As a semi-retired epidemiologist, in a higher risk age group and with attendant co-morbidities, I have followed the Covid-19 pandemic with scientific curiosity mixed with a tinge of personal anxiety.  Much of the data being reported is of abysmal quality, and it’s a major professional disappointment to me that, after more than four months, the situation hasn’t improved much.

As a semi-retired epidemiologist, in a higher risk age group
and with attendant co-morbidities, I have followed the Covid-19 pandemic with scientific
curiosity mixed with a tinge of personal anxiety.  Much of the data being reported is of abysmal
quality, and it’s a major professional disappointment to me that, after more
than four months, the situation hasn’t improved much.

Family members and friends, some of whom I haven’t heard
from in years, continue to pepper me with their well-intentioned questions,
fueled by the latest reports in the mainstream and social media.  Like many others, they have a difficult time sorting
through the multitude of competing claims – many of which are downright crazy
-- to make sense of things.

Growing weary of the conflicting and confusing reports, the
locally mandated “stay at home” orders and the dire consequences to their
personal finances, many Americans are clearly frustrated. A surprising number
is no longer heeding the CDC’s advice to avoid crowded in-door settings, practice
social distancing, wear masks in public and frequently and vigorously engage in
hand washing.  The public’s trust in
science, already shaky even before the pandemic, has become further eroded—and too
many are now dismissing public health advice.  


Did "endocrine disrupting chemicals" at trace levels cause coronavirus to spread? There is no plausible hypothesis for how that's even possible but it doesn't stop Linda Birnbaum and Fred vom Saal from writing it might be so.

I witnessed this first-hand recently when we finally were
able to gather together to bury my mother-in-law who passed away in early
March.  The lack of compliance was
alarming. Like other public health experts, I fear that such behavior will
spawn further waves of infection and a devastatingly higher than necessary
death toll.

Some may want to place the blame for rampant misinformation
solely at the feet of the media (and they certainly deserve their share of the
blame), but some scientists and other experts are also an important source of
the problem.  Of course, the most blatant
example has been the sudden
retraction of two studies from prominent medical journals due to possible
fraud, but there are many others, as well. 

Perhaps you also read Tommaso
Dorigo’s interesting article “The Virus That Turns Physicists Into
Crackpots” on Science 2.0.  His
conclusion, “…the scientific method is something to treasure and hold dear
and protect” certainly resonated with me. 
He further noted, “It is not something we can give for granted, or
something that once you learn to apply will stick with you for the years to
come. Scientific truths can only be learnt by a painful, slow process made
of small uphill steps.” Unfortunately, too many scientists these days
have forgotten this and, often motivated by personal agendas, continue to try
to short-cut the process by jumping directly to policy-making from incomplete,
inaccurate and uncertain science.

 

A closer look: Unfounded
allegations about chemicals and COVID-19 outcomes

As another example, I recently came across a series of four
Op-Eds one by
Heindel and Birnbaum, a second
by vom Saal and Cohen, a third
by Myers and a fourth
by Trasande and Ghassabian that allege that low level exposure to purported
endocrine disrupting chemicals (EDCs) has contributed to high prevalence rates
of selected chronic diseases in the US population that are alleged to have been
shown to render Covid-19 patients more vulnerable to severe complications,
including increased mortality. 

A small, yet clearly coordinated
echo chamber

Although published separately by four groups, the articles
should NOT be considered independent of one another as at least four of the
authors (Birnbaum, Heindel, vom Saal and Myers) have worked closely together
for more nearly 30 years to promote their unconventional views.  This fact, the overlapping messages, and the
close timing of all of the four Op-Eds, strongly suggests the authors have
collaborated in an attempt to amplify their message in the media.  They seem to operate most comfortably in
an echo chamber they have created for themselves, and unsuspecting readers
might be given the impression that their claims are more mainstream than they
really are.  Further evidence of their
collusion is the June 18
webinar organized and delivered by authors from three of the groups.

For many years, these authors have been pushing an unproven
and dubious hypothesis, i.e., that exceedingly low level exposures (far below those of more potent
natural exogenous or endogenous hormones) to certain synthetic chemicals
are an important cause of many chronic diseases, and are now opportunistically
exploiting the Covid-19 crisis to further their cause.  (In the case of vom Saal and Cohen, they are
also trying to exploit the situation to selfishly promote sales of their
forthcoming book, which they none to subtly advertise at the end of their
article.) Trasande also recently published a book pushing the hypothesis and
has been shamelessly traveling the country promoting sales. 

At best, their efforts should be considered a distraction
that takes the public’s eye off of the most important things they can do at
this time to protect themselves and their loved ones. At worst, it is nothing
more than blatant opportunism exploiting a global tragedy that is
reprehensible and should be called out for what it is by the entire scientific
community.

