Experiment Eleven

by Peter Pringle

  The reporter credited Waksman, and Waksman alone, with the discovery of streptomycin. Albert Schatz was never mentioned. A single paragraph dealt with the lawsuit as a bid for money from a former student. Like other journalists before him, the reporter was easily charmed by the “small, stocky compact man ... in rumpled and un-pressed clothes [and] high-buttoned, un-shined shoes ... [who] badly needed a haircut.” The story was Waksman’s carefully crafted fable, half true at best.

  OUT OF THE popular media spotlight, thousands of miles away from fawning American reporters, Dr. Waksman’s career was under scrutiny of a very different kind. Behind closed doors, the faculty of Stockholm’s Royal Caroline Institute was deciding who should be awarded the highest honor in the medical world, the Nobel Prize in Physiology or Medicine.

  Each year since 1900, the institute has sent out requests for nominations from academics and practicing doctors. The nominations have to be submitted by February. They are evaluated through the spring and summer by a committee, then voted on by the twenty-five full professors of the institute. The award is announced in October, the month of Alfred Nobel’s birth, and is presented by the Swedish monarch in Stockholm in the second week of December to commemorate the anniversary of Nobel’s death on the tenth of that month.

  In 1952, for the seventh year in a row, Waksman had been nominated for his work on antibiotics. The first nomination had come in 1946 from a professor of pharmacology at the University of California, San Francisco. Those were early days for streptomycin, which had only just been approved for general sale. The recommendation was for Waksman’s “work on soil organisms, and the development of streptothricin and streptomycin.” But he didn’t even make the short list for at least one good reason. The year before, Alexander Fleming, Howard Florey, and Ernst Chain had been given the prize for penicillin. The Caroline Institute had already recognized the discovery of how antagonistic microbes can provide wonder drugs, and the second discovery, streptomycin, although full of promise for ending the scourge of tuberculosis, had not quite proved itself.

  As the wonders of streptomycin became more established with each passing year, though, the pressure was building to notice its place in the galaxy of inventions. The next year, 1947, Waksman had been nominated five times, twice on his own for “work on antibiotics” and three times with William Feldman and Corwin Hinshaw. Those nominations had combined the two stages of the discovery: the “identification” of streptomycin and the “experimental and clinical investigation of its properties.”

  The word “discovery” only started to appear in the 1948 nominations. Of the five in that year, two were proposed by Turkish physicians from Istanbul, one by an Italian neuropsychiatrist from Rome, one by a German professor of surgery from Göttingen, and only one by an American, a professor of medicine from New York. The Nobel Committee for Physiology or Medicine determined that the discovery of streptomycin, which it attributed to Waksman alone, was worthy of a prize, but it was concerned about the real effectiveness of the drug and decided to wait for more clinical tests.

  In 1949, and again in 1950 and 1951, the committee concluded that the clinical results were sufficient for a prize, but Waksman lost out to two brain researchers in 1949, to three researchers on adrenaline in 1950, and in 1951 to a researcher who had discovered a breakthrough in the treatment of yellow fever.

  At the beginning of 1952, Waksman was nominated again—four separate times—and so, for the first time, was Albert Schatz. A Yugoslav professor of medicine, Jevrem Nedelkovitch, who had experienced the powers of streptomycin at his hospital in Belgrade, had read the scientific papers announcing the discovery of streptomycin and nominated Schatz, Betty Bugie, and Waksman, in the order that they appeared on the 1944 paper announcing the discovery.

  During the summer, the Nobel Committee asked for opinions from two leading members of the Caroline Institute, Professor J. O. Strombeck, a prominent plastic surgeon, and Einar Hammersten, the institute’s professor of chemistry.

  Strombeck was asked to give his opinion on Waksman, who had been proposed in a general way for his work on streptomycin. On the basis of the success of the clinical trials of streptomycin in Britain, the United States, and Sweden, Strombeck concluded that streptomycin’s effect, primarily against TB infection in humans, deserved a prize. In short, Waksman should be given the award.

