AIDS Research at the NIH: A Critical Review

drug-induced neuropathies and myopathies, and for the development of therapies for these
conditions;
* NINDS should increase its extramural support for work on the neurological opportunistic infections
of AIDS, especially orphan Ols such as PML;
* NINDS should be commended for its periodic Science Reports which succinctly and
comprehensively catalogue the institute's work on AIDS.
11/7. National Institute of General Medical Sciences (NIGMS)
Established in 1963, NIGMS supports 6 extramural basic biomedical research and training programs [it has
no intramural research of any kind]: Cellular and Molecular Basis of Disease Program; Genetics Program;
Pharmacological Sciences Program; Biophysics and Physiological Sciences Program; Minority Access to
Research Careers (MARC) Program; Minority Biomedical Research Support (MBRS) Program. NIGMS
funds over half of the predoctoral trainees and 1/3 of all trainees who receive assistance from NIH. The
current NIGMS Director is Ruth Kirschstein, MD, who also recently served as acting associate director of
the NIH Office of Research on Women's Health. NIGMS first awarded $180,000 for AIDS in 1987, and now
provides over $15 million in extramural research and training awards.
The NIGMS extramural FY 1991 AIDS portfolio of 81 awards totalling $15,548,253 was divided into $9.7M
for "HIV and HIV genome" (1A1) and $5.8M for "research training" (1F1), but the former might also be coclassified as 1D1 "therapeutic agents - development." The NIGMS abstracts make for fairly dry reading
unless you are a synthetic chemist. 30 abstracts for awards totalling $9 million are on-line in CRISP for
R01 and P01 awards. Six P01 awards (Research Program Projects) totalling $5,191,352 and involving at
least 21 subprojects in which heavy duty high-tech molecular biology is brought to bear on the problem of
elucidating the shape of HIV proteins in their native forms and when bound to substrates, and developing
pharmacological agents to inhibit viral enzymatic activity. 17 R01 awards (traditional research projects) and
one FIRST R29 award totalling $2,736,280 are examining the structural biology of idiotypic and antiidiotypic antibodies, 3-D DNA mapping of HIV provirions, the 3-D structure of GM-CSF by X-ray
crystallography, synthesis of pradimicin A analogues for anti-HIV and anti-fungal activity, synthesis of betaketo phosphonates, rational design of biological receptor ligands to inhibit gpl20/CD4 binding, synthesis
of boradeoxyribonucleosides (in which boron replaces carbon in deoxyribonucleosides), synthetic
transmembrane anti-HIV agent carriers, comparison of antigenicity of differentially glycosylated peptides
by T- and B-cells, glycosidation inhibitors, synthesis of avarol derivatives, and the role of the "zinc finger"
amino acid sequences of retroviral g a proteins. Training Awards. 51 abstracts are missing for $6 million
in training awards and interagency agreements. Because these abstracts are missing, and their listed titles
uninformative, it is unclear how, if at all, these awards - especially the training awards - relate to AIDS.
The training awards are intended to help fill the gap in qualified basic researchers. 3 S06 Minority
Biomedical Research Support (MBRS) Grants are supported by NIGMS for AIDS. These grants are
intended "to strengthen the biomedical research and research training capability of ethnic minority
institutions," and are in this case supporting work at Fisk University, and at Rio Piedras in Puerto Rico.
Recent Proaress. NIGMS held its Sixth Meeting of Groups Studying the Structures of AIDS-Related
Systems and Their Application to Targeted Drug Design on June 8-10 at the Hyatt Regency Bethesda.
Papers were presented on reverse transcriptase, virus-cell fusion, gpl20/CD4 binding, CD4-pseudomonas
exotoxin as an antiretroviral agent, Qag proteins, integrase, ta mtev and protease. Eddy Arnold presented
the three-dimensional structure of HIV-1 RT recently published in Nature.

42