Shots in the Dark
THE WAYWARD SEARCH FOR AN AIDS VACCINE

By Jon Cohen

W. W. NORTON & COMPANY

Copyright © 2001 Jon Cohen. All rights reserved.
ISBN: 0-393-05027-0



Chapter One


Fast Predictions


THE WHITE HOUSE
Office of the Press Secretary


PRESS BRIEFING BY
LARRY SPEAKES
October 15, 1982
The Briefing Room
12:45 P.M. EDT


* * *


Q: Larry, does the President have any reaction to the announcement—the Centers for Disease Control in Atlanta, that AIDS is now an epidemic and have over 600 cases?
MR. SPEAKES: What's AIDS?
Q: Over a third of them have died. It's known as "gay plague." (Laughter.) No, it is. I mean it's a pretty serious thing that one in every three people that get this have died. And I wondered if the President is aware of it?
MR. SPEAKES: I don't have it. Do you? (Laughter.)
Q: No, I don't.
MR. SPEAKES: You didn't answer my question.
Q: Well, I just wondered, does the President—
MR. SPEAKES: How do you know? (Laughter.)
Q: In other words, the White House looks on this as a great joke?
MR. SPEAKES: No, I don't know anything about it, Lester.
Q: Does the President, does anybody in the White House know about this epidemic, Larry?
MR. SPEAKES: I don't think so. I don't think there's been any—
Q: Nobody knows?
MR. SPEAKES: There has been no personal experience here, Lester.
Q: No, I mean, I thought you were keeping—
MR. SPEAKES: I checked thoroughly with Dr. Ruge this morning and he's had no—(laughter)—no patients suffering from AIDS or whatever it is.
Q: The President doesn't have gay plague, is that what you're saying or what?
MR. SPEAKES: No, I didn't say that.
Q: Didn't say that?
MR. SPEAKES: I thought I heard you on the State Department over there. Why didn't you stay there? (Laughter.)
Q: Because I love you, Larry, that's why. (Laughter.)
MR. SPEAKES: Oh, I see. Just don't put it in those terms, Lester. (Laughter.)
Q: Oh, I retract that.
MR. SPEAKES: I hope so.
Q: It's too late.


On October 15, 1982, Larry Speakes, then the spokesperson for President Ronald Reagan, like most people in the world, had no idea that a new epidemic disease, acquired immunodeficiency syndrome, was racing around the United States, Europe, and Africa.

    The disease that eventually became known as AIDS likely has existed in Africa for many decades, if not many centuries. The most probable scenario is that humans caught it from chimpanzees when trapping or butchering the animals. Because people with AIDS die from complications like unchecked tuberculosis, wasting, or pneumonia, no alarm bells would have sounded, as nothing would have looked unusual. This is especially true given the sorry state of health care for most Africans, where many children die young and, in some countries, the majority of adults never reach their 50th birthday.

    It is easy to see how, as Africans began migrating to burgeoning cities and syringes became more common in public health campaigns, AIDS could have flourished but still remain undetected. Air travel then brought the disease to Europe, Haiti, and the United States in the late 1960s and early 1970s. The sexual promiscuity of gay men in these liberated years, where it was not uncommon for people to have 50 partners in a year, offered the disease a chance to firmly establish itself on these more developed continents. And these were places where doctors had been trained to take note of odd cases, such as young men dying from pneumocystis carinii pneumonia, a normally wimpy disease.

    Five cases of this rarely fatal disease in gay men indeed caught the attention of a Los Angeles physician in 1981, and he reported his findings on June 5, 1981, in the Morbidity and Mortality Weekly Report, a no-frills, but widely read publication issued by the U.S. Centers for Disease Control (CDC) to alert the medical community to public health issues. By October 1982, when Speakes joked about the emerging epidemic, MMWR had published 11 reports on AIDS. Articles had appeared in the major medical journals. True, the popular media had been shy about covering the story, but even by that point it had appeared on the network news and on front pages of major daily newspapers. Larry Speakes, in short, should at least have known that AIDS existed. And his ignorance highlighted the Reagan Administration's indifference—and even outright hostility—toward homosexuals. It also foreshadowed how unprepared the people at the top were to lead the battle against this burgeoning epidemic, especially when it came to organizing the search for a vaccine.