  Hammersten had a more difficult task. Because of his expertise in chemistry, he was asked to look at all the nominations: the set that proposed Waksman alone; the set proposing Waksman and two chemists, Karl Folkers from Merck and Oscar Wintersteiner, of New York; the set proposing Waksman, Feldman, and Hinshaw; and, finally, the nominations of Schatz, Waksman, Bugie, and Boyd Woodruff (for his work on the extraction techniques for streptothricin).

  Hammersten then reviewed the evaluations of Waksman going back to the “preliminary assessment” in 1946, when Waksman’s entry had not made the crucial transition to a “special assessment” by the Nobel Committee (the short list). In 1947, Waksman, Feldman, and Hinshaw were nominated for the “identification of streptomycin and experimental and clinical investigation of its properties and of other antibiotic agents” together by three professors of medicine at the Mayo Foundation Graduate School of the University of Minnesota. Hinshaw was invited by the Nobel committee to go to Stockholm to show his data. The three men qualified for a “special assessment,” and even though streptomycin was now available to the public in America, they were not found worthy of a prize because the committee still wanted to see more data of streptomycin’s effects on human infectious diseases.

  In 1948 and through 1951, there had been a clear consensus that Waksman alone was worthy of the prize, and Hammersten started by grading Waksman against the chemists.

  For this, Hammersten went back to the discovery of streptothricin, the second antibiotic found by Waksman and Woodruff in 1942. The method they had used to extract and purify the drug had consisted of adsorption onto carbon and the elution, or removal, of the antibiotic with weak acid. This had not been a groundbreaking method, as Woodruff himself had made clear in his deposition during the lawsuit. But under examination by Eisenberg, Woodruff had gone to great lengths to explain that the novelty had not been in any one method, but in the “association of steps” taken.

  Eisenberg had asked, “Were the methods that you used, or were used in the isolation of the antagonists that produced actinomycin and streptothricin, novel?”

  “Well, novel is a hard word to define in laboratory work ...,” Woodruff had responded.

  Later, Eisenberg had pressed the question, and Woodruff had replied that it was “the association of steps, known steps in the right order leading to the isolation of a concentrated purified or crystalline material which can be considered novel.”

  EISENBERG: In other words the steps by themselves, taking each step separately, was not a novel procedure?

  WOODRUFF: That’s right.

  EISENBERG: But the order in which these steps were taken you say was the novelty?

  WOODRUFF: Yes.

  But Hammersten, under the Nobel protocol set up for evaluating candidates, was required to consider “only scientific publications concerning the work of and by prospective candidates.”

  He relied solely on the published scientific papers, and not at all on the lawsuit transcripts, in making his evaluation. He argued that the chemists had done complimentary work and would have to share a prize, but also that their isolation and purification work had not gone far enough beyond Waksman’s original crude attempts at purification to warrant an award. What the chemists had done was extraordinary work, but was not, in the end, prize-worthy, because Waksman had shown the way. Hammersten concluded that credit should go to Waksman for using a method of extraction for streptothricin that could be later applied to streptomycin.

  Hammersten then turned to the question of the part played by Waksman’s collaborators in these extraction experiments. In this early work, he noted, Woodruff was a “medarbetare�
��—literally “with work,” and with a general meaning in Swedish of “colleague” or “collaborator,” but when applied in this sense, of a master and his apprentice in the laboratory, definitely meaning “apprentice.” The signal to the Nobel Committee of the Caroline Institute was clear, and Hammersten did not have to spell it out: Woodruff was too junior in rank to be considered as an equal to Waksman, and therefore the credit should go to Waksman alone. If Hammersten had considered him as Waksman’s equal, he would have written “collega,” a colleague of equal merit.

  So, thus far, Waksman alone had been approved for a prize, by Strombeck for the discovery and by Hammersten for his part in the extraction. That left yet another assessment of the relative parts played by Waksman, Bugie, and Schatz.

