Conferring at NIH director’s advisory committee meeting are (left to right) John Coffin, William Paul, and David Baltimore.

Some of NIH’s anti-AIDS forces converged at Building 31 in June for the semiannual meeting of the advisory committee of NIH director Harold Varmus. AIDS wasn’t the only issue on the committee’s agenda, but it was the only one etched in urgency by a presidential directive: that NIH spearhead the development of a vaccine against AIDS within 10 years.

The multilayered discussion on this topic elaborated not only plans for a new building on campus dedicated to AIDS-vaccine research—initially one "without walls"—but also the ways in which the activities of the Office of Aids Research, the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and NCI’s Frederick-based research arm would be woven together into an AIDS-research quilt.

Varmus specifically invited Tufts University molecular biologist John Coffin, newly recruited to Frederick on a part-time basis to pursue his research on HIV drug-resistant mutants (see "Frederick’s Field of Dreams"), to apprise the advisory committee of the program he’s establishing at FCRDC.

Varmus recapped the rationale for the newly created AIDS Vaccine Research Committee, chaired by CalTech’s president, David Baltimore, and for the establishment of a Vaccine Research Center (VRC) within the NIH intramural research program, a collaborative NCI-NIAID venture.

"Ultimately," he said of the VRC, "this will be a physical presence, a separate building that includes at least some manufacturing capacity. For now, we are trying to assemble a center without walls of interested NIAID and NCI intramural researchers."

Increased funding for AIDS-vaccine research at NIH (33 percent over the past two years) has not been secured at the price of diminished funding in the AIDS budget as a whole, OAR Director William Paul assured the group. The budget for his program at Frederick, John Coffin told The NIH Catalyst, "is big enough to keep me happy."

"Clearly, my work in diversity and mechanisms of variation is related to vaccine development, but I’ll leave [vaccine research, per se] to him," he said, turning to David Baltimore, "and to Larry Arthur," whose AIDS vaccine-related research continues at Frederick in Building 535, where Coffin will reside.

Baltimore sees a "formidable challenge" in designing an HIV vaccine. "We have tested almost nothing that might work because all candidates thus far have been based on laboratory strains of the virus—and they need to be tested against wild-type virus. What was [Robert] Gallo’s enormous advance—adapting HIV to high-titer growth in the lab by altering the envelope glycoproteins—now constitutes the problem. These altered glycoproteins are much more easily neutralized by antibodies. We need to determine their crystal structures," he said.

Coffin outlined his program for the advisory group: it will encompass a wide array of disciplines, from viral enzymology and crystallography to in vivo studies of how HIV evolves in individuals. "Clinical virology," he said, "includes such issues as the dynamics of HIV replication in humans, detecting in patients the presence of resistant virus, preventing transmission of resistant virus, and ascertaining whether we can incorporate resistance to resistance in drug design. Some clinical issues may be difficult to bring in at the Frederick site," where clinical protocols have been discontinued, he added.

"This will not be a problem for you," Varmus promised. "You can use the Clinical Center resources."

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