    Presidents can make enormous differences when it comes to conquering disease. Fifty years earlier, when thousands of children in the United States were being crippled each year by polio, President Franklin Delano Roosevelt organized charity balls on his birthday "to dance so others may walk." These balls evolved into the National Foundation for Infantile Paralysis, colloquially known as the March of Dimes, which would successfully lead the campaign to research and develop the first polio vaccines. But then, FDR had polio himself. He also appointed his former law partner, Basil O'Connor, to run the March of Dimes. Ronald Reagan for many years refused even to say the word "AIDS" in public. And Reagan's top aides had as difficult a time with AIDS as he did. Consider this exchange between Speakes and journalists at a White House Press briefing on June 13, 1983:


Q: Larry, does the President think that it might help if he suggested that the gays cut down on their "cruising"? (Laughter.) What? I didn't hear your answer, Larry.
MR. SPEAKES: I just was acknowledging your interest—
Q: You were acknowledging but—
MR. SPEAKES: —interest in this subject.
Q: —you don't think that it would help if the gays cut down on their cruising—it would help AIDS?
MR. SPEAKES: We are researching it. If we come up with any research that sheds some light on whether gays should cruise or not cruise, we'll make it available to you. (Laughter.)
Q: Back to fairy tales.


    Could the person who handled the press for FDR publicly have made jokes about polio and lived to see the inside of the White House again?


    * * *


AT THE TIME Larry Speakes was making fun of gay cruising, Margaret Heckler had been the Administration's top health official for three months and was preparing for a speech the next day to the U.S. Conference of Mayors, at which she would declare that AIDS was the "number one health priority."

    A lawyer by training, Heckler had represented Massachusetts in the Congress for 16 years before Reagan appointed her to head the Department of Health and Human Services (HHS), a mammoth agency tasked with overseeing both the National Institutes of Health (NIH) and the CDC. Heckler's chief of staff, C. McClain "Mac" Haddow, recalled that his boss knew little about AIDS when she took the HHS post. So Haddow, a former Utah state representative, and other staffers scheduled a briefing for her.

    To educate Heckler about the disease, they brought in James Mason, head of the CDC in Atlanta, Georgia. Edward Brandt Jr., the assistant secretary for Health, also came to the gathering in her office, as did a gay man who had been a close aide to Heckler since her time on Capitol Hill. Mason walked Heckler through the basics of how AIDS appeared to be transmitted, explaining that it focused on homosexuals and why that might be. "He was talking about anal intercourse and Heckler got this shocked look on her face and said, `What?'" recalled Haddow. "Jim Mason, who's a very straight-laced Mormon and was having a little difficulty with this, said the rectal wall was more fragile than the vaginal wall."

    "Anal intercourse?" said Heckler, looking at her trusted, gay staffer. "You do that?"

    Ed Brandt looked at Haddow. "I think we better come back and discuss this a little later," said Brandt.

    Haddow said that everybody in the room was stunned. "Mrs. Heckler didn't understand that homosexuals engaged in anal intercourse."


    * * *


ON APRIL 23, 1984, MARGARET HECKLER summoned Robert Gallo into her office at the Hubert H. Humphrey Building in Washington, D.C. A prominent and controversial researcher at the National Cancer Institute (NCI), Gallo had just raced home from a scientific conference in Italy to attend what would turn out to be one of the most awkward, confused—and talked about—scientific press conferences in history: in a few hours' time, Heckler would announce that Gallo's lab had found the cause of AIDS, firing the starting gun for the vaccine search. But before she made this grand declaration, she wanted Gallo's input about the amount of time it would take to translate his laboratory's discovery into an AIDS vaccine.

    Scientists who make discoveries in basic research long have shied away from offering predictions about practical outcomes, and reporters long have hounded scientists to offer just such predictions. Mac Haddow wanted Heckler to be able to address this question head on, and for days he had been pressuring the NIH to give him a time line. "The NIH public affairs office was asked, and they came up with a whole list of possible answers," said Haddow. "The bottom line was it was going to have to be Gallo's call. And he would have to be comfortable with it."

