Legions Of Life Scientists Will Be Called To The Front, As War On AIDS Intensifies

With the pandemic mounting and no sure remedies in sight, experts foresee the growing recruitment of skilled researchers On May 21, the World Health Organization announced that 14 million people have been infected with HIV so far, and the global figure could hit 40 million by the year 2000. And the ninth international AIDS meeting in Berlin earlier this month yielded little startling information beyond the general agreement among scientists that they have been, in effect, stymied thus far in their quest to counter the virulent pandemic. But science's pursuit of a magic bullet--or arsenal of heavy artillery--to battle the scourge is picking up speed. And, while fundamental questions about AIDS remain unanswered, preparation for vaccine trials is under way worldwide, and the need for scientists in AIDS research will skyrocket, experts from diverse fields agree. Although a precise counting of AIDS researchers is nearly impossible, the number is probably in the tens of thousands, according to several estimates and extrapolations. "For fiscal 1992, 1,894 principal investigators were on [National Institutes of Health] AIDS-related grants and contracts," says Robert Eisinger, senior program analyst in NIH's Office of AIDS Research. That support amounted to more than $1 billion of the agency's $10.3 billion 1992 budget, with $450 million going to the National Institute of Allergy and Infectious Diseases (NIAID). When one factors in the number of AIDS investigators working in other government agencies, academia, and industry, the AIDS research work force is enormous, scientists say. "There are close to 50,000 researchers, I'd estimate. At AIDS meetings, you get 15,000 attending, and their labs are still running, so there's a huge reserve," says Peter Duesberg, a retrovirologist at the University of California, Berkeley. Several offices contacted at the Centers for Disease Control and Prevention (CDC) in Atlanta could not provide exact numbers of AIDS researchers at CDC. However, a perusal of the agency's Morbidity and Mortality Weekly Report (MMWR) indicates that CDC researchers are indeed hard at work on AIDS issues and problems in the fields of behavioral studies, public health, and epidemiology. Recent MMWRs dealt with the effect of retired Los Angeles Lakers basketball star Magic Johnson's announcement of his HIV-positive status on sexual behavior of clinic patients; use of prevention strategies by minorities and in correctional facilities; and infection of workers using simian immunodeficiency virus in vaccine research. Most of these studies were conducted by teams of scientists at city and state health departments and CDC epidemiologists and public health experts. The Financial Picture For now, at least, most new hiring of scientists for AIDS-related research is in academia and government--companies have their AIDS teams fairly set and generally not slated for expansion, officials in these areas report. "We are doing a lot of work on the clinical level, and that has been in place for several years now. We are looking at three compounds with anti-AIDS potential, but not starting anything new, unless something promising comes up in preclinicals," says Darien Wilson, manager of public policy at Hoffmann-La Roche Inc. in Nutley, N.J. "A lot of the basic research is at the government level. They target a lot of compounds, look at them in preclinical trials, and, if they look favorable, do initial clinical trials to test them. Then they license them out to companies. At the government and university level, AIDS research has expanded a lot in the past five to 10 years." Larry Bauer, a spokesman for Sandoz Research Institute in East Hanover, N.J., agrees. "In general, we do not plan an increase in AIDS research funding, since to do so would require that we have products to increase our efforts behind. At this time, unfortunately, there's not that many in the pipeline that would actively qualify for increased effort," he says. Hiring is also on hold at the Virogenetics Corp., according to Jim Tartaglia, HIV project leader at the small Troy, N.Y.-based biotech firm that is working on an AIDS vaccine. The lack of expansion among companies at the basic research level is confirmed by Bridgette Bidle, manager of biotechnology at Radford Associates-Alexander Consulting Group in San Jose, Calif. She is conducting a confidential survey of research areas and salaries in a sample of 260 biotech firms, and finds that only about 50 of them have AIDS programs. AIDS researchers are paid on the same scale as other scientists-- generally higher in industry than in academia or government, say Bidle and others. "There is no `danger pay.' We have proper training to work with viruses, even HIV," says Jill Taylor, senior scientist at Virogenetics. NIH does offer a special incentive to its intramural scientists, the Loan Repayment Program for AIDS Research (LRP). "In addition to a salary or stipend for working at NIH on a quality AIDS research program, the lender [of a researcher's student loan] receives up to $20,000 per year in repayment," says Marc Horowitz, director of the program, which was established by Congress in November 1988. An applicant must first land a position at NIH and be sponsored by a laboratory or branch chief. Many Ph.D. scientists who received stipends and tuition waivers in graduate school use the LRP to repay undergraduate loans, Horowitz adds. He lists the types of researchers that the agency is particularly interested in, who also