Cells in a Petri dish are not people, and experiments with cells can easily give the wrong answers

Autism's False Prophets: Bad Science, Risky Medicine, and the Search for a Cure
Answers to the wrong questions.
The moral message of this short story, taken from Paul Offit’s inspiring Autism’s False Prophets, is that fuzzy thinking about biology and human health can easily lead people and activist movements to do well intentioned, but tragically dangerous and stupid things.
Lyn Redwood is a nurse practitioner who lives in Atlanta, Georgia. By the time her third child, Will, was born, she had been a medical professional for twenty years. “My son Will weighed in at close to nine pounds at birth,” she said. “He was a happy baby who ate and slept well, smiled, cooed, walked, and talked all by one year of age.” But after his first birthday, Will began to change. “He lost speech, eye contact, and suffered intermittent bouts of diarrhea, [then he was] diagnosed with pervasive developmental delay, a form of autism.” When the AAP issued its press release in July 1999 urging the immediate removal of thimerosal from vaccines, Redwood called her doctor’s office. “I reviewed [Will’s] vaccine record and my worst fears were confirmed,” she said. “All of his early vaccines that could have possibly contained thimerosal, had.” Redwood believed she had found the cause of her son’s autism.
Paul Offit goes on to describe how, in the 2000s,  the mercury containing vaccine preservative thimerosal was viewed as the cause of autism by some scientists, and by many parents, such as distraught parents like Lyn Redwood who were entangled in the very trying circumstances of their own child having the behavioural patterns of autism.
In vitro means artificial biology out of the body.
Simplification is a very powerful way of making scientific progress in biology, because intact biological systems, such as people and human communities are very complicated. Around the year 2004, a simplified scientific method led to thimerosal chemical (which is a preservative that is added to vaccines) being fingered as the cause of the developmental disorder autism in children.
One part of this  simplified approach was — rather than directly testing the effects of thimerosal on intact whole animals or people — to test the chemical for effect on living organism human cell components separated away of the body. This involves doing experiments involving mercury or thimerosal exposure to artificially cultured living human cells proliferating as artificial thin layers of tissue growing in Petri dishes.
This in vitro investigation method is easier than doing more expensive, complicated  and ethically difficult studies on humans themselves as whole living organism’s, and simpler even more than directly investigating what’s happening with real human disease in populations of living people who suffer actual health problems.
But in interpreting the outcomes of these experiments it is important to bear in mind that cells artificially cultured outside the body are in a much more sensitive situation when it comes to exposure to chemical agents. The normal protective barriers of skin and intestinal layers and blood brain barriers are absent, excretion systems such as the kidney are missing, and doses of chemicals in in vitro tests can be unrealistically high compared to what dose will appear inside the body in a real-life situation.
The dose makes the poison.
The dose of chemical to which the potential target of chemical damage is exposed is always a crucial factor in determining whether any toxic effects on the body will happen. The dose makes the poison, and in fact everyone of us is exposed every day to very low doses of mercury, but we don’t all suffer from mercury poisoning.
It’s always important in biology to ask “What happens inside the living organism — in vivo?” A simplified “in vitro” approach can give you answers, but when you do investigations away from the living organism you always should check rigorously to see whether the simplified system is giving answers to the wrong questions.
Science-in-reverse can get you into trouble, and put the cart before the horse
Paul Offit uses the expression “science-in-reverse” to explain how simplified biological experiments can give misleading answers about causes of autism. He’s referring to the logical trap of jumping the gun, and using “in vitro” experiments with isolated component of the human body exposed to mercury compounds in Petri dishes to formulate a presumptive mechanism for how the disease occurs, before checking carefully and conclusively that exposure to mercury compound in a living human actually does cause autism.
The crucial problem with this science-in-reverse is that microscopic behaviour of a body component in an artificially devised system may be irrelevant to the real disease process. Answers can be found, but they are misleading answers because the wrong questions are being posed. It’s putting the cart before the horse.
In a later passage of the book to that given above, Paul Offit relates how this presumed mechanism-based microscopic dissection approach — science-in-reverse — seemed in the year 2004 to be giving answers to what causes autism:
… Boyd Haley, a professor and chairman of the department of chemistry at the University of Kentucky, was a superb researcher who had published several papers in the Proceedings of the National Academy of Sciences—a publication of the National Academy of Sciences and a highly respected scientific journal internationally. Haley proposed that tubulin, a protein in cells necessary for their movement, was damaged by thimerosal. “Inhibit tubulin function with thimerosal injections,” he said, “and you inhibit the immune response {causing autism].” Lyn Redwood [as an anti-vaccine activist] was happy to have Boyd Haley on her side. “He understands the levels of exposure that our infants received,” she said. “That’s why Dr. Haley is such a wonderful advocate for us. He reads the science and understands it.”
Soon Boyd Haley was joined by another biochemist: Richard Deth, a professor of biochemistry at Northeastern University in Boston. In 2004, Deth had written a paper published in Molecular Psychiatry that weighed in on the thimerosal debate. Using nerve cells grown in laboratory flasks, Deth had found that thimerosal inhibited an important metabolic pathway. He reasoned that some children were probably better able to use this pathway to excrete mercury, and to avoid its toxic effects, thanothers. And, like the Geiers, Deth believed he had found a cure. Testifying before Dan Burton’s Committee on Government Reform, Deth said, “The good news that goes along with this [knowledge] is that metabolic interventions are proving to be effective for autism. These treatments include [vitamin] B12 itself, which can produce dramatic improvements in some kids. Giving B12 turns out to be an antidote for [mercury].” Richard Deth believed he had found a cause (alteration in cellular metabolism) and a treatment (vitamin B12) for autism.
The big problem with this line of argument is that it was an illusion, because thimerosal in vaccines was not the cause of autism.
The encouraging findings in the quoted passage just above were indeed answers to the wrong questions. Subsequent investigations, and the well documented experiences of countries which withdrew thimerosal preservative from vaccines, found that autism rates continue to rise even without any thimerosal in vaccines, proving conclusively that there was no connection between presence of thimerosal in vaccines and development of autism in children. In fact, vaccines don’t cause autism.
But chasing after the wrong explanation of autism — science-in-reverse — not only gave us the wrong answers about biology, it was also dangerous because it suggested treatments for autism which are not only useless, but harmful. And many people were exposed to these dangerous treatments, as described vividly and comprehensively in  Autism’s False Prophets and other books about the anti-vaccination tragedies of recent years. Worse still, wrong answers about thimerosal added to general parental confusion about whether vaccines were safe, and vaccination rates fell in many communities in the USA and Europe, leading to many cases of unnecessary disease and tragic death from vaccine preventable disease.
It important to get  the scientific method right when people’s lives and health at stake. Autism’s False Prophets shows why bad science, risky medicine, and the search for a cure can be dangerous.
***
Autism’s False Prophets: Bad Science, Risky Medicine, and the Search for a Cure. Paul A Offit MD, Columbia University Press 2008
David Tribe

