Vaccinated (15 page)

Szmuness gradually worked his way up from lecturer to professor at Columbia's School of Public Health. By 1973 he was directing hepatitis testing for the gay community at the New York Blood Center. An epidemiologist, clinician, public health official, and hepatitis virus researcher, Szmuness was the perfect choice to direct Hilleman's vaccine trial. He quickly recruited a thousand homosexual men who had never been infected with hepatitis B virus. By October 1979 Szmuness had injected half of them with three doses of hepatitis vaccine and half with placebo. In June 1980, almost two years after the trial started, Szmuness and his colleagues carefully analyzed the results. Men who got the vaccine were 75 percent less likely to get hepatitis than were men who didn't get the vaccine. Hilleman's hepatitis B vaccine worked.

This controversial trial would later cause some to blame Hilleman for the AIDS epidemic in America. Although it was clear that AIDS had entered the United States well before Hilleman's hepatitis B vaccine trials, Alan Cantwell Jr., a dermatologist, said in his 1988 book
AIDS and the Doctors of Death
, “To my surprise, I quickly discovered that much of the scientific knowledge that has accumulated on the spread of AIDS in America has come from the surveillance and blood testing of large groups of gay and bisexual men who volunteered as human test subjects in the original hepatitis B vaccine trials, which took place in six American cities during the years 1978–1981. Was it coincidental that these were the beginning years of the new mystery disease in gays, and the years just before AIDS became ‘official'?” Cantwell reasoned that Hilleman's hepatitis B vaccine contained HIV and was therefore responsible for spreading AIDS in America. Later, researchers tested Cantwell's hypothesis by examining the incidence of AIDS in men who had or hadn't received Hilleman's hepatitis B vaccine. There was no difference. Although HIV was likely present in the blood from which he had made early preparations of his vaccine, Hilleman's choice of pepsin, urea, and formaldehyde had completely destroyed it. (The publisher of Alan Cantwell's book, Aries Rising Press, was founded by Cantwell himself to promote his uninformed views of the origin of the AIDS epidemic.)

 

B
EFORE
M
AURICE
H
ILLEMAN COULD SELL HEPATITIS
B
VACCINE TO THE
public, he had one more obstacle to overcome: Baruch Blumberg. While at Fox Chase, Blumberg had patented “a vaccine against viral hepatitis essentially consisting of Australia antigen,” U.S. patent number 3,636,191. The patent stated that the vaccine should be made by a process that “comprises substantially removing impurities including infectious components,” that there should be a step “to attenuate any virus that might remain,” and that the vaccine should be “free of blood components other than Australia antigen.” Patents aren't usually issued for ideas; they're issued for specific methods. Blumberg, like everyone else in the field, knew that the hepatitis B vaccine shouldn't contain live hepatitis B virus, that it shouldn't contain any other viruses, and that it shouldn't contain other blood proteins. But he didn't know how to do it. Hilleman saw Blumberg's patent as a lot of handwaving. “People in the hepatitis field were aghast at the guts of this son of a bitch,” recalled Hilleman. “Somebody had actually issued a patent for that crap.”

Hilleman feared that Blumberg's patent might stand in the way of Merck's vaccine. So he went to the Fox Chase Cancer Center to talk to him. In a spacious room overlooking the wooded grounds of Fox Chase, Hilleman sat uncomfortably among a group of administrators who knew little about viruses or vaccines. Blumberg wasn't in the room. “We needed to go out and talk to [the Fox Chase] people because we wanted this for an international product,” recalled Hilleman. “So we went out there and said that we would like to manufacture this product. But we didn't want any interference on sales and marketing. A financial officer speaking on behalf of Fox Chase said, ‘Here are the conditions. Blumberg will be the director of the program.' So I went over to the blackboard and I drew a picture.” It was a picture of Hilleman submerged in a lake. “Under your proposal this is me,” said Hilleman. Then he drew a stone, tied it around his neck, pointed to the figure, and said, “I'm under the water drowning, and that's a millstone, the Blumberg millstone.” Hilleman was furious. He wasn't going to give up control of the manufacture and testing of his vaccine—especially to someone who he felt knew little about viruses or immunology. He continued to attack the Fox Chase administrators. “If you're so dumb as to think that somebody who knows absolutely nothing [about viruses] is going to be the director of a program in which we're going to invest hundreds of millions of dollars, you're crazy. I said, ‘Divest yourselves of that idea.'” The Fox Chase administrators relented, licensed the patent to Merck, and abandoned the idea of having Blumberg run the program.

