Experiment Eleven (30 page)

On December 6, Schatz wrote to the king. He and Waksman had agreed “under oath and publicly” that the discovery had been a joint rather than an individual accomplishment, but the prize had been awarded to “only one,” and the one who received a large share of the royalties. Schatz had “signed away his patent rights without personal profit on the joint understanding that all royalties would be used exclusively for the benefit of mankind.”

“Since the Nobel prize is awarded for a specific discovery,” he continued, “the question arises:
By what standards of morality
and conscience may one of the two acknowledged co-discoverers presume to accept this honor without recognizing the only other co-discoverer?”

Of course, Schatz was not privy to Wallgren's last-minute efforts, or the fact that the Nobel Committee had already taken care of his objection.

BY THE DAY
of the award ceremony in Stockholm, Dr. Wallgren had put together introductory remarks to cover Schatz's complaints and still give the prize to Waksman. The committee now understood that it could not give the prize as announced, “for the discovery” itself, so the prize was given for Waksman's “
ingenious, systematic and successful studies
of the soil microbes that have led to the discovery of streptomycin, the first antibiotic remedy against tuberculosis.”

In his introduction, Wallgren said that Waksman had led a “team” in a “long-term, systematic, and assiduous research by a large groups of workers,” an “untiring search” for new antibiotics starting in 1939. Repeating Waksman's exaggerated claims, Wallgren said that “no less than
10,000 different soil microbes
had been studied for their antibiotic activity” since the start of the program. The year, 1939, was indeed correct. The figure of 10,000 was one of Waksman's “stories.”

In another overstatement, Wallgren said that at the time that Waksman had begun his research, “the word antibiotic had not been coined,” and Waksman had “introduced” the word as representing an antibacterial substance. Waksman did not “coin” or “introduce” the word “antibiotic,” although he was always happy to have the story repeated. Waksman was certainly the first to use “antibiotic” as a noun in a published context, in his
1945 book on microbial antagonism.
That is different
from coining the word, however.

To put the Schatz affair to rest—at least for the ceremony—Wallgren deliberately mentioned Schatz by name as “one of those” who had worked with Waksman on the team. He also credited Schatz with the isolation of two strains of actinomycetes that produced streptomycin. But Wallgren stressed that the strains were “identical” to the strain of
S. griseus
“discovered by Dr. Waksman in 1915.” The difference was that the “rediscovered” microbe “was shown to have antibiotic activity.” The suggestion was that Schatz had only “rediscovered” Waksman's original microbe, when in reality he had found an entirely new strain of
griseus
that produced streptomycin.

Waksman must have been pleased with Wallgren's introduction. In his own acceptance speech he avoided the delicate matter of the discovery altogether. The word “discovery” was not even in the title of his lecture, “Streptomycin: Background, Isolation, Properties and Utilization.”

And his description of the discovery was “
summarized briefly
.” In a 6,113-word lecture, he never mentioned Schatz's isolation of the two strains 18-16 and D-1, nor did he mention Schatz's experiments to test the antibiotics from those strains against the virulent H37Rv tuberculosis germ. Instead, he devoted most of his lecture to the chemical nature of streptomycin, its antibacterial properties, its toxicity, its effect on infections and diseases, and the resistance of bacteria to streptomycin. The name Albert Schatz appeared only in an appendix, as number twelve in a list of nineteen assistants who had helped Waksman in his research over the years. Half of them had not even been at Rutgers when Schatz had discovered streptomycin. That is how Waksman wanted the world to see Albert Schatz.

IN JANUARY, A
month after the award ceremony, Schatz received a reply from the Swedish royal court, not from the king himself, of course, but from his private secretary. It read,

Having made Himself acquainted with the contents of your letter as well as of its appendixes, His Majesty has
commanded me to bring
the
following facts to your attention. The Nobel Foundation is a free and independent institution which by no means is submitted to directions from state authorities. The decisions taken by the different organs of the Foundation regarding the award of the Nobel Prizes—in this case by the Council of the Caroline Medico-Surgical Institute—are, according to express instructions, final and thus not liable to alterations by any superior instances.

The preceding will, I trust, have convinced you that your appeal is not of a nature to call for action on the part of His Majesty.

BY 1953, THE ANTIBIOTIC REVOLUTION WAS
the driving force behind a rapidly changing pharmaceutical industry. Besides the “miracle cures” and “wonder drugs” like penicillin and streptomycin, a wide range of new medicines flowed from the expanding drug companies—vitamins, hormones, antihistamines, blood plasma extenders, antimalarials, drugs for hypertension. But antibiotics led the way in the industry's transformation. As American companies screened hundreds of thousands of microbes, a Parke, Davis researcher would famously say that they were finding so many candidate antibiotics that they had to install “an
IBM machine
” (a computer) to keep track of them. In addition to eight American corporations, companies in other countries began harvesting wonder drugs from the soil—three in France, two in England, two in Italy, one in Sweden, and four in Japan. At the Rutgers Department of Soil Microbiology, Waksman and his students found more than a dozen antibiotics, although only two—neomycin and candicidin—would find widespread practical use.

On his world tours, Waksman was honored and feted by those who had experienced relief from meningitis and TB, and he kept a scrapbook at Rutgers on his “Streptomycin Babies,” the children who had survived tuberculosis. In addition to the piles of letters thanking Waksman, and rarely Schatz, for the discovery, however, there were also letters of complaint from those who had experienced toxic side effects.