could benefit from the LRP program: "Physicians and doctoral-level researchers will be needed to support the following biomedical goals for NIH research: etiology, pathology, natural history, and epidemiology of AIDS; developing therapeutics and vaccines; and behavioral research." Foundations Of Basic Science Funding agencies and institutions are bearing the majority of the costs of directed research of AIDS. "In the 1994 presidential budget, slightly more than 50 percent [of support for the Office of AIDS Research, the arm of NIH that channels AIDS funds] is targeted to basic research," says NIH's Eisinger. The Howard Hughes Medical Institute of Chevy Chase, Md., doesn't have a program specific to AIDS, but many of its investigators are making basic research contributions to the field. "Most of our work is basic, and it takes all different approaches. We have biologists studying the structure of CD4 [a T-cell surface protein to which HIV binds]; immunologists asking basic questions about T cells; geneticists manipulating genes that the virus uses to replicate," says Frank Blanchard, senior information officer at HHMI. The scientists' grants are not categorized by specific topic, Blanchard says, making an estimate of HHMI's AIDS-related efforts difficult, although he adds that a "substantial number" of institute investigators are working on the disease. And at the Los Angeles-based American Foundation for AIDS Research (AmFAR), basic research is high priority, foundation officials say. "Generating a cure or treatment against any virus, including HIV, requires a lot of knowledge at the basic molecular level," says Matilde Krim, an adjunct professor of public health at Columbia University and chairwoman of the board of AmFAR, citing the example of antisense approaches to silencing HIV activity. "Basic research is needed in molecular structure and the genetics of viruses and in immunology. "There are very fundamental viral processes that we do not understand yet." Krim left a post at Memorial-Sloan Kettering Cancer Center in New York, where she was studying the antiviral activity of interferon, in 1986 to work with AmFAR. One reason agency officials give for the difficulty in determining exact numbers of supported researchers and grants is the vast amount of collaboration in AIDS research. For example, a project investigating compounds that remove zinc from transcription factors called zinc fingers as a way to incapacitate HIV is supported by the National Cancer Institute (NCI), CDC, Emory University School of Medicine, the University of Maryland, San Francisco State University, and Octamer Inc. of Tiburon, Calif. Vaccines One of the most intense areas of AIDS research is the quest for a vaccine. Potential AIDS vaccines fall into two broad categories-- therapeutic vaccines to stop HIV infection from progressing to AIDS, and preventive vaccines to block initial infection. Efforts run the gamut of vaccine strategies, from Jonas Salk's whole- virus approach, to numerous subunit vaccines consisting of envelope proteins and adjuvants, to HIV genes cloned into smallpox virus, to products based on core HIV structures. The stakes for the winner in the vaccine race are high, scientists say. "There is a ton of money to be made, with 20 million vaccine recipients in the U.S. alone," says I. Edward Alcamo, a professor of microbiology at the State University of New York College of Technology in Farmingdale and author of AIDS: The Biological Basis (Dubuque, Iowa, Wm. C. Brown Communications Inc., 1993). Montgomery Securities of San Francisco estimates that the worldwide HIV vaccine market will reach $1.5 billion by 1997. Competition, understandably, is fierce. When Congress appropriated $20 million to the Department of Defense in November 1992 for exclusive testing of a vaccine produced by MicroGeneSys of Meriden, Conn., DoD and NIH quickly convened expert panels that voiced loud objections. In a recent meeting involving FDA commissioner David Kessler, former NIH director Bernadine Healy, and DoD acting assistant secretary for health affairs Edward Martin, a decision was reached that the funds will be more equitably distributed among several vaccine candidates. AIDS vaccines are being tested internationally. "The WHO [World Health Organization] has already set up a mechanism for phase III trials in Africa," says Alcamo. "They have trained individuals, identified people who would be recipients, set up depots for receiving and distributing vaccine. All the WHO is waiting for is the vaccine." Domestic efforts at coordinating vaccine trials are gearing up, as well. "In 1992, eight U.S. cities received awards from the National Institute of Allergy and Infectious Diseases for a program called PAVE--Preparation for AIDS/HIV Vaccine Evaluation. The program develops both domestic and international sites for infrastructure development, such as identifying cohorts of high- risk populations to potentially evaluate vaccines in phase III studies," says Eisinger. Another NIAID program provides $4.2 million to support four to eight National Cooperative Vaccine Development Groups to develop and evaluate new approaches to AIDS vaccines. Tracking HIV Combating HIV requires knowing not only what HIV is, but also where it is, scientists say. The inability to detect large amounts of HIV in body fluids was a mystery until very recently, when refined versions of the polymerase chain reaction (PCR) used directly on nucleic acids from patients' cells (in situ hybridization) revealed the virus in lymph nodes throughout infection, including the long