Experiment Eleven (8 page)

When Feldman heard about Waksman's new research into antibiotics, he asked for samples, first of the fungus-produced clavacin, which sounded promising. Waksman was cautious. All four of the antibiotics discovered in his lab—actinomycin and streptothricin from the actinomycetes
and fumigacin and clavacin from fungi—were too toxic. Even so, he invited Feldman to visit Rutgers.

Feldman spent several hours talking with Waksman in the upstairs laboratory, offering to carry out “co-operative studies” if and when Waksman's lab produced a new antibiotic. Waksman said he would let Feldman know. Before they parted, Waksman introduced Feldman to Schatz, but only briefly, and he never mentioned Schatz's new discovery of streptomycin. Waksman's loyalty was to his sponsor, Merck.

ON DECEMBER 14
, Schatz began Experiment 33, using extracted streptomycin on an H37 strain of TB, apparently from the strains of uncertain viability Dr. Seibert had sent Waksman back in June. The results were again promising.

Schatz was astonished to have found not one but two likely candidates so quickly. What the future held for his discovery, however, no one could really say. His chosen two might be eliminated as quickly as the other four because of toxicity. And while he assumed that Dr. Waksman would do all he could to make his discovery a reality and give him full credit for it, sometimes Schatz was not quite so sure.

Waksman's permanently wrinkled attire gave the impression of an eccentric academic absorbed in lofty scientific principles and novel ideas, a professor dedicated to pure research. And his passion for the little-known actinomycetes added to the image of unworldly benevolence. However, Schatz and the other researchers knew another side of their professor.

Selman Waksman was the best-organized, the most practical, and the best-connected professor at the College of Agriculture. Beneath his bonhomie, the twinkle in his bright eyes, the Friday brown-bag lunches, and the informal summer picnics on the Jersey Shore with “kosher” hot dogs wrapped in bacon, there was a traditional European department head who followed a rigid code of rank when it came to his apprentices.

One unsettling story about Waksman's relationship with his students had become a legend at Rutgers. Oddly, it involved another Russian Jewish immigrant,
Jacob Joffe
, a fiery character who was born in Lithuania and had immigrated to America on the eve of World War One. He became one of Waksman's first graduate students. He finished his dissertation on
a bacterium that had the remarkable ability to turn sulfur compounds into sulfuric acid, which could then be used to free up phosphates in the soil, a natural fertilizer. This was a major breakthrough in soil fertility at the time, and Joffe completed his Ph.D. thesis in 1922.

Waksman cooks “kosher” hot dogs wrapped in bacon at a Department of Soil Microbiology picnic in 1945. (Courtesy Vivian Schatz
)

A few months later, Waksman wrote about these experiments in a scientific paper, putting his name first as the senior author. Joffe was shocked. He believed he was the one, not Waksman, who had discovered the microbe. Though he stayed on at Rutgers, becoming a professor at the college and an authority on soil science, Joffe nourished a dislike for Waksman, never ceasing to complain that, in his view, Waksman had stolen his work.

As an undergraduate, Schatz had taken a course with Joffe; he had gotten to know him well and had
heard him complain
that Waksman had not given him due credit. “Joffe would, not in class, but in his office, rant and rave about Waksman,” Schatz later recalled. Some believed Joffe, others Waksman. The disagreement was never resolved, and the incident had left a question mark over Waksman's apparently amiable stewardship of the Department of Soil Microbiology.

Most of the time that he worked for Waksman, Schatz never gave the Joffe legend, and what he knew about it, a second thought. But now that he had his own discovery, he began to wonder how Waksman would respond. The two scientists had a close relationship at that point—partly,
Schatz was sure, because they were both Jewish, with roots in Russia. Waksman was not only his teacher but had also become a father figure, the male guide and mentor that he had not found in his own childhood growing up on a dirt farm in Connecticut.

He wrote up his results and gave them to Waksman to check and edit. The
first scientific paper
announcing streptomycin was published in the
Proceedings of the Society for Experimental Biology and Medicine
in January 1944. Schatz was thrilled. Waksman had acknowledged the crucial work Schatz had done by putting his name first, then Betty Bugie's. Waksman's name came last. It seemed that Schatz had no cause for concern that the Joffe case might be repeated, with him as the loser this time. But he was not privy to the behind-the-scenes struggle over the next stage of the discovery, the race to publish the effects of streptomycin on the deadly human strain of tuberculosis.

AT THE MAYO CLINIC, WILLIAM FELDMAN
received a copy of the three-and-a-half-page paper announcing streptomycin in February 1944. He and Hinshaw read down the list of twenty-two bacteria vulnerable to the new antibiotic and were astonished to find, among the usual test germs,
M. tuberculosis
. They were also amazed that there was no discussion anywhere in the text explaining the nature of the strain, whether it was the harmless kind or the deadly H37Rv. In reality, it was harmless, as Hinshaw would learn much later. Waksman told him that the strain of
Mycobacterium
used by Schatz was a
non-pathogenic strain
from the Department of Soil Microbiology collection. Waksman added that he would “not permit any pathogenic tuberculosis culture in his laboratory for fear of infection to students and technicians.” But this rule was about to change—for Schatz's experiments in his basement lab. In reading the paper, Feldman also found it odd that Waksman had not mentioned this discovery when Feldman had visited Rutgers a few months earlier, though he must have known about it. The lead time on such journal articles was a month at least.

