Testing and Gene-based Medicine
how a particular gene is spelled in an individual can serve quite
a few uses:
Genetic analysis now can classify some conditions, like colon cancer
and skin cancer, into finer categories. This is important since
classifying diseases more precisely can suggest more appropriate
treat- ments. The same approach will soon be possible for heart
disease, schizophrenia, and many other medical conditions, as the
genetic underpinnings for these diseases become more completely
is a new word that scientists and drug developers use. It describes
the idea of tailoring drugs for patients, whose individual response
can be predicted by genetic fingerprinting. For example, cancer
patients facing chemotherapy may experience fewer side effects and
improve their prognoses by first getting a genetic fingerprint of
their tumor. This fingerprint can reveal which chemotherapy choices
are most likely to be effective. Better understanding of genetics
promises a future of precise, customized medical treatments.
Prognosis Diagnosing ailments
more precisely will lead to more reliable predictions about the
course of a disease. For example, a genetic workup can inform a
patient with high cholesterol levels how damaging that condition
is likely to be. And doctors treating prostate cancer will be able
to predict how aggressive a tumor will be. For many diseases, such
genetic information will help patients and doctors weigh the risks
and benefits of different treatments.
Prevention Once scientists figure
out what DNA sequence changes in a gene can cause disease, healthy
people can be tested to see whether they risk developing conditions
like heart disease, diabetes, or prostate cancer later in life.
In many cases, this advance warning can be a cue to start a vigilant
screening program, to take preventive medicines, or to make diet
or lifestyle changes that might prevent the disease altogether.
example, those at risk for colon cancer could undergo frequent colonoscopies;
those with hereditary hemochromatosis, a common disorder of iron
metabolism, could donate blood periodically to remove excess iron
and prevent damage to the body. Some women at risk for breast cancer
could benefit from tamoxifen; a young person at risk for developing
lung cancer may become particularly motivated to quit smoking; those
with familial hypercholesterolemia could begin treatment to lower
their cholesterol levels and prevent heart attacks and strokes.
Unfortunately, our ability to predict a disease sometimes precedes
our ability to prevent or treat it. For example, a genetic test
has been available for Huntington disease for years, but no treatment
is available yet. As a result, only a minority of people at risk
have chosen to be tested.
Newborn screening A particular
form of predictive testing, newborn screening can sometimes help
a great deal. For example, babies in the United States and a few
other countries are routinely screened for phenylketonuria (PKU),
a metabolic disorder that prevents the breakdown of phenylalanine,
one of the building blocks of proteins and a component of the artificial
sweetener Aspartame. Excess phenylalanine in the body is toxic to
the nervous system. In the past, children with the condition became
severely mentally retarded, but the screening program identifies
children with the enzyme deficiency, allowing them to grow normally
on a diet that strictly avoids phenylalanine.
Carrier screening For some genetic
conditions, people who will never be ill themselves can pass a disease
to their children. Some couples choose to be tested for this risk
before they marry, especially in communities where a feared childhood
disease is particularly common. For example, carrier testing for
Tay-Sachs disease, which kills young children and is particularly
common in some Jewish and Canadian populations, has been available
and widely used for years.
Gene therapy Replacing a misspelled
gene with a functional gene has long been an appealing idea. Small
groups of patients have undergone gene therapy in clinical trials
for more than a decade, but this remains an experimental treatment.
Eventually, it likely will become a common treatment for some conditions.
Gene-based therapy Great medical
benefit likely will derive from drug design that's guided by an
understanding of how genes work and what exactly happens at the
molecular level to cause disease. For example, the causes of adult-onset
diabetes and the resulting complications remain difficult to decipher
and, so, to treat. But researchers are optimistic that a more precise
understanding of the underlying causes will lead to better therapies.
In many cases, instead of trying to replace a gene, it will be more
effective and simpler to replace the protein the gene would give
rise to. Alternatively, it may be possible to administer a small
molecule that interacts with the proteinas many drugs doand changes
One of the first examples of such a rationally-designed drug targets
the genetic flaw that causes chronic myelogenous leukemia, a form
of leukemia that mostly affects adults. An unusual joining of chromosomes
9 and 22 produces an abnormal protein that spurs the uncontrolled
growth of white blood cells. Scientists have designed a drug that
specifically attaches to the abnormal protein and blocks its activity.
In preliminary tests, blood counts returned to normal in all patients
treated with the drug. And, compared with other forms of cancer
treatment, the patients experienced very mild side effects.
Instead of having to rely on chance and screening thousands of molecules
to find an effective drug, which is how most drugs we use today
were found, scientists will begin the process of drug discovery
with a clearer notion of what they're looking for. And because rationally
designed drugs are more likely to act very specifically, they will
be less likely to have damaging side effects.