AIDS Research at the NIH: A Critical Review

a colony of monkeys for NCI intramural research. $877,000 went for intramural work on animal models.
Extramural researchers studied transgenic KS mouse models; primate type D retroviruses; EBV and
oncogenesis; the SIV 2ol gene; SIV and murine type C viruses; immune responses to SIV and murine
retroviruses; role of T cells in FIV; pathogenesis of FIV; EIAV gene expression; protective immunity and
vaccines for CAEV; SIV genetic diversity; mice coinfected with HIV and CMV; CMI in MAIDS; cytokines in
MAIDS; BIV pathogenesis; EIAV genes and virulence; copathogens in FAIDS; and HIV-1 transgenic mice.
Vaccines. NCI spent $15M on vaccine development in 1991, of which $11.6M was extramural (of which
$6.5M went to Frederick - they just can't get enough!) - and $2.5 intramural. $2.1M went to the US Army
research facility in Fort Detrick, Maryland, for their vaccine development efforts. Another $100,000 provides
for administrative support for Dr. Broder's office. $2.4M went to contracts for technical support to intramural
labs providing for production of mAbs and polyclonal antibodies, small quantities of purified human
retroviruses and large quantities of viral proteins; Ab testing of sera for HTLV-1 and HIV; maintenance of
colonies of subhuman primates, mice, rats, goats, and rabbits; and supplies of tissue and cell lines. One
$263,000 R01 vaccine development grant supported the design of synthetic multicomponent immunogens
for protective HIV vaccines combining epitopes eliciting NAbs, ADCC, ACC, and T-helper and CTLs.
Epidemiologyav, Transmission, Cofactors. NCI spent $18,549,000 in 1991 on risk assessment and
prevention research including surveillance studies, sexual, hemophiliac, perinatal and other transmission
studies, and natural history and cofactor studies. Studies focus on HIV-associated lymphomas, HPV and
cervical or anal intraepithelial neoplasia (CIN + AIN), KS, and HIV/HTLV-I coinfections. NCI cosponsors
the MACS with NIAID. An additional $500,000 went to fund a study by Margaret Fischl of Miami to assess
the likelihood of household transmission of HIV in a cohort of discordant heterosexual cQuples.
NCl Intramural AIDS Research. In 1991, NCI spent $75M on intramural AIDS research. This figure rises
to $81M by 1993. This is about 46% of NCI's AIDS budget, the largest intramural amount of any of the
NIH. In February 1992 we met with Dr. Broder and several intramural researchers including Gene Shearer
of the Experimental Immunology Branch (EIB), Jay Berzofsky of the Metabolism Branch (MB), Robert
Yarchoan of the Clinical Oncology Program (COP), and Steven Creekmore of the Biological Resources
Branch (BRB) to leamrn about NCI's in-house AIDS efforts. Berzofsky and Shearer described their research
and Steven Creekmore detailed the work of the Biological Response Modifiers Program.
DIVISION OF CANCER BIOLOGY + DIAGNOSIS (DCBD). Laboratory of Pathology, Comparative
diagnosis of pulmonary complications of AIDS. Experimental Immunology Branch: Gene Shearer PhD:
TH1-TH2 cross-regulation in HIV infection; Mario Clerici MD: Exposure to HIV-specific T helper cell
responses before detection of infection by PCR and serum antibodies; Allan Weissman MD: Immuneinhibitory role(s) of HIV-1 gpl20. Laboratory of Molecular Biology: Immunotoxin, oncotoxin therapy;
conjugates of Pseudomonas exotoxin + TGF-alpha, IL-2, IL-4, IL-6, IGF1, acidic FGF, CD4, anti-Tac (Fv),
or antitransferrin (Fv) to treat cancers or HIV. Laboratory of Biochemistry: Samuel Wilson MD: HIV RT,
DNA synthesis in mammalian cells. MetabolIsm Branch: Jay Berzofsky MD, PhD: Vaccines for malaria
and AIDS. Laboratory of Cell Biology (LCB): E. Appella: T-cell antigen recognition and tumor antigens;
Laboratory of Mathematical Biology (LMB): JN Weinstein: Dipyrimadole and AZT.
DIVISION OF CANCER TREATMENT (DCT). Clinical Oncology Program: Basic and clinical studies,
including novel antiretroviral therapies and treatments for lymphomas. Nucleoside resistance studies.
Development of novel HIV-1 protease inhibitors. Nucleoside prodrugs. Laboratory of Biological
Chemistry: Myristoylation and retroviral replication. Pharmaceutical Resources Branch: Tooling with
prodrugs. Pediatrics Branch: Philip Pizzo MD: drugs for kids with AIDS and cancer. Medicine Branch:
Carmen Allegra MD: Tyrosine protein kinase regulators as T cell activation blockers. Laboratory of
Molecular Immunoregulation (LMI, Frederick), Francis "Frank" Ruscetti, PhD. Cellular regulation of
retroviral expression. William Farrar, PhD: Growth factors, cytokine receptors and HIV. A transcriptional

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