A lack of restraint, a lack of evidence

On a positive note, I should start by acknowledging that,
after many months of being bombarded with conflicting information about
COVID-19, the public has not totally lost trust in public health experts. A
recent survey conducted by the New York Times and Siena College shows a
large majority of Americans registered to vote quietly trust the advice of
medical experts.  But the research also
shows two key factors tend to dilute trust in public health: political
polarization and mixed and confusing messages. 
Both are present in the current Covid-19 crisis and are trending in the
wrong direction.  As a another sign of
the fragility of public trust, consider that one-third
of Americans said they would NOT get vaccinated against Covid-19, even if a
safe and efficacious vaccine is widely available at low cost.  

A significant irony exists when one contrasts the
meticulous, science-driven approach taken by Dr. Anthony Fauci, Director of the
National Institute of Allergy and Infectious Diseases, when he discusses the
Covid-19 outbreak, with the more freewheeling, speculative approach taken by the
authors whose claims are the subject of this analysis. Fauci sticks to what has
been firmly established through the scientific method (e.g., he insists
on well-designed and conducted clinical trials to evaluate potential
preventative as well as therapeutic treatments and weight of the evidence
evaluation) and refuses to engage in speculation.  By contrast, the authors of the four Op-Eds
employ much less rigorous scientific standards and seem to revel in
speculation.

Although I was initially reluctant to write anything about
these articles for fear of giving them more attention than is warranted, I’m
convinced that, if left unchallenged, their messages will ultimately do more
public harm than good.  One reason for my
concern? The authors are clever – they skillfully weave well-established
facts and mere speculation seamlessly together to make their points.  Below, I will try to disentangle the two to
bring greater clarity to the situation.

Facts

 

  • Although it is true that
    the prevalence of certain chronic health conditions (e.g., obesity, and
    type 2 diabetes) have been rising in the U.S, the CDC and
    most scientists believe this is largely or wholly attributable to:
    high-calorie, low-nutrient foods and beverages; not getting enough
    physical activity; sedentary activities such as watching television or
    other screen devices; medication use; and poor sleep routines.  Most authoritative reviews of the
    causes for obesity and type 2 diabetes do not even discuss a possible role
    for purported EDCs.

 

  • The trends in the
    prevalence of other diseases that were lumped together by the authors of
    the four op-eds are more complex than they acknowledge as is explained
    below.  Once again, most
    authoritative reviews of causes for these diseases do not even mention a
    role for purported EDCs.
    • Chronic Respiratory
      Disease      :  A 2017
      published study       found mortality from chronic respiratory disease
      increased in the U.S. from 1980 to 2002, but has been declining
      since.  Chronic respiratory disease
      includes: chronic obstructive pulmonary disease (COPD), interstitial lung
      disease and pulmonary sarcoidosis, asthma, and all other chronic
      respiratory diseases.  The op-ed
      articles highlight asthma, however, the asthma mortality rate actually
      declined by 46.5% between 1980 and 2014. 
      Nearly three-quarters (73.4%) of deaths due to chronic respiratory
      disease in the United States have been attributed to tobacco smoke,
      including 81.8% of deaths due to COPD. 
      Occupational exposure to certain dusts (asbestos, coal dust and
      silica) is a significant risk factor for mortality from chronic
      respiratory diseases, particularly pneumoconiosis; however, long-term
      declines in mortality attributed to these dusts, follows the
      establishment and enforcement of exposure limits in the 1960s and 1970s,
      as well as declining participation in occupations associated with
      exposure.
    • Cardiovascular Disease
      (CVD)       – From
      1970 to 2010, the death rate from CVD dropped in half in the US and this
      has been attributed to improved pharmacological management, advances in
      surgical techniques, and healthier lifestyles.        Since 2010, the pace of
      decline in the death rate from CVD has slowed for unknown reasons.        According to the
      CDC, the most important risk factors for CVD are high blood pressure,
      high cholesterol and smoking      . 
      Other contributing factors include: diabetes, obesity, unhealthy
      diet, physical inactivity, and excessive alcohol use.
    • Autoimmune System
      Diseases/Dysfunction      : A
      2015 systematic review       found the following:
      • Multiple publications
        exist, describing past or actual incidences/prevalence of individual
        autoimmune diseases, however, long term studies on selected populations
        are scarce.
      • Results: The means ±
        s.d. of the net % increased /year incidence and prevalence of autoimmune
        diseases worldwide were 19.1 ± 43.1 and 12.5 ± 7.9, respectively.
        Rheumatic, endocrinological, gastrointestinal and neurological
        autoimmune diseases revealed the following annual % increases per year:
        7.1, 6.3, 6.2, and 3.7, respectively.
      • In all of these,
        differences between old vs new frequencies were highly significant
        (p 0.0001). Comparing various autoimmune diseases, celiac disease
        increased the most and the highest increase in incidence, comparing old
        to new surveys is allocated to myasthenia gravis. Despite considerable
        variations between the countries, celiac, type 1 diabetes and  myasthenia gravis frequencies
        increased the most in Canada, Israel and Denmark, respectively.
      • Frequencies of the
        autoimmune diseases increased significantly in the West and North when
        compared to East and South, respectively. Rheumatic, endocrinological
        and gastrointestinal autoimmune diseases in Israel, Netherlands, USA and
        Sweden increased the most.
      • These observations point
        to a stronger influence of environmental factors as opposed to genetic
        factors on autoimmune disease development; however, the definition of
        environmental factors should be interpreted in its broadest sense (i.e.,
        including lifestyle factors) and the precise factors that contribute are
        unknown.

