Experiment Eleven (10 page)

Then Waksman told the assembled physicians of his background on the Rutgers college farm, of his longtime interest in the actinomycetes, and of his transition from compost and humus to antibiotics. Two events in 1939, he said, “provided the necessary stimulus.” One was a former student's work on gramicidin—he did not mention René Dubos by name. The other was World War Two and the need for new agents.

He recalled finding the first antibiotic, actinomycin, but determining that it was very toxic. The second, streptothricin, was “a great step forward,”
but it was also toxic. Finally, “in September, 1943,
my assistants and I
[emphasis added] succeeded in isolating in our laboratory an antibiotic which possessed properties similar to those of streptothricin but was less toxic.” This was streptomycin.

Albert Schatz was not at the lecture, and Waksman did not mention his name. Feldman and Hinshaw were in the audience, but in Waksman's retelling of the events, they were not mentioned either. Waksman gave equal importance to streptothricin and streptomycin, even though he had already been informed by Merck that, in its opinion, streptothricin was too toxic for use as an injected drug.

His paper was published on November 15 by the Mayo Clinic, and this time his name came first and Schatz's last, with Betty Bugie's in the middle. Schatz's prospective paper on his in vitro work on H37Rv, where his name would be first and Waksman's second, was mentioned in a footnote as being “in press.” Feldman and Hinshaw's work was not mentioned. In addition, Waksman created a myth about how Schatz had isolated his streptomycin-producing strain of
A. griseus.
He told the Mayo physicians that antibiotics in his lab were isolated according to a “
six-step
” method that, he implied, he had devised. He wanted to leave the impression that he should be given credit for the way Schatz had isolated his microbe. The first two of the six steps were ways of finding which bacteria were likely to produce antibiotics, including soil enrichment. (The other four steps, including the streak test, involved testing the microbes, once found, to see which germs they were capable of destroying and then how to produce the antibiotic.)

In Waksman's Mayo Clinic paper, he said that “both streptothricin and streptomycin were isolated and studied by the use of these procedures.” This was not true, and as the supervisor of Schatz's thesis, and one of his examiners, he should have known that. The thesis shows that Albert Schatz did not use the first step in isolating his microbe. And when he used the second step, he got no positive results. If he had used only Waksman's “six steps,” the chances are that he “would not have isolated”
A. griseus
because those first two steps
did not produce a clear zone
. He isolated the streptomycin-producing strain through random selection, using the same kind of intuition that a gardener might use to pick a good, healthy plant for breeding. However, Waksman's myth would create the impression among many observers of his antibiotic program that all his graduate
students, including Schatz, followed a strict method, laid out before Schatz started his Ph.D. That Schatz found his microbes through the serendipitous method of random selection and that “
perhaps some intuition
was needed” would not be acknowledged by Schatz's peers for another half century.

THAT EVENING AT
the Mayo Clinic, Waksman left a manuscript of Schatz's in vitro paper with Feldman, who, again prodded by Hinshaw, asked for at least a footnote on their own work to be included. “It would very properly give you the credit for recognizing the importance of the in vivo studies before speculating as to possible chemotherapeutic efficacy,” he said. Such a footnote, he continued, might read, “At the suggestion of the authors the effect of in vivo tests of streptomycin on
M. tuberculosis
is now being studied by Feldman, Hinshaw and Heilman, Mayo Foundation, Rochester, Minnesota. The results of their study will be the subject of an early report.” The
footnote was printed
in the paper, but without the last sentence. Waksman had successfully concluded his first move to control the story of the discovery of streptomycin.

BY THE SPRING OF 1944, THE
American companies producing penicillin were making enough to meet Allied demand. From D-day, June 6, 1944, onward, the death rate from infected wounds was reduced dramatically, and by 1945 penicillin was available for civilians. As streptomycin continued to show promise during the summer of 1944, Dr. Waksman was rarely seen in the “salt mines,” as Doris Jones had christened the laboratories where the graduate students toiled, poring over their petri dishes for zones of antagonism. Waksman's onetime fascination with new species of mold, with watching them grow and perform weird tasks against their cousins, had long since faded. He was now preoccupied with turning streptomycin into a new wonder drug. In an astonishing move, Merck would give up its exclusive right to produce streptomycin—the right that Waksman had negotiated in return for Merck's giving three hundred dollars a month to his department. Under a new arrangement, the patent rights would be owned by the nonprofit Rutgers Endowment Foundation, which would license companies to produce the drug, paying the foundation a 2.5 percent royalty. Waksman would be in charge of arranging those licenses. He would become the overlord of streptomycin.

Any thoughts he might have had about leaving Rutgers for a better job at a bigger university, or even giving up academic life altogether and going into industry, quickly disappeared. He would stay at Rutgers, despite the tiny size of his department, despite Rutgers's lower academic standing when compared with larger “aggie” colleges such as Cornell or Wisconsin,
and despite the school's meager level of funding. At fifty-six, Waksman was about to have his world transformed—and so were the drug companies.

The official reason for Merck giving up the patent was that Merck and Rutgers, realizing how significant the new drug could be, had agreed that no one company should have a monopoly. Streptomycin should be produced by as many companies as possible, just like penicillin. More would be produced at a cheaper price because of the competition. Merck was seen as magnanimous in relinquishing what was about to be a grand money-spinner, and Waksman was seen as a great humanitarian for persuading the company to take this extraordinary path. While there was some truth in these official explanations, the reality, as with so many things unfolding in the streptomycin story, was somewhat different.

