The Wall Street Journal - 15 May 1992
Marilyn Chase

Both growth hormone and a related protein called insulin-like growth factor are being tested in an attempt to replenish the body's stores of infection-fighting white blood cells. Such cells, known as T-4 cells, are the very cells targeted for destruction by the AIDS virus.

Animal studies are encouraging. In tests by Daniel Longo and his co-workers at the National Cancer Institute, levels of T-4 cells rose in SCID mice, special research animals given tissue transplants to simulate a human immune system.

If human studies prove successful, growth factors might be used one day in concert with antiviral drugs such as AZT to try to rebuild the immune system. To date, only a handful of AIDS patients have received growth hormone in an NCI clinical trial. Scientists caution that they have no clue whether the hormone therapy will be effective.

Scientists Splice Genes Into HIV to Derail It

GENE THERAPY, already deployed in the fight against cancer and hereditary disease, is being aimed at HIV, the virus that causes AIDS.

Viruses, which act as parasites in human cells, live by splicing their own genes into the genetic code of the host cells. They then commandeer the host cells, transforming them into tiny factories for the production of more viruses.

Thus, "viral infections . . . can be thought of as acquired genetic diseases," explained Richard Morgan and W. French Anderson of the National Heart, Lung and Blood Institute in a recent presentation at an AIDS symposium in Keystone, Colo. Dr. Anderson, already a genetherapy pioneer in the current effort to treat children with an enzyme deficiency, plans a multipronged effort against HIV, including inserting into the virus a mutant version of HIV's "rev" gene, which performs an essential role in the virus's life cycle.

Another genetic weapon called "antisense" is being employed to block rev by Mary Klotman and colleagues at the NCI. This strategy uses a strand of genetic material that blocks the "sense," or coded message of the rev gene, thus preventing it from producing a protein that helps the virus replicate. "No rev, no new viruses," she says.

Still other scientists, such as John Walker at Viagene, are harnessing genes to deliver helpful proteins to activate patients' immune systems to make special killer cells that can destroy HIV-infected human cells in culture.

There's even a project to implant "suicide genes" in AIDS-infected cells. David Klatzmann of the Hopital de la Pitie-Salpetriere in Paris spliced into T-cells a gene from the herpes simplex virus. This gene renders the cells sensitive to the common herpes drug acyclovir. In the test tube, when these cells are infected by HIV, they switch on the herpes enzyme, activating the attack by acyclovir and triggering their own destruction.

Combing the Plant World For Anti-HIV Compounds

LET OTHERS harness biotechnology or probe HIV's genes for answers. One National Cancer Institute team does nothing but screen thousands of plants and animals in a search for novel antiHIV compounds.

James B. McMahon of the NCI's Laboratory of Drug Discovery recently reported that his group has cast a wide net, contracting with 80 collection teams around the world, and screening 30,000 collected compounds in the test tube for potential activity against the virus.

So far, three exotic substances look promising: sulfolipids from cyanobacterium, a marine microbe found in the Pacific Ocean; prostratin from the tropical tree homolanthus accuminatus; and michellanine from the tropical vine ancestrocladus abbreviatus. The U.S. has patented the three compounds while early testing continues.

But probing the world's flora and fauna for a potential cure entails more than a rustic romp to gather wildflowers. Dr. McMahon says collectors have had their car stolen and even been shot at while on assignment in war-torn countries in Africa. But he says the effort is worth it, adding: "We eat, sleep and breathe this stuff."

`Silent Carriers' of Virus Appear in Israeli Study

DESPITE THE HOPE inspired by new therapeutic approaches, the AIDS epidemic continues to produce sobering news.

A recent report from Zvi Bentwich of the Ruth Ben Ari Institute of Clinical Immunology in Rehovot, Israel, reignited concern about "silent carriers" who test negative for antibodies to HIV even though they are infected.

Dr. Bentwich's study examined a group of Ethiopian Jewish immigrants to Israel. Of 12 couples given a standard AIDS test, eight were "discordant" for viral antibodies -- with one spouse testing positive for antibodies, the other negative. Yet upon closer look, five of these eight "negative" partners tested positive by PCR technology -- a highly sensitive direct test for the virus -- or by other tests.

Existence of "silent carriers" requires more study, Dr. Bentwich says, cautioning against an alarmist approach. He even offers an optimistic spin, suggesting that people in endemic areas may evolve a way to control the HIV infection.

Moreover, he contends, little is known about African patterns of HIV disease. "Africans are exposed to many infections in their lifetime. They are a different kind of host to the virus," he says. "Their background may allow this to happen."

However, several researchers view the results with skepticism, suggesting that the African patients might simply be testing positive for another viral infection.

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