 

 

 

 

Speculation

 

  • As evidence of the type of
    speculation in which these authors engage, consider the following quote
    from vom Saal and Cohen:
    • “In the U.S., these
      chronic diseases have been steadily increasing over the past 50 years,
      associated with the dramatic increase in chemical production for use in
      plastics, construction materials, pesticides, personal care products,
      furniture, cookware, food packaging, textiles, and many other products
      that are steadily infiltrating every aspect of human life.”
    • First, as discussed above,
      the trends in prevalence of these diseases has not been uniformly
      increasing during the past 50 years as is alleged.  Also, the correlation they hypothesize
      is really quite crude, and, at the risk of insulting readers its worth
      remembering that correlation does NOT equal causation.  One needs to only consider the many
      other changes that have taken place in society in the past 50 years
      (dietary changes, less physical activity, computer and internet usage,
      rate of consumption of alcohol, volume of air travel, etc.) to understand
      how over-simplified the authors’ logic is.
  • The authors of the Op-Eds
    claim that causal links have been established between exposures to EDCs
    and the chronic health conditions they list; however, this is mere
    speculation on their part and there is not a consensus among scientists
    that this is true. 
  • In prior publications by
    these authors and their collaborators they have been guilty of
    cherry-picking the scientific literature, including only the studies that
    support their hypothesis and excluding those that don’t.  They have often relied heavily on novel
    toxicology studies that failed to conform to international guidelines, and
    which have not been independently replicated. These studies have often
    employed small numbers of uncommonly used strains of animals, questionable
    dosing and flawed statistical methods. 
    In formulating their allegations, these authors have also relied
    heavily on observational epidemiology studies that cannot, in and of
    themselves, reliably establish causal relationships between putative EDCs
    and health effects.  Such studies
    are often limited by small population sizes, poor assessment of exposures,
    and suffer other flaws which make it impossible to rule out bias, confounding
    or chance as alternative explanations for the associations they report.
  • The following quote from
    the Heindel and Birnbaum op-ed is telling:
    • “While we can't pin the
      elevated U.S. disease numbers solely on exposures to endocrine disrupting
      compounds, it is clear that all of the disease and health conditions
      listed above (diabetes, obesity, heart disease, immune system
      diseases/dysfunction and respiratory diseases) have been linked to
      exposure to a variety of endocrine disrupting compounds in animal models
      and human epidemiology studies.”
    • The use of the phrase
      “…linked to…” seems to be a tacit acknowledgement that causation has NOT
      been firmly established.  As
      noted above, most authoritative reviews by scientists who study those
      chronic diseases do NOT even acknowledge EDCs among the risk factors they
      identify.

 

  • And according to Trasande
    and his colleague:
    • “Is the evidence perfect?
      Hardly. And we have to rely on observational studies – you can’t run a
      randomized controlled trial of potentially toxic mixtures of virus and
      chemical exposures. There are ethical and logistical challenges to
      running these kinds of studies. But absence of evidence doesn’t mean
      absence of harm.”
    • No one could disagree
      that the evidence these authors rely on is far from perfect – in fact, as
      Trasande acknowledges it is largely absent.

 

  • Heindel and Birnbaum also
    include the following quote:
    • “Improving our diet and
      nutritional status and reducing our exposure to endocrine disrupting
      chemicals are pivotal changes that will profoundly benefit our health and
      welfare.”
    • They focus exclusively on
      diet and EDCs to the exclusion of many other far more important risk
      factors such as: tobacco use, alcohol and drug abuse, untreated high
      blood pressure, untreated high cholesterol, lack of physical activity,
      sedentary lifestyles, etc.  This
      does NOT constitute sound public health advice.

 

  • Similarly, vom Saal and
    Cohen state:
    • “Individual lifestyle
      changes, which include increasing intake of nutrient-rich, unprocessed
      fresh or frozen foods that do not contain endocrine disrupting chemicals,
      drinking water without pollutants, improved sleep, stress management, and
      regular aerobic exercise, are regarded as cornerstones in reducing risk
      for developing most chronic diseases.”
    • They fail to mention
      tobacco use, alcohol and drug abuse, untreated high blood pressure, and untreated
      high cholesterol and thus are also guilty of miserably failing to
      educate their readers on the most important risk factors.