Written by David Tribe

David Tribe’s research career in academia and industry has covered molecular genetics, biochemistry, microbial evolution and biotechnology. He has over 60 publications and patents. Dr. Tribe's recent activities focus on agricultural policy and food risk management. He teaches graduate programs in food science and risk management as a Senior Lecturer in the Department of Agriculture and Food Systems, University of Melbourne.

8 comments

  1. Actually Dvaid, if one does a pubmed search for “thimerosal autism” they will get references to 146 papers. Of these papers, 78 generate original, published data. If one reads these studies, they will find that 75% support the thimerosal/autism link. You’re just repeating a vaccine manufacturer’s talking point.

  2. Thimerosal has been banned in a number of states in the US, yet the ‘autism epidemic’ continues unabated. On a related note, the ‘autism epidemic’ has been shown to be an artifact of rampant mis-diagnosis.

  3. Hi Joe, I would like to learn more. Do you have a list of which papers prove the link and which do not? I did the search and didn’t see any on the first two pages that claim a link between autism and thimerosal, but perhaps I’m not looking for the right things.
    I did find 2 different review articles right on the 1st page of search results that found no link: Closer look at autism and the measles-mumps-rubella vaccine and Does thimerosal or other mercury exposure increase the risk for autism? A review of current literature. Hmm. Perhaps these researchers aren’t looking at the right papers either.
    I look forward to a list! Maybe a link to a public Google doc?

