Quantifying Moral & Legal Culpability with
Epigenetics
Case Studies with PTSD, BPA, and Fetal Alcohol Syndrome
Julia McGirr
Julia_mcgirr@brown.edu
Brown University
Dept. of Molecular Pharmacology, Physiology, and Biotechnology
Introduction
What if there was a way we could quantify moral and legal culpability? One of
the reasons morality is so abstract and legal culpability is so complex is because we lack
the ability to measure our social interactions and quantify the negative and positive
effects we have on each other. Epigenetics could provide a way for us to do exactly that
by providing that elusive, mechanistic link between our environmental experiences and
our biological and physiological functioning. Epigenetics can supplement and shape our
current system of law and governance by providing a means to measure what we could
only guess at with intuition before. We could see a paradigm shift as for the first time,
instead of the law seeking to govern biotechnology, we could see biotechnology aiding in
the implementation of the law itself.
Abstract
Here I present a proposal for and evaluate the practicality of using the epigenetic
changes within a victim as a means to gauge the moral and legal culpability of the given
offender or offenders. Using a series of case studies, the applicability of this idea on the
micro, macro, and transgenerational scales is explored. The implications of this proposal
will continue the dialogue on the theory, purpose and practice of the law itself while
beginning a new dialogue on how it could be altered by epigenetics.
Background
Epigenetics is the study of gene expression not related to the actual DNA
sequence. Instead, epigenetics is related to how tightly the DNA is wrapped into
packages called nucleosomes or how active the promoters of the genes are, both altering
gene expression. The main point of differentiation between epigenetics and genetics is
that epigenetic modifications of DNA are dynamic, are influenced by the environment,
and are sometimes trans-generationally heritable.
The most well-studied epigenetic modification is carried out by enzymes called
DNA methyltransferases. These proteins add methyl groups to the promoter regions of
genes, which represses the transcription of these genes by blocking crucial transcription
factors from binding and activating transcription. Another type of epigenetic modification
is carried out by histone acetyltransferases. These enzymes add acetyl groups to the
histone proteins which the DNA is wrapped around, decreasing the tightness with which
the DNA is wrapped and therefore increasing gene expression. DNA methyltransferases
and histone acetyltransferases, together with other epigenetic enzymes, create an
epigenome which is dynamic and is constantly altering which genes at a given time are
expressed within our bodies.
Figure 1: A diagram of how histone modifications change gene expression.
(http://www.resverlogix.com/programs/epigenetics/#.U9AJRKjgWrs)
To date, the effects on the epigenome of diet, stress, and chemicals have been
well-documented [1], and our collection of knowledge regarding environmentallyinduced epigenetic changes only continues to grow. Overall, epigenetics provides a
unique translational promise of being able to directly tie our experiences and
environmental stimuli to the corresponding physiological changes within our bodies that
occur as a result of measurable changes in gene expression.
The intersection between traditional genetics and the law has so far been mainly
reserved to the use of DNA testing as forensic evidence. In this instance, genetics is
applied in a black-and-white manner as it is decided whether or not the defendant has
committed a given crime based on the matching of their DNA to the DNA found at the
crime scene. This is a valuable tool for law enforcement because our DNA sequence is
unique to us and unchanging over time. On the other hand, the use of epigenetic data by
law enforcement would present an entirely new scenario because our epigenome (which
genes within our DNA sequence are expressed) does change over time. Thus, epigenetics
will provide us with a grayscale application rather than a black and white one. However,
once it has been determined that a defendant has committed a given crime, this grayscale
could potentially be well suited to providing a means by which the justice system can 1)
quantify the severity of the crime committed and 2) calibrate the appropriate
corresponding sentence.
