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TIME THE FUTURE OF MEDICINE On the Horizon BY MICHAEL D. LEMONICK; ALICE PARK; CLARE THOMPSON
Gene therapy and gene-based drugs are two
ways we could benefit from our growing mastery
of genetic science. But there will be others as
well, including new kinds of vaccines, new
sources of transplant tissue, even techniques
doctors may someday use to stave off the aging
process. Here are just a few of the remarkable
therapies on the cutting edge of genetic research
that could make their way into mainstream
medicine in the coming years:
Tomorrow's Tissue Factory
While it's true that just about every cell in the
body has the instructions to make a complete
human, most of those instructions are
inactivated, and with good reason: the last thing
you want is for your brain cells to start churning
out stomach acid or your nose to turn into a
kidney. The only time cells truly have the
potential to turn into any and all body parts is
very early in a pregnancy, when so-called stem
cells haven't begun to specialize.
Yet this untapped potential could be a terrific
boon to medicine. Most diseases involve the
death of healthy cells--brain cells in Alzheimer's,
cardiac cells in heart disease, pancreatic cells in
diabetes, to name a few. If doctors could isolate
stem cells, then direct their growth, they might
be able to furnish patients with healthy
replacement tissue.
It was incredibly difficult, but last fall scientists at
the University of Wisconsin managed to isolate
stem cells and get them to grow into neural, gut,
muscle and bone cells. The process still can't be
controlled, and may have unforeseen limitations.
But if efforts to understand and master stem-cell
development prove successful, doctors will have
a therapeutic tool of incredible power.
The same applies to cloning, which is really just
the other side of the coin. True cloning, as first
shown with Dolly the sheep two years ago,
involves taking a developed cell and reactivating
the genome within, resetting its developmental
instructions to a pristine state. Once that
happens, the rejuvenated cell can develop into a
full-fledged animal, genetically identical to its
parent.
For agriculture, in which purely physical
characteristics like milk production in a cow or
low fat in a hog have real market value, biological
carbon copies could become routine within a few
years. This past year scientists have done for
mice and cows what Ian Wilmut did for Dolly, and
other creatures are bound to join the cloned
menagerie in the coming year.
Human cloning, on the other hand, may be
technically feasible but legally and emotionally
more difficult. Still, one day it will happen. The
ability to reset body cells to a pristine,
undeveloped state could give doctors exactly the
same advantages they would get from stem
cells: the potential to make healthy body tissues
of all sorts, and thus to cure disease. That could
prove to be a true "miracle cure."
--By Michael D. Lemonick
Spiking the Potatoes
We all know that eating fruits and vegetables is
good for us, but within the next decade we could
be eating broccoli not just to make Mom happy
but also as a way to deliver drugs that stave off
infectious diseases or that treat various chronic
conditions. "The idea of vaccinating people with
edible plants is very new," says Dwayne Kirk of
the Boyce Thompson Institute for Plant Research
in Ithaca, N.Y. "But it's a lot friendlier than
injections."
Because their cells naturally produce large
quantities of protein, potatoes and tomatoes
seem for now to be the most efficient vehicles for
the new approach. Instead of mixing viral or
bacterial DNA in a formula for injection, for
example, scientists could insert it into soil
bacteria. When the bacteria are taken up by the
plant, therapeutic DNA material is stitched into
the plant's genome. Another method of getting
genes into plants is to coat tiny particles of
tungsten or gold with foreign DNA, then shoot the
particles directly into plant cells. Either way, the
plant's cells start to produce whatever proteins
the new genes are designed to make.
Immunization begins when the plant or its fruit is
eaten, prompting the body to churn out the
appropriate antibodies.
Plant-based vaccines are particularly attractive
for Third World countries, where storage and
distribution of drugs are a problem. Eventually,
people in these areas may inoculate themselves
against diseases simply by growing a crop of
genetically engineered fruits or vegetables and
eating a few several times a year.
The technique does not have to be limited to
infectious diseases, however. It may even be
useful for conditions such as Type I diabetes, in
which a patient's own immune system destroys
essential insulin-producing cells in the pancreas.
For diabetics, eating insulin-bearing tubers could
eventually train the body's defenses to stop
reacting to insulin as if it were a foreign material,
all without the bother--or risk--of a needle.
--By Alice Park
A Shot for Aging Body Parts?
Eight years ago, scientists discovered that the
tips of chromosomes in tissue cells shorten each
time the cells replicate--until a point is reached
where the cells stop dividing altogether. That
point, called the Hayflick limit, comes after about
50 replications, and may be at the heart of the
process we call aging.
Scientists have tried ever since to reactivate the
enzyme that lengthens the tips, known as
telomeres. Last January they succeeded: Andrea
Bodnar and colleagues from the Geron Corp. in
Menlo Park, Calif., activated the enzyme
telomerase, extended the telomeres and
lengthened the life-span of cells in culture by at
least 20 divisions past the Hayflick limit. In
November, Geron scored another first by
reconstituting the telomeres of embryonic stem
cells, which are renowned for their ability to turn
into any type of cell, making it theoretically
possible to rejuvenate parts of any organ with a
simple injection.
Not everyone is convinced. Leonard Guarente, a
specialist on aging from the Massachusetts
Institute of Technology, observes that "telomeres
seem to be important in getting cells to divide in
vitro, but the onus is to show that short
telomeres affect aging in vivo. I don't think we
know that yet." --By Clare Thompson
Beyond Vaccination
Most of us can't remember our first vaccination,
but chances are, it was a shot filled with a
crippled microbe or perhaps parts of the bug's
proteins--just enough to produce a mild infection but not the full-blown disease. Immunizing people against a host of infections in this way has worked reasonably well for more than a century, but geneticists think they can do better.
The vaccines of tomorrow are likely to be far more sophisticated concoctions, made up of snippets of raw DNA from the genome of a virus, bacterium or parasite. Using DNA, as opposed to proteins made by a microbe, elicits a more vigorous, aggressive response from the immune system. While most of the current vaccines do a good job of marshaling antibodies against an invading marauder, they often don't reliably coax the body into churning out killer T cells, the smart bombs of the immune system that strike at the offending microbes with great specificity. In early tests, DNA-based vaccines triggered both responses. For example, immunologists reported last fall that patients injected with an experimental DNA-based malaria vaccine showed not just malaria antibodies but also significant levels of killer T cells.
The potential goes beyond bugs. Because gene-based vaccines can easily be manipulated by adding or deleting DNA, doctors are applying the technique to treat various forms of cancer. The work is still limited to animals, but researchers have developed inoculations made up of tumor cells that act as a red flag to rally an animal's immune system against the tumor. "There is a long road ahead" for these cancer vaccines, says Duke University's Dr. Eli Gilboa. "But it's very promising."
--By Alice Park
© 1999 TIME Magazine
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