Dr. Albert Schatz Lecture

Dr. Albert Schatz Lecture

1993

[Welcoming applause]

DR. SCHATZ:Thank you. I really should terminate my talk now while I’m ahead on the applause.

[audience laughter]

DR. SCHATZ:Doug Eveleigh was kind enough to prepare some copies of this article, which I wrote. If you’re interested in it, you may take them. This article was written for TheSmithsonian Magazine, which decided not to publish it. The Smithsonian had published an account of a sick chicken being involved in the discovery of streptomycin. This sick chicken was brought to Waksman, who isolated a culture of Streptomyces griseus from the throat of this sick chicken, by which streptomycin was produced. The sick chicken never existed.

[audience laughter]

First of all, farmers brought sick chickens to Dr. Beaudette in the Department of Poultry Pathology. Secondly, the person who swabbed the throat of healthy chickens, was Doris Jones, and she was trying to find out if there were any microflora in the throats of healthy chickens, which exhibited and produced antiviral substances and protected chickens from viral diseases such as New Castle and, I think, fowl laryngotracheitis. That is in her Masters Degree thesis.

Waksman was the chairman of her committee and should have known that there was no sick chicken involved. In her dissertation, she specifically states that she worked with healthy chickens and that she gave me some of the plates which she had swabbed from the throats of these chickens after she took the colonies that she was interested in.

So I wrote this article for the Smithsonian Institution, which would not publish it, and I have had the unique experience of having an article accepted for publication without my ever having submitted it. It’s a wonderful experience. I’d never had it before.

[audience laughter]

DR. SCHATZ:I sent this manuscript, a copy of this, to George Luedemann in Tucson. George Luedemann had published a very extensive paper on, what was it, Douglas, gentamycin?

DR. EVELEIGH: Yes, gentamycin.

DR. SCHATZ: In the journal, Actinomycetes, the editor of which is Romano Locci at The Udine University in Udine, Italy, and Romano Locci wrote George that he would like to reprint this paper if it appears in The Smithsonian. If not, he would like me to elaborate, expand it and he would publish it. So George sent me the letter of acceptance, and I subsequently expanded the paper, sent it to Romano Locci. So it was an interesting experience. It was a first for me. Usually, I have to submit an article and then keep submitting it after it’s been rejected by one editor, until I get an editor who accepts it.

But this sick chicken, which also appeared in the winter issue of The Rutgers Magazine, if you’ve seen it. It’s remarkable. I don’t know what the normal lifespan of a chicken is, but this sick chicken has been alive for half a century! [audience laughter]. It’s amazing! [Dr. Schatz’ laughter]

DR. KAHN: Perhaps someone’s egging it on.

DR. SCHATZ:Yes, egging it on. Yes. I usually don’t talk a lot about streptomycin, about certain aspects of it, but I will tell you, because of some of the comments that were made about some of the things that go on at academic institutions involving research versus teaching faculty and grants, royalties and so forth. You probably know that I had the audacity to sue Waksman and the Rutgers Research and Endowment Foundation, and this is another first for me because I generally don’t mention what I’m about to tell you in public, but I think it may be of interest.

Now, the question has always come up, since I was the one who did the work, quite independently of Waksman. He was not enthused. First of all, in the Army, I finished, I graduated Rutgers in May of 1942, and we had an accelerated year because this was during the War, and the idea was to get us out of the university, graduate us as quickly as possible so we could go into the armed forces.

I spent the first six months, from May of ’42 until November of ’42, doing graduate work in the Department of Soil Microbiology. I worked on fumaric acid production by a rhizopus, a mold. I worked on the production of actinomycin, clavacin, fumigacin and streptothricin, and then I went in the Army.

I was originally scheduled for Cooks & Baker’s School, and the alternative was bomb-site mechanic [audience laughter] But a most remarkable thing happened. Someone made the comment that the term, “military intelligence” is a contradiction because the two can’t exist together. But someone in personnel realized that with my background in microbiology, I really should be in the medical area, and so I was assigned to a medical detachment of The Air Force, and worked in laboratories in Miami Hospital and Clinic Laboratories, and at that time, some of the very seriously-wounded servicemen from the North, particularly from the North African Campaign, including some who would probably, if they lived, spend the rest of their lives in VA hospitals, were in some of the hospitals, and where I was stationed. And I was the one who isolated and identified the causative agents of their infections, which in many cases, were gram negative bacteria, most, in many cases, Pseudomonas aeruginosa; I think it was aeruginosa.

And I was hospitalized myself because of a bad back, and at times, I went to the laboratory and worked. The alternative was to lay in a bed and look at the ceiling. And I also spent time with some of the servicemen, who were literally dying, and I was with some of them who did die, and I was the one who isolated the gram negative organisms, which literally killed them. So I developed a very healthy respect for gram negative pathogens, which at that time, were not controlled by penicillin. The sulfa drugs were not very effective, compared to penicillin, with gram positive bacterial infections.

When I was discharged from the Army on June 13, 1943, I resumed graduate work and wanted to look for an antibiotic against gram negative bacteria. Waksman approved that project in June of ’43, and not too long after that, William Feldman, either alone or with Corwin Hinshaw, from The Mayo Clinic – Feldman was a veterinarian and Hinshaw was an MD - either Feldman alone or the two of them visited Waksman and suggested that he look for an antibiotic against TB. Waksman discussed this with me. I was working in the third-floor laboratory at the time. He had two third-floor laboratories in the Administration Building, which is now called the Martin Building. Martin, at that time, was Dean, and his office. Starkey had his office, Robert Starkey, the other member of the department. So there were two laboratories on the third floor and two offices, and a laboratory in the basement.

When Waksman told me about the idea to look for an antibiotic against tuberculosis, he expressed concern because he was scared to death of tuberculosis, and with good reason. I offered to take that on as an additional problem, at which point, he transferred me to the basement laboratory. The reason was that I wanted to work with a virulent strain of Mycobacterium tuberculosis. For the research with gram negative bacteria, the search for an antibiotic against gram negative bacteria, I included some gram positive bacteria, including Mycobacterium phlei, which is a common, non-pathogenic mycobacterium. But for tuberculosis, I wanted to work with a virulent strain. I had experience working with pathogenic bacteria in the Army, and so I obtained from Feldman the H-37, or HR-37, strain, which was the most virulent strain of human tubercule bacilli at the time. And at that point, Waksman transferred me to the basement laboratory. He never visited the basement laboratory. He also told me, under no circumstances was I ever to bring any TB cultures up to the third floor. And Feldman himself told me that this really was dangerous work, and he had good reason to say that. Feldman had done a lot of work with tubercule bacilli at the Mayo Clinic, and he subsequently did develop tuberculosis, and his physician, Corwin Hinshaw, who also was his research collaborator, concluded that the strain which had invaded William Feldman was the H-37 strain, the same one that he had given me, and with which we were both working.

I produced, in the basement laboratory, the streptomycin, which was used for the first toxicity and in vivo efficacy tests in guinea pigs at the Mayo Clinic by Feldman, Corwin and Hinshaw, by Feldman, Hinshaw and one other person. I also produced there the first streptomycin which was used in the first in vivo tests here at the Ag School, which were done by Doris Jones in the Department of Poultry Pathology with chick embryos. So to produce that streptomycin, I ran two or three stills, perhaps, two at times and at other times, three stills, in the basement laboratory in the Martin Building.

I’m smiling because I see you have, I assume this is beer.

DR. KAHN:Yes.

[audience laughter]

DR. SCHATZ: And wine. I am extremely sensitive to alcohol, so I don’t drink.

DR. KAHN: Poor fellow.

DR. SCHATZ: As a matter of fact, I was with some people socially, and I was getting woozy, and I knew them very well, and I said to one of them in our home, I said, “You know, I just can’t drink. I’ve got to go up and lay down for a while”, and she says, “But you don’t have any alcohol. That’s a Pepsi Cola you have in your hand”.

[audience laughter]

DR. SCHATZ:Anyway, these stills that I ran remind me of the time when I was seven or eight or nine years old. This was in Connecticut, during Prohibition, and a major source of our income was production of alcohol, and we had a still in our chicken coop, and it was my job to run the still, which I knew how to do. There’s really nothing to it. What is that?

AUDIENCE MEMBER: That’s where the sick chicken came from.

[audience laughter]

DR. SCHATZ: [laughing] Maybe. And one of the problems was that we had a chimney on the chicken coop, and it would look suspicious if we had smoke coming out of the chimney during the summer.

[audience laughter]

DR. SCHATZ:So we ran that still at night. But during the winter months, it was run all the time. And not too long after that, when I was in Passaic, New Jersey - and I lived part of the time on the farm in Connecticut and part of the time in New Jersey - I was visiting a classmate of mine whose father was what we called, a “rum runner”. He used to import, illegally, whiskey into this country, mostly from France, and apparently, he decided to produce his own, and he was having problems with the yield, and I was pouring lead soldiers with my friend and I overheard this conversation between his father and two or three people who were obviously operating the stills, and they weren’t getting a good yield. So I went in and asked them how they were fermenting their mash, and they weren’t using hydrometers. So I explained you need a hydrometer; it tells you when to distill because you know how much alcohol you’ll get. So I see the wine and beer, and I talk about the stills I ran, and that’s what was going through my mind.

[audience laughter]

DR. SCHATZ:But I produced the streptomycin. I often slept in the laboratory, and on the stills in Florence flasks, I would put a mark with a red pencil, and if I was asleep, the night watchman, if the liquid had boiled down to that level, would wake me up, and I would add more.

So there were several interesting aspects with respect to the discovery of streptomycin. People often wonder: What was the element of chance? First of all, I isolated not one, but two, strains of Actinomyces griseus, both of which produced the same antibiotic, which was streptomycin. One came from a healthy chicken’s throat, and the other came from a heavily-manured field soil in the immediate vicinity. Probably that field soil is no longer field soil, but the basement of a building or something else.

