brdgt | Science Tuesday - Streptomycin, TB, and Prometheus

Notebooks Shed Light on an Antibiotic’s Contested Discovery
By PETER PRINGLE, The New York Times, June 11, 2012

NEW BRUNSWICK, N.J. — 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 Dr. Waksman and his graduate student Albert Schatz over who deserved credit.

Dr. Waksman died in 1973; after Dr. 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 Dr. 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, Professor 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, Dr. Waksman slowly began to drop Dr. 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 Dr. Schatz were awarded; Dr. Schatz received nothing.

Dr. Schatz became aware of the deal when Dr. Waksman started sending him $500 checks — $1,500 altogether — that he said came from funds he had been receiving for the sales of streptomycin. Dr. 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, Dr. Schatz, who had by then earned his Ph.D., sued Dr. Waksman and Rutgers, and after a year of legal back-and-forth, the professor and the university agreed to a settlement that recognized Dr. Schatz as “co-discoverer” of streptomycin and gave him a share of the royalties.

But the scientific establishment sided with Dr. Waksman, scolding Dr. Schatz for having the effrontery to challenge his professor. And two years later Dr. Waksman alone was awarded the Nobel Prize for the discovery. Dr. Schatz protested, but the Nobel committee ruled that he was a mere lab assistant working under an eminent scientist. Dr. 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 Dr. Schatz might not have told the truth about his experiments because he had removed a page from his notebooks.

“One fine day,” Dr. 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,” Dr. 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, Dr. Waksman acknowledged that he did not know what the missing page contained. And Dr. 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 Dr. 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 Dr. 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 Dr. 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 carefully opened it, however, there, loosely piled inside, were five clothbound notebooks — just like Dr. Waksman’s, but marked “Albert Schatz.”

In the notebook for 1943, on Page 32, Dr. Schatz had started Experiment 11. In meticulous 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 Dr. Schatz.

One of the pages in Experiment 11 had indeed been cut out, but the page was toward the end of the experiment, after Dr. Schatz had made his discovery. There was no evidence of a break in the experiment to suggest that Dr. Schatz might have removed the page to conceal something he didn’t want the rest of the world to know.

And in Dr. 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 bluntly that it was a distraction. As one lawyer wrote, the missing page was “insignificant.”

As for the professor’s story that Dr. Schatz’s uncle had carried off the key 1943 notebook, Dr. 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 Dr. Waksman had deliberately spread doubt and confusion about Dr. 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 somehow added after they were cataloged, is not clear. When Ms. 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.”

Peter Pringle’s new book, “Experiment Eleven: Dark Secrets Behind the Discovery of a Wonder Drug,” is being published by Walker & Company.

China: Survey Reveals a Growing Number of Drug-Resistant Tuberculosis Cases
By DONALD G. McNEIL Jr., The New York Times, June 11, 2012

China has a “serious epidemic of drug-resistant tuberculosis,” according to the first national survey of the disease, which was carried out by the Chinese Center for Disease Control and published last week in The New England Journal of Medicine.

Of the roughly 4,000 tuberculosis patients tested, a third of those with new cases and half of those with previously treated cases had drug-resistant disease.

Moreover, a quarter of the previously treated patients had multi-drug-resistant, or MDR, strains. Eight percent of those had “extensively drug resistant” TB, as defined by its resistance to four antibiotics: isoniazid, rifampin, ofloxacin and kanamycin.

Strains resistant to that many drugs are nearly incurable. Even treating MDR tuberculosis can require several years and cost $16,000 for drugs and far more for hospitalization. China, which has about one-fifth of the world’s people, has about a quarter of its drug-resistant TB cases, the Chinese center estimated.

The report made it clear that China’s current treatment strategies were a failure. More than 40 percent of those treated for MDR tuberculosis had not taken their last dose. The problem was particularly acute among people seen in general hospitals.

Despite the fact that many newly infected patients had drug-resistant strains of TB, clinics did not test them for this. Some patients had been started on drugs without even receiving a firm diagnosis.

The World Health Organization recommends the use of a new machine, the GeneXpert, above, which can diagnose TB and test for resistance simultaneously, but it is relatively expensive.

‘Prometheus’ Offers a Creationist Indulgence for Science Geeks
By JAMES GORMAN, The New York Times, June 10, 2012

“Prometheus,” the new movie from the director Ridley Scott, operates on several levels. Most importantly and impressively, it is an unforgettable reminder not to open anything, ever. Doors, caves, containers — never open them!

But it is also a scientific and spiritual quest. I don’t think it is spoiling anything to say that the scientists in the movie think somebody or something else created us.

Creationism? Yes, in a way, but creationism for geeks, of the sort that science fiction writers and scientists have long indulged in. It does not run counter to the idea of the process of evolution; it just sets the beginning of the whole business somewhere and some time other than the Earth.

Fred Hoyle, an astronomer, is one of the best-known scientists to suggest that life may have had an extraterrestrial origin. Others, like Francis Crick, who with James Watson discovered the structure of the DNA molecule, have flirted with the idea. Crick even suggested at one time that intelligent extraterrestrials might have gotten the ball, or helix, rolling.

Thomas Gold, an Austrian astrophysicist, suggested in 1980 that perhaps life on Earth came from garbage left by extraterrestrials. And among the writers, Arthur C. Clarke suggested in a brief commentary, “The Toilets of the Gods,” that since fecal matter had been detected on satellites and spacecraft (from the astronauts, presumably), and since something similar would happen with any physical life form, extraterrestrials who passed through the solar system desperately looking for a rest stop might constitute a whole new explanation for where life on Earth came from.

Does this geek creationism conflict with the idea of evolution by natural selection? Not that I can see. A character in “Prometheus” argues that the scientists who have come up with the weird interstellar quest in the movie are throwing out several hundred years of Darwin.

But there is nothing about the scientific method or about Darwinian evolution to suggest that it all had to happen on Earth. The basic notion that some organisms leave more offspring than others, and that their genes are preserved, works regardless of location.

I should say that the scientific consensus is that life did start on Earth. These outlying ideas I have mentioned have not panned out, at least so far, but they are not in themselves antiscientific, because they can be tested. You can look to see what arrived in meteorites. And none of these ideas involve anything other than the material universe.

Religious beliefs are different. Some make claims about the physical world that are demonstrably wrong. The earth is not 10,000 or 6,000 years old. Humans did not coexist with T. rex. Other religions posit a deity who is not physical, neither matter nor energy, but spiritual, existing in a realm that science cannot touch.

In either case, these beliefs do not bear any resemblance to geek creationism, which is no more than the adolescent wish for big, scary, intelligent things out there in the dark.

I myself am not really fond of monsters. My own particular science fantasy is that life on Earth developed from some biological Lego parts lost by a superbeing toddler. I don’t really believe this, but the world is a bit like some broken toy, so I am keeping an open mind.

I hope “Prometheus” and the several “Alien” movies are preserved for future generations who may actually venture out into space — not for the science, or the hints of spirituality, or the myths that they use, but to impress upon our adventurers what we all teach our children about anything that oozes unidentifiable goo.

Don’t touch it!