In reality, the sheen had come off streptomycin. The gray-green culture of
S. griseus
, produced by companies in huge steel vats, was susceptible to a
virus, an “actinophage,” capable of infecting and destroying the streptomycin-producing mold. This problem was quickly solved, but negative clinical effects were a more enduring issue. Although the drug was nontoxic at low dose levels, the higher doses needed to cure tuberculosis continued to cause the side effects first noticed by William Feldman and Corwin Hinshaw in 1945 and then publicized by British researchers. The Mayo team considered toxicity as one of several “
limitations
” of streptomycin. Tests showed that streptomycin, and its derivative, dihydrostreptomycin, which had reduced toxicity, could attack nerves responsible for hearing and balance. Among the symptoms were a
ringing sound
in the ears, vertigo, nausea, rash, fever, and nystagmus—a rapid involuntary movement of the eyeballs. In most cases, however, the symptoms “largely disappeared” within sixty to ninety days after the treatment had been stopped, the Mayo team reported.

A group of tuberculous Italian children pose with Dr. Waksman and his wife at the Children's Hospital in Ostia. The children were being treated with streptomycin in 1950. (Special Collections and University Archives, Rutgers University Libraries
)

Eventually, one of the “
most serious obstacles
” for streptomycin—as with other antibiotics—was the emergence of drug-resistant strains of the disease bacteria. In some cases, doctors had to increase the initial dose by one thousand times to stop the growth of the TB germ.

The solution came from the synthetic drugs. In the early 1940s,
Jörgen Lehmann
, a Danish scientist living in Sweden, had been working on an
idea to stop TB that was, in fact, considerably more elegant than Waksman's plodding method of screening hundreds of cultures from the soil.

Around the same time that Albert Schatz had isolated
A. griseus
, Lehmann had been inspired by a 1940 paper in the journal
Science
reporting that the TB germ seemed to grow at a rapid rate in the presence of the main ingredient of ordinary aspirin, salicylic acid. Lehmann thought that if he could make “a look-alike chemical”—a derivative of aspirin—that had the opposite effect, inhibiting the growth of the TB germ, he might have an agent against TB. The new chemical was para-aminosalicylic acid, known as PAS. But the Swedish medical establishment was skeptical. PAS was indeed capable of inhibiting the TB germ, but it was not as effective as streptomycin.

While Waksman found ready American sponsors in Merck, the Mayo Clinic, and the Commonwealth Fund, Lehmann, in war-torn Europe, could barely find funds for clinical trials. The German doctor Gerhard Domagk, who had isolated prontosil, found a new class of compounds, known as thiosemicarbazones, that also seemed to arrest the growth of tuberculosis. Despite wartime difficulties, Domagk tested derivatives of these compounds and found one, named
isoniazid
, that was a potent anti-TB agent. By 1949, however, Lehmann had discovered that a combination of streptomycin and PAS worked much better than one drug on its own. In the end, all three drugs, streptomycin, PAS, and isoniazid, would be needed to defeat the TB germ.

One of the first patients to receive this sort of combination therapy was William Feldman. At the end of 1948, after many years of work with H37Rv, he contracted pulmonary tuberculosis and was treated by Corwin Hinshaw with promin, one of the sulfa drugs; streptomycin; and PAS. He made a complete recovery from the “
damnable disease
” after a year.

THE DRUG COMPANIES
now turned their attention to the new so-called broad spectrum antibiotics, which covered a wider range of diseases. The first was chloramphenicol, found by Paul Burkholder, a Yale microbiologist. Searching for microbes beyond America's farmland, Burkholder called his colleagues around the world and asked them to send him a pot of their local soil, and he subsequently isolated around seven thousand actinomycetes,
of which nearly two thousand produced effective drugs. From these he chose four that showed an ability to destroy a wide spectrum of germs—Gram-positive and Gram-negative. Burkholder's champion was
Streptomyces venezuelae
, which he had received from a colleague in Venezuela. It proved its worth during a typhus epidemic on the Peru-Bolivia border in 1947.

With the new antibiotics, the drug companies
sought exclusive patents
. The thirteen companies producing penicillin, for which there was no patent, had made competition so keen that the
price had dropped
from twenty dollars for one hundred thousand units in 1943 to four and a half cents in 1950. The downward trend was similar for the eleven companies producing streptomycin. In March 1950, John McKeen, the president of Pfizer, observed, “
If you want to lose your shirt
in a hurry start making penicillin and streptomycin.” Streptomycin was characterized as “distress-merchandise,” with production running at 200 to 300 percent above domestic demand.

But the antibiotic hunters, dazzled by the success of streptomycin—the royalties kept rolling into Rutgers's coffers at more than half a million dollars a year—couldn't bear to give up the chase.
Business Week
summarized the position: “The trouble is—from the competitive point of view—that nobody goes out of business. And that is partly because nobody knows what's going to happen tomorrow. A company which is struggling along now in penicillin may come up with a better way of administering it, or a new way of making it. But there is a bigger reason for everyone wanting to hang on. That is the hope that the scores of researchers working in every company's laboratory can come up with an antibiotic it can patent as its own.”