  Schatz was the senior author on both the 1944 papers, but, as is the custom in such publications, the text gave no clue as to who had done what in the experiments leading to the discovery. This was, as always, a complex matter of personalities and actual lab work. The experiments had been written up impersonally in the passive tense. The paper said that streptomycin “was isolated from two strains of an actinomycete.” The person who had isolated the strains could be identified only by reference to the laboratory notebooks. But, again according to the rules, Hammersten could not delve deeper than the scientific papers—he did not look at the lawsuit file, the patent application, or the lab notebooks.

  In examining the first paper, announcing the discovery of streptomycin, Hammersten therefore missed the later affidavit that Betty Bugie had given to the Patent Office acknowledging that she had had “nothing to do with the discovery of streptomycin.” He didn’t consult Schatz’s Ph.D. thesis, or Schatz’s laboratory notebooks, which showed, beginning with Experiment 11, that Schatz had been the first to isolate streptomycin and had also prepared crude extracts by the traditional method of adsorption on carbon and then elution with acid.

  From the second paper, reporting streptomycin’s effect on the TB germ, on which Schatz was the first and Waksman the second author, Hamersten could not have known that it had been Schatz, working alone in the basement laboratory, who had risked catching TB while testing streptomycin against the virulent strain of the disease.

  Finally, Hammersten reviewed Waksman’s work on the griseus strain that Schatz had used to make the discovery. Hammersten concluded that Waksman alone had isolated S. griseus in 1919 and in 1942 had found, together with other students including Woodruff but not Schatz, that the actinomycetes were especially promising producers of antibiotic substances.

  This paragraph not only has the year of Waksman’s isolation wrong (it was 1916), but is a reductio ad absurdum view of the history of the griseus strain. As mentioned in earlier chapters of this book, Waksman was not the first to isolate griseus. It was first isolated, and named because of its grayish color, by the Russian researcher Alexander Krainsky in 1914. Streptomycin was indeed isolated by Albert Schatz from a strain of S. griseus, but not the strain that Waksman had isolated in 1916, which did not produce an antibiotic. Schatz had found a new streptomycin-producing strain. In addition, Russian researchers had in fact already mentioned that the actinomycetes were promising producers of antibiotics substances.

  Hammersten, bearing in mind the award of the Nobel Prize to Fleming, Florey, and Chain in 1945, also pointed out that Waksman had developed streptomycin further than Fleming had developed penicillin, and Waksman had been involved in the methods used to extract and purify streptomycin.

  Hammersten summed up his review by saying that because of Waksman’s well-known and leading position in the discovery of streptomycin, and because only Waksman’s name appeared on the three most important papers announcing the discovery, he alone should be considered as the discoverer. Albert Schatz was a medarbetare, an assistant of inferior rank.

  20 • “A Dog Yapping at the Heels of a Great World Figure”

  IN THE WEEK OF OCTOBER 20, 1952, reporters from Swedish newspapers began calling Waksman for interviews. They had heard he was going to share the Nobel Prize in Physiology or Medicine. Then photographers called to arrange to take pictures. And on Thursday, October 23, at four o’clock in the afternoon, the Royal Caroline Institute announced that Selman Waksman, alone, had won the prize “for the discovery of streptomycin, the first antibiotic which is effective in cases of tuberculosis.” The citation was specific. It was for the discovery itself. The next day, October 24, the New York Times ran a front-page story, WAKSMAN WINS NOBEL PRIZE FOR STREPTOMYCIN DISCOVERY. Waksman’s prize “crowned decades of relentless effort that root back almost to the moment he set foot in America.”

  Reporters and television crews turned up on the cramped third floor of the Administration Building, where the sixty-four-year-old Waksman told them, “This is the culminating point of my life’s work begun in 1915 with the study of a humble group of soil microorganisms, the actinomycetes. I feel particularly proud for the field of science which I represent, microbiology, and for the institution where I have done my major work, the College of Agriculture and Experiment Station of Rutgers, the State University of New Jersey.” For the occasion, he selected his oft-repeated quote from Ecclesiastes about medicines coming from the soil. “The Lord created medicines out of the earth, and he that is wise shall not abhor them.”

