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Source:
Actinomycetes: Vol. IV, Part 2: 27-39: August, 1993
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The
True Story of the Discovery of
Streptomycin
by
Albert Schatz
Prologue
"For
the historian of science,
few documents are as valuable as
the description of
a discovery by the scientists involved
in the
action. Unfortunately few scientists take the time
to record for posterity the course of events which led to
the discoveries which were the fruit of their labor"
(Lechevalier, 1991).
"I
have often thought how much more interesting science
would
be if those who created it told how it really
happened, rather
than reported it logically and
impersonally, as they often
do in scientific
papers" (Beadle, 1992).
"Over
the years, the story of
streptomycin's discovery has been
terribly garbled.
I think ... it would be a great service
if ... Dr.
Schatz told his own accurate and interesting account
of his finding. Streptomycin turned out to be a milestone
in the history of drugs to treat tuberculosis and other infections.
Dr. Schatz's role has been largely ignored. The record about
this discovery should be set straight" (Doris Jones
Ralston, a fellow graduate student when I did the streptomycin
research).
The
Story of the Sick Chicken
This year, 1993, is the 50th anniversary of the discovery
of streptomycin. It was on October 19, 1943, at about 2:00
in the afternoon, that I realized I had found a new antibiotic.
The report of its discovery was published in January of 1944
(Schatz et al., 1944). But I prefer to begin this story of
the discovery of streptomycin with a 50-year-old fairy tale
about a sick chicken. That fictitious account of the discovery
of streptomycin recently appeared as follows in the Smithsonian
magazine (Chowder, 1992).
"A
New Jersey farmer was upset: his chickens were catching
a strange infection from barnyard dirt. He took the birds
to the Rutgers University laboratory of microbiologist Selman
Waksman, who analyzed the barnyard soil and isolated the
problem - a peculiar fungus. In the process, Waksman fortuitously
discovered that the microorganism had properties besides
the ability to make chickens sick. The fungus produced a
chemical agent that slowed the growth of certain
bacteria".
The Rutgers
Magazine also recently retold this myth
(Smolen, 1992). These accounts egregiously distort and misrepresent
the circumstances involved in the discovery of streptomycin.
I want to present the true story of the discovery of streptomycin
which I am uniquely qualified to do because I literally lived
it! I began the research that led to streptomycin when I was
in the army during world War II.
How
And Where It All
Began
In
May, 1942, I graduated from Rutgers University with a major
in Soil Science. The day after I received my Bachelor of Science
degree, I became a student again. But this time I was a graduate
student who wanted a Ph.D. degree. I worked for six months
in Selman Waksman's Department of Soil Microbiology at Rutgers
University on the production of fumaric acid and three antibiotics:
actinomycin, clavacin and streptothricin. Unfortunately, these
antibiotics were too toxic to have practical value in treating
human infectious diseases. Nevertheless, this work gave me
an introduction to the field of antibiotics.
World War II interrupted the lives of many students. In November,
1942, I became a bacteriologist in the Medical Detachment
of the Air Force, and was stationed in army hospitals in Florida.
This experience provided me with firsthand knowledge of the
inability, at that time, to control many infectious diseases.
Sulfa drugs were useful in some cases but had serious limitations.
The antibiotics tyrothricin, gramicidin and tyrocidin could
be applied topically, but were too toxic for systemic use.
Penicillin was a new antibiotic that was active against gram-positive
bacteria.
There was no
means of effectively controlling tuberculosis
and
infections caused by gram-negative bacteria. I therefore
began devoting my spare time, when I was off duty, to a search
for an antibiotic that would be effective against gram-negative
bacteria. For this purpose, I isolated and tested molds and
actinomycetes from contaminated blood culture plates and from
Florida soils, swamps and coastal sea water. I sent Waksman
cultures that I thought merited further testing which I could
not do in army hospitals. Waksman acknowledged that I had
done that work in Florida. In his pretrial deposition (testimony
under oath, in a lawsuit that will be discussed) he stated
that I had sent him cultures from Florida (Anonymous, 1950).
In a publication which he coauthored with Elizabeth Bugle
he reported that one culture, which they tested, "was
isolated by Private A.Schatz while stationed at the Miami
Beach Military Hospital in April of 1943 from a meningococcus
blood agar plate" (Anonymous, 1950). My research
in the army was terminated when I was discharged on June 15,
1943, due to a back injury sustained in the army.
I could then have gotten a well-paying job in a chemical or
pharmaceutical company. Instead, I chose to work for a Ph.D.
degree with an income of only $40.00 a month. I told Waksman
that I wanted to continue my search for an antibiotic against
gram-negative bacteria as my doctoral research project. Waksman
agreed. He knew this would be a continuation of the work I
had been doing during my off-duty hours in army hospitals.
