May 01, 1996
Tracking a New Virus
By
December, 1994,
Don Ganem
knew his team would not be the first to identify a new virus behind a puzzling
cancer in gay
men.
Scientists at Columbia University had recently pulled pieces of
viral DNA from a Kaposi's sarcoma (KS) tumor biopsy. The rare,
disfiguring skin cancer was stealing headlines--and lives--as it
swept through the homosexual community.
“We want to use the blood test to address the question of whether transmission occurs through sexual contact.”
Don Ganem
The Columbia team's viral DNA bore striking similarity to
several herpes viruses, and the group dubbed their find KSHV, for
Kaposi's sarcoma-associated herpes-like virus. Finally, it seemed,
researchers were on the track to pinning down a viral cause for
KS.
Ganem was determined to play a role.
A Change of Direction
When Ganem first joined HHMI in 1991, he and his team at
the University of California, San Francisco (UCSF), had been
working on hepatitis for more than a decade. He was considering
a change of direction. Research on Kaposi's sarcoma caught his
eye.
"I realized that KS was a great scientific problem and an
important medical problem, and, unlike hepatitis B, nothing was
known about the cause of KS," Ganem said. "I told myself that
with the support provided by Hughes, I wouldn't just continue to
go on in the same direction that I had been going in the previous
decade. I would use that new support to create new projects and
to take some risks."
At the time, epidemiological studies pointed to some form of
sexual transmission behind Kaposi's sarcoma. But many scientists
rejected the notion that a virus caused KS.
Still, Ganem was intrigued by the virus idea. His lab reasoned
that if a virus did occupy KS tissue, it would leave behind telltale
evidence. So, peering at KS cells, the team began to search for
pieces of viral DNA absent in normal tissue. Similarly, they
hunted for unusual messenger RNAs and protein antigens unique
to KS.
Clinical Questions
Unbeknownst to Ganem, the team at Columbia University was
working on the same problem. In December, 1994, the Columbia
group reported in Science that they had recovered
DNA fragments from a KS tumor specimen. The DNA showed up
in most AIDS KS tissue samples and in the lymph nodes of AIDS
patients.
"This suggested to us that it was viral DNA, and it could
be found in people at risk for KS," Ganem said. Going from
suggestion to proven fact, however, is no easy task. To determine
that KSHV causes KS--or that the virus is sexually transmitted--
researchers must perform epidemiological studies based on a blood
test that detects KSHV in infected patients.
Ganem is working in that direction. His team has produced
enough of the elusive KSHV to make the first electron
micrographs of the virus, which appeared in the March 1 issue of
Nature Medicine
. The team's virus-production capability offers
scientists a source of KSHV to use in testing anti-herpes drugs or
in developing a blood test to detect KSHV's presence.
"We want to use the blood test to address the question of
whether transmission occurs through sexual contact," Ganem said.
"We're also interested in the question of whether there's
blood-borne spread of the virus. Is it present in normal, otherwise
healthy blood donors?"
The change of research direction that Ganem envisioned
back in 1991 has drawn him into a new world of questions about
Kaposi's sarcoma.
In science, as in life, change can be very good.
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