw paper. Exley is Reader in Bioinorganic Chemistry and
Honorary Professor, UHI Millennium Institute at the Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, in the United Kingdom.
In a November interview, Exley emphasized that all the papers published in JIB are rigorously peer reviewed.
“I recognized that the topic of this paper was potentially controversial, and it was essential that the research be reviewed by experts who were likely to be hostile to the findings. This paper went through a very tough peer review process, and the reviewers called for major revisions. But no one called for it to be rejected, and once the revisions were in, the paper was not inflammatory. The only thing left was science.”
Exley said that one of the experts who provided peer review of the paper had previously worked with the Food and Drug Administration on vaccine safety and two were academics with publications of their own on environmental impacts of aluminum. He added that two of the three reviewers felt the application of Hill’s criteria to the paper’s findings was relevant, while one was skeptical on that point.
Told of Dr. Offit’s assertion the paper should not have been published, Exley said:
“I believe this paper was beneficial. It raises something that I feel requires further investigation. We know that infants are particularly vulnerable to aluminum impacts. This is something that should be discussed. There is nothing wrong with the science in this paper. It is very solid and tight. The case that aluminum is causal in autism is not made in the paper, but the case for further research is.”
Also rejecting the claim that Tomljenovic and Shaw’s research should not be published or discussed is Dr. Rob Tarzwell, clinical instructor in psychiatry at UBC. Although he is clearly in favor of vaccination, describing it as “the biggest public health improvement in human history after clean water,” Tarzwell is partnering with Shaw in organizing a program of speakers and discussions on vaccine issues at Green College on the UBC campus (18.) during 2012. The Columbia Journal has been advised the series will begin in September of this year with a presentation by Dr. Jennifer Craig, formerly of the UBC school of nursing , on vaccine history. Details on timing and on other speakers slated to appear will be on the college website this summer. The goal, Tarzwell said, is “to demonstrate that hot topics can be conducted fruitfully. We want to see the highest form of civilized and scientific discourse.”
Tarzwell, who first met Shaw when they debated vaccine safety issues on a radio show, said that although he often draws different conclusions than his UBC colleague, he thinks that open debate is the best way to settle their differences.
“Although I can see where Paul Offit is coming from in his comments, I believe that no idea in and of itself should be repressed in a free society.”
Full disclosure: I have known Shaw for several years and he has been a visitor to the board of directors meetings of the BC Civil Liberties Association, on which I sit, from time to time.)