Download Genes, Disease and Difference

Health Dialogues
December 2006
“Genes, Disease and Difference”
Notes for Partner Stations
The idea of this show is to discuss how gender, race, and ethnicity impact
our susceptibility to illness, and how researchers are using biological
differences between different groups and individuals to tailor more effective
treatments.
The mapping of the human genome has been heralded as a groundbreaking
advance in science and medicine. The hope is that researchers will be able to
create and target treatments more effectively. Researchers are looking at
genetic variation among individuals, but also among groups, including men
and women, and different races and ethnicities.
As of now, our plan for the statewide show is to speak with researchers who
are on the cutting edge of this science, to find out what advances have been
made, what questions are still open. We want to examine how genetic
medicine may address some of the health disparities that are experienced by
these different groups. Can it help alleviate some of the disparities? Could it
create others? In addition to researchers, we will look for someone who can
bring it to the community level – perhaps a health worker who is familiar
with disparities and efforts to address them. We would also like to have an
ethicist or someone who can discuss the pitfalls of what’s called race-based
medicine. We’re also interested in exploring clinical trials, and efforts to
have them include a more representative population.
Background
In the realm of genomics, there is a lot of basic research going on, and in
many ways the idea of more individualized medicine is still more hope than
reality. We can discuss what advances have in fact been made, what
questions are still wide open, and what ethical dilemmas are posed by
increased knowledge and use of people’s genetics.
There is a general awareness that people of different sexes, races and
ethnicities have different incidences of disease and react differently to
treatments. But a lot of the studies also leave open the question of whether
these disparities are due to biological or environmental and cultural factors.
There is a great deal of discussion about health disparities between different
groups. Many of the reasons behind these disparities are social, ie access to
care. So we’ll need to decide how we want to approach that side of things,
and how that will play into our discussion of biological differences.
Sex/Gender
Men and women have different vulnerabilities to disease, react differently to
some treatments, and may have different symptoms. Women are 2 to 3 times
more likely to suffer from depression and three out of four people suffering
from autoimmune diseases are women – this includes lupus and multiple
sclerosis. Cardiovascular diseases, diabetes, alcoholism, and lung cancer
affect men earlier and more often. Medications, including antibiotics and
antihistamines, can induce different reactions and side effects in men and
women. In some of these cases, the reasons for the differences are known,
but in most of them, scientists are just beginning to explore the reasons.
Women were historically excluded from clinical trials for reasons including
potential harm to fetuses and because researchers feared their results would
be compromised by interference from hormonal changes. In 1985, a report
concluded that women’s health was suffering because of this.
In the two decades that have passed since that report there has been more
emphasis placed on the unique nature of women’s health compared to
men’s. More women are now being included in clinical trials. However, the
General Accounting Office found that data from trials is rarely analyzed by
sex. The GAO also concluded that the FDA doesn’t monitor research closely
enough to track how sex differences affect drug safety and effectiveness
For a long time, there was a perception that men and women were mostly the
same biologically, and only differed in reproductive and urological
functions. Recent research shows that they differ in many ways, right down
to the cellular level. This impacts their likelihood to develop a disease and
their response to treatment. Differences between men and women are also
often thought to be a result of hormones, but new genetic research is
showing that in addition to homones, a lot of difference is based on genes.
In March, a group of scientists mapped the X chromosome. This has opened
a huge window for researchers to examine the health of men and women. In
particular, it should help scientist better understand 300 diseases linked to
the X chromosome, which mothers pass on to sons, ie hemophilia and
Duchene muscular dystrophy.
Another paper published at the same time revealed insights into the way the
X chromosomes operate in women. It was long thought that in women, one
of the X chromosomes was largely silent. This would prevent them from
having two copies of the same gene. But researchers at Duke and Penn State
found that in some cases, the genes on the second X chromosome aren’t
silenced, as originally believed. Researchers now believe this could explain
some of the biological differences between men and women. Huntington
Willard, the Duke researcher who made these findings, plans to study
whether the genes his team identified may explain why certain diseases
occur in different frequencies in women and men.
Race and Ethnicity
People of different races have different vulnerabilities to disease, and react
differently to treatments. For instance, blacks face a greater risk for lung
cancer than most ethnic groups, according to a study that appeared in the
February issue of the New England Journal of Medicine. It’s unclear
whether the reason is genetic or environmental.
The human genome project is opening the possibility that researchers will
look more closely at how genetics impact the health of different ethnic
groups. But this approach is fraught with controversy. There is fear that any
effort to identify races on a genetic level will only feed racism. Social
scientists argue that there is no biological basis for race, that it is a social
construct. Research shows that black men are more likely to be hypertensive
than whites, but social scientists say the reasons are social pressures and
prejudices that people experience, not their genes.
The FDA recently approved Bidil, the only medicine targeted towards a
particular race. It’s used to treat heart failure. Bidil isn’t prescribed based on
a particular genetic marker that black patients were found to have. Rather,
clinical trials simply showed that it was simply more effective in black
patients, whose heart failure is often more severe and harder to treat than in
non-blacks.
In the same way that women often weren’t included in clinical trials, there is
also not a lot of ethnic diversity, so there is little evidence of the different
ways in people react to new medications.
Treatment
Personalized Medicine/Targeted Therapies are treatments that are
specifically targeted to a slice of the population who have a particular
genetic makeup. This is also known as pharmacogenetics. Genentech’s
breast cancer drug Herceptin is often cited as the best example of this. It
only targets patients with high levels of a particular protein in their tumors.
It seems as though “personalized medicine” has been heralded as the
promise of biotechnology for many years, but there aren’t a lot of other
successes besides Herceptin.
Questions worth exploring: How real is this promise? When will it be more
widespread? Is there also a risk that some people will be left out when
medicines are more targeted? What are the barriers to making this work?
(People have to be tested before the treatment is prescribed, which is another
cost; Smaller market may make this type of treatment less attractive to
biotech companies.)