Johns Hopkins Gazette: December 4, 1995

Part II: Genetic Fortune-Telling
The Results Are In, Now What?

Mike Field
Staff Writer

Genes may 
be able to 
tell our future. 
But do we 
really want 
to know?

     Last month, a group of 50 internationally prominent doctors,
researchers and ethicists met in closed session at a weekend
conference in Chicago. The private meetings, sponsored by the
National Institute on Aging and the Alzheimer's Association, were
held to try to sort out a thorny issue that may, in fact,
represent the first volley in the coming wars of genetic testing.

     At the center of discussion was the test for a specific gene
variant--labeled Apo E4--the presence of which is known to
increase the risk of heart disease by 30 to 50 percent. Tens of
thousands of patients nationwide are currently being tested for
the gene, which, in its normal state, produces a protein that
reduces cholesterol in the blood. People with a faulty copy of
the gene typically suffer from abnormally high cholesterol

     Those who test positive for the gene will be able to alter
their diets, take cholesterol-lowering drugs or pursue other
treatment options that, it is believed, will substantially
improve their chances of avoiding a heart attack.

     The trouble is, at the same time cardiologists were linking
the Apo E4 gene to increased likelihood of heart attack, a
different set of scientists began proposing a startling theory:
they produced evidence that individuals with two copies of the
Apo E4 gene (one from each parent) may be as much as six times
more likely to contract Alz-heimer's disease, and that even one
copy of the gene may increase the risk of Alzheimer's
dramatically. Further, the gene may also affect the age of onset
of disease symptoms, indicating some cases where patients will
come down with the debilitating mental disintegration as early as
their 50s. 

     Currently, there is no known way to prevent Alzheimer's, and
only one drug--with very limited effectiveness--has been approved
for treatment of the disease. Even identifying Alzheimer's has
proven difficult during the early stages of the disease, and to
date, no simple medical test has been developed to aid physicians
in making a diagnosis. A genetic test that could confirm a
suspected case of the disease would be useful to physicians,
families and patients alike.

     However, as is so often the case in the largely unmapped
terrain of genetic fortune-telling, inheriting this particular
gene does not guarantee a person will contract Alzheimer's, and
there are people who get the disease without inheriting the gene.
Furthermore, recent evidence suggests that people with Apo E4
genes seem particularly at risk of developing Alzheimer's after
having suffered blows to the head. For instance, many boxers who
become demented, it is thought, are likely to have at least one
copy of the gene.

     The dilemma facing the medical researchers who gathered in
Chicago was, perhaps, prototypical of the kinds of issues facing
medical science as the human genome is unraveled and mapped:
should patients tested for Apo E4 by their cardiologists be
warned they may also learn unwanted news about an incurable
disease? What is the predictive value of the new test, and how
should it be employed? Should boxers with the gene be prevented
from earning a living at their sport? Or students with Apo E4
prevented from playing contact sports at school?

     The Apo E4 dilemma highlights the Pandora's Box quality of
genetic research, where much new knowledge is being unlocked
without anyone's quite knowing what we are going to do with it.
Should, for instance, individuals whose genes predict they will
contract an incurable deadly disease early in their lives be
tested and made aware of the fact right from birth?  What is the
value of informing individuals they run a high probability--but
not a certainty--of developing an illness that can be neither
prevented nor treated? And what of the possibility that certain
genes might strongly indicate--but not guarantee--a behavioral
predisposition to violence or other problems?

     "The current developments associated with the Human Genome
Project will soon enable us to rapidly, and fairly easily,
collect tremendous amounts of information about the genetic
characteristics of individuals," said university professor of
medical genetics Victor McKusick, who has spent more than 38
years in the field. In 1957 McKusick founded the Division of
Medical Genetics within the School of Medicine's Department of
Medicine, making Hopkins one of the first hospitals in the nation
with a clinical practice specifically devoted to hereditary

     McKusick has written and spoken widely about the changes
that are now occurring. "We are now in the midst of a biological
revolution and the information revolution, both of which converge
in the human genome initiative," he said. "This creates two big
problems: First, it increases the gap between what we know how to
diagnose and what we know how to treat. For instance, we can now
predict that John Doe will contract Huntington's disease,
probably in his 40s, yet we have no way of preventing or treating
him for this deadly illness."