Shortly thereafter, William
Feldman at the Mayo Clinic suggested
to Waksman that
he look for an antibiotic to treat human tuberculosis.
However, Waksman was reluctant to do that because, he told
me, he was afraid to have Mycobacterium tuberculosis (hominis),
which causes human TB, in his laboratory. When I
told him
I wanted to work with that organism and
include the search
for an antibiotic against
tuberculosis as part of my Ph.D.
research, Waksman
informed Feldman that he would take on the
TB
project. I then had two problems to work on: finding an
antibiotic active against the tubercle bacillus and an antibiotic
active against gram-negative bacteria.
Waksman originally thought there was little likelihood of
my finding an antibiotic that would be effective in treating
tuberculosis
because of the external
waxy coating which protected the tubercle
bacillus.
He also knew that tubercle bacilli got into the
soil. "It is estimated that the thirty pounds of
moist feces produced daily by the average cow would contain,
in the case of diseased animals, 37,000,000 microscopically
demonstrable tubercle bacilli" (Lipman, 1921). And
he knew that tubercle bacilli "survive in the soil
for many years without losing their virulence" (Waksman,
1932).
There was
nothing fortuitous about the discovery of streptomycin
in the sense that the Smithsonian article implies (Chowder,
1992). The research I did in 1943, reported in my doctoral
dissertation (Schatz, 1945) and my publications (Schatz et
al., 1944; Schatz and Waksman, 1944, 1945), was specifically
designed to achieve the two above-mentioned objectives. The
wording of these objectives in my doctoral dissertation is:
"Two problems, therefore, appeared to be of sufficient
interest to warrant investigation; namely ... a search for
an antibiotic agent possessing ... activity against gram-negative
eubacteria and a search for a specific antimycobacterial agent"
(Schatz, 1945) active against the tubercle
bacillus.
There are comments in the literature that Waksman and I did
not at first fully appreciate the importance of streptomycin.
That may have been true for Waksman, but it certainly was
not true for me. I wanted to find an antibiotic that would
be effective in treating human tuberculosis. That is why,
as reported in my doctoral dissertation (Schatz, 1945), I
specifically worked with a virulent human strain of the tubercle
bacillus. It is true that I did not point out the potential
importance of streptomycin for treating tuberculosis in the
paper I wrote about streptomycin inhibiting the tubercle bacillus
in vitro (Schatz et al., 1944). But there was insufficient
information at that time about toxicity and in vivo efficacy.
I therefore did not want to raise people's hopes with claims
that might subsequently be refuted.
Two
Strains of Streptomyces
griseus
I isolated two strains of Streptomyces griseus from two separate
sources. Both strains produced streptomycin. And streptomycin
was effective against both gram-negative bacteria and the
tubercle bacillus. I called one strain of S.griseus
18-16 because it was the 16th actinomycete I isolated from
a heavily manured field soil. That was the 18th soil from
which I obtained actinomycetes to test for antibiotic activity
(Schatz, 1945). I isolated another strain of S.griseus
from a petri dish which my fellow graduate student Doris Jones,
now Doris Ralston, had streaked with a swab from a healthy
chicken's throat. S.griseus is an actinomycete that
is widely distributed in soils. Its spores can be blown around
in the air and inhaled by people and animals. At that time,
Doris was working in the laboratory of Frederick Beaudette,
a veterinarian and poultry pathologist in the Department of
Poultry Science at the Rutgers University College of Agriculture
and the New Jersey Agricultural Experiment Station. She was
studying The Effect of Microorganisms and Antibiotic Substances
on Viruses (Jones, 1945). Doris gave me some of her petri
dishes with colonies of various microorganisms after she had
made transfers from those colonies that she wanted for her
research. I called that second isolate D-1 because it was
the first (No. I) actinomycete I isolated from the plates
that Doris (D) gave me.
To eliminate any doubt about the source of the D-1 strain
of S.griseus, I am quoting the following information
from Doris Jones' master's degree dissertation. "It
had been suggested by Dr.Beaudette that the flora of carrier
birds might in some way differ from those of infected, immune
and normal fowl, and that certain microorganisms might be
responsible for the reduction or elimination of the virus.
Accordingly, an attempt was made to survey the tracheal flora
of well (emphasis by A.S.) birds with a view to comparing
this with the flora of carriers and victims of respiratory
virus diseases. Over a period of several weeks, tracheal swabs
were streaked out on nutrient agar plates... It was noted
at the time that the phenomenon of microbial antagonism occurred.