SINCE THE BEGINNING
of the war, the Allies had become increasingly concerned about the enemy's possible use of biological weapons. Among the secret reports was one concerning a
bizarre prewar operation
in February 1939. Japanese agents tried to buy yellow fever virus at the Rockefeller Institute, in New York, but the plot was uncovered by the Federal Bureau of Investigations. In October 1941, the secretary of state for war, Henry Stimson, had called on the National Academy of Sciences to form a committee to assess the current state of knowledge about biological warfare. A “war bureau of consultants,” a dozen scientists led by Dr. Edwin Fred, professor of bacteriology at the University of Wisconsin, assessed the enemy's possible offensive and defensive arsenals. In May 1942, President Roosevelt authorized Secretary Stimson to establish a secret civilian agency, the War Research Service, to develop biological weapons, which the United States would keep in reserve and never be the first to use. A site was chosen at Fort Detrick, in Maryland, an old army base. The War Research Service was made part of the Federal Security Agency to obscure its existence, and George Merck, who had proved his patriotism with his “Command me” remark to Vannevar Bush, was named director.

In 1942, intelligence reports on enemy development of biological weapons escalated. An FBI informant in Tokyo had overheard drunken German doctors saying they were teaching the Japanese about biological weapons, including anthrax and typhus. Another informant, in Los Angeles, warned that Japanese saboteurs had cans of a jellylike substance containing typhus
and bubonic plague. No such containers were ever found. A Swiss report said that the Germans would use “
bacteria of every description
” on Allied forces. Yet another said that Germans were making biological weapons in laboratories in Brazil. In March 1943, a memo from the War Department on the enemy's “resort” to biological weapons talked about possible contamination of the U.S. domestic food supply.

Although U.S. policy on biological weapons was strictly defensive, that did not prohibit the Office of Strategic Services, the forerunner of the Central Intelligence Agency, from asking Merck's War Research Service to recommend “three or more” of its “most potent organisms” for use in covert operations, with directions on how to use them. At a special meeting chaired by George Merck to deal with the OSS request, the experts, led by Dr. Fred, suggested “two types” of organisms—“those extremely pathogenic and those that reduce the efficiency, but may not be fatal.” The “
most promising
” were “B. anthrax and Cl. botulinum,” and “perhaps a dysentery organism of the
Shiga
type, the plague organism [and] brucellosis of the
Suis
strain should be studied.” Streptomycin had shown promise against the plague and brucellosis. Later the OSS would ask for pellets or capsules of
Staphylococcus aureus
for “definite war use.” Albert Schatz had used
S. aureus
as one of his test organisms in his hunt for streptomycin.

GEORGE MERCK HAD
a clear conflict of interest. Under the deal with Waksman, his company would have monopoly control over streptomycin, which, he knew, had already proved itself to be effective in fighting the kinds of diseases that might be spread by the enemy in a biological weapons attack. And he was the chairman of the president's committee charged with finding such a drug and producing it as quickly and as cheaply as possible. In addition, Merck was under constant pressure to increase supplies of streptomycin, and it had experienced production problems. At one point, they lost the entire contents of three of the big thirty-thousand-gallon fermentation tanks producing streptomycin because of a virus invasion that killed the culture. George Merck took the only path open to him: He gave up the company's monopoly rights—but on his terms. Dr. Waksman understood Merck's position very well. Since 1942, he had been advising Merck's committee on how to deal with fungus infestations of
clothing in the tropical climates where U.S. forces were fighting. And he was prepared for this moment.

In October 1943, after Schatz became convinced of his discovery of streptomycin, Waksman had informed Merck's Randolph Major that he had received a dramatic British report about the treatment of burns. “We can keep
most of the burns
uninfected for the first 10 days or so (by the use of sulphonamides and penicillin),” the report said, but to defeat subsequent infections, it continued, the British doctors needed a new antibiotic active against Gram-negative organisms.

At the time, Waksman still hoped Merck would be able to turn streptothricin, discovered by Waksman and Boyd Woodruff in 1942, into that much-needed drug. Under his contract with Merck, Waksman had agreed not to give out samples of streptothricin to any other companies for testing. But he asked Merck to waive this rule.

“It is
hardly fair
on my part not to place a material that we have isolated and that proved to be active against Gram-negative bacteria, especially a non-toxic preparation, in the hands of those that need it,” Waksman wrote. He still hoped that somehow it could be detoxified.

Major “
quite understood
” Waksman's position. He agreed to release the cultures “if you find it necessary.” The only reason Merck had felt justified in asking Waksman to withhold these cultures, he said, “was that I understood that you did not object to doing this.”

This was evidently the beginning of several conversations and letters between Waksman and Merck during which Waksman told the company of his “feeling” that he should be “free to make available for development by other organizations antibiotic agents which may be of value to the armed forces in the present emergency.”

By the end of 1943, the OSS had reported again that the Germans might be planning a biological weapons attack. While the evidence was still inconclusive, secret defensive work on biological weapons in the United States, Britain, and Canada was producing “
concrete information
” that such an attack “was
feasible
.” In the New Year, “all work in this field” was stepped up, so that by the summer of 1944 a large part of the program had been handed over to the War Department. President Roosevelt established a new overall manager, the U.S. Biological Warfare Committee. Merck was appointed chairman. His conflict of interest remained and, if anything, was heightened.