    When Haddow first began seeking an answer to this question, he thought he would have several weeks to find an answer. Plans called for announcing the explosive news of the Gallo lab's discovery in concert with the May 4 issue of Science, which would contain four back-to-back papers describing how the lab had fingered a new virus as the culprit and grown large quantities of it. But Haddow's PR plans became fouled up when news stories hinting at the discovery began to dribble out during the second week of April. Creating further grief for HHS, the White House had high hopes of using the news during this election year to confront criticisms about the Reagan Administration's AIDS record. At Ed Brandt's urging, Gallo and NIH director James Wyngaarden, who had traveled together to the conference in Italy, both hastily returned home to attend this Monday afternoon press conference.

    When Gallo, Wyngaarden, and NCI director Vincent DeVita Jr. arrived at Heckler's office that morning, Haddow quickly dressed them down for a story that had appeared the day before on page 1 of the New York Times. Headlined "Federal Official Says He Believes Cause of AIDS Has Been Found," the article was not about the findings in Gallo's lab. Rather, it quoted James Mason, head of the CDC, describing the work of researchers at the Pasteur Institute in France, and Mason said he had not yet seen the papers from Gallo's lab. Haddow was livid about the perception that the CDC and the NIH—both of which are part of HHS—were at odds with each other, and contended that the NIH was to blame for some of the tension between the institutes. After the bickering about who was at fault died down, Haddow asked how long it would take to develop a vaccine. The question caught Gallo unawares. "I hadn't thought about it before we went in there," said Gallo. "I didn't even anticipate the question."

    DeVita and Wyngaarden attempted to convince Haddow that the idea of offering a time line was a mistake. "People have tried to make vaccines against all sorts of things, and the record is generally one of failure," Wyngaarden said. Wyngaarden had little respect for Haddow, who he thought was "authoritarian" and "gave the scientific point of view no shrift." The NIH director, who personally oversaw a $4.5 billion budget (1% of which went to AIDS) and had extensive clout on Capitol Hill, also had little respect for Heckler. "The woman was one of the worst listeners I've ever encountered in any capacity," he said. "She'd listen to one sentence or two, and then her mouth wouldn't close again."

    By all accounts, Gallo came up with the official line: within two years, an AIDS vaccine would be ready for human testing. "I assume as much credit or blame for that as anyone," Gallo later acknowledged. Haddow recalled having "a lengthy discussion about why it was defensible." Said Haddow: "I wanted to be sure before Heckler said it and was brought into it that there was a reasonable expectation that we could accomplish that goal."

    Brandt, who was also part of these discussions, put great faith in Gallo's enthusiasm. "He was convinced that he had all the makings of a vaccine, that he was fully prepared to move on that very quickly, as a matter of fact," said Brandt. "I really had great confidence in Gallo's ability to pull that off."

    Heckler, who had a severe case of laryngitis that day, invited Gallo into her office for a one-on-one chat.

    "Will we be able to get a vaccine?" she asked in her scratchy voice.

    Gallo said he believed so. "I just said, `I think, you know, due to the fact we have an unlimited amount of virus now and we're sure it causes the disease, I can't think that this should take that long.' I didn't perceive the difficulties."


    * * *


HUNDREDS OF JOURNALISTS jammed into the first-floor auditorium of the Hubert H. Humphrey Building for the 1:15 P.M. press conference. Heckler stepped up to the lectern first. She had a dyed blonde head of helmet hair, and its cartoonish effect was exaggerated by her bright red dress, which sported a high white collar. Behind her, a dramatic, 20-foot-high blue curtain served as a backdrop. Flanking Heckler were Gallo and the agency's top brass: HHS assistant secretary Brandt, NIH director Wyngaarden, CDC director Mason, and NCI director DeVita.

    Heckler opened the proceedings with a joke. "As I believe you anticipate, this press conference will be devoted to the subject of AIDS, in which area there is, of course, important news," she said from behind the thicket of microphones sprouting from the lectern. "But, unfortunately, we have not made similar breakthroughs in the field of laryngitis. So I apologize for the state of my voice today."

    Heckler continued in an increasingly faltering voice. "Today, I am pleased to whisper"—the reporters laughed—"that the arrow of funds, medical expertise, research, and experimentation with the Department of Health and Human Services, and its allies around the world, have [sic] aimed and fired at the disease AIDS, and has hit the target only two or three rings from the bullseye itself."