Several plates exhibiting zones of antagonism were examined
by Mr.Schatz and from one of them was isolated an active strain
of S.griseus" (Jones, 1945). Waksman was chairman
of Doris Jones' graduate committee. If he had read her dissertation,
as he should have done, he would have known that the chicken
was healthy, not sick. The story about the sick chicken is
therefore a fairy tale that Waksman concocted as evidence
that he had in some way participated in the isolation of the
D-l strain of S.griseus. The sick chicken is the only link
he had with the actual discovery of streptomycin. He never
saw the plates which Doris Jones gave me. Milton Wainwright
published a detailed account of how this poor, sick chicken
was created and passed around (Wainwright, 1991).
Farmers who had sick chickens routinely took them to the poultry
pathologist, Beaudette, not to the soil microbiologist, Waksman.
The saga of the sick chicken which Waksman sired was only
the beginning of the false history of the discovery of streptomycin
that he fabricated. "Waksman once told a famous numbers
story as follows: 'We isolated one hundred thousand strains
of streptomycetes' (formerly known as actinomycetes), 'ten
thousand were active on agar media, one thousand were active
in broth culture, one hundred were active in animals, ten
had activity against experimental T.B. and one turned out
to produce streptomycin'. 'Dr.Lechevalier, who told this story
in 1975, went on to say: of course, this whole arithmetic
is phony and what this story shows is an obsession for numbers'
" (Luedemann, 1991).
None of Waksman's above-mentioned comments apply to the discovery
of streptomycin. I isolated all the actinomycetes that I tested.
Waksman did not isolate a single one of them. My streptomycin
research began in late June of 1943, shortly after I was discharged
from the army. On October 19, 1943, I realized I had found
a new antibiotic, and decided to call it streptomycin. The
publication announcing the discovery of streptomycin appeared
in January, 1943. During the four month interval between June
and October, 1943, I worked day and night, and often slept
in the laboratory. I prepared my own media and washed and
sterilized the glassware I used. This work was done 50 years
ago with glass petri dishes that were reused, and test tubes
with cotton plugs. I was the first and probably the only one
who ever worked with the tubercle bacillus in Waksman's laboratory.
I could not possibly have isolated and tested 100,000 actinomycetes
against the tubercle bacillus in four months! Finally, Waksman's
own writing (Wainwright, 1991) confirms what I reported in
my doctoral dissertation (Schatz, 1945); namely, that I had
isolated two strains of S.griseus, not one, which
produced streptomycin. Even before I began my doctoral research,
Waksman knew that the strain of S.griseus which he
had isolated in 1916 and kept in his culture collection did
not produce any antibiotic.
I
Worked In The Basement
Laboratory
Waksman was therefore not directly involved in any way with
the early stages of my streptomycin research, which I did
independently of him in a basement laboratory. For one thing,
he was away at Woods Hole, Massachusetts, and elsewhere for
much of that time. Secondly, I did not need him or anyone
else to tell me what research to do, how to do it and how
to interpret the results. The techniques and equipment I used
were simple and familiar to students who had taken undergraduate
courses in Soil Microbiology and Chemistry. Also, I had done
isolation and testing in an army hospital before I began my
streptomycin research in Waksman's laboratory. I translated
the relevant French and German literature as well as the works,
in Russian, of Krassilnikov, Koreniako, Nakhimovskaia, Kriss
and others (Lipman, 1921). Their research on microbial antagonisms
and antibiotic action by actinomycetes during the 1930s antedated
Waksman's debut in that field. Waksman does not comment on
microbial antagonism in his book Principles of Soil Microbiology
published in 1932 (Waksman, 1932). Nor does his book refer
to the work of Papacostas and Gate who in 1928 used the term
antibiotic and reported clinical applications of antibiotic
substances (Papacostas and Gate, 1928). In 1943, I lent Waksman
my copy of Papacostas and Gates book which he never returned.
I could translate the
above-mentioned Russian publications
because I
learned Russian as a young boy on my grandparents'
farm in Connecticut. Later, in the summer between my third
and fourth undergraduate years at Rutgers University, I learned
more Russian in a course I took at Columbia University. I
was at that time interested in Pedology - the science of the
origin, formation and distribution of soils; and planned to
get a Ph.D. in that field. I therefore wanted to be able to
translate the original Russian works of Dokuchaev, Glinka
and others who established the science of Pedology. In my
research in Pedology, I introduced the concept of chelation
as a major mechanism in the formation and fertility of soils
(Tompkins and Bird, 1989).
I therefore did not need a tutor for my streptomycin research.
There was simply no need for Waksman to do anything after
he arranged for me to receive a monthly stipend of $40.00.
