Heaven, Regulatory Hell
Comments by Dr. John Peterson Myers
International Scientific Symposium on Endocrine Disruption
28 November 2002
you, Dr. Mori.
is an honor to be with this group again. This is my 4th year at
the International Scientific Symposium on Endocrine Disruption in
Japan. I am very pleased to see how much progress we are seeing
made with every year, with every addition of new scientific results.
I would like to do in my allotted time is to ask you to rise above
the very tight focus we have had on specific details, to, instead
of looking at the trees, look at the forest of the issues that we
have been discussing. What I would argue is that as you think about
endocrine disruption and children’s health, we are in scientific
heaven but regulatory hell.
do I mean by that?
are living midstream in a scientific
revolution that is radically changing our understanding of the
links between contamination and health. The papers presented at
this meeting are carrying us forward in that revolution; just in
the last presentation we learned new things about hypospadias and
Bisphenol A. It is truly astounding.
you go to an academic library today, and carry out a search in one
of the computer databases on how many publications have there been
within the last year on one substance, on Bisphenol A, for example,
it is quite remarkable from how many different laboratories, on
how many different endpoints, how many different methods people
are now using around the world to look at these links between contamination
will find publications on aggression and behavior, findings
from Japan on concentrations in human biological fluids, and
some really remarkable
results looking at the interference of Bisphenol A with the
standard treatment for prostate cancer.
from Ehime University examines possible involvement of Bisphenol
A in increasing the conversion rate of pre-adipocytes to adipocytes,
raising the possibility that Bisphenol A is involved in the epidemic
of obesity that the world is now experiencing.
results like these are being published virtually every week, making
it difficult even for specialists to keep up with this torrent of
science. It is truly extraordinary to see what is happening.
it leads us to regulatory hell. I can imagine the regulators who
are trying to keep track of just this one compound, Bisphenol A.
It must be like the Dutch boy and the dam, where there is one leak
in the dam over here, and there is another leak over here, a 3rd
one over here, a 5th one over here, but all of the sudden in a completely
unexpected direction the dam breaks because we have completely new
results coming from a completely unexpected direction.
have heard a lot today and over the last couple of days about some
deep issues related to this regulatory hell. One of them was an
issue that Fred vom Saal touched on earlier, which is the inadvertent
contamination of experiments through endocrine disruptors in food
that is not yet understood or endocrine disruptors in some of the
lab equipment that are giving us false
controls and leading us to a literature that is probably now
polluted with many false negatives.
deeply, we are also seeing data from multiple studies of endocrine
disrupting compounds that are repeatedly falsifying the operating
assumptions at the heart of risk assessment process as it is currently
practiced. I am going to summarize what some of those core operating
assumptions are for you.
the dose makes the poison. The simplistic application of this assumption
is now clearly falsified by a whole host of data showing low dose
effects with non-monotonic
dose response curves. In fact, at the Yokohama conference we
had a panel of scientists including industry spokesperson Dr. Jim
Lamb agree that this is no longer a valid assumption. So that is
have seen some elegant work looking at thresholds
of effects. Dr. Daniel Sheehan, David Crews, and others have
shown that for systems in which hormonal systems are already activated,
there is no practical threshold for effect in that system. So that
one is out.
heard an elegant
paper by Andreas Kortenkamp this morning rejecting the notion
that you can derive useful regulatory guidelines by basing your
work only on single chemicals at a time. This is just no longer
adequate in this modern era. So that is out.
also have an assumption, increasingly prevalent, that you have to
demonstrate adverse effects in order to start regulating. But when
you look at what we really understand between changes in biological
systems and the ultimate developmental processes, you can see that
we would be incredibly arrogant to assume that we can predict adverse
effects based on our current understanding of what those changes
actually mean. So that is out.
if you listened to Dr. Elizabeth Guillette earlier this afternoon
you heard an absolutely spectacular discussion demonstrating that
the animal studies that prevail throughout regulatory science, as
important as they are, are probably not sufficiently sensitive to
get to the endpoints that parents really care about.
has been some work trying to employ operant conditioning techniques
and behavioral studies with animals to get at more sublte behavioural
effects, but they do not play a very large role in the regulatory
process and they do not get us to the sorts of endpoints that Dr.
Guillette was talking about in her work.
we have got to be looking for other sources of guidance. Is epidemiology
a good source? Epidemiology has some real problems in dealing with
endocrine disrupting compounds, also.
nonmonotonic dose response curves are deeply challenging to human
epidemiology as it is currently practiced. So is the fact that as
development unfolds in the womb, the same compound at different
times in development can lead to completely different disruptive
patterns. How does epidemiology currently cope with that? Not at
all, at least in in utero studies.
converse is also true: disruption of the same developmental process
in that same developmental window by different compounds can lead
to the same effect, dramatically increasing the statistical noise
in epidemiological work, unless at the same time you are able to
monitor all the relevant compounds that might be interfering with
that developmental process.
as Dr. Mori mentioned, long latencies can intercede between cause
and effect, decades sometimes between exposure and impact.
what is the regulatory answer here? First of all, we have to acknowledge
that the current process is fatally flawed by its dependence upon
falsified assumptions and polluted literature. We have got to start
have got to build a new science-based approach, not one that is
based on false assumptions, but is based on real data, that begins
with models that are incorporating some of the factors that I mentioned:
incorporating the low-dose non-monotonic response curves, incorporating
the fact that there can be no threshold, incorporating a focus on
mixtures at the core, and demonstration that if we find an effect
in regulatory research, we find an effect in a developing organism,
we should then reverse the burden of proof so it is not incumbent
upon us to demonstrate an adverse effect, it is instead incumbent
upon those who would wish to use the product to demonstrate that
an effect is not adverse. This will require a compete reversal of
the burden of proof.