Still other problems plague the researchers in their quest for an effective and non-toxic anti-viral drug--some of them not involving science. Groopman has encountered peculiar problems in the AZT study. "There is tremendous political pressure," Groopman says. He only has room for 20 patients while 60 AIDS and ARC patients want to take part in the experiment. So he will choose patients only on a "first-come, first serve basis."
The two laboratories are also trying to arrest the disease before it gains a foothold in a larger segment of the population by developing vaccines which would help protect the body from infection. (See story below)
Because so little is understood about how HTLV-III attacks the body, much of today's clinical research is directed at determining exactly how the virus interacts with the white blood cells. Both Hirsch and Groopman are involved in this basic work, labelled cell biology.
To most questions, now, the answer is still, "We don't know," but Groopman says they are making progress. The most recent discovery came out of both laboratories simultaneously, and may lead scientists to an understanding of how the virus damages the neurological system.
Both Groopman and Hirsch have found in laboratory tests that HTLV-III attacks not only the T-helper lymphocytes, but also another type of white blood cell, called a macrophage, that has been linked to cells in the brain. The macrophage or disease-fighting white blood cell is not killed by the virus, Groopman says, but instead is used as a breeding ground.
Hirsch adds that it is possible that the virus is carried to brain by the macrophages, but is unsure how this will effect the search for a treatment. "Macrophages can support the replication of this virus," he says. "Whether this will affect the future of anti-viral studies, it's too early to tell."
Cofactors and Cohorts
Hirsch and Groopman are also eagerly looking into other critical questions about the nature of AIDS. Who gets it and why? Who dies and who lives? How is the virus transmitted?
Hirsch is currently conducting a study of cofactors to determine whether the effect of the HTLV-III virus is exaggerated by certain lifestyles or diseases that target the immune system. For nearly four years, Hirsch and his MGH team have been following 170 gay men in the Boston area, seeing them at regular three-month intervals. This study, begun before scientists had discovered HTLV-III, was originally designed to determine the cause of AIDS. Although they have not yet formulated any conclusions, Hirsch says they will continue to study cofactors, placing special emphasis on the herpes group viruses which often infect AIDS patients.
Groopman has begun a similar study of how AIDS is spread, involving as many as 500 patients over the course of three years. He plans to look at AIDS patients and their partners to determine what cofactors may be involved.
Other reseachers including Dr. William Haseltine, however, are skeptical about cofactors. "In my personal opinion, the cofactor issue has yet to be proven," he says.
Another area of AIDS research Hirsch is examining is transmission of the HTLV-III virus. HTLV-III is only known to be transmitted by contaminated blood and semen. Researchers have not yet determined whether the virus can be transmitted by female genital fluids, although Hirsch has found evidence that such fluid may contain the virus. The virus can, however, be transmitted from mother to unborn child, by contaminated needles and transfusions. Since April 1985, blood banks have screened blood donations for signs of the virus.
"We would like to see whether female to male transmission can be demonstrated conclusively," Hirsch says of the future. "We would like to see how new-borns become infected, and how often they do become infected."