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Monday, June 25, 2018

Notebooks shed light on an antibiotic’s discovery

A lab notebook discovered in a dusty archive at Rutgers may help settle a 70-year argument over credit for the Nobel-winning discovery of streptomycin

Written by New York Times | Published: June 17, 2012 3:09:42 am

For as long as archivists at Rutgers University could remember,a small cardboard box marked with the letter W in black ink had sat unopened in a dusty corner of the special collections of the Alexander Library. Next to it were 60 sturdy archive boxes of papers,a legacy of the university’s most famous scientist: Selman A. Waksman,who won a Nobel Prize in 1952 for the discovery of streptomycin,the first antibiotic to cure tuberculosis.

The 60 boxes contained details of how streptomycin was found—and also of the murky story behind it,a vicious legal battle between Waksman and his graduate student Albert Schatz over who deserved credit.

Waksman died in 1973; after Schatz’s death in 2005,the papers were much in demand by researchers trying to piece together what really happened between the professor and his student. But nobody looked in the small cardboard box. The story of streptomycin is no ordinary tale of discovery. It began in August 1943,when Schatz,a 23-year-old graduate student at the Rutgers College of Agriculture,isolated the powerful antibiotic produced by a bacterium,Streptomyces griseus,that had been found in a pot of farmyard soil.

His supervisor,Waksman,arranged for the Mayo Clinic in Rochester,Minn.,to test the substance in guinea pigs,and then in humans. It worked. Streptomycin cleared up infections,including TB,that had defied even the first wonder drug,penicillin.

As word of the discovery spread,reporters flocked to Rutgers to record the amazing event. But in telling and retelling the story,Waksman slowly began to drop Schatz’s name and claim sole credit. He also arranged with Rutgers to receive hundreds of thousands of dollars in royalties from the patent that he and Schatz were awarded; Schatz received nothing.

Schatz became aware of the deal when Waksman started sending him $500 checks—$1,500 altogether—that he said came from funds he had been receiving for the sales of streptomycin. Schatz wanted to know more,but the professor wouldn’t tell him. So he turned to an uncle,who found a sharp Newark lawyer willing to take on his nephew’s case. In 1950,Schatz,who had by then earned his Ph.D.,sued Waksman and Rutgers,and after a year of legal back-and-forth,the professor and the university agreed to a settlement that recognized Schatz as “co-discoverer” of streptomycin and gave him a share of the royalties.

But the scientific establishment sided with Waksman,scolding Schatz for having the effrontery to challenge his professor. And two years later Waksman alone was awarded the Nobel Prize for the discovery. Schatz protested,but the Nobel committee ruled that he was a mere lab assistant working under an eminent scientist. Schatz disappeared into academic obscurity and died with the full story still untold.

Among the Waksman papers is a court transcript from the lawsuit,in which the professor charged that Schatz might not have told the truth about his experiments because he had removed a page from his notebooks. “One fine day,” Waksman said in a deposition,“one of my assistants reported to me that Schatz’s uncle broke into the laboratory and carried off Schatz’s notebooks,” which,he continued,were returned 48 hours later.

“I didn’t pay any attention and,of course,I wouldn’t go over every page,” Waksman went on,adding that later he looked at the notebook and discovered that a page covering a crucial experiment had “been very neatly taken out,and worse than that,Schatz with his own handwriting very carefully corrected all the corresponding pages.” “Well,then.” he concluded,“there is a question for Sherlock Holmes.”

Later in the deposition,Waksman acknowledged that he did not know what the missing page contained. And Schatz angrily rejected the insinuation that he or his uncle had done anything wrong. “Not true,incredible,” he wrote on his personal copy of the transcripts. “Nonsense.”

But Waksman’s damaging allegation was now on the record. When the professor’s papers were transferred to the archives,his own sand-colored,clothbound 5-by-8-inch notebooks,which covered the period of the streptomycin discovery,were included in the 60 boxes. But Schatz’s notebooks were not there.

In 2010,in researching my book on the discovery of streptomycin,I began looking for the notebooks in the university’s libraries and laboratories,but found nothing. Douglas E. Eveleigh,a professor of microbiology at Rutgers,took up my cause; the missing notebooks represented “a major,even classic loss,” he said,and issued a campus alert to search “every cubbyhole.” Thomas J. Frusciano,the head archivist of the Alexander Library special collections,recalled that the Waksman papers had been acquired in 1983,10 years after the professor’s death,and had even included a vial of streptomycin. He asked a member of his team,Erika Gorder,to search the stacks.

She remembered seeing the small box next to Waksman’s papers. “I must have passed by it a million times,” she said,“but I always thought it must contain miscellaneous material from the Waksman papers when they were cataloged.” When she pulled down the box and opened it,however,there,loosely piled inside,were five clothbound notebooks—just like Waksman’s,but marked “Albert Schatz.”

In the notebook for 1943,on Page 32,Schatz had started Experiment 11. In cursive,he had written the date,Aug 23,and the title,“Exp. 11 Antagonistic Actinomycetes,” a reference to the strange threadlike microbes found in the soil that produce antibiotics. Underneath the title he recorded where he had found the microbes in “leaf compost,straw compost and stable manure” on the Rutgers College farm,outside his laboratory.

The following pages detailed his experiments and his discovery of two strains of a gray-green actinomycete named Streptomyces griseus,Latin for gray. Each strain produced an antibiotic that destroyed germs of E. coli in a petri dish—and,he was to find out later,also destroyed the TB germ. The notebook shows that the moment of discovery belongs to Schatz. One of the pages in Experiment 11 had indeed been cut out,but the page was toward the end of the experiment,after Schatz had made his discovery. There was no evidence of a break in the experiment to suggest that Schatz might have removed the page to conceal something he didn’t want the rest of the world to know.

And in Waksman’s own papers – in the 60 boxes – there was confirmation that the professor knew the missing page was not a real issue. His legal advisers had told him it was a distraction. As one lawyer wrote,the missing page was “insignificant.” As for the professor’s story that Schatz’s uncle had carried off the key 1943 notebook,Waksman’s own documents make clear it could not have been true. At the time the key notebook was not at Rutgers; it was with university-appointed agents who were preparing the streptomycin patent application. Here,indeed,was evidence that Waksman had deliberately spread doubt and confusion about Schatz’s Experiment 11 in a campaign to belittle the work of his student.

Whether the small cardboard box had come to the archives at the same time as the other Waksman papers,or was added after they were cataloged,is not clear. When Gorder found the notebooks in the box,she was thrilled but not altogether surprised.

“When papers are accessioned,” she said,“all sorts of things are thrown into cardboard boxes.”

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