 

  • The authors allege there
    are numerous EDCs in commerce, yet they often confuse chemicals that are
    merely endocrine active with those that are true EDCs.  The WHO defines an EDC as “an exogenous
    substance or mixture that alters function(s) of the endocrine system and
    consequently causes adverse health effects in an intact organism, or its progeny,
    or (sub)populations.”  By the WHO
    definition, there are far fewer EDCs in commerce than has been alleged.

 

 

  • The authors also speculate
    a role for some EDCs in causing inflammation without citing a convincing body
    of scientific evidence.  They
    further speculate on possible synergy between poor nutrition and exposure
    to EDCs to create an abnormal inflammatory response, but once again there
    is little to no scientific evidence to support this.

Just last week, The
Intercept published an article that picked-up on the hypothesis from these
authors and included reference to some additional research that they and their
colleagues are planning.  For instance, Philippe
Grandjean, a Danish scientist and frequent collaborator with this group, is
reportedly in the process of collecting blood samples of people who were
hospitalized with Covid-19 , analyzing them for PFAS levels, and comparing them
with PFAS levels from the blood of people who were infected with the
coronavirus but not hospitalized. 
Presumably, he will be employing a cross-sectional study design with a
single-point-in-time measurement of exposure after disease has already been
diagnosed.

I’ve previously discussed the severe inherent
limitations of such an approach to identifying potential causal relationships
between purported EDCs and disease and have argued that it is time to move beyond cross-sectional studies
to more reliable epidemiology study designs. Supporting my contention, just
recently, the European Food Safety Authority opined
that they considered the evidence from cross-sectional studies as too
unreliable to give them much
weight in their safety assessments.

Others are using
animal experiments to explore how chemical exposure affects the impact of the
coronavirus. Paige Lawrence, a professor of environmental medicine at the
University of Rochester School of Medicine and Dentistry, plans to infect mice
with a mouse-adapted human coronavirus that was built from the 2003 SARS
pandemic and study how exposure to PFAS alters the course of the viral
infection.  As others have pointed out, the viruses that cause SARS and Covid-19
resemble one another at some level, nevertheless there are distinct features
that will inevitably call into question the generalizability and relevance of the
results (e.g., SARS had a much higher case fatality rate, whereas Covid-19 is
far more infectious).

When the results of
these planned studies are published readers would be advised to treat them
skeptically, at least until other scientists have had a chance to independently
replicate them using stronger and more relevant methods.  One of my favorite quotes is from an article by Julia
Belluz and Steven Hoffman:

 

“That science can fail, however, shouldn’t come as a surprise to anyone.
It’s a human construct, after all. And if we simply accepted that science often
works imperfectly, we’d be better off. We’d stop considering science a
collection of immutable facts. We’d stop assuming every single study has
definitive answers that should be trumpeted in over-the-top headlines.
Instead, we’d start to appreciate science for what it is: a long and grinding
process carried out by fallible humans, involving false starts, dead ends, and,
along the way, incorrect and unimportant studies that only grope at the truth,
slowly and incrementally.”

 

“A theory that explains everything, explains nothing”

In conclusion, after conducting a detailed review of the
articles in question, I can say with confidence that the authors have blatantly
mischaracterized the weight of scientific evidence linking chemicals to chronic
disease by weaving together a narrative that tries to blur the lines between
fact and speculation. They implausibly link EDC exposure to a broad range of
chronic diseases, which calls to mind for me the quote from the brilliant
science philosopher Karl Popper, “A theory that explains everything,
explains nothing.”  At risk is a
further undermining of public trust in science and public health advice that
are critical to controlling the spread of this novel, and dangerous virus.

Unfortunately, given
the significant flaws in the evidence cited to support their hypothesis, and
the previous track records of the authors in question, readers are unfortunately
left to deduce that the authors may in fact be shamelessly exploiting a global
tragedy to promote their own personal agendas.

By publishing this piece, my hope is that other scientists
with similar concerns will also join in calling them out for it.

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Gregory Bond

Dr. Gregory Bond obtained a Ph.D. in Epidemiology after receiving a Bachelor of Science degree in Microbiology and a Masters in Public Health, all from the University of Michigan. Dr. Bond has published more than sixty peer-reviewed journal articles on epidemiology research and product stewardship. In 1988, he was elected a Fellow in the American College of Epidemiology. He has served as an advisor to various government agencies, including the U.S. Environmental Protection Agency, the National Institute for Occupational Safety and Health, the National Cancer Institute, the Agency for Toxic… Read more
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