Case Studies
Micro Scale: PTSD
Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder that develop in a
subset of people in the aftermath of a traumatic experience [2]. The research regarding
the epigenetics involved with PTSD has centered around alterations in levels of brainderived neurotrophin factor (BDNF) which is crucial for fear memory extinction and
emotional learning [3]. It has been speculated that the underlying cellular mechanism of
PTSD is altered hippocampal BDNF methylation, and an association has been effectively
shown in a rat model of PTSD [2]. It has also been demonstrated in rats that BDNF
mRNA levels were decreased as a result of mistreatment during early life. This suggests
that early life exposure to stressful conditions could lead to epigenetic alterations of the
BDNF promoter which could then in turn affect production of BDNF later in life [3].
Figure 2: A diagram of how fear conditioning can induce epigenetic modifications via
(a) increased histone acetylation or (b) decreased histone methylation. (Adapted from
Maddox et al)
The case study of PTSD allows us to examine how epigenetics might be applied
on a micro scale where there is one victim and one offender. For example, in a case of an
assault or rape, the epigenetic changes, for example the BDNF pathway, within the victim
can be assessed and the sentencing can be adjusted accordingly. This presents us with a
relatively simple scenario in which only one person’s epigenome must be assessed. It gets
slightly more complicated once the use of epigenetics is moved to the macro scale.
Macro Scale: BPA
Bisphenol-A (BPA) is a compound found in many commercial plastics and
consumer goods that acts as a synthetic xenoestrogen by mimicking the effects of
estrogen and activating nuclear and membrane estrogen receptors [4]. This inappropriate
activation of the estrogen receptors causes a feminization effect that has been
demonstrated in Xenopus tadpoles [5] as well as in male rats and their unexposed male
progeny [6]. The adverse effects to humans caused by the environmental prevalence of
BPA and other endocrine-disrupting compounds (EDCs) has lead to the push for the reencapsulation of BPA from the environment and the water supply [7][8][9].
Figure 3: The structures of these compounds are similar to that of naturally-occurring
estradiol, explaining their effects as endocrine disrupting compounds.
BPA exposure can also alter DNA methylation patterns [1]. If genes that should
be repressed are hypomethylated, then those genes will be ectopically or over-expressed
as a result of BPA exposure, which could lead to adverse physiological outcomes. These
alterations in DNA methylation patterns however can be utilized in order to quantify the
effects of BPA being used in products and/or being released into the environment. Once
the epigenetic changes have been assessed within a given exposed population, this data
can help inform public policy regarding the commercial use of BPA or can be used as
evidence in cases brought against companies who have perpetuated the release of BPA
into the environment.
Figure 4: BPA induces alterations in DNA methylation, which is harmful in that it can
adversely affect gene expression but also is potentially useful as a gauge of an
individual’s exposure to BPA. (Adapted from Feil and Fraga 2011)
Also of potential interest is that the metabolism of BPA is faster in female rats
than in male rats. This is due to different levels of UGT2B1 which is the enzyme that
converts BPA into a less toxic and estrogenic form [10]. This suggests sex-specific
susceptibility levels to BPA which should be taken into account if the epigenetic changes
within a certain group are being tested.
Overall, the use of epigenetics with the case study of BPA demonstrates the larger
challenges that arise in the application of this proposal on the macro scale. Many victims
are involved and potentially many companies are responsible for the perpetuation of BPA
levels in the environment. However, if these challenges can be sorted out, epigenetics
would provide a tremendously useful tool to guide and inform our public policy
regarding the release of chemicals like BPA into the environment or their use in
consumer goods.
Transgenerational Scale: Fetal Alcohol Syndrome
Fetal Alcohol Spectrum Disorders (FASD) encompass a wide variety of
phenotypes seen in the offspring of mothers (and fathers)[11] who engage in alcohol
consumption before and during pregnancy. Physical manifestations include craniofacial
dysmorphology, pre- and post-natal growth retardation, and abnormal development of the
central nervous system [12].
Figure 5: Ethanol exposure during pregnancy creates small for gestational age
offspring, with the most severe response when the ethanol was given early in the
pregnancy (day 6). (Adapted from Gundogan et al)
FASD provides a useful case study for application of the proposal on the transgenerational scale because consumption of ethanol during pregnancy affects at least three
generations: the mother, the developing fetus, and the germ cells (future sperm or eggs)
within the fetus that will create the next generation (Figure 5). Epigenetic changes are
known to span these three generations and potentially beyond as epigenetic remodeling
during the crucial window during development in utero can have tremendous future
implications (Figure 6).