latency period (Giuseppe Pantaleo, et al., Nature, 362:355, 1993; and Janet Embretson, et al., Nature, 362:359, 1993). George Shaw and colleagues at the University of Alabama in Birmingham and Genelabs Technologies Inc. of Redwood City, Calif., have found that such quantitative competitive PCR is 60,000 times as sensitive in detecting HIV as is culturing the virus (M. Piatak, Jr., et al., Science, 259:1749, 1993). And Steven M. Wolinsky and Bruce K. Patterson at Northwestern University Medical School combined PCR with in situ hybridization and flow cytometry (a method to isolate genetically identical cells from a suspension of mixed cell types) to detect single-copy DNA and rare messenger RNAs faster and more accurately than can be done by human eyes scanning microscope slides (Bruce K. Patterson, et al., Science, 260:976, 1993). In some tissues, Wolinsky and Patterson report, they can detect a telltale HIV nucleic acid sequence in 1 in 10 cells. The finding of HIV in lymph nodes is a basic research discovery that may alter the direction of applied research into the disease. The virus is now thought to be held in check in the lymph nodes by a lattice of follicular dendritic cells (FDCs). When the FDC labyrinth breaks down, HIV enters the bloodstream. Discussions at the Frontiers in AIDS Pathogenesis meeting, held this spring in Albuquerque, N.Mex., indicate that some researchers' attentions will switch from the blood to the lymph nodes. Opportunistic Infections Intense research is focused on treating the ever-increasing variety of opportunistic infections (OIs) and malignancies that invade when immunity fails. NIAID devotes a third of its AIDS clinical trials group protocols to "anti-OI" therapies. The OI causing the most concern among public health officials is tuberculosis. According to WHO, 4.4 million HIV-positive people are infected with TB, and the number is rising. Several of the national institutes have diverted more 1993 funds to studying TB, and increased funding for basic research, developing new diagnostics and therapeutics, devising vaccines, and training researchers in the biology of tuberculosis are part of NIH's plan. Some grant programs focus on other AIDS-related illnesses. NCI, for example, is offering eight four-year grants of $1.5 million annually to study the development of lymphomas in AIDS patients. Similarly, a joint grant from NCI and NIAID seeks to encourage collaboration between scientists and physicians to understand the pathogenesis of Kaposi's sarcoma. AIDS Drugs Hundreds of companies are investigating immunomodulating agents and antiviral, bacterial, fungal, and neoplastic agents to fight the disease. The handful of FDA-approved drugs to treat AIDS includes such standards as pentamidine, discovered to attack protozoa in 1939 and used to treat Pneumocystis carinii pneumonia in people with AIDS, and such new agents as a genetically engineered version of the kidney-secreting growth factor erythropoi-etin, used to treat anemia caused by the best-known AIDS treatment, zidovudine (AZT, which was first synthesized in 1964, and its antiviral properties discovered in 1980). Many other treatments for the various maladies associated with AIDS may come from existing pharmaceuticals, causing many firms to take second looks at old drugs. Gynex Pharmaceuticals Inc. of Vernon Hills, Ill., for example, entered the AIDS battle when researchers discovered that a low-dose estrogen anabolic steroid, oxandrolone, being tested to treat the rare Turner's syndrome (females with one X chromosome instead of the normal two) promotes weight gain. It is now being tested to ameliorate HIV wasting syndrome. Also targeting weight loss in people with AIDS is New York-based Bio-Technology General Corp., whose candidate treatment is human growth hormone, approved in Europe and Japan to treat pituitary dwarfism. "About three years ago, we began to look at wasting in cancer and AIDS. We have completed phase I studies [for safety] in HIV-positive people and those with AIDS, and will start phase II trials [for efficacy] in the next few months," says manager- administrator Leah Berkovits. "We are not attempting to cure the disease, but to extend life and improve the quality of life. We have already seen weight gain in the phase I trials." Other new AIDS treatments may come from combinations of drugs. On April 19, 15 U.S. and European drug companies announced the Inter-Company Collaboration for AIDS Drug Development. The firms will share data at the phase I stage, making combination trials possible sooner in the drug development process. After AIDS When AIDS is vanquished, will the world still need the legions of researchers trained to chase HIV? Absolutely, says Kenneth Bridbord, a chemical engineer turned pediatrician who is chief of the international studies branch of the Fogarty International Center at NIH, where he coordinates the training of foreign AIDS researchers in the U.S. "The skills [for studying AIDS] are easily transferred to the biomedical and public health issues that are emerging, and also to reemerging microbes and diseases. We need people all over the world who are sensitive to what we should be looking for. Will there be different epidemics 10 to 20 years from now? A glut of scientists with a broad spectrum of skills? I'd be glad to face that dilemma!" Ricki Lewis is a freelance writer based in Scotia, N.Y., and is the author of biology and human genetics texts.

Legions Of Life Scientists Will Be Called To The Front, As War On AIDS Intensifies

Interested in reading more?

Become a Member of