TIME: Almanac 1993/TIME Almanac 1993.iso/time/081291/0812300.000

Text File | 1992-08-28 | 8.6 KB | 193 lines

                                                                                SCIENCE, Page 54

Ultimate Gene Machine


A method of multiplying DNA is revolutionizing medical diagnosis,
speeding forensic work and solving old mysteries

By J. MADELEINE NASH/CHICAGO -- With reporting by Anne Constable/
London and Andrew Purvis/New York


    Imagine an amplifier powerful enough to convert the
inaudible whir of butterfly wings into a mighty roar. That's
what a new tool called PCR routinely does to the most
infinitesimal snippets of DNA, the molecule that carries the
genetic blueprint for all living things. Within the space of a
few hours, an unprepossessing aluminum box stuffed with test
tubes can create a billion copies of what started out as a
single strip of DNA. A dividing cancer cell would take at least
a month to perform the same stupendous feat. "This technique,"
marvels Dr. Harley Rotbart, a microbiologist at the University
of Colorado School of Medicine, "can reproduce genetic material
even more efficiently than nature."

    PCR stands for polymerase chain reaction, polymerase being
the enzyme that triggers the replication of DNA inside dividing
cells. All PCR does is reproduce, in a test tube, this basic
biological process, turning it into a chain reaction that can be
endlessly repeated by having a machine alternately raise and
lower the temperature in the test tube. "The beauty of PCR is
that it's technically so simple," observes cell biologist Peter
Parham of Stanford University.

    Since the first working machine was developed six years
ago by a team of Cetus Corp. researchers, including biochemist
Kary Mullis, PCR has enabled researchers to study even the
faintest, most fragmentary traces of DNA found in specks of
dried blood, strands of hair, chips of bone. In the journal
Nature last week, for example, a team of British researchers
recounted how they successfully identified a teenage murder
victim from skeletal remains eight years old. First they
extracted DNA from bone cells in the dead girl's femur. Then
they obtained DNA from blood samples donated by the couple
believed to be her parents. Using a PCR machine as their
microscope, they went on to magnify and examine the unique
genetic markers the dead girl shared with her parents. The
evidence helped to convict two men of the crime earlier this
year.

    To date, PCR has been used to compare the DNA of extinct
animals with their closest living relatives. It has assisted the
U.S. military in identifying the remains of soldiers who died
during Operation Desert Storm. It is beginning to help
physicians detect small numbers of cancer cells circulating in
the bloodstream and make prenatal diagnoses of genetic diseases
such as sickle-cell anemia, as well as ensure better matches
between organ donors and transplant recipients.

    PCR may also soon aid scientists in solving a number of
historical mysteries. Among them: whether the man who drowned
in Argentina in 1979 really was Nazi war criminal Dr. Josef
Mengele, and whether Abraham Lincoln suffered from Marfan's
syndrome, an inherited disease characterized by gangly limbs,
poor eyesight and a weak heart. "The applications of this
technology are literally as wide as your imagination!" exclaims
University of Virginia geneticist Dr. Thaddeus Kelly.

    Among the areas where PCR is starting to make important
inroads:



    MEDICAL DIAGNOSTICS. Already PCR has begun to help
physicians determine which babies born to AIDS-infected mothers
also harbor the virus. Since all newborns carry their mother's
antibodies whether or not they are actually infected, standard
antibody tests are inconclusive. PCR, however, can home in on
the minute quantities of viral DNA that may be present in only
1 out of 100,000 cells. A positive diagnosis means the baby can
immediately begin therapy with AZT.

    PCR-based diagnostic tests are also under development for
Lyme disease, tuberculosis and viral meningitis. Present tests
for tuberculosis, which involve culturing and growing the
bacteria, take up to a month to confirm a diagnosis. PCR can do
the job in a few hours. Current tests are unable to distinguish
viral meningitis quickly from the far more dangerous bacterial
form of the disease, which is most common in infancy. As a
result, all babies found to have meningitis are treated as if
they had the more lethal form. With a PCR diagnosis, those with
viral meningitis could be spared unnecessary hospitalization and
medication. "There is a big financial saving, a big emotional
saving, and substantial reduction in risk to the baby," says
Colorado's Rotbart, who is helping to develop the test.



    FORENSIC SCIENCE. Amplified by PCR, the DNA in a single
sperm cell can link a suspect to a rape victim. Theoretically,
a single epithelial cell found in saliva can be traced back to
the person who, say, licked a stamp on a letter bomb. In
California's San Mateo County, charges against a man arrested
and jailed for a brutal rape were dropped in 1988 after a PCR
test showed he could not have been the attacker. A year later
another man was arrested in another rape case. Not only did a
DNA marker make him a suspect in the unsolved rape, but the
victim's jewelry was found in his girlfriend's possession and
his fingerprint matched one found on the victim's car. Result:
a conviction.



    EVOLUTIONARY BIOLOGY. Thanks to PCR, it is now possible to
extract badly degraded DNA sequences from ancient sources and
enlarge them like photographic prints. Thus far, PCR has been
used to examine minuscule fragments of DNA taken from the brain
cells of humans buried 8,000 years ago in a Florida bog.
Analysis of such DNA can shed light on the emigration patterns
of ancient peoples and perhaps some of the diseases that
afflicted them. The technique has also been used to examine DNA
from animal skins in natural-history museums and from the frozen
remains of woolly mammoths. Among the unresolved questions that
PCR may eventually shed light on is whether the Neanderthals
were an unsuccessful offshoot of the evolutionary tree or the
direct ancestors of modern humans. It may also be able to
unravel the mystery of what happened to the ancient Celts, who
once populated most of Western Europe. "Now," says University
of Leicester geneticist Alec Jeffreys, "there is a genetic time
machine for looking back into the past."

    Sometimes PCR is compared to a computer that speedily
executes the most complex calculations. But its significance far
exceeds a simple increase in efficiency and productivity. Like
the radio telescope and the electron microscope, it represents
an advance of a fundamental nature. Before PCR, scientists could
not consider analyzing the DNA contained in a single cell, much
less the degraded DNA recovered from dried blood or old bones.
PCR, says Dr. Barry Eisenstein, chairman of the Department of
Microbiology at the University of Michigan Medical School, "is
enabling us to answer questions we only dreamed of five years
ago."

    Ironically, the technology's biggest virtue is also its
major drawback: it is so sensitive to tiny bits of DNA that even
the most minute contamination of laboratory samples can lead to
false results. This sometimes vexing problem, however, has not
stopped the flow of creative and occasionally wild ideas about
PCR's applications. Researchers at Hoffmann-La Roche Inc.,
which recently agreed to pay Cetus $300 million for the rights
to PCR, are interested in developing a whole series of DNA
identification tags. To foil counterfeiting, for instance,
everything from paper currency to designer jeans and compact
discs might be laced with DNA markers. Oil carried in tankers
and toxic chemicals carried in trucks might similarly be
"branded" by molecules of synthetic DNA. With PCR, a spill of
unknown origin could then be traced back to the responsible
party.

    Like many, Arthur Caplan, director of the Center for
Biomedical Ethics at the University of Minnesota, believes that
PCR will revolutionize everything from medicine and biology to
anthropology and history. It is a prospect he finds both
exhilarating and disturbing. Technically, it would be possible,
by examining DNA samples from the descendants of Thomas
Jefferson and those of his slave Sally Hemings, to determine
once and for all whether Jefferson, as rumored, fathered some
of Hemings' children. Would this be an appropriate use of the
new technology? "Let me put it this way," says Caplan. "Because
of PCR, I'm not worried about going out of the bioethics
business anytime soon."