I subsequently learned that that was the lowest stipend of
all graduate students in his department at the time. I was
23 years old, skinny, and weighed only 120 pounds. But I had
an overwhelming compulsion to find something that would control
infections caused by gram-negative bacteria and the tubercle
bacillus.
It is hard to
imagine what life was like in the pre-antibiotic
era. During my early years in school, some of my classmates,
friends and relatives died of infectious diseases. When I
worked in army hospitals in World War II, I saw first-hand
the tragedy of uncontrollable gram-negative bacteria. They
were killing wounded servicemen, some of whom had been flown
back to the U.S. from the North African campaign. I isolated
and identified the deadly bacteria. That was the easy part.
I often spent many hours at night with servicemen as they
were dying. That was the hard part.
Why did I also take on the seemingly impossible challenge
of finding an antibiotic that would be effective in treating
tuberculosis? Again, as a young boy in a working class family,
I knew people who died of tuberculosis. Tuberculosis has killed
more people than any other infectious
disease. It is responsible for the death of a thousand million
human beings.
To
keep body and soul together when I was a graduate student,
I lived rent-free in a small room in one of the Plant Physiology
greenhouses. In return, I prepared mineral solutions for research
on the hydroponic growth of plants, watered and fertilized
other plants growing in soil, swept the floor of the workroom
area, maintained the proper temperature during winter months,
and did other chores. Because my income was only $40.00 a
month, I ate fruit, vegetables, and dairy products which I
obtained free from the respective departments at the Agricultural
Experiment Station.
Waksman had three laboratories. His office and two laboratories
were on the third floor of what we called the "Administration
Building. The third laboratory was in the basement of the
same building. Waksman assigned me to work in the basement
laboratory because he wanted to be as far away from the tubercle
bacillus as he could. That is also why he never visited me
in the basement laboratory during the entire time I did my
streptomycin research. He stayed away from me and what I was
doing for several reasons.
1. Waksman told me he was deathly afraid of tuberculosis,
and with good reason. Tuberculosis, also known as The Great
White Plague, is responsible for the deaths of an estimated
one billion people.
2. There was at that time no effective treatment for tuberculosis.
3. I
insisted on working with the H-37 strain of the tubercle
bacillus which I obtained from William Feldman at the Mayo
Clinic, because it was the most highly virulent strain then
available. Feldman advised me to be very careful with it because
what I was doing was very dangerous. Waksman insisted that
I never bring any TB culture up to the third floor where he
was located. Feldman himself subsequently developed tuberculosis
which his doctor believed was caused by the same strain of
the tubercle bacillus he had sent me and with which he and
I had been working. This is why Frank Ryan wrote that "The
fears of Albert Schatz' colleagues, who had refused to work
with such a dangerous bacterium, were now amply justified"
(Ryan, 1992). Fortunately, Feldman's life was saved by
"combination
chemotherapy with PAS
(para-aminosalkylic acid) and streptomycin
... How
fitting that it arrived just in time to help save
the life of the wonderfully unassuming William Feldman"
(Ryan, 1992).
4. The
basement laboratory in which I worked was set up for
soil microbiology. It therefore had none of the safety features
of a modern TB laboratory, such as a special inoculation chamber
with ultraviolet light, and positive air pressure to circulate
the laboratory air through a filter. I did not even have a
special incubator for my TB cultures. In retrospect, I feel
good because no one who used that laboratory and no one who
worked elsewhere in that building developed tuberculosis.
But I developed a positive tuberculin reaction.
Waksman became interested in and involved himself in my research
only after I had isolated the two strains of S.griseus,
demonstrated that they both produced the same antibiotic,
established that streptomycin (which I named) was a new antibiotic,
identified S.griseus, and found that streptomycin
inhibited the growth of the tubercle bacillus in vitro.
Waksman then had others in his two third-floor laboratories
verify the results I had obtained up to that time, except
for the work I did with the tubercle bacillus. He was afraid
to have others work with that organism in his third-floor
laboratories, one of which was next to his office.
I also produced in that
basement laboratory the streptomycin
which Doris
Jones et al. used in the first in vivo
tests at Rutgers (Jones et al., 1944), and which Feldman used
for the first toxicity tests and the first animal experiment
with the tubercle bacillus at the Mayo Clinic. For large-scale
production, I used endless numbers of one liter Erlenmeyer
flasks containing 250 milliliters of broth. I also ran two
or three stills 24 hours a day until I had enough streptomycin
to satisfy Feldman's needs. During that time, I slept on a
wooden bench in the laboratory. I drew a horizontal line with
a red glassmarking pencil on the flasks from which I was distilling.
If I was asleep when the liquid boiled down to the red mark,
the night watchman woke me up and I added more liquid. This
was during World War II when rationing was in effect. I therefore
recycled organic solvents that I used in sufficiently large
volumes to justify recycling. I worked day and night to produce
that streptomycin because I wanted Feldman to do toxicity
and in vivo tests as soon as possible, and because
Waksman did not assign anyone to help me. But the night watchman
helped. I believe that S.griseus is the first actinomycete
used for large-scale industrial production. The stills in
the basement laboratory recalled a small still I ran, during
Prohibition, to convert grain to alcohol when I was a young
boy on a farm in Connecticut.
In 1963, William Feldman and his wife, Ruth, visited my wife
Vivian and me in Santiago, Chile, when they were on a group
tour of South America. I was at that time a professor at the
University of Chile. When we talked about the early days of
streptomycin, Feldman was surprised to learn that I had prepared
the first streptomycin he used at the Mayo Clinic. He said
Waksman never told him that.
I earned my Ph.D. degree in two-and-a-half years without having
a master's degree. Those two-and-a-half years do not include
the five months I worked on the production of fumaric acid,
actinomycin, clavacin and streptothricin, which had nothing
to do with my dissertation research on streptomycin. I drove
myself because I knew how serious tuberculosis and gram-negative
infections were, and how important it would be to find antibiotics
to control those diseases. What I was working for was, therefore,
much more meaningful to me than simply meeting the minimum
requirements for a Ph.D. degree.
However, I did have time to meet and go walking with a young
woman, Vivian Rosenfeld, who was an undergraduate student
in the Rutgers University College of Agriculture. Because
of my production schedule in preparing streptomycin for the
Mayo Clinic and because neither of us had much money we each
earned $10.00 a week - we frequently dated in the basement
laboratory. When Vivian knocked on one of the laboratory windows,
I went to the front door to let her in. Vivian may have subsequently
saved my life. In 1947, when Waksman recommended me as the
soil microbiologist for the nuclear bomb test in the Bikini
Atoll, Vivian insisted that I not go. (This was one of the
only two jobs Waksman ever recommended me for). The navy wanted
a soil microbiologist to study the microflora before and immediately
after the nuclear blast. Many servicemen and others who participated
in this and other nuclear bomb tests died of radiation-induced
illnesses.
Albert
Schatz producing streptomycin in 1943 in the basement
laboratory at Rutgers University. This batch of streptomycin
was used by William Feldman in the first guinea pig test
with Mycobacterium tuberculosis at the Mayo Clinic. |
This is the true factual account of how I discovered streptomycin.
I have already enumerated what I did, independently of Waksman,
before he became interested in and actively involved in my
work. In addition, I subsequently wrote and am the senior
author of the publications which report the discovery of streptomycin
(Schatz et al., 1944), its bacteriostatic and bactericidal
activity on the tubercle bacillus (Schatz and Waksman, 1944),
and strain variation of S.griseus (Schatz and Waksman,
1945). It is unprecedented for a graduate student to be the
senior author of three publications which report a discovery
of major importance. But Waksman knew that everybody in his
department was well aware of what I had done, and how hard
I had worked to do it. That's why he permitted me to be the
senior author on those three papers. Waksman, who was chairman
of my graduate committee, and the other two members (Robert
Starkey, Professor of Soil Microbiology, and Walter Russell,
Professor of Biochemistry and Dean of the Graduate School
at Rutgers University) all accepted my doctoral dissertation
as fulfilling the university requirement of original and creative
research for the Ph.D. degree. Finally, my name is on several
streptomycin patents in the United States and other countries.
"In the United States it is required that a patent
application be filed in the name of the inventor or inventors
... A patent in the United States is an important document
helping to establish the creativity of an individual just
as a technical publication is ... Technically in the United
States a patent which does not bear the name of an inventor
or which bears the name of a person other than the inventor(s)
is an invalid patent" (Luedemann, 1991).
On May 3, 1946, Waksman and I, at his insistence, both signed
the streptomycin patent assignment which stated that each
of us would receive $1.00. He did not tell me that he had
a previous agreement with the Rutgers Research and Endowment
Foundation. According to that agreement, which was contingent
on my signing the patent assignment, he would receive 20%
of the streptomycin royalties. When I learned, in 1949, that
Waksman was secretly receiving royalties, contrary to his
personal assurance to me that neither of us would do so, I
started a lawsuit. Pretrial depositions taken for that lawsuit
revealed that Waksman had, by that time, secretly received
$350,000 in royalties, although he had publicly denied receiving
any royalties. The Rutgers Research and Endowment Foundation
had received $2,600,000 in royalties. I had received no royalties.