     The second issue has to do with the difficulty in
deciphering the real importance of specific gene abnormalities,
such as the Apo E4 variant. "There is a gap between what we think
we know and what we really know," McKusick said. The one-to-one
correlation between a gene and a disease represents only a
fraction of all medical illness. In most cases, genes will be a
factor, but only one factor in the etiology of disease. "This
will be especially true in behavioral traits, where the
likelihood is that weak associations will be found between
particular genes and certain presumed characteristics such as
criminality or alcoholism or elements of intelligence or
performance," he said.

Role of genetic counseling

     As medical science increases physicians' abilities to make
genetic diagnoses, the potential moral and ethical dilemmas in
making those predictions grow with it. Increasingly, the task of
interpreting genetic test results and helping patients decide
what to do with the information has become the domain of genetic
counselors, a new type of health-care professional sure to play
an increasing role in the medicine of the 21st century.

     "Counselors work as part of a team with the medical
geneticists," said Virginia Corson, assistant professor of
gynecology and obstetrics within the School of Medicine. Corson
received her master's degree in genetic counseling at Sarah
Lawrence College, where the nation's first genetics counseling
program was established in 1969. "Our concentration is in working
with the family to help them cope with complicated information,
understand the risks involved and find support systems that may
prove helpful."

     Corson has spent 20 years at Hopkins, primarily counseling
potential and expecting parents in the hospital's Prenatal
Diagnostic Center. "Most of the couples I see are anxious about
having healthy children," said Corson, who notes that more than
95 percent of her patients do in fact have perfectly healthy
babies. "Most people know very little about genetics, so giving
them a sense of understanding helps them deal with that anxiety."

     Even before today's sophisticated genetic tests were
available, genetic counselors could provide information about the
likelihood of many heritable disorders based on the laws of
Mendelian genetics. Parents with a family history of a variety of
diseases ranging from dwarfism to cystic fibrosis or sickle cell
anemia could be counseled about the likelihood of passing the
trait on to their children. Now, with the advent of sophisticated
genetic decoding that can identify specific gene abnormalities,
parents can also look for diseases in the womb through analysis
of cells in the amniotic fluid that surrounds the fetus. Yet as
in so many other instances involving genetic testing, additional
knowledge leads to a whole new set of questions, many of them
profoundly difficult to answer.    

     "In some situations where we have more tests, we create more
anxiety, especially when it puts couples in a position of having
to make a decision," Corson said. For instance, amniocentesis can
reveal a range of genetic information about an unborn child,
ranging from anencephaly (absence of the brain), to Down's
syndrome to the sex of the child. Even the Apo E4 gene can be
discovered this way, although currently it is not looked for. 

     Yet this capability raises a host of thorny issues. Parents
might elect to terminate a pregnancy if the child is developing
with no brain and will certainly die; but what if it will be
moderately or severely retarded through Down's syndrome? Or may
be at risk for developing Alzheimer's late in life? Or is a girl
when the parents were counting on a boy?

     "Technology gives us a greater opportunity to make choices,
but it doesn't make these choices any easier," Corson said. "The
job of the genetic counselor is not to make these choices for
patients, but rather, to offer them all the options and discuss
all the possibilities and then let them make the decisions
themselves. The idea is to give people choices as opposed to
cures or treatments. Very often, the cures or treatments simply
don't exist."

     When your genes say you'll contract a debilitating disease,
should your insurance company be told? Genetic privacy and the
right to know in the conclusion of "Genetic Fortune-Telling."

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