    It would be quickly forgotten, but at the time of this announcement, several far-flung theories about the cause of AIDS still competed with each other. Some researchers recently had argued that a fungus caused AIDS. Others maintained that AIDS was the result of using amyl nitrate inhalants, called poppers, that many gay men snorted to strengthen the power of orgasm. The list of suspected causes also included cytomegalovirus, Epstein-Barr virus, swine flu virus, herpesvirus, and the fanciful idea that several of these possible causes were assaulting the immune system in concert. Gallo himself for a time tried to pin the disease on one of the two known human T-cell leukemia viruses, HTLVs, obscure pathogens recently discovered by his lab.

    Only a year before, Gallo and his coworkers had thrust HTLV-I and HTLV-II into the spotlight when they published, again in Science, two papers arguing that these viruses were the possible cause of the then two-year-old AIDS epidemic. Another paper in that 1983 issue from a group headed by Luc Montagnier—a researcher at the Pasteur Institute in Paris, France, who would later enter a protracted battle with Gallo about who deserved credit for discovering the cause of AIDS—bolstered the case. In the subsequent year, Gallo and his colleagues refined their argument, and now they were contending that the cause was a new member of this viral family, HTLV-III.

    The Gallo lab's four 1984 Science papers showed that they had isolated HTLV-III from 48 patients with the disease and spelled out how to grow the virus continually in laboratory cultures, a critical feat because it routinely killed the cells it infected. Heckler emphasized to the journalists that the ability to grow the virus in mass quantities would allow scientists to characterize the agent in detail, understand its behavior, and develop a blood test in as little as six months. "Finally, we also believe that the new process will enable us to develop a vaccine to prevent AIDS in the future," she said. "We hope to have such a vaccine ready for testing in approximately two years."

    Heckler proceeded to apportion credit for this discovery to the people sitting behind her. The next paragraph in her prepared statement, which had been distributed to the press, praised the work of researchers at the Pasteur Institute. But Heckler, her voice jumping into what sounded like a helium-induced register, abruptly abandoned the prepared statement, asking Gallo and Brandt to come forward.

    A hunch-shouldered Gallo moved into the spotlight. With his perpetually unkempt steel-wool hair, a too-casual camel-colored sport coat, and a slightly crooked tie, Gallo looked every bit the academic, which was in keeping with the NIH style. He proceeded to explain himself in a tortured English. "Many of you, or all of you, have seen discussions about work in Paris," he said. "There was. There is not. There has never been any fights or controversies between us and a group in France.... We have active collaboration in the coming month. If what they identified in Science a year ago is the same as what we now have produced more than 50 isolates of and in mass production, and in detailed characterization, if it turns out to be the same, I certainly will say so, and I will say so with them in collaboration."

    Gallo fielded several questions, finally passing on this one: "How many years will it be before there is a marketable vaccine, based on previous experience?" Brandt, at Gallo's urging, came forward. "We're estimating a minimum of two years, probably more like three years," Brandt said. "In two years, we think it's possible to begin to start human trials. But I think we have a—one of the first steps that has to he accomplished is to mass-produce this virus in sufficient quantity to accomplish that. So I think we're talking about probably three years. We're going to hustle." There. Brandt had said it. Three years until a vaccine was on the market.

    "Excuse me," the reporter said. "The French told me this morning that they would predict at least five years. And Luc Montagnier"—this was the first mention of Montagnier's name at the press conference by anyone—"said he thought it might be five to 10 years. Why are you more optimistic than the French are?"

    "I'm more optimistic, I guess," said Brandt. "I don't know. I'm more optimistic. Except that I believe it can be done, that's all."

    An astute reporter pointed out that there were a number of viruses, "known for as long as two decades," that scientists had yet to defeat with vaccines. "Why are you confident that you can get one for AIDS in two years?"

    Gallo finally spoke his mind on the question, backpedaling mightily and, in effect, undermining what he had told Heckler and Haddow earlier. "I believe that the reason that there's a wide difference in what time it takes, you know, it obviously is not in the interest of the scientist to give a fast prediction," he said. "You'll only press us all, say, `Remember what you said eight months ago, four months ago?' You'll be giving us a clockwatch.... Now your question gets tricky. How do you know you'll have one that really works in AIDS patients? Of course, the prediction for that is impossible. You have no hundred percent proof that it will be two years, a hundred years, or it may never come from vaccination. It depends on the subtleties of biology. But the principles are there. The likelihood, the best we can say in science, with the technology available, we should have things ready to be able to be tried by then."