The lawsuit also revealed that Waksman, during the entire
time I was doing research, had a secret agreement with a pharmaceutical
company which paid him $300 a month for consulting, and for
giving that company exclusive information about the research
going on in his laboratories, along with patent rights. When
that lawsuit was settled on December 29, 1950, I received
a small percentage of the royalties. In that settlement, defendant
Waksman acknowledged that "As alleged in the complaint
and agreed in the answer, the plaintiff' Albert Schatz "is
entitled to credit legally and scientifically as co-discoverer,
with Dr.Selman A.Waksman, of streptomycin" (Anonymous,
1950). If Waksman had denied I was a co-discoverer of streptomycin,
he would have invalidated all streptomycin patents and stopped
payment of all royalties.
Robert C. Clothier, President of Rutgers University and President
of the Rutgers Research and Endowment Foundation, issued a
press release on December 29, 1950, the day the lawsuit was
settled. In it, he said, "It has never been disputed
that Dr.Schatz was a codiscoverer of streptomycin. That has
been a matter of public record since 1945, when Dr. Waksman
and Dr.Schatz jointly applied for the streptomycin patent".
But Clothier neglected to mention me in his 1949-1950 annual
report to the Governor of New Jersey. That report is required
by the New Jersey State Legislature and the U.S. Congress,
which appropriates funds to Rutgers University. In that report,
dated September 1, 1950, Clothier informed the governor about
"the discovery of the antibiotic, streptomycin, by
Dr. Waksman".
Waksman disregarded what he had agreed to in the lawsuit,
when he accepted the Nobel Prize awarded specifically for
the discovery of streptomycin. He also disregarded the oath
which he and I had jointly signed as part of the patent application.
In that oath, Waksman swore that he "verily"
believed that he and I were "the original, first
and joint inventors" of streptomycin (Anonymous,
1948). Waksman also disregarded his February 9, 1945, affidavit,
which he submitted to the patent office, in which he referred
to "streptomycin, the new antibiotic that Schatz
and I have discovered" (Anonymous, 1948). He also
disregarded the February 9, 1945 affidavit of Elizabeth Bugie,
a fellow graduate student who confirmed some of my original
findings. In her affidavit, also submitted to the patent office,
Bugie wrote, "As an assistant to Dr. Waksman, I first
learned from him about streptomycin, which he and Dr.Schatz
had discovered" (Anonymous, 1948). However, by 1949,
when I asked Waksman what was being done with the royalties,
he had already received fame and a substantial amount of those
royalties. "By that time he had convinced himself
that Schatz's contribution to the discovery of streptomycin
was 'only a small one'" (Wainwright, 1988).
"All's
Well That Ends Well"
Although this is the 50th anniversary of the discovery of
streptomycin, it is only within the past few years that the
true story of that discovery has become widely known.
One way to evaluate the importance of my contribution is to
separate the actual discovery of streptomycin from the developmental
work that was subsequently done to produce it for wide-spread
use. In this respect, Luedemann wrote: "The important
thing is to get the culture to start with ... If you don't
have anything to work with ... you're not going to get very
far ... Without the organism, you don't have the antibiotic
(Carlos C. Carpenter) ... Discoveries are made by individuals,
and it rarely can be any other way ... After all, how many
collaborators can dance on the point of a discovery?"
(Luedemann, 1991).
My contribution can also be evaluated in another way. "As
of the end of 1978, we estimate the amounts of royalties received
by Rutgers at 12 million dollars for streptomycin ... In 1954,
the Institute of Microbiology of Rutgers University opened
its doors. This institute had been made possible by a grant
of 3.5 million dollars by the Rutgers Research and Endowment
Foundation to Rutgers University" (Lechevalier, 1980).
By 1954, all or almost all of the royalties came from streptomycin
patents. I reàeived considerably less. royalties than
Waksman did. (Originally I received none). It therefore follows
that I contributed more of the $3,500,000 streptomycin royalties
for the Institute than Waksman did.
This is the story of what I did and how and why I did it.
What Waksman did was have others confirm my original results
(except my in vitro work with the tubercle bacillus),
and continue the research I initiated on the production and
purification of streptomycin. He also began to trivialize
me and what I had done. Waksman explained why he did that
in a conversation with Doris Jones. In a pretrial deposition,
Doris recalled Waksman's comment. "Dr. Waksman told
me confidentially that the reason why he didn't let Al have
more credit for the discovery of streptomycin was that he
was so aggressive, and if he were allowed this credit, it
would go to his head and, therefore, Dr.Waksman was protecting
Al, since he was older and could assume credit for this discovery.
That was why he hadn't pushed Al's name" (Anonymous,
1950).
