The Bay Area Reporter - June 12, 1998
Jeff Gustavson, ACT UP/Golden Gate Writers Pool

Q: Let's lay the groundwork. What is basic science in relation to HIV?

A: Basic science is seeking answers to fundamental questions in the biology or pathogenesis of the disease. The difference between a basic and an applied study is that the basic might have implications beyond the initial questions that were asked. Many studies address both applied and basic questions simultaneously. An example of such simultaneous research would be a study of the thymus [the organ where T-cells mature and take their name] in vivo : how it develops normally, how it ages - basic or fundamental information - as well as telling us how HIV may affect it.

What about translational research?

Translational research is a term around which there is no consensus. This lack of a uniform definition creates a great deal of confusion both among investigators and lay people. A fair definition might be that translational research involves asking questions that are both clinical in impact and basic in nature.

Why should the average HIV-positive person care?

It has been said that "the most applicable form of research is basic research." Although this may appear to be a contradiction, basic science creates an essential and broad foundation of knowledge upon which to base new ideas for improved diagnosis, prevention and therapy. Without new knowledge, we would quickly run out of ideas to take into the clinic.

What are the great unsolved questions of HIV pathogenesis?

The biggest question that surprisingly is not yet known is how HIV causes depletion of CD4 [T-helper] cells. Many mechanisms have been proposed, but the relative importance of each is unclear. The second question that all would agree is extremely important is whether and how the immune system can control and/or eliminate HIV. For the most part, all the studies we do in our lab, as well as many others in their respective labs, are in one way or another answering those two questions. Other important issues include where and how is the virus hiding (latency), why is the CCR5 coreceptor so important to disease, and how does HIV cause disease in non-lymhoid tissues, such as the brain.

What is your lab currently working on?

Our lab is particularly interested in the mechanisms behind immune depletion. Like many others, we believe that specific properties of the virus may be triggering the loss of CD4 cells, which eventually leads to AIDS in people. One of those properties is the glycoprotein envelope of the virus that determines which coreceptors [CXCR4, CCR5, CCR2, etc.] are used, which specific types of cells are infected, and which cells are killed during infection. There is a causal relationship among these features, and we are trying to define what that causal link is.

How do you negotiate the tension between the "go your own way" traditional investigator-initiated research, and the more top-down business style approach of project management?

I am a very strong believer in the enormous power of investigator-driven research. Although I understand how this process can be perceived as meandering, it is extremely effective at promoting creative, thoughtful, and productive scientific efforts. Who better to determine the proper questions than the people at the bench, as long as they are paying close attention to the disease and clinical relevance. Investigator-initiated research can sometimes result in dead ends, but you don't know they're dead ends until you run into them.

Managing the process from the top down requires you to have a very good sense of where you should be at some point in the future. We [activists and scientists] share a long term goal of ultimately eradicating this disease, but there is no obvious single path to achieve this. Micromanaging can really impair the process. On the other hand, encouragement through focused funding mechanisms can in fact be very effective at stimulating progress in underserved areas of research.

We have to remember that had the NIH [National Institutes of Health, part of the Public Health Service, which, in turn is part of the Department of Health and Human Services] only funded targeted research to the exclusion of investigator-driven research, Ed Berger would never have discovered coreceptors. This breakthrough discovery created a new paradigm that affects our understanding of this disease and creates new targets for intervention. [Trimeris' T-20 is the furthest along in exploiting this knowledge, now in Phase II human clinical testing].

Is there an overreliance on postdoctoral fellows, who may not be in any lab beyond a couple of years?

Virtually every scientist around would prefer to spend their time at the bench than in the office. Bit we rely on trainees at all levels, along with permanent staff for several reasons. One main reason is that investigators in training bring maximal levels of creativity to the process. A second is that trainees often stimulate more thoughtful and careful analysis with extraordinary professionalism. Thirdly, science requires a constant exchange of ideas, and new research labs will be headed by former postdoctoral fellows, who have benefited through this process.

Often, important discoveries are made in basic science that are reported by the newspapers in such a vague fashion as to be nearly meaningless - "a protein important in the immune system" - and sometimes incorrect. At the same time, scientific journals are beyond the reach of most of the public. Can you comment on this?

There are lots of potential downsides to lay press reporting, yet it is critical to maintain contact between the public and the scientific enterprise. It is ultimately the responsibility of the scientific community to communicate what we do to those who pay for it. This task would be facilitated by a better science curriculum in the school system to create a vocabulary and conceptual framework for understanding scientific discussion. My colleagues at the Gladstone Institute and the broader UCSF scientific community would be delighted to communicate with nonscientists in organized symposia. Many of us already do this.

Many people have a clear recollection of Reagan's HHS Secretary Margaret Heckler saying on TV in April of 1984 that now that Bob Gallo had discovered the virus responsible for AIDS, a vaccine would be two years away, and implying a cure would not be much further. In the '60s, JFK began a program to put a man on the moon in less than ten years. Why, 17 years into the epidemic are we still so far from either a vaccine or a cure?

A technology mission like the Apollo project is both exciting and inspiring, but follows a much more direct path than does the discovery process required for understanding a newly discovered human pathogen - which is not to say we haven't made tremendous significant decreases in morbidity and mortality [sickness and death]. Extraordinary discoveries about the virus and immune system have been made that have profound implications beyond HIV including cancer and other human disease. HIV has had ages to evolve its destructive pathogenecity. We've only had a decade or two to unravel it.
980612
BR980602

Always watch for outdated information. This article first appeared in 1998. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1998. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .