SELMAN WAKSMAN (1888-1973)
Streptomycin and Antibiotic Progress
by King-Thom Chung, Department of Biology, The University of Memphis
Medicine has not always been as effective as it is now. Until recently, being a physician could be a hard challenge since there was limited knowledge and control over many diseases.
One major breakthrough in the world of medicine was the discovery of antibiotics. Penicillin was among the first to be discovered. It had many attributes and performed wonders on many diseases, but one thing it could not do was cure tuberculosis. Selman Waksman wanted to find the antibiotic that would do this very thing that penicillin would not. He made outstanding contributions to soil microbiology and to the development of antibiotics. His life would be devoted to this task.
Waksman was born in Prikilu, a small peasant village near Kiev, in 1888. His mother, Fradia, supported the family. Even though Czarist Russia was very much against Jewish boys earning a diploma, Waksman earned one from a gymnasium in Odessa. He was intrigued by living processes, how they functioned, and what basic chemical process these involved. He studied these propcesses for the rest of his life.
At the age of twenty-two, in 1910, Waksman emigrated to the United States to live with his cousins on a five-acre farm in Metuchen, New Jersey. Here he milked cows, fed chickens, weeded vegetable gardens, and learned the English language from the children. It may seem that this has little to do with studying to be a microbiologisat, but all of these things were necessary and he accepted them. "I loved the smell of the soil, the crops, the chicken, the cows. I wanted to know what life was. How did it begin? How did it function? What chemical reactions were there?"
A friend of Waksman, Jacob Lipman, who was head of the Rutgers College of Agriculture, encouraged Waksman to study microbiology, but Lipman wanted him to learn more about the subject in a school of agriculture rather than a school of medicine. Waksman took this advice and entered Rutgers. During his time here, he studied the effects of soil microbes on each other, on the fertility of the soil, and on the formation of humus. This led to the discovery of a microbes in the soil which he named Streptomyces griseus. At this time he did not realize the value this discovery would have. In 1915, he graduated from Rutgers, and went on to get a Ph.D. in biochemistry at the University of California at Berkeley. Afterwards he accepted a teaching and research post at his old school, Rutgers, earning $1500 a year. His school career may have reached completion, but his learning never stopped.
Once again, Waksman's main interest was in microbes in the soil. He knew that they lived in the soil together day after day and wondered in what ways they affected each other. Did they help or destroy each other? What were the relationships? As he began to explore this territory, he found a soil microorganism which produce antimicrobial compound he named gramicidin. Upon this discovery, his good friend Dr. René Dubos urged him to look for more microbes that could destroy disease-causing microorganisms.
With this encouragement from his friends, he turned from ordinary microbes to parasitic, disease-causing microbes. His first discovery in 1940 was the antibiotic actinomycin. He taught and did research on the group of microbes producing actinomycin and found a major drawback. The toxicity of the drug was great and prevented good use. It had to be laid aside, creating a terrible blow to Waksman, but he continued on. Little did he know more trials were yet to come. At one time he almost lost his job because the University needed to make budget cuts. His job was seen as "playing around with microbes in the soil", and the president almost fired him. But he owed the job to his friend Lipman intervening; Waksman got to keep his job doing exactly what he loved to do, searching for more improved ways to treat disease.
But this time Waksman directed his efforts towards a single goal. He began to search for antibiotics that would prove useful for patients with tuberculosis. His research began with one thousand different soil cultures. After testing, only one hundred showed any promise, and further elimination showed that only ten of these could be readily isolated. Taking these ten, Waksman began testing and eliminating the poorest, one by one.
The best sample was found in 1943 from a sick chicken. Some dirt in its throat and peculiar mold growing on it that was of the same species as Streptomyces griseus. (Remember this is the species he had found in his days as a student at Rutgers.) Waksman pitted the mold against the steely-coated tubercle bacilli, and it killed them. Coincidentally, the microbes was of the same species he had unearthed in his graduate days. The antibiotic produced from this microbe he found from the chicken he called streptomycin. It was toxic, like others, but not too dangerous for use. It was very effective against a wide variety of bacteria and also effective against tuberculosis. This is what Waksman hoped for.