When I discovered streptomycin in 1943, I was a 23-year-old,
idealistic graduate student. Waksman, my department head,
was a business-oriented consultant to a pharmaceutical company.
But I did not know that until my lawsuit in 1950. When Waksman
realized that streptomycin was a major discovery with considerable
financial potentiality, he set himself up (on the third floor
of the Administration Building) as the fountainhead of information
about streptomycin. He kept me in the basement laboratory
and, after a while, no longer introduced me to or even told
me about reporters and others who interviewed him. I learned
about what was going on when I read magazine articles, newspaper
accounts and other reports. These were written by people who
got all their information from Waksman. They did not know,
because Waksman never told them, that I was in the basement
laboratory of the same building where and when they were interviewing
him. Waksman also participated in the large-scale development
of streptomycin for use world-wide; negotiated patent arrangements
with pharmaceutical companies, from which he profited handsomely;
and eventually took full credit for the discovery of streptomycin.
Others, however, have recognized and acknowledged my role
in the discovery of streptomycin. After penicillin was discovered
in 1929, it laid dormant for several years. But streptomycin,
which was discovered in 1943, was destined to receive immediate
attention. That would have occurred even without Waksman's
involvement in its industrial development. World War II, which
needed penicillin, also needed streptomycin.
Waksman created the myth that he, and he alone, had discovered
streptomycin, just as he created the myth of his sick chicken.
Until I read the articles in the Smithsonian and
in the Rutgers Magazine, I assumed that Wainwright
had laid the myth of that poor, sick chicken to rest (Wainwright,
1991), as he had done with the myth that Waksman wove around
himself (Wainwright, 1988, 1989, 1990, 1991). Wainwright concluded
that "Streptomycin was in fact discovered by one
of Waksman's research students, Albert Schatz" (Wainwright,
1989). And, "There can be no doubt that streptomycin
was actually discovered by Albert Schatz" (Wainwright,
1988). "Anyone who reads Schatz's thesis ... cannot
doubt that it was he who made streptomycin a reality"
(Wainwright, 1988). In his book, Miracle Cure: The Story
of Antibiotics, Wainwright wrote, "The history
of streptomycin ... in Chapter 8 ... is the first detailed
account of this story to be published, and in it I have once
again attempted to redress an historical imbalance, this time
in favor of Albert Schatz, one of its co-discoverers. In so
doing, I hope I have not been unfair to the memory of Selman
Waksman, the co-discoverer who received all the credit for
streptomycin" (Wainwright, 1990).
Frank Ryan also discussed my role in the discovery of streptomycin
in his recent book Tuberculosis: The Greatest Story Never
Told. Among other things, he wrote, "So, calmly
and methodically, Albert Schatz, barely twenty-three years
old, now performed an experiment that would ultimately prove
one of the most important in the history of medicine. He tested
streptomycin against tuberculosis" (Ryan, 1992).
Both Milton Wainwright and Frank Ryan visited me in Philadelphia,
independently of one another, to interview me at length, for
four days, for the books they were writing.
Peter Tompkins and Christopher Bird pointed out that "Albert
Schatz, Ph.D., discovered the wonder drug streptomycin",
in their book Secrets of the Soil (Tompkins and Bird,
1989). In 1991, George Luedemann commented on "the
discovery of streptomycin by Albert Schatz" and
then went on to say: "This antibiotic was useful
against tuberculosis and was significantly less toxic than
the antibiotics that had previously been found ... Thus the
golden age of antibiotics was born - an age of miracles and
magic bullets - substances produced without seeming reason
by esoteric microbes which had previously been studied mostly
because of the diseases they caused in plants, animals and
men. It seemed as if yesterday's villainous microbes had suddenly
become today's heroes".
Epilogue
On April 15, 1993, the Theobald Smith Society, which is the
New Jersey Branch of the American Society for Microbiology,
acknowledged my role in the discovery of streptomycin. I received
the Selman A.Waksman Honorary Lectureship Award Medal. The
title of my lecture was Looking Back on Fifty Years of
Research. This lecture was historically connected with
a paper I presented at a meeting of the Theobald Smith Society
fifty years ago. As a graduate student, I had been invited
to speak on streptomycin as a new antibiotic and its potential
in treating tuberculosis. That was the first report about
streptomycin presented to a scientific society. It was also
the first time I spoke at a scientific meeting. So great was
the curtain of silence that Waksman wove around my role in
the discovery of streptomycin that only recently have I been
again invited to tell my story in the United States.
This is the second article I have written in the 50 years
that have elapsed since the discovery of streptomycin in 1943.
I am grateful to the editor of Actinomycetes for publishing
this account of my role in that discovery.