DR. KAHN:Parking lot.

DR. SCHATZ: Or a parking lot. Secondly, both strains produced streptomycin in sufficient quantities to justify further investigation. But interestingly enough, both strains were active against both the gram negative and the tubercle bacillus, so that the two problems then became one problem. What I will say now – I don’t usually say but in view of some of what I understand has been going on here, I will make these comments – the people often ask. Incidentally, I was the senior author on the paper, announcing the discovery of streptomycin, on the paper, announcing its in-vitro effect on the tubercle bacillus, and on the third paper, which discussed strain variation and the production of streptomycin. I wrote those three papers. I’m also on the patent. And the question has come up often as to why Waksman didn’t acknowledge my role, particularly with respect to the Nobel Prize, or before that, because he would have lost nothing. In view of the lawsuit, which subsequently occurred, that would have prevented the lawsuit. And if he also had. And Milton Wainwright, who is in Soil Microbiology at the University of Sheffield, was particularly interested in this; he wrote the book, Miracle Cures, and had written an article. Douglas has this book, Miracle Cures, with a chapter about streptomycin. And Milton had written an article in the – what is it - The Journal of General Microbiology, about my role in the discovery of streptomycin, in which he concluded that I was the one who actually did it. He was particularly concerned about why Waksman did not acknowledge my role and give me some credit. In his book, I am told – and I’ve never read his book – he refers to me as a “laboratory assistant” or a “laboratory technician”. He does not refer to me by name, except, I am told, in the list of publications.

I usually don’t mention these things when I talk publicly, but you may be interested in them. I have something here which I would like to read you. Doris Jones – now Doris Ralston – is the individual, as I said, who gave me the plates from which I isolated one strain of streptomycin, Streptomyces griseus. And on July 26, 1949, Doris was at the University of California, where she was working for her Ph.D. degree. She received her Masters Degree here. Doris wrote me because I had told her that she probably would be contacted by attorneys from the Rutgers Research and Endowment Foundation, since they were taking depositions just as we were. And she wrote, I think it was on that occasion, and this is a letter from her, but this is what she testified to on her deposition. “I think it was on that occasion that Dr. Waksman voiced his opinion of your position in the streptomycin work, saying that he felt you were too aggressive and would harm yourself if you were allowed to go unbridled. For that reason, he said, he did not want you to be given so much credit for streptomycin. Streptomycin would go to your head. You were too young to accept fame humbly”.

[audience laughter]

DR. SCHATZ:This is true. This is in her pre-trial deposition, which is testimony under oath. “You were too young to accept fame humbly, and Dr. Waksman, on the other hand, was mature enough to handle the honors bestowed upon him. I cannot quote his words verbatim, since as you know, all this occurred in 1945, and I never could keep a whole conversation like that in my head word for word. However, the incident left a strong impression, as I realized, or should I say, analyzed, his actions, to mean he was actually not trying to help you, so much as he was attempting to explain and justify his stand”.

DR. KAHN:Sounds like a Rutgers administrator.

DR. SCHATZ:Sounds like a Rutgers administrator?

DR. KAHN:…..

DR. SCHATZ:Well, there’s another story. When I entered my freshman year at Rutgers in September of 1938, Jacob Lipman was Dean of the Ag School, and Jacob Joffe was Professor of Pedology. There was a Department of Soil Science, which included Soil Chemistry, Pedology and Soil Microbiology. Joffe was in Pedology. Fuhrman Bear, at that time, who replaced Lipman, who had previously been Chairman of Soil Science and was moved up to Dean, Fuhrman Bear taught the Soil Chemistry with others. Waksman taught Soil Microbiology, Waksman and Starkey. But even as a freshman, and all incoming freshman took Joffe’s course in Pedology, a first-semester course. And Joffe would, not in class, but in his office, rant and rave about Waksman, and at faculty meetings, as I subsequently learned, he would get up and accuse Waksman of being a liar and a thief, and he did not speak to Waksman, and the reason was that Joffe did his graduate work under Waksman, and Joffe isolated Thiobacillus thiooxidans, which is an autotrophic bacterium that derives its energy from the oxidation of elemental sulfur. And Joffe developed a process of mixing a slurry of rock phosphate, a little soil, if I recall, sulfur, and inoculating it with sulfur Thiobacillus thiooxidans, which produce sulfuric acid, which reacted with the rock phosphate and produced a precursor of superphosphate. Now, it’s done with sulfuric acid. And Joffe accused Waksman of having stolen – that was his word – credit for the isolation of Thiobacillus thiooxidans, and for making money on the process, which he, Joffe, had developed. And this was well known when I was a freshman because faculty members were talking about this. This was in 1938, and it went back to 1920, or perhaps earlier. This controversy and contention had existed from 1920 or earlier to 1938.