Figure 6: Summary of some of the modifications resulting from in utero ethanol exposure
that lead to the transgenerational symptoms of FASD. (Adapted from Ramsay 2010)
The concept of trans-generational justice is controversial. Should a mother be held
responsible for the deformations and impaired motor coordination of not only her
children, but grandchildren and great-grandchildren because she drank alcohol while
pregnant? It is a complicated issue, but one in which epigenetics can be utilized as a way
to track the physiological changes in the offspring due to the actions of the mother. Once
this direct chain of events is illuminated and can be demonstrated on a case-by-case basis,
we could potentially see this sort of trans-generational justice being implemented by the
courts.
And so, this last case study represents perhaps the most complicated use of this
proposal in the real world. Not only are multiple victims involved but there is a
separation in time between each victimization that could prove challenging to deal with.
However, if all that arises from further trans-generational epigenetic research is an
increased awareness of the consequences our actions have on future generations in a real,
quantifiable way, then we are already improving as a society for the better.
Practicality
Although there are many other factors to consider in order for epigenetics to be
used as an effective gauge of legal culpability, there are two necessary components for
practical application: 1) a relatively cheap and facile way to assess epigenetic
modifications and 2) a control for comparison. The source for comparison can be based
on the individual’s epigenetic profile prior to the insult, but this would require a preexisting profile on record. This would be further complicated by the fact that epigenetics
varies depending on tissue and cell type. The other possibility would be a case-controlled
population comparison in which the epigenetic profile in question is compared to samples
from people in the population that (as best determined) have not been exposed to the
insult. The feasibility of both approaches depends on the exponential growth in the
accessibility of the assays and the compilations of large amounts of shared, digitized
epigenomic data.
Bioethical Questions
As reviewed by Rothstein et al [13], the application of epigenetics on the macro
scale could be stalled by all sorts of complications arising from other hard-to-control-for
factors in a world of ubiquitous toxin exposure. As a result, this epigenetic system most
likely would see best practice on the micro level. The use of epigenetic data on the micro
scale to create a system of “personalized justice” was a concept put forth by Wong et al
in 2010. However, while Wong wanted to use the epigenetic profile of the defendants in a
criminal case to testify to mitigating factors in their actions [14], epigenetics can also be
used to testify to a victim’s predisposition to developing PTSD and/or to quantify the
severity of the defendants’ action. While Wong et al did have it right that not all victims
are the same due to their epigenetic make-ups, it is important to extend the same
consideration to the victims. Some are more prone to developing PTSD than others, and it
is an important conversation that needs to be had whether or not the sentences of the
offenders should be adjusted accordingly.
The use of epigenetics to dole out different punishments depending on the
severity of the epigenetic insults the victim has suffered raises some important questions
about the role of the law in society. To base a criminal’s punishment on the quantified
consequences of his or her actions instead of on the action itself automatically favors a
consequentialist system of ethics. It is an important dialogue to have whether this new
consequentialist proposal will fit into the current system of law we have in America.
Conclusion
Overall, there are several important factors that must be considered in any legal
case such as motive and circumstances. It is my proposal that epigenetics can and will
provide us with a crucial means of quantifying what we could previously only guess was
the emotional, psychological and physiological impact on the victims. However, the use
of this system will bring up important questions regarding our responsibilities to future
generations and will force us to think more deeply about how our actions can influence
people we might never come into contact with. Lastly, the use of epigenetics in the legal
and policy systems favors a consequentialist system of ethics, and it remains to be seen if
this method of scientific quantification will be embraced by the slow-turning and slowchanging wheels of the justice system.
Acknowledgments
I would like to thank the Yale Interdisciplinary Center for Bioethics, and especially Carol
Pollard, for fostering my growth in the field of Bioethics and for allowing me to present
my work at the Symposium.
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