In the summer of 1948, a little boy lay very still in his cot on the paediatric ward at Clatterbridge general hospital in Cheshire. His name was Peter. Not yet two, he had contracted tuberculous meningitis, a particularly vicious form of the disease. Penicillin, the world’s first antibiotic, was then just starting to save lives, curing acute bacterial infections such as pneumonia and septicaemia – but it was powerless against one of the main killers of the time: tuberculosis.
People called TB the white plague, and feared it more than the bubonic plague. Highly contagious, essentially incurable and capable of causing death decades after infection, it has decimated mankind since the time of the pharaohs. In the past two centuries alone, it has killed more than one billion people – more than every war, famine and other epidemic put together. Chopin, Orwell, Emily Brontë, DH Lawrence and Chekhov all died of the disease.
Until around 1950, the most effective treatment was rest, in one of the hundreds of sanatoria scattered across Europe and the US. People tried all sorts of remedies, from fermented mare’s milk to bleeding by leeches and exposure to the sun. But, for most, there was no cure and no relief – they slowly wasted away, emaciated, breathless and exhausted, coughing blood until their weakened bodies could stand no more.
At Clatterbridge, Peter seemed lost. “There was nothing we could do,” remembers Doreen Roby, a student nurse on the ward at the time. “Children like Peter never recovered. We knew as soon as they came in that they would die – I was terribly upset.”
But there was news of a miracle drug, streptomycin, then being developed in America. Clatterbridge was one of the first hospitals in Britain to have access to the drug and Peter one of the first patients to receive it. The result was astonishing. “We couldn’t believe our eyes,” says Roby. “Gradually, the fever came down and Peter regained consciousness. He started eating again.” After a few weeks, the little boy was bouncing all over the ward.
Soon, the drug was in use around the world. Selman A Waksman, a world-renowned microbiologist credited with its discovery, was inundated with letters from grateful parents and feted everywhere he went. He visited hospitals worldwide, observing with emotion the dramatic effect his new antibiotic had on mortally ill TB patients. In 1952, he was awarded the ultimate accolade, the Nobel prize. “Streptomycin, the first antibiotic remedy against tuberculosis, has already saved thousands of lives,” he was told as he stood before the king of Sweden. “We regard you as one of the greatest benefactors to mankind.”
But Waksman was not, in fact, the man who discovered streptomycin. The antibiotic was isolated by his postgraduate student Albert Schatz, an intense, skinny 23-year-old who worked in a basement lab three floors below Waksman’s office at Rutgers University, New Jersey. While the professor collected prizes and honours, his student sank into scientific obscurity, consumed by a sense of injustice.
The story of streptomycin – of scientific triumphs, all-too-human scientists and a long quest for justice – lies somewhere between these two men. But until 1990, when a British scientist launched a campaign to rehabilitate Schatz, history credited one man alone: Waksman.
Now 82, Schatz wants his side of the story told. He is a small man, fit and trim, with twinkling black eyes. He sits at the dining room table in the home he shares with Vivian, his wife of 58 years, in Philadelphia. Their grandson’s wooden train track snakes under the table. There are rows of books on home-made shelves, lush plants by the windows, and on the walls paintings by one of their two daughters and artefacts gleaned from their travels. Piled on the table in front of him are legal documents, research papers, letters and articles. He wants, he says, to be able to substantiate every claim and statement he makes.
An emigrant from tsarist Russia, Waksman was the head of the soil microbiology department at Rutgers college of agriculture in the 1930s, and the world authority on his subject. In 1937, after hearing that an Oxford University team had managed to purify penicillin, he switched his laboratory’s line of research to the search for new antibiotics. He was convinced that ordinary soil was capable of generating antibiotic- producing organisms, and started a screening programme to find them. Between 1940 and 1952, his lab isolated more than 10 antibiotics produced by actinomycetes, a group of soil organisms capable of inhibiting the growth of bacteria and fungi. Of these, streptomycin was the most extraordinary.
“Waksman was an absolute phenomenon at the pinnacle of science,” says Douglas Eveleigh, current head of microbiology and biochemistry at Rutgers. He was also accessible, says Doris Ralston, a former postgraduate student and the only contemporary of Schatz still alive: “He was wise, demanding, yet understanding. He was not pretentious. He was our great white father. I worshipped him.”
Ralston worked in the basement poultry pathology lab, where she handled chicken viruses. Next door was a larger lab with a sink that was always full of dirty glassware, a steaming, antiquated autoclave, and stacks of petri dishes, flasks and tubes – this was Albert Schatz’s domain.
The son of a Russian Jew and an Englishwoman, Schatz was born in 1922 in Norwich, Connecticut. He grew up during the Depression on a spartan, isolated farm where his extended family survived on what they could grow and the sale of milk from their 12 cows. The farm had no heat, no running water, no electricity, no bathroom, no telephone and no radio. “My mother used to say, ‘Eat it up, wear it out, make do, do without,’ ” he summarises.
In spite of his family’s poverty, Schatz grew up bright, happy and self-confident. He loved the land and initially studied soil microbiology with a view to becoming a farmer. He was awarded a scholarship to Rutgers in 1938: “A poverty-stricken, brilliant student who worked with a burning intensity,” Ralston says.
In 1942, he began work for his PhD under Waksman’s supervision, and the two soon became close. The professor was impressed by his young pupil’s sharp mind and dedication: on more than one occasion, he referred to Schatz as “the most brilliant student I have ever had”. Schatz, in turn, “admired and respected” his professor. “He was my mentor.”
Five months later, Schatz was drafted into the army. As a bacteriologist at a Florida military hospital, he witnessed first-hand the failure of penicillin and sulpha drugs against certain bacterial infections (called gram-negatives), and against TB in particular. “I saw servicemen dying of these infections. They were men my own age. I got to know them,” he says. He began to devote all his spare time to the search for a new, more effective antibiotic.
After being discharged because of a bad back, Schatz returned to Rutgers, where he asked to be allowed to continue his search for an antibiotic that would be effective against gram-negative bacteria, as well as TB. Waksman agreed, but because his student would be working with the virulent tubercle bacillus, which causes the disease, relegated him to the basement and never visited him there.
Schatz threw himself into his research, testing hundreds of different colonies of actinomycetes. “I generally began my work between five and six in the morning and continued until midnight, or even later. I was isolating and testing everything I could find.” The young researcher often ate in the lab – vegetables, fruit, dairy products donated by colleagues in other departments – and sometimes even slept there on a bench, because he was too tired to go home (a room in a greenhouse in the plant pathology department, where he lived rent-free in exchange for maintenance work).
He worked hard partly because, with a stipend of $40 a month, he couldn’t afford a social life, but also because he felt an “overwhelming compulsion” to find an effective antibiotic. “When I was a boy, I knew children at school and neighbours who had tuberculosis. I saw them lose weight and waste away. None of them could afford to go to a sanatorium, so they remained home, coughed and infected others.”
After just three and a half months, and against all the odds, Schatz’s hard work paid off. He isolated not one but two highly active strains of actinomycetes (subsequently renamed Streptomyces griseus ), which stopped the growth of several virulent bacteria known to resist penicillin, including the dreaded tubercle bacillus. One strain had come from heavily manured field soil; the other from a swab from the throat of a healthy chicken, which Ralston had passed him through the basement window after she had finished working with it.
“On October 19 1943, at about 2pm, I realised I had a new antibiotic,” says Schatz. “I named it streptomycin. I sealed the test tube by heating the open end and twisting the soft, hot glass. I first gave it to my mother, but it is now at the Smithsonian Institution. I felt elated, and very tired, but I had no idea whether the new antibiotic would be effective in treating people.”
At this point, Waksman began to participate actively in the research, directing his students to verify results and perform in vivo tests. A few weeks later, Drs William Mitchell and Corwin Hinshaw at the Mayo Clinic in Rochester, Minnesota, began the first toxicity tests, then the first tests on guinea pigs, and later the first clinical trials. At every stage, streptomycin proved successful beyond everyone’s wildest dreams. The preliminary tests were so promising, in fact, that Waksman convinced the pharmaceutical company Merck to set up a production plant immediately, to provide the large quantities of streptomycin necessary for clinical trials. By 1944, the first large-scale trials in the US and England proved beyond doubt that streptomycin was miraculously effective against TB. It also proved effective against bubonic plague, cholera, typhoid fever and other infectious diseases caused by gram-negative bacteria.
During that time, Schatz “also found something much more important”: Vivian Rosenfeld, a tall, sunny young woman, who studied at New Jersey College for Women. Looking up from her newspaper, Vivian smiles. “He was very handsome and so funny. He showed me how to look for slime moulds, fungi and rock lichen.” They married in March 1945; the groom took his actinomycetes cultures on honeymoon.
For the young scientist, however, things then began to turn sour. While Schatz worked around the clock to produce the streptomycin needed for the Mayo’s tests, Waksman was giving lectures on streptomycin and Rutgers’ public relations department began to publicise the discovery as Waksman’s. “At first, he’d invite me to his office to meet journalists, but after a while he stopped. I learned about what was going on, even the exciting developments at the Mayo Clinic, from magazines and newspapers. They were written by people who got all their information from Waksman. Eventually, he took full credit for the discovery.”
As one newspaper article after another eulogised Waksman, Schatz grew resentful. “I was fed up with his apologies and explanations that he was just a pawn in the hands of the public department.” After completing his PhD, Schatz decided to leave Rutgers. He left the university not only bitter, but penniless, too: in 1946, at Waksman’s request, he had signed over his royalty rights from the streptomycin patent to the Rutgers Research and Endowment Foundation, on the understanding that neither he nor the foundation would profit from the discovery. He was later asked to sign over all his foreign patent rights, too. “I agreed because I felt that streptomycin was so important it should be made as readily available, and therefore as inexpensively, as possible.”
He was shocked to discovered three years later that Waksman, contrary to his personal and very public assurance, had another agreement with the foundation, giving him 20% of all streptomycin royalties, which in that period had amounted to $350,000. (In fairness, Waksman channelled much of that money back into the university, creating the research institute that bears his name.)
But as far as Schatz was concerned, this was the last straw. “I had received nothing,” he says. In March 1950, the young scientist decided to sue his former mentor and the Rutgers foundation, demanding his share of the royalties and recognition as streptomycin’s co-discoverer. “I knew it was very risky, but I just felt I had to do it,” says Schatz wearily. “It was a matter of principle.” He sighs, slowly massaging his temples. “Waksman certainly deserved some credit, but he took all the formal awards and honours, some of which included a considerable amount of money. All given for the discovery of streptomycin, and all accepted without even mentioning me.”
For Waksman, the lawsuit came as a vicious and unexpected blow. “He came from the old European school, which considered graduate students as apprentices lucky to be given an opportunity to work alongside a master,” says Milton Wainwright, a microbiologist at Sheffield University, who researched the streptomycin discovery for his book Miracle Cure (Blackwell, 1990). “[Waksman] considered himself chiefly responsible for the discovery, which he saw as a natural step in the research programme he had designed.”
The publicity of the lawsuit was deeply embarrassing to Waksman and Rutgers, and within a year, they settled out of court. Schatz was entitled to legal and scientific credit as co-discoverer of streptomycin, and received a lump sum of $120,000 for the foreign patent rights (of which 40% went to Schatz’s lawyer) and 3% of the royalties, which amounted to about $15,000 annually for several years.
