Looting the medicine chest: how MicroGeneSys sought the inside track on an AIDS drug.

How Micro GeneSys sought the inside track on an AIDS drug

In a variation on a Georges Clemenceau theme ("War is too serious a matter to be left to generals") the U.S. Senate pulled on white coat and rubber gloves last fall and moved into the battle against AIDS.

Acting in its closing days, with hardly a dissenting vote, the 102nd Congress adopted a Senate amendment adding $20 million to the Pentagon's appropriation for fiscal 1993, earmarking the sum specifically for large-scale tests of one particular vaccine among several being developed against the human immunodeficiency virus (HIV).

The sum involved was trivial - 1/125 of 1 per cent of the $260 billion military budget and 2 per cent of the $1 billion allotted to AIDS research by the National Institutes of Health. But the principle involved was important: Though members of Congress often finance pet projects by tacking last-minute riders onto appropriations bills, this was the first time legislators presumed to usurp medical judgments made by people who had solid scientific credentials.

There is more behind the AIDS amendment than just the usual wrongheadedness of such powerful figures as Democrat Sam Nunn of Georgia and Republican John Warner of Virginia, who introduced it on the Senate floor. They had help and encouragement - lots of it - from an influential ex-Senator turned lobbyist, Democrat Russell Long of Louisiana.

Nunn and Warner, respectively chairman and ranking minority member of the Senate Armed Services Committee, in collaboration with Long, former chairman of the Senate Finance Committee, brought insider politics to a new flowering, even in a milieu where the term "Congressional ethics" is viewed as an oxymoron.

The AIDS-amendment caper is best understood against the backdrop of a few facts about this troubling disease. From the time it was publicly identified in 1981 through September 30, 1992, acquired immune deficiency syndrome has been diagnosed in 242,146 persons in the United States, of whom 160,372 have died. In addition to the 81,774 still living, there are an estimated one million Americans who are "HIV-positive" - that is, infected with the virus and both susceptible and contagious, but lacking classic AIDS symptoms. From what is known of the virus and its effects, it is reasonable to assume that these infected individuals will progress to actual AIDS, for which there is no cure and no effective medical prevention.

Immunization, along the lines of the now-obsolete smallpox vaccine, would be an obvious answer, and indeed a quest has been under way almost since the causative virus was isolated in the early 1980s. Overly rosy predictions surfaced immediately, beginning with one by Margaret M. Heckler, then Secretary of Health and Human Services and later Ambassador to Ireland, who prophesied at a 1984 press conference that a vaccine would be available within two years. Three years later, Dr. C. Everett Koop, then Surgeon General of the United States, was asked publicly what had happened to Heckler's promised vaccine. "I guess she must have taken it to Ireland with her," he said.

Some palliative progress, but not a cure, has been achieved since then-notably the drug AZT, which got fast-track approval several years ago and is now the mainstay of AIDS therapy for those who have the money to pay for it. The ongoing search for a vaccine has branched, the first path toward a preventive one (which would immunize people not yet exposed to the virus) and the second toward a therapeutic one (which would suppress, reverse, or even eliminate symptoms in infected individuals).

The therapeutic route now seems the more promising and is the focus of lively competition among several gene-splicing companies bearing such science-fictionesque names as Genentech, Chiron, Biocene, and MicroGenesys (pronounced "micro-genesis"). All have come up with genetically engineered candidates - a total, in fact, of sixteen allegedly therapeutic AIDS vaccines, seven of which the National Institutes of Health is evaluating as part of the overall AIDS research program. On the basis of preliminary tests, all seem safe enough, but whether they are effective is still an open question. Each sponsor touts its candidate over the others, but disinterested scientists question the long-term effectiveness of any of them.

The sponsoring companies all have know-how in the field of genetic engineering, but MicroGeneSys, a small company based in Meriden, Connecticut, has something else that may prove even more important: know-who. One day last September, as the 102nd Congress neared adjournment, ex-Senator Long strolled onto the floor of his old clubhouse and watched while his old chums, Nunn and Warner, cut the cards and started to deal. Long, son of Huey Long, the fabled Kingfish of Louisiana, was taking advantage of the lifetime visitation privileges that former Senators enjoy, and this day he had more than auld lang syne on his mind; he was there in his new, post-Senatorial role of Washington lobbyist, with a mission to boost the fortunes of MicroGeneSys.

The company had hired Long's firm (and Long's know-who) to get a break for its candidate vaccine, known by the cryptic name gp-160. With Long watching like a father at a Lamaze delivery, Nunn proposed an amendment providing "that $20,000,000 of the funds appropriated in this paragraph may be made available in the Acquired Immune Deficiency Syndrome program element only for a large-scale Phase III clinical examination of the GP-160 [sic] vaccine...."