Feldman was about to contact Waksman when a letter came from the Rutgers professor himself, in which he offered to supply
a sample of streptomycin
to the Mayo laboratories for guinea pig trials. Feldman accepted immediately, telling Waksman he needed ten grams, which he estimated “from the meager knowledge available” would be enough for a small test—say,
four to six guinea pigs
. In exchange, Feldman agreed to send Waksman
a culture of the virulent human strain, H37Rv, which Schatz needed for his in vitro (test tube) experiments.

In his basement lab, Schatz cranked up his small stills, frothy brews in glass flasks, to provide Feldman with ten grams. Schatz did not have to be told how to run a still; he had learned the tricks at an early age during Prohibition on the family farm in Connecticut. In the basement lab he now ran stills twenty-four hours a day, sleeping on the lab floor. He had an arrangement with the night watchman that if, on his rounds, he found Schatz asleep and the liquid in the flasks had evaporated below a red line, he was to wake him up. This punishing routine left Schatz permanently exhausted, and one morning he left the lab at about two o'clock and collapsed in the snow outside. Fortunately, the night watchman found him unconscious and called an ambulance to take him to the emergency room.
He had pneumonia
and spent a week in hospital. Waksman was the
only member of the staff
who didn't visit him.

Back at work after a week, Schatz began the crucial tests to see how his microbes would deal with the H37Rv strain. He took what precautions were available. The safety equipment had not progressed much beyond the crusted and cracked rubber aprons of the 1930s. By modern standards they were pitiful. He grew the germs in narrow test tubes, trying to limit exposure of the growing TB cultures to the open air when he removed the cotton wool caps. He had to sterilize all his own glassware. This meant putting the test tubes into the autoclave before leaving the lab—often in the early hours of the morning. The tests took much longer than those of the other germs because H37Rv was one of the slowest-growing—multiplying every two days instead of every twenty minutes like most bacteria. He started his first H37Rv test on March 24 and noted it as Experiment 10 in his new 1944 notebook.

It was a potentially deadly operation, handling germs that had killed millions of people without gloves or face masks or proper ventilation. The TB germ spreads on airborne droplets, but Doris Jones later remembered seeing Schatz wash out his mouth with antiseptic after a day's work. No other remedies were available. For the entire time he was using the virulent strain of TB, he later recalled, Waksman never came near the laboratory, and he told Schatz never to bring the germs to the upstairs labs. Schatz believed that his professor was afraid. It was not an unreasonable
belief: In his retelling of the discovery of streptomycin, Waksman never mentioned being in the basement laboratory during these crucial experiments.

Rows of test tubes showing how streptomycin destroys the human strain of tuberculosis, H37, in Albert Schatz's experiments in the basement laboratory. At left, the tubes start with the TB microbes, which are gradually destroyed. (Photograph by Julius Schatz, courtesy Vivian Schatz
)

By the middle of April, Schatz had made enough streptomycin to send ten grams to the Mayo Clinic, and Feldman and Hinshaw started tests with four guinea pigs on April 27, quickly running through the initial supply. Schatz obliged by keeping his stills going night and day.

THE MAYO GUINEA
pig experiment presented a major
problem of logistics
. The animals had to be injected with streptomycin every five hours, which meant Feldman and Hinshaw driving through the winter snows to the lab, plus dealing with gas shortages and a lack of lab staff because of the war. Feldman, with Waksman's permission, brought in a third researcher, with “
one of the finest labs
,” to test animals infected with bacteria other than TB. Initial results were promising on everything but cholera.

Waksman began to worry that he was somehow losing control of streptomycin. In the fiercely competitive world of patents and scientific discovery,
priority matters. The recognition and the rewards go to the scientist who publishes first. The research field was suddenly crowded. Schatz had done the initial isolation. Doris Jones had done the first toxicity tests on chick embryos. The vet at Rutgers was testing streptomycin on mice. Merck researchers were working on ways to extract the drug from the nutrient broth in which
A. griseus
, the streptomycin-producing microbe, was grown, and the company had also done animal tests. And besides TB, the Mayo Clinic was also testing streptomycin on plague, tularemia, pneumonia, and cholera. Understandably, Waksman wanted his results—or, more correctly, Schatz's results—on in vitro experiments with H37Rv to be published first. The Mayo researchers had a quick and easy route to publication through their own
Proceedings of the Mayo Clinic
, which was published every two weeks. The publishing routes for Waksman took a month at least—as Feldman had surmised.