Blazing a Genetic Trail in Medicine
Pines, Maya, ed. "Blazing a Genetic Trail." Bethesda, MD:
Howard Hughes Medical Institute, 1991.
The miraculous substance that contains all of our genetic
instructions, DNA, is rapidly becoming a key to modern medicine. By
focusing on the diaphanous and extraordinarily long filaments of DNA
that we inherit from our parents, scientists are finding the root
causes of dozens of previously mysterious diseases: abnormal genes.
These discoveries are allowing researchers to make precise diagnoses
and predictions, to design more effective drugs, and to prevent many
painful disorders. The new findings also pave the way for the
development of the ultimate therapy - substituting a normal gene for a
malfunctioning one so as to correct a patient's genetic defect
Recently, scientists have made spectacular progress against two fatal
genetic diseases of children, cystic fibrosis and Duchenne muscular
dystrophy. In addition, they have identified the genetic flaws that
predispose people to more widespread, though still poorly understood
ailments - various forms of heart disease, breast and colon cancer,
diabetes, arthritis - which are not usually thought of as genetic in
While many of the researchers who are exploring our genetic wilderness
want to find the sources of the nearly 4,000 disorders caused by
defects in single genes, others have an even broader goal: They hope
to locate and map all of the 50,000 to 100,000 genes on our
chromosomes. This map of our complete biological inheritance "the
marvelous message, evolved for 3 billion years or more, which gives
rise to each one of us," as Robert Sinsheimer of the University of
California, Santa Barbara, calls it - will guide biological research
for years to come. And it will radically simplify the search for the
genetic flaws that cause disease.
Once scientists have identified such a flaw, they need to understand
just how it produces a particular illness. They must determine the
normal gene's function in human cells: What kind of protein does it
instruct the cells to make, in what quantities, at what times, and in
what specific places? Then the researchers can ask whether the genetic
flaw results in too little protein, the wrong kind of protein, or no
protein at all - and how best to counteract the effects of this
For most genetic disorders, researchers are still at the very
beginning of the trail. They have no clues to the DNA error that
causes a disease, and they are still trying to find large families
whose DNA patterns can help them track it down.
By contrast, scientists who work on cystic fibrosis and a few other
diseases have covered much of the trail. They have already succeeded
in correcting the gene defect inside living human cells by inserting
healthy genes into these cells in a laboratory dish - an achievement
that may lead to gene therapy.
The farther scientists go along the trail, the broader the
implications of their findings. For example, the discovery of the
gene defect that causes Duchenne muscular dystrophy, a muscle-wasting
disease, led scientists to identify a previously unknown protein that
plays an important role in all muscle function. This gives them a
clearer view of how muscle cells work and allows them to diagnose
other muscle disorders with exceptional precision, as well as devise
new approaches to treatment.
Any new treatment will need to be tested on animals. In fact, the
next explosion of information in medical genetics is expected to come
from the study of animals - particularly with defects that mimic human
disorders. The techniques for producing animal models of disease are
improving rapidly. Even today, "designer mice" are playing an
increasingly important role in research.
The growth of powerful computerized databases is bringing further
insights. Only a month after the discovery of the genetic error
involved in neurofibromatosis, a disfiguring and sometimes disabling
hereditary disease, a computer search revealed a match between the
protein made by normal copies of the newly uncovered gene and a
protein that acts to suppress the development of cancers of the lung,
liver, and brain - a key finding for cancer researchers.
Such revelations are becoming increasingly frequent. "If a new
sequence has no match in the databases as they are, a week later a
still newer sequence will match it," observes Walter
Gilbert of Harvard University.
Brain disorders such as schizophrenia or Alzheimer's disease may be
next to yield to the genetic approach. "We won't know what went wrong
in most cases of mental disease until we can find the gene that sets
it off," says
Watson, co-discoverer of the structure of DNA.
Progress in medical genetics is picking up speed. Every day, more
pieces of the puzzle fall into place. As a harried but exultant
geneticist declared at a scientific meeting recently, "This is a very
exciting time. . . I encourage you to stay tuned."
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