For Schatz, it proved a pyrrhic victory. The scientific community closed ranks against him, feeling that he had unjustifiably attacked a world-famous scientist in order to grab credit that he didn’t deserve. He applied for work to more than 50 universities and research institutions, but was only offered a position at a small private agricultural college in Pennsylvania. “More than once, I was told I was the most qualified applicant, but wouldn’t get the job because I was a litigious character. Many people told me: ‘Of course, you were justified in suing Waksman, but one doesn’t do that sort of thing in academia.’ ”
After a silence, he adds, “I had done nothing wrong, I only tried to justify my position. That was the hardest. Many people who didn’t know the story had strong opinions, so I was put on the defensive. I felt I’d be blackballed for the rest of my life.”
Few of the scientists who sided against Schatz knew the details of the case, however. Ralston, his former colleague, did. “My heart has been filled with sadness for him. He worked so hard, was so smart and had such high ideals. Coming from a poor family, he had hopes that streptomycin would help lots of needy people.” Searching for the right words, she adds, “I believe that he would willingly have given up any monetary benefit if Waksman had not started collecting honours and great amounts into his personal bank account. He deserved so much more recognition.”
The final blow for Schatz came in October 1952, with the news that Waksman would be awarded the Nobel prize for the discovery of streptomycin. “I was devastated. The lawsuit had firmly established I was the co-discoverer,” he says, his voice trailing off. The vice-president of the agricultural college where he worked wrote to the Nobel prize committee asking its members to reconsider, sending along substantiating facts and documents. He also asked Nobel laureates and other scientists to intercede in Schatz’s favour. Only a few did.
“It was the McCarthy era,” says Vivian quietly. “It was a hard time to be on the wrong side of the fence. People couldn’t risk supporting us.”
And so, on December 12 1952, Waksman was awarded the Nobel prize. Professor A Wallgren of the Swedish Caroline Institute tried to defuse the tension by declaring that Waksman had been awarded the prize for his “ingenious, systematic and successful studies of the soil microbes that led to the discovery of streptomycin”, instead of “for the discovery of streptomycin”, as had first been announced.
In his acceptance speech, Waksman did not once mention Schatz, using the royal “we” instead. Nor is there any reference to Schatz in Waksman’s 1958 memoir, My Life With The Microbes – he is named only as “the graduate student”.
“It was a grave injustice,” says Karl Maramorosch, an emeritus professor at Rutgers who has campaigned for Schatz’s rehabilitation. “The Nobel has made a few mistakes, but this was one of the worst.” Other faculty members at Rutgers are more cautious. Douglas Eveleigh of the microbiology and biochemistry department, who also lobbied on Schatz’s behalf, believes nonetheless that there was no malice on Waksman’s part. “I feel he genuinely believed he deserved the credit,” says Eveleigh in his office overlooking the campus. “There is no doubt that Albert deserved all the credit for the discovery and that it was not fair to read in textbooks that Waksman discovered streptomycin. But he was part of a generic system of the time in which professors, especially in Europe, had an aura around them, and people bowed, and all the credit went to the head of the department.”
This still happens all too often in science, says Peter Lawrence, a developmental biologist at the Medical Research Council’s laboratory of molecular biology in Cambridge, who recently published a polemic on the subject in the science journal Nature. “It is a military way of thinking that the responsibility and credit go to the person of higher rank, but it is inappropriate for creative discovery and should be resisted.” And it can, adds Lawrence, citing César Milstein, the brilliant immunologist who died in March: Milstein made a lifetime contribution to his field but, when he discovered monoclonal antibodies with his postdoctoral student Georges Kohler, he gave Kohler due credit; the two shared the 1984 Nobel prize for their discovery.
After being awarded the Nobel, Waksman went on to oversee the production of many other life- saving antibiotics, co-authored 500 scientific papers and wrote or edited some 28 books. He died in 1973 at the age of 85, widely regarded as “the father of antibiotics”. Schatz never again worked in a first-class microbiology lab, but managed to make some important contributions to fields as diverse as science education, nutrition, pollution and water fluoridation. In the early 1960s, unable to find work in the US, he took his family to South America, where he worked as a professor at the University of Chile, while Vivian was director of the US school in Santiago.
