The
Future of the Scientific Practice of Prevention
By Ralph Tarter
Many
summer afternoons were spent with my father in the
cheap seats rooting for the Montreal Royals, then
the triple A farm club of the Brooklyn Dodgers.
My dad, like thousands of men, wore a white shirt,
tie and fedora. Fast forward six decades, men today
at the ballpark typically wear a tee shirt (if any),
never a tie, and baseball cap (often pointed backwards).
Changing norms pertaining to dress mirror relaxation
of behavioral norms. Ubiquitous examples of currently
normative behavior that were only recently beyond
societal boundaries include “body art”
(previously confined to criminals and sailors),
babies born outside of marriage (currently the majority
for women under 30), and ornamental jewelry skewered
to many body parts apart from traditional earlobes.
Attributions of these changes to “secular
trends”, “birth cohort” or “historical
period effect” do not account for the causes.
Because prevention is modification of processes
predisposing to a disorder, it is essential to understand
the causes of the disorder for the intervention
to be effective. This approach to prevention is
consistent with the NIH Roadmap. Indeed, it is a
cardinal principle medicine.
Prevention is directed at either averting expression
of phenotypes comprising the prodrome (primary prevention)
or disturbance portending the clinical disorder
(secondary prevention). Since all biobehavioral
characteristics (phenotypes) result from the environment
impacting on the genotype, effective prevention
thus involves modifying gene expression. The outcome
of this intervention is the desired phenotype.
Within this framework, the concept termed individual
norm of reaction is central to prevention practice.
This concept asserts that the individual’s
genotype predisposes to a range of phenotypes (e.g.
IQ between 90 and 112). The person’s specific
expressed phenotype (e.g., IQ = 103) is the result
of the individual-specific environment affecting
expression of the genotype so as to produce a cascade
of biochemical reactions resulting in numerous neurobiological
events that ultimately manifest as physiological
and psychological traits. Clearly, this process
is enormously complex. Nevertheless, the overarching
effort in scientifically grounded prevention practice,
albeit a daunting one, requires marshalling the
appropriate environmental resources to potentiate
development of desired phenotypes. However, because
the range of possible phenotype outcomes (i.e. the
individual norm of reaction) is set by the individual’s
genotype, a discomforting reality is that the genotype
may not have the potential to realize the desired
outcome.
Let me illustrate: The average Dutch male is 6’1”
tall. During the past 200 years mean height of Dutch
men increased 7”. Because the genetic pool
of the Dutch population has not changed within this
period, the increased height is due to societal
(environment) changes enabling previously unrealized
genetic potential. Specifically, universal access
to healthcare, food availability, policies preventing
destitute poverty, social safety net that lowers
stress (and consequent psychiatric and medical disorders),
cultural norms fostering physical fitness (one quarter
of the population are members of athletic clubs)
and lifestyle emphasizing exercise (e.g. walking
and bicycling) all contribute to the increase in
stature. Dutch men are the tallest in Europe and
surpass U.S. men by an average of four inches! Nevertheless,
many Dutch men are shorter than the average American
male. Hence, despite an environment that facilitates
height, the genotype of many Dutch men prevents
attaining even the average height of Americans.
In effect, commensurate with the individual norm
of reaction principle, the genotype constrains the
benefit of the environment.
What does this mean for the scientific practice
of prevention? Essentially, the answer is that prevention
practice will avert disorders and diseases by engineering
the environment tailored to the individual’s
genotype to promote optimum phenotypes. This will
be neither easy nor straightforward. There are ~20,000
genes with numerous functional polymorphisms. Since
most disorders are polygenic, complexity is further
magnified by gene-gene as well as gene-environment
interactions. Nevertheless, there is reason to believe
that this complexity can be managed using computers
which today already have reached the network performance
of quadrillions of operations per second. Ethical
and policy considerations notwithstanding, prevention
practitioners in the future will have an armamentarium
of tools to potentiate impact of the environment
on the genotype to promote desired biological and
behavioral phenotypes.
You may have noticed that this future has arrived.
If not, check out 23andMe.com (founded by Anne Wojcicki,
the wife of Google co-founder Sergey Brin). Send
this company some saliva and for a small fee your
genetic risk for a variety of diseases or for an
adverse reaction to some medications is estimated.
The Federally-funded Person Centered Oriented Research
Innovation Institute (PCORI) places human individuality
at the center of the big question of “what
works for who”. The International College
of Person Centered Medicine, a network of scientific
and professional societies (including the WHO) is
one key organizational leader of this movement.
Having had the privilege of being present at the
founding of SPR, I believed then as I believe now
that prevention is essentially the practice of ecology.
That is, the goal is to maximize a good fit between
the individual and multiple environments within
a lifespan framework. Adaptation conceptualized
in this fashion is contingent on acquisition of
a large array of biological and psychological characteristics
(phenotypes) that are related to lowered risk of
disease and disorder. Accordingly, the scientific
practice of prevention will directly connect to
an understanding of etiology, and as such, deploy
environmental resources tailored to the individual
genotype to maximize expression of optimum phenotypes.
This is the mission of SPR as I see it from my seat
in the bleachers.
Ralph E. Tarter, Ph.D. is Director
of the NIDA-funded Center for Education and Drug
Abuse Research (CEDAR), Professor of Pharmaceutical
Sciences at the University of Pittsburgh School
of Pharmacy and a founding member of the Society
for Prevention Research.