    Brandt and Gallo traded off answering questions, which ranged from uninformed to insightful, a reflection that the conference had attracted both general assignment reporters and those who regularly covered the science beat. The smartest questioners kept returning to the subject of vaccines. "Dr. Brandt," asked one, "in talking about approval of a vaccine, aren't you sort of blithely leaping over what could be a very difficult ethical problem, namely, the testing of this for safety and efficacy on healthy individuals?"

    Brandt misunderstood the clairvoyant question. "Absolutely not. I mean, we would certainly test any vaccine," he said.

    Another sharp reporter asked whether they intended to test a live- or a killed-virus vaccine. These are the traditional methods of making a viral vaccine: either killing the virus or weakening a live version of it. These modified versions of the virus then safely can teach the immune system how to defend itself should the real thing ever invade. "Can you comment on the difficulty of human clinical trials of such a vaccine?"

    Brandt, an earnest and well-meaning man, did not seem to understand this question either. "Well, we're going to develop the vaccine first," he said. "Then we'll be able—it depends entirely on what kind of vaccine comes out of it. So we certainly are not going to test in humans any vaccine that would put those people at risk of the disease."

    The reporter, obviously baffled, kept pressing Brandt, who accused the journalist of "presupposing the kind of vaccine" they intended to develop. "I'm not presupposing anything," the journalist snapped back.

    "We don't have a vaccine at the moment," said Brandt. "And we would certainly take all ..."

    "You're talking about having one in a couple of years," the journalist interrupted, raising the question again about how they planned to stage tests of the vaccine in healthy volunteers.

    "Well, as soon as we see the vaccine, then I'll be able to answer that question."

    Had Brandt understood vaccine development better, this testy exchange need not have happened. Long before AIDS came around, scientists well recognized that the testing of a vaccine against a lethal disease raises difficult ethical questions. Inevitably, the issue comes down to weighing risks against benefits—and carefully describing the two sides of the scale to anyone who volunteers for the trial. What is more, Brandt's charge that the journalist was "presupposing" the type of AIDS vaccine that would be developed was particularly off-base because if anyone was presupposing anything about the formula for an AIDS vaccine, it was Gallo, as he revealed in a subsequent answer.

    "You keep asking about the vaccine, when it comes up, what's going to be available in two years," Gallo said to a reporter who had not asked about the vaccine. "As best as a scientist can calculate. We can't predict anything 100%. But you've got to give some answers."

    Gallo, who had never made a vaccine against anything, went on to detail a recipe for an AIDS vaccine that, instead of relying on the entire virus like the traditional live and killed approaches, only called for using a piece of the agent that had been produced with genetic engineering techniques. Just such a hepatitis B vaccine was then being engineered that contained the surface protein, or envelope, of that virus. When it came to AIDS, said Gallo, the same logic would apply. "In my view, you'd vaccinate with the envelope prorein of the virus," said Gallo. "We'll go to recombinant technology, we are doing that now, and we will produce the protein that way. That protein, I would certainly be willing to take if I were a high-risk person, and I'd do it voluntarily.... That's the direction we're kind of thinking about."


    * * *


A COUPLE DAYS AFTER THE PRESS CONFERENCE. June Osborn, then a University of Wisconsin virologist who headed the NIH's AIDS Advisory Committee, received a phone call from an outraged gay researcher she knew in Los Angeles. The researcher explained to her how hard he and his colleagues had been working to convince the gay community in Los Angeles that sex clubs and bathhouses were spreading AIDS. Before the press conference, the researcher said these businesses were empty. But Heckler's enthusiasm about the development of a vaccine had created a euphoric sense that the end of the epidemic was near. Last night, he complained, he saw a bathhouse with a four-hour waiting line.