  Waksman would remember the day as being filled with telegrams from all over the world, from former students, colleagues, well-wishers, tuberculosis sufferers and “foreign groups proud of the accomplishments of an ‘immigrant boy.’” His office was “bedlam ... swamped with reporters, photographers, radio and television groups.” He “had to answer all sorts of questions.” But his life was now so full of awards and honors that the award was really only “another surprise” in his busy life.

  A few days later the Associated Press wire service chose Waksman as man of the year for science in its annual awards. President Dwight Eisenhower won for politics, Queen Elizabeth II was woman of the year, Ernest Hemingway was honored for literature, Marilyn Monroe for entertainment, and the boxer Rocky Marciano for sports.

  In his interviews celebrating the award, Waksman did not mention Albert Schatz. But the newspapers did. The New York Times noted that Waksman was the fourth researcher in antibiotics, after Fleming, Florey, and Chain in 1945, to receive the prize. In a paragraph inside brackets, the Times also reported that while Waksman was widely credited with the discovery, he had acknowledged in 1950 that Dr. Albert Schatz, an assistant to Dr. Waksman, at the time was “entitled to credit legally and scientifically as co-discoverer.”

  The Philadelphia Inquirer went further. “Progress today,” it editorialized, “in any field, but particularly in medicine, is usually achieved only by the co-operative effort of many persons.” Much depended “on the individual researcher” who “may be the head of a project or one of the rank and file. If the latter, he deserves a share in the honor.”

  Albert Schatz had left his job at Brooklyn College and moved to a new research post at a small school, the National Agricultural College, in Doylestown, Pennsylvania. Fifty miles from Rutgers, in the converted farmhouse he now used as a laboratory, Schatz was stunned. He could not believe what the Nobel Committee for Physiology or Medicine had done. How could it have ignored the published evidence of his involvement—the two crucial scientific papers that named him as the senior investigator in the discovery, and the court settlement, on which the ink was barely dry, honoring him as the co-discoverer of streptomycin? He kept staring at the citation: for the discovery of streptomycin. He felt as though he had been dealt a blow that denied his “entity as a human being.” At an Ivy League college, missing the award might have been taken in stride—there would be other opportunities to win a Nobel—but the leaders of the tiny National Agricultural College decided to protest what they saw as a great injustice. Within a week, the college’s vice president, Elmer Reinthaler, had drafted a letter to the secretary of the Nobel Committee for Physiology or Medicine, Professor Göran Liljestrand. Reinthaler exp
ressed the “amazement” of the college’s administration and faculty that the award had been made solely to Waksman.

  Choosing his words carefully and respectfully, Reinthaler wrote, “We are certain that so distinguished a body as the Council of the Caroline Institute could not have been aware of, and yet ignore, certain most pertinent facts regarding the discovery of streptomycin and the original co-discoverers thereof.” He cited the 1945 Nobel Prize in Medicine, which had been awarded “in the most equitable manner” to Fleming, Chain, and Florey. If penicillin could have more than one prizewinner, why not streptomycin? He enclosed a short history of the discovery, with the relevant scientific papers showing the part played by Schatz, adding that the college was “convinced that further consideration by your Council would be well warranted.”

  At the same time, Schatz launched his own appeal. He drew up a list of colleagues he thought might support him and prepared a “resolution” that he planned to ask them to sign. The resolution “assumed” that the nominations submitted to the committee had “neglected to stress the role played by Dr. Schatz in this discovery, thus depriving him of his rightful share in the prize.” Addressing the matter of rank, in case the committee had given the prize solely to Waksman because he was the head of the laboratory, Schatz argued that he should not have been excluded from the award simply because his thesis had been supervised by Waksman. There was “ample precedent” in the history of Nobel awards to the contrary: the Polish-French Marie Curie, for physics, in 1903 (she had shared the award with Pierre Curie); the Swede Svante Arrhenius, for chemistry, in 1903; and the French Louis de Broglie, for physics, in 1929. The work for which they had received Nobel Prizes had been “largely embodied in their doctoral dissertations.” So it was with Schatz’s thesis on streptomycin.