Schatz’s contribution to the field of antibiotics might have gone unnoticed altogether if it hadn’t been for Milton Wainwright at Sheffield University. Researching the history of streptomycin, he went to Rutgers to look into the archives. He was puzzled by what he found: why hadn’t he heard of this Albert Schatz? He decided to investigate, studying all the scientific papers and legal documents, interviewing former staff and students, and meeting Schatz himself.
A soil microbiologist himself, he understood exactly the steps involved in Schatz’s research. “I was totally confident that he discovered streptomycin alone. I felt very emotional because I could feel he had been gravely wronged,” says Wainwright over coffee in a Sheffield diner. He wrote a few articles in scientific journals about his findings and included Schatz’s story in his book on antibiotics, but failed to generate much support within the scientific community.
Wainwright’s visit, however, had intrigued professors at Rutgers. They decided to meet with Schatz and, finally convinced that he had been the victim of a grave injustice, began to lobby for his rehabilitation. On April 28 1994, the 50th anniversary of the discovery of streptomycin, Albert Schatz, then 74, was awarded the Rutgers medal, the university’s highest accolade. Many others have since recognised his role as well.
The belated recognition didn’t quite make up for the Nobel prize, but it did heal some old wounds. “I no longer needed to be on the defensive, I didn’t need to justify myself any longer,” says Schatz. “It also re-established my connection with Rutgers and restored to Vivian and me a part of our lives that we’d considered dead for almost half a century. During that time, we rarely talked about what had happened, and did not discuss it even with our two daughters.”
Schatz is now lobbying scientific institutions and museums to have them include his contribution in exhibits, websites and brochures pertaining to streptomycin. He has even written to the king of Sweden, asking him to correct “misinformation about the discovery of streptomycin” on the Nobel Museum website, and is hoping to travel to Stockholm to scrutinise the Nobel committees’ deliberations on streptomycin when they are made public next January. He is also writing an autobiography, “to set the record straight”.
But if anyone has the last word in the story of streptomycin, it is not Schatz, nor Waksman, but tuberculosis itself. After years of steady decline, the disease that Schatz helped beat is now back with a vengeance, often in deadlier, drug-resistant strains acting in synergy with HIV/Aids. The white plague is back.
Streptomycin and TB
Streptomycin saved thousands of lives, but it soon became apparent that it caused serious side-effects, too, among them vertigo, nausea and deafness, and that bacterial resistance to the drug was developing at an alarming rate. The new antibiotic was then successfully used in combination with two non-antibiotic drugs – isoniazid (discovered in the US in 1952) and PAS (para-aminosalicyclic acid, discovered in Sweden by Jorgen Lehmann in the same year as streptomycin, but delayed because of the war). These combined drugs, and a few others, remain the frontline in the battle against TB.
For a while, the three-drug therapy, together with improved living standards, pasteurisation of milk and the introduction of the BCG (bacille Calmette-Guérin) vaccine, seemed to be winning the war against tuberculosis in western industrialised countries. One by one, the sanatoria closed and the terror of TB began to fade from people’s mind. The United Nations and World Health Organisation (WHO) launched anti-TB campaigns in the developing world with some success. By the 1960s, incidence of the disease was beginning to drop in Africa and health officials confidently spoke of eliminating it.
But TB never really disappeared. Slowly, all over the world, strains resistant to all major anti-TB drugs emerged. By the end of the 1970s, TB deaths began to rise again, especially among the poor, overcrowded, malnourished, and those whose immune systems have been weakened by HIV/Aids. According to the WHO, it now kills two million people a year worldwide, and the global epidemic is growing, particularly in developing regions such as Africa and south-east Asia. Even in industrialised countries, it is rising – in Britain, for example, cases of TB are at their highest since 1983, with two-thirds of the rise in London, and more than half affecting the homeless and foreign-born people.
Overall, one-third of the world’s population is currently infected with the TB bacillus (5%-10% will become sick or infectious). The WHO estimates that between now and 2020, nearly one billion people will be newly infected, that 200 million people will get sick, and that 35 million will die from TB if control is not further strengthened.