  4. Joe,
    Here is what Pubmed has to say about the epidemiological evidence, which is the most important evidence.
    1: Price CS, Thompson WW, Goodson B, Weintraub ES, Croen LA, Hinrichsen VL, Marcy
    M, Robertson A, Eriksen E, Lewis E, Bernal P, Shay D, Davis RL, DeStefano F.
    Prenatal and infant exposure to thimerosal from vaccines and immunoglobulins and
    risk of autism. Pediatrics. 2010 Oct;126(4):656-64. Epub 2010 Sep 13. PubMed
    PMID: 20837594.
    2: Schechter R, Grether JK. Continuing increases in autism reported to
    California’s developmental services system: mercury in retrograde. Arch Gen
    Psychiatry. 2008 Jan;65(1):19-24. PubMed PMID: 18180424.
    3: Thompson WW, Price C, Goodson B, Shay DK, Benson P, Hinrichsen VL, Lewis E,
    Eriksen E, Ray P, Marcy SM, Dunn J, Jackson LA, Lieu TA, Black S, Stewart G,
    Weintraub ES, Davis RL, DeStefano F; Vaccine Safety Datalink Team. Early
    thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J
    Med. 2007 Sep 27;357(13):1281-92. PubMed PMID: 17898097.
    4: Fombonne E, Zakarian R, Bennett A, Meng L, McLean-Heywood D. Pervasive
    developmental disorders in Montreal, Quebec, Canada: prevalence and links with
    immunizations. Pediatrics. 2006 Jul;118(1):e139-50. PubMed PMID: 16818529.
    5: Madsen KM, Lauritsen MB, Pedersen CB, Thorsen P, Plesner AM, Andersen PH,
    Mortensen PB. [Thimerosal and the occurrence of autism. Negative ecological
    evidence from Danish registry-data]. Ugeskr Laeger. 2004 Sep 13;166(38):3291-3.
    Danish. PubMed PMID: 15496004.
    6: Andrews N, Miller E, Grant A, Stowe J, Osborne V, Taylor B. Thimerosal
    exposure in infants and developmental disorders: a retrospective cohort study in
    the United kingdom does not support a causal association. Pediatrics. 2004
    Sep;114(3):584-91. PubMed PMID: 15342825.
    7: Heron J, Golding J; ALSPAC Study Team. Thimerosal exposure in infants and
    developmental disorders: a prospective cohort study in the United kingdom does
    not support a causal association. Pediatrics. 2004 Sep;114(3):577-83. PubMed
    PMID: 15342824.
    8: Hviid A, Stellfeld M, Wohlfahrt J, Melbye M. Association between
    thimerosal-containing vaccine and autism. JAMA. 2003 Oct 1;290(13):1763-6. PubMed
    PMID: 14519711.
    9: Madsen KM, Lauritsen MB, Pedersen CB, Thorsen P, Plesner AM, Andersen PH,
    Mortensen PB. Thimerosal and the occurrence of autism: negative ecological
    evidence from Danish population-based data. Pediatrics. 2003 Sep;112(3 Pt
    1):604-6. PubMed PMID: 12949291.
    10: Stehr-Green P, Tull P, Stellfeld M, Mortenson PB, Simpson D. Autism and
    thimerosal-containing vaccines: lack of consistent evidence for an association.
    Am J Prev Med. 2003 Aug;25(2):101-6. PubMed PMID: 12880876.
    It’s a pretty reassuring case when you look at the details.
    I’m not repeating vaccine manufacturers talking points. Whatever made you think I am?
    Fortunately the mentioned book by Paul Offit is not the only one. There is also Seth Mnookin’s The Panic Virus which if a super read. Then also a later book by Paul Offit, Deadly Choices.
    As far as the increasing reporting of autism, this is helpful:
    http://sfari.org/news-and-opinion/in-brief/2012/clinical-research-rates-of-autism-rise-based-on-birth-year
    QUOTE: The likelihood of being diagnosed with autism has increased for children born each year since 1992, especially for individuals at the higher-functioning end of the autism spectrum, reports a study published 7 December in The International Journal of Epidemiology1.
    The results provide a lens through which to investigate theories about the rising prevalence of the disorder. Specifically, they suggest that greater social awareness of the disorder and changes to diagnostic standards are responsible for the increase, the researchers say….

  5. I really appreciate your evidence-based focus in your writing and response to comments. How refreshing to find a blog not fraught with emotional reactionary-ism. I will look forward to reading your writing in the future.

  6. There’s another example of similar mistakes with Petri dish grown cells discussed here
    The Science of Things That Aren’t So
    http://www.forbes.com/sites/henrymiller/2012/02/22/the-science-of-things-that-arent-so/
    By Bruce Chassy & Henry I. Miller
    Chemistry Nobel Laureate Irving Langmuir related in a landmark 1953 speech his visit to the laboratory of J.B. Rhine at Duke University, where Rhine was claiming results of ESP experiments that could not be predicted by chance, and which he ascribed to psychic phenomena. Langmuir discovered that Rhine was only selectively counting the data in his experiments, omitting the results from those he believed were guessing in order to humiliate him.
    The evidence? Rhine felt that some of the scores were too low to have occurred by chance, and that it would, therefore, actually be misleading to include them.
    Langmuir dubbed this deviation from the principles of the scientific method “pathological science,” the “science of things that aren’t so.”
    Virtually all scientists would agree that Rhine’s methodology crosses the line of incompetence and sloppiness and falls into the category of scientific misconduct, but that line is blurred today by some scientists whose research reflects an obvious political agenda. Often, that agenda is intractable opposition to and obstruction of whatever research, product or technology they happen to dislike.
    A current example of a scientist who is less guilty of actually fudging data to get the desired answer than of performing poorly designed experiments and grossly misrepresenting the results is the French biologist Gilles-Eric Séralini, who has made a specialty of poorly designed, irrelevant, uninterpretable (but over-interpreted) experiments intended to demonstrate harm from genetically engineered (also known as “genetically modified,” or GM) plants in various highly contrived scenarios….

  7. Eric, Thimerisol was not banned, it was voluntarily removed from most childhood vaccines. It remains in a few, even today. The removal was in response to the hysteria, a PR move, not a CYA move.

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