Medical explorers only recently identified the group of
viruses that cause hepatitis, and they still have no cure
for the disease. Although hepatitis is not new—the
ancient Greek physician Hippocrates called it “infectious
ikteros,” after a yellow bird—the viruses are highly selec-
tive and refuse to grow in the laboratory where they
might be studied.

Yet the hope of curing an illness often lies in under-
standing its course. By knowing the steps from onset to
termination, researchers can look for a foothold against
the disease’s progress.

Scientists at Stanford recently found a relative of hepa-
titis B that thrives in squirrels. Now UCSF virologist
Harold Varmus and postdocs Don Ganem and Barbara
Weiser are studying a colony of infected squirrels in cap-
tivity. Early results of their study show several simi-
larities between the squirrel! and human viruses: both
exist in multiple strains; both grow only in the liver; both
are transmitted via blood; and both shed similar particles
from the liver into the bloodstream.

By taking minute liver samples while the animals are
under anesthesia, the UCSF group hopes to learn how the
hepatitis-B-like squirrel virus reproduces, and how it
damages the liver. The squirrels provide an unlimited
supply of infected liver tissue for study; shortage of this
tissue previously hampered research on human hepatitis
B. Already, though, the UCSF group has discovered
several novel forms of viral DNA in the squirrel liver
tissue. The role these new structures play in the viral life
cycle is being actively investigated. The group also is
attempting to grow the squirrel virus in cell culture for
further studies.

The virologists also are studying viral DNA from hu-
man hepatitis B, inserting fragments of the DNA into a
type of mouse tumor cell called an L-cell. L-cells that are
infected with cloned viral DNA will make small amounts
of the viral coat protein. The researchers have used this
system to study which regions of the viral DNA are needed
for mammalian cells to produce the protein from the
gene. By constructing mutants of the virus that lack parts
of the viral DNA, then putting these mutant viral genes
into mouse cells, the researchers can determine the spe-
cific changes that interfere with coat-protein production.
Already this work has pinpointed several regions in the
DNA that control the protein’s synthesis. Because these
control regions work similarly in all mammalian cells, the
L-cell study eventually might lead to construction of a
mammalian cell system that synthesizes a vaccine against
hepatitis B.

Postdoc Don Ganem in Harold Varmus’
tumor virology laboratory explains drawing
of hepatitis B viral genome. Center, Harold
Varmus. Below, squirrel in USF laboratories.
Opposite page: David Aliman sits at desk
piled with computerized records of chronic
active hepatitis patients.