Years later, when other companies started to make their own blood-derived hepatitis B vaccines, Hilleman showed them the patent that he had licensed from Fox Chase. He assumed that Merck still had exclusive rights. “They laughed like hell,” remembered Hilleman. “‘You call that a patent?' they asked. ‘You paid them money for that?' If I had it to do all over again, I'd wish I'd never gone out to Fox Chase. But I'm one of those guys who don't want war. I'd rather pay somebody a reasonable amount. I felt that [Blumberg] deserved some remuneration for having discovered [Australia antigen]. I thought that his finding was really significant. It opened a door. But that's as far as it went.”

Mary Lasker poses with Lasker Award winners Maurice Hilleman (center, back) and Saul Krugman (back, second from right); both won the award for their work on the blood-derived hepatitis B vaccine, November 16, 1983 (courtesy of the Bettmann Archives).

In his book
Hepatitis B: The Hunt for a Killer Virus
, Baruch Blumberg claimed that the hepatitis B vaccine was his invention. Maurice Hilleman's name is mentioned once: “In 1975, Fox Chase Cancer Center licensed Merck to develop the vaccine. Dr. Maurice Hilleman, who had considerable experience in the development and manufacture of vaccines and in hepatitis research, was the executive in charge of the program.” Blumberg failed to mention that it was Hilleman who had figured out how to inactivate hepatitis B virus, how to kill all other possible contaminating viruses, how to completely remove every other protein found in human blood, and how to do all of this while retaining the structural integrity of the surface protein. Blumberg had identified Australia antigen, an important first step. But all of the other steps—the ones critical to making a vaccine—belonged to Hilleman. Later, Hilleman recalled, “I think that [Blumberg] deserves a lot of credit, but he doesn't want to give credit to the other guy.”

Maurice Hilleman's blood-derived hepatitis B vaccine, licensed by the FDA in 1981, was on the market until 1986, but doctors were reluctant to use it. They remained concerned about the source of the blood, unconvinced by the science. “When we brought [the vaccine] onto the market, we had one hell of a time,” recalled Hilleman. “The doctors and the nurses did not want to be vaccinated with human blood.” Hilleman knew that his method of inactivation killed all known human viruses. But he also knew that asking physicians to understand the science of viral inactivation was asking a lot. “Chemicals are chemicals,” he said. “It doesn't matter where the blood comes from. But it took a really enlightened person to understand the story.”

Ironically, Hilleman's blood-derived hepatitis B vaccine, made from the most dangerous starting material ever used, was probably the safest, purest vaccine ever made.

But because clinicians in the United States were uncomfortable using a vaccine made from human blood, Hilleman had to find another way to make it. (Although Hilleman's blood-derived hepatitis B vaccine is no longer made by manufacturers in North America or Europe, it is still made by several companies in Asia.) Fortunately, in the early 1970s, two researchers eating lunch at a delicatessen in Hawaii struck a deal that gave Hilleman the technology he needed to make another hepatitis B vaccine. Its creation would also help to usher in the age of genetic engineering.

 

H
ERBERT
B
OYER AND
S
TANLEY
C
OHEN STARTED A REVOLUTION IN
biology.