I have been asked on several occasions why my first article,
Some Personal Reflections on the Discovery of Streptomycin,
was published in the Pakistan Dental Review, in 1965 (Scatz,
1965). That article was an address'I delivered on November
5, 1964, at a ceremony in the Thorax Hospital, Santiago, Chile,
when I was honored for the discovery of streptomycin. I had
previously, over a period of several years, submitted that
article to editors of many U.S. journals, who either rejected
it or never acknowledged receiving it. By 1965, I had done
considerable research on dental caries, and was an associate
editor of the Pakistan Dental Review. That is why
my first article was published in that journal.
REFERENCES
Anonymous (1948). U.S. Patent Office File Wrapper and Contents.
Improvement in Streptomycin and Processes of Preparation.
No. 2,449,866. Granted Sept. 21, 1948, to S.A. Waksman and
A.Schatz.
Anonymous (1950). Civil Action Judgment. Albert Schatz, Plaintiff,
versus Selman A Waksman and Rutgers Research and Endowment
Foundation, a corporation of New Jersey. Superior Court of
New Jersey, Chancery Division, Middlesex County. Docket No.
C-1261-49. December 29
Beadle, G.W. (1992). Biochemical genetics: some recollections
In: J.Cairns, G.S.Stent & J.D.Watson (eds.) Phage and
the Origins of Molepular Biology. Cold Spring Harbor Laboratory
Press. New York, pp. 23-32
Chowder, K. (1992). How TB survived its own death to confront
us again. Smithsonian, 23: 180-194
Jones, D. (1945). The Effect of Microorganisms and Antibiotic
Substances on Viruses. Master's Degree Dissertation. Rutgers
University
Jones, D., H.J.Metzger, A.Schatz & S.A.Waksman (1944).
Control of gram-negatives in experimental animals by streptomycin.
Science, 100:103-105
Lechevalier, II. (1980). The search for antibiotics at Rutgers
University. In: J.Parascandola (ed.) History of Antibiotics,
A Symposium. American Institute of the History of Pharmacy.
Madison
Lechevalier, H.A. (1991). Preface. In: G.Luede mann Free Spirit
of Inquiry. The Uncommon Common Man in Research and Discovery.
The Gentamicin Story. Actinomycetes, 2 (Suppl.1):
Lipman, J.G. (1921). Bacteria in Relation to Country Life.
Macmillan Co., New York
Luedemann, G. (1991). Free Spirit of Inquiry. The Uncommon
Common Man in Research and Discovery. The Gentamicin Story.Actinomycetes,
2 (Suppl.1)
Papacostas, G. & J.Gaté (1928). Les Associations
Microbiennes, Leur Applications Thérapeutiques. Doin,
Paris
Ryan, F. (1992). Tuberculosis: the Greatest Story Never Told.
Swift Publishers, Worcestershire
Schatz, A. (1945). Streptomycin, an Antibiotic Produced by
Actinomyces griseus. Ph.D. Dissertation. Rutgers University
Schatz, A. (1965). Antibiotics and dentistry. Part I: Some
personal reflections on the discovery of streptomycin. Pakistan
Dental Review, 15: 125-134
Schatz, A. & S.A.Waksman (1944). Effect of streptomycin
upon Mycobacterium tuberculosis and related organisms. Proc.
Soc. Exptl. Biol. & Med., 57:244-248
Schatz, A. & SA.Waksman (1945). Strain variation and production
of antibiotic substances. IV. Variations among actinomycetes
with special reference to Actinomyces griseus. Proc. Nat.
Acad. Sci., 31: 129-137
Schatz, A., E.Bugie & S.A.Waksman (1944). Streptomycin,
a substance exhibiting antibiotic activity against gram-positive
and gram-negative bacteria. Proc.Soc.Exptl.Biol. & Med.,
55: 66-69
Smolen, M. (1992). A Nobel quest. Rutgers Magazine, 71: 43-45
Tompkins, P. & C.Bird (1989). Secrets of the Soil. Harper
& Row, New York. 1989.
Wainwright, M. (1988). Selman A.Waksman and the streptomycin
controversy. Soc.gen. Microbial.
Quarterly, 15: 90-92
Wainwright, M. (1989). Nobel infallibility. Nature, 342: 346
Wainwright, M. (1990). Miracle Cure: The Story of Antibiotics.
Basil Blackwell, Cambridge (USA)
Wainwright, M. (1991). Streptomycin: discovery and resultant
controversy. Hist.Phil.Life Sci., 13: 97-118
Waksman, S.A. (1932). Principles of Soil Microbiology. Williams
& Wilkins Co., Baltimore
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