Phase III trials involving actual patients are the final hurdle that any pharmaceutical product must clear (after safety and probable efficacy are established) before going on the open market. In effect, Nunn and his co-sponsor Warner were offering MicroGeneSys a head start in what could be a huge market: Its drug would not have to compete with other, perhaps more effective products in trials involving thousands of individuals. In medicine as in other high-tech fields, the first product to go on sale has a tremendous edge.

Who asked for this $20 million (aside from lobbyist Long, of course)? Nunn said on the Senate floor that the money was being added at the Army's request, but acknowledged that Russell Long had "brought this matter to our attention." Warner subsequently amplified: "Our former colleague and friend ... was present on the floor of the Senate today, as is his right as a former Senator." Though a Nunn aide told the journal Science that playing footsie with lobbyists "[is]" not how Senator Nunn works," the pawprints of that old legislative fox, Long, were all over the amendment, which further provided that if the gp-160 project should fall through for any reason, "the Secretary of Defense may use these funds only for other AIDS research needs of the Department of Defense" (emphasis supplied). In other words, the national AIDS effort under Dr. Anthony S. Fauci at NIH could not get access to the Nunn-Warner money.

Except for the facts that (1) Long and Nunn are old pals and (2) Nunn heads the Armed Services Committee, there was no apparent reason for choosing the military to run gp-160 trials. About 92 per cent of all confirmed AIDS cases have occurred in male homosexuals or drug abusers - two groups not welcome in the military. Furthermore, the continued spread of infection (as exemplified by tennis champion Arthur Ashe, basketball star Magic Johnson, and Mary Fisher, the HIV-positive speaker who added a touch of sorely needed class to the Republican national convention) is not reaching people of primary concern to the military. In fact, there is evidence that the Army, far from requesting the trials, didn't want to be bothered with them. In a written statement to Science, the Army said it "feels that it is premature to initiate a large-scale trial until the current studies of gp-160 are completed and the data analyzed."

Nunn's amendment left one avenue by which the Phase Ill trials could be aborted: It gave the Secretary of Defense, the director of the National Institutes of Health, and the head of the Food and Drug Administration six months to come up with "a written certification containing a determination not to proceed (along with) the reasons for that determination and an assessment of the gp-160 vaccine." As noted, the certification would not loosen up the money for use outside Pentagon auspices, as much as such research might be needed. Furthermore, if any one of the three officials supported the trial, it could go ahead over the majority's opposition.

The $20 million appropriation drew wide censure from medical experts, but it wasn't the money, as they saw it, it was the principle. "[This] opens the door for a tremendous amount of lobbying abuses in the system," said William Haseltine, a viral researcher at the Dana Farber Cancer Institute on Harvard's medical campus in Boston. Ron Desrosiers, an AIDS research scientist at the New England Primate Research Center. added: "There are a lot of good products that deserve to be tested, and to sneak one through is ridiculous."

Even some Congressional colleagues found this particular bit of pork too gamy for their taste. Representative John Dingell, the Michigan Democrat sometimes called "Tailpipe John" for his understanding attitude about auto exhaust emissions and no mean boodler himself, called the Senate amendment "deeply flawed," and added that decisions on what drugs to test and how "should be left to scientific peer review and not made by the Congress in this manner."

Nunn and Warner, in batting the ball across the legislative net, dropped it squarely in front of the director of NIH, Dr. Bernadine Healy, who at this point (November 5, two days after the defeat of her political sponsor, George Bush) found herself with apparently little to lose. Healy, the only female and by all odds the most confrontational among the six directors NIH has had in its thirty-seven-year history, convened a special panel on AIDS vaccines and showed up at its first meeting ready to do battle. Her first reaction to the amendment had been, "It's really scary," but that was mild compared to such subsequent remarks as this: "If we're going to have legislators determining what drugs we test in people, I think that as physicians and scientists we're potentially facing as large a moral dilemma as we have ever faced in medical science."

Later, she told the advisory panel, "It would appear that the Congress has signed an uninformed consent form for patients with AIDS" (Healy's emphasis). At the same meeting, Food and Drug Commissioner David Kessler (also a short-timer) vowed that "FDA will not abrogate its fundamental responsibilities in respect to new therapies [and is] not going to short-change the process.... We will not lower our standards."

The advisory panel's mission was to recommend to Healy by December 2 a course of action to follow in response to the Nunn-Warner amendment: oppose it, cave in, or do something in between.

The panel eventually punted. On November 23, after a second meeting, it indicated that - in Fauci's words - the gp-160 trial "should be done in combination with other related products and that the trial should be done not just in the military ... but in a good representation of the HIV community in the country." And on December 2 - Healy's deadline - this indeed is what the panel recommended to the NIH director, to MicroGeneSys's great chagrin.

Drs. Nunn and Warner have since pulled off their rubber gloves and hung up their white coats, for the time being at least. But whatever happens later, Dr. Long is standing by with an ampule of adrenalin at the ready should anything untoward threaten the well-being of MicroGeneSys's gp-160.