Boyer was born in Derry, a dark, industrialized corner of western
VACCINATED
Pennsylvania best known for its mines, railroads, and quarterbacks; Jim Kelly, Joe Namath, Johnny Unitas, and Joe Montana all played high school football in western Pennsylvania. Boyer also played football as an offensive lineman. But Boyer's football coach was also his science teacher, and his coach's passion for science influenced Boyer more than his passion for football. After high school, Boyer studied biology and chemistry at St. Vincent's College in nearby Latrobe, Pennsylvania, followed by graduate studies at the University of Pittsburgh and postgraduate work at Yale. Then he traveled west, arriving in San Francisco at the height of the 1960s counterculture. With a broad round face, impish smile, thick walrus-like mustache, and a wardrobe of leather vests, blue jeans, and wide, open-collared shirts, Herbert Boyer looked like the rock musician Jerry Garcia from the Grateful Dead. And, like Garcia, he was active in the civil rights movement and vigorous in his protests against the war in Vietnam.

But Boyer had come to California to pursue his love of science, not the counterculture. He took a job as an assistant professor of biochemistry at the University of California in San Francisco. By 1969
Escherichia coli,
or
E. coli
, a common intestinal bacterium, had caught his attention. Boyer found that
E. coli
made enzymes that neatly and specifically cut DNA. In 1972, while he was in the middle of these studies, Boyer traveled to Honolulu for a scientific meeting. There he met Stanley Cohen, a scientist from Stanford who was also working on bacteria. Cohen had found that some bacteria resisted the killing effects of antibiotics, while others didn't, and that bacteria could transfer this resistance to bacteria living next to them. Then Cohen discovered how they did it. Bacteria carried the genes for antibiotic resistance on small circular pieces of DNA that he named plasmids. Plasmids were promiscuous, easily moving from one bacterial cell to another.

At the Hawaii conference, Boyer and Cohen were each intrigued by the other's work. They decided to meet later that evening. Sitting over corned beef and pastrami sandwiches, they had an idea for how their research could be combined. To test it, they performed an experiment that would generate four hundred product licenses from the FDA, form the basis of fourteen hundred biotechnology companies, and launch an industry with annual revenues of $40 billion. Cohen took Boyer's DNA-cutting proteins, cut a plasmid DNA that contained one antibiotic-resistance gene, and inserted a gene that resisted a different antibiotic. Then the two researchers repaired the plasmid so that it again formed a circle. Now the plasmid had genes that resisted two antibiotics. Cohen reinserted this new plasmid into a bacterium and found that they had created a new bacterium that could now resist killing by both antibiotics. Boyer and Cohen reasoned that any gene, even human genes, could be inserted into bacterial plasmids. Every time these genetically engineered bacteria reproduced and made their own proteins, they would also be making human proteins; bacteria could become tiny factories that mass-produced a wide variety of human products. The new field of research launched by Boyer and Cohen was called recombinant DNA technology, or genetic engineering.

The value of this invention wasn't lost on a venture capitalist named Robert Swanson, who called Boyer and asked to meet him in a San Francisco bar. There, the twenty-nine-year-old Swanson and forty-year-old Boyer drank beer and discussed the commercial value of synthesizing human proteins in a laboratory. On paper napkins, they sketched out plans for the first biotechnology company based on genetic engineering. Boyer named it Genentech, a contraction of
genetic engineering technology
. When Genentech went public in 1980, the stock had the most dramatic escalation in the history of Wall Street, raising more than $38 million in capital and making multimillionaires of its founders. Later that year, Boyer's picture was on the cover of
Time
magazine under the heading “Shaping Life in the Lab: The Boom in Genetic Engineering.” Genentech's first product was human insulin. No longer did insulin have to be purified from the pancreas of cows and pigs; it could be made by bacteria in a laboratory. Later Genentech made proteins that helped children grow, broke down clots in the arteries of heart attack victims, and helped people with hemophilia clot their blood. Without having to rely on human blood to supply the clotting factors they needed, people with hemophilia were no longer at risk for HIV from blood transfusions.