    Media reports from the press conference did dutifully report Heckler's comment that an AIDS vaccine would be ready for testing in about two years. They also by and large left out Brandt's more declarative statement that, by three years, a vaccine probably would be on the market. Still, regardless of the specific language used in the distilled and packaged versions of what was said in the Hubert H. Humphrey auditorium on April 23, 1984, the public heard a simple message: An AIDS vaccine was just around the corner.

    Looking back on the press conference nearly 14 years later, many of the participants had serious regrets about the vaccine predictions. Brandt said he still "winced" every time he heard reference to an AIDS vaccine being tested in two years, and he had completely forgotten about his own declaration of a marketed vaccine in three. "Certainly there wasn't much experience with the whole idea of a vaccine," acknowledged Brandt. "There was a general belief moving about at the time that this was really going to be a fairly easy nut to crack. It was just a matter of time until some quick breakthrough, or whatever the word is, until that happened. I suspect if we really understood the complexity of the organism at that time, things might have happened differently."

    Gallo aknowledged that, at the time, he had "zero previous experience in my life on a vaccine" and only the crudest understanding of the basic immune mechanisms that protect people from infectious diseases. "You can't imagine the level of my own feeling of confidence at that time," he said, by way of explaining his role in the optimistic predictions, ills lab had just played major roles in the discoveries of HTLV-I and HTLV-II, as well as uncovering a critical immune system messenger, interleukin-2, that tells cells to grow. With AIDS, they had convincing evidence for the first time that a virus isolated from ailing people caused the disease. Their ability to mass-produce this so-called HTLV-III—which later became known as human immunodeficiency virus, HIV, when it proved to have no relationship to the other HTLVs—laid the groundwork for a blood test, treatment, and a vaccine. They were hot on the trail of discovering which cells the AIDS virus preferred, the various ways it was transmitted, and what genes it had. "There was so much data pouring in that I, too, thought—probably believed—we could have solved the whole bloody thing, you know?"

    Gallo's greatest regret is that the press conference was held at all, as it violated an agreement he had made with Montagnier and the other Pasteur researchers earlier that month—and seriously incensed them. "I was terribly, terribly nervous," remembered Gallo. "I had massive conflicting emotions. I felt this shouldn't have been done. I didn't act strong enough that we should have waited until we compared the virus with the French and made a joint announcement." The perception that Gallo made a credit grab was compounded by Heckler's laryngitis, which forced her to skip the parts of her prepared statement that acknowledged the Pasteur's contributions.

    There is, of course, no way of knowing for certain whether an HIV vaccine would be any closer to market had the announcement of the discovery of the cause of AIDS been handled differently. But the April 23, 1984, press conference and the attendant backroom imbroglios communicated in bold type that the search for an AIDS vaccine was off to a bad start.


    * * *


THE WHITE HOUSE
Office of the Press Secretary


PRESS BRIEFING BY
LARRY SPEAKES
December 11, 1984
The Briefing Room
12:03 P.M. EST


* * *


MR. SPEAKES: Lester's beginning to circle now. He's moving in front. (Laughter.) Go ahead.
Q: Since the Center for Disease Control in Atlanta—(laughter)—reports—
MR. SPEAKES: This is going to be an AIDS question.
Q: —that an estimated—
MR. SPEAKES: You were close.
Q: Well, look, could I ask the question, Larry?
MR. SPEAKES: You were close.
Q: An estimated 300,000 people have been exposed to AIDS, which can be transmitted through saliva. Will the President, as Commander-in-Chief, take steps to protect Armed Forces food and medical services from AIDS patients or those who run the risk of spreading AIDS in the same manner that they forbid typhoid fever people from being involved in the health or food services?
MR. SPEAKES: I don't know.
Q: Could you—Is the President concerned about this subject, Larry—
MR. SPEAKES: I haven't heard him express—
Q: —that seems to have evoked so much jocular—
MR. SPEAKES:—concern.
Q: —reaction here? I—you know—
Q: It isn't only the jocks, Lester.
Q: Has he sworn off water faucets—
Q: No, but, I mean, is he going to do anything, Larry?
MR. SPEAKES: Lester, I have not heard him express anything on it. Sorry.
Q: You mean he has no—expressed no opinion about this epidemic?
MR. SPEAKES: No, but I must confess I haven't asked him about it. (Laughter.)
Q: Would you ask him Larry?
MR. SPEAKES: Have you been checked? (Laughter.)