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, and M. bovis (rare), which are closely related mold-like bacteria. They can produce gross lesions of a gelatinous nature on the lungs, organs, and tissues. When they attack the lungs, they cause people to cough up salty, warm blood. They are tired all the time with a feeling of misery, and often lose weight. Death eventually was the major escape from this misery, but it was a slow, painful process. The kidneys, spine, liver, lymph glands, and the eyes are also targets of infection. Until Waksman's time, the methods of treatment were limited to bed rest and surgery, but this would soon change.
On November 20, 1944, a young woman with advanced pulmonary tuberculosis who had undergone stringent surgery that did no good was given streptomycin. This was the first administration of the drug, and, it was by physicians at the Mayo Clinic in Rochester, Minnesota. The woman's life was saved.
With streptomycin, people no longer had to worry about sure death from tuberculosis and misery was reduced. The discoveryof streptomycin was literally a life-saver. Another instance revealing the power of the drug was in 1946. Waksman administered the drug to a world-renowned geophysicist while lecturing in the Soviet Union. He was a dying man not expected to live, but after taking the drug he survived and lived for decades. From that point on, death from all forms of "T.B." were usually escaped. The death from T.B. in the United States dropped from forty-two per one hundred thousand to less than ten per one hundred thousand.
Streptomycin can not take the full credit as being the sole benefactor, but it is recognized as the first major step towards the great defeat of tuberculosis. Because the tubercule bacilli developed resistance to the antibiotic, it had to be combined with the drug isoniazid. Isoniazid proved to be the safe and effective during an administration test by Dr. Selikoff and Dr. Robitzek. After trying the drug on themselves, not wanting to endanger anyone else, they found it safe and gave it to ninety-two people with very severe cases of advanced tuberculosis of the lungs. Within a few weeks, all the patients were greatly improved. Some improved even in a few days. Since tubercule bacilli became resistant to streptomycin, isoniazid was greatly appreciated.
Although streptomycin required additional support in T.B., the drug proved to be effective against plaque and some infections of the digestive tract, respiratory infections, and many skin disorders. These discoveries paved the way for Waksmans further support.
In 1952, Waksman received the Nobel Prize in medicine and physiology. After the award, great offers were made to him. Waksman could have made a fortune, but he would not accept the offers. He was not in work for money. Instead he gave all funds to Rutgers where he first started his education of microbiology. Streptomycin, of course, was the reason the money was coming in, so his reasoning was to invest it back into his area of scientific interest to make more advances. He suggested that Rutgers build an Institute of Microbiology, so the research could continue. His request was granted. Merck & Co. and several other drug manufacturers paid sizable royalties for the right to make streptomycin. Waksman turned most of the initial money over to Rutgers. But he was well rewarded. After the institute was build, money was divided between his graduate assistants and laboratory associates. He was able to set up a research foundation of his own.
The microbiologist can also learn from the final years of Waksman's life. Everything does not go smoothly in life. Waksman soon discovered this when he was sued by a laboratory assistant in court. The assistant claimed that he, the assistant, and not Waksman was the discoverer of streptomycin. Since Waksman had published numerous papers given lectures and directed all work in the laboratory, scientists were astonished at the effrontry of this lawsuit; to the scientists it had absolutely no merit. But Waksman discovered something every microbiologist needs to learn---weight in the laboratory and classroom do not mean weight in the courtroom! The case, amazingly, went in favor of the assistant---obviously a miscarriage of justice. But these do happen.
Waksman was seventy years old and decided to retire at this point. But he did not slow down . He wrote three large volumes on antibiotics and lectured widely in the United States. Microbial disease occupied his attention until he died. in 1973. When asked what motivated his research, he said that, at first it was curiosity, but later he was motivated by the thought of helping sick people get well. He was a man who delighted in life and all living processes, which he considered miraculous. He had a happy marriage and was greatly concerned about his wife and her health. It is ironic that in spite of his concerns and fears for her that she outlived him.
Selman Waksman was inspired by the life of Pasteur and once quoted him: "To him who devotes his life to science, nothing can give more happiness than increasing the number of discoveries; but the cup, of joy is full when the results of his studies immediately find practical applications. "
The simple statement reflects the life of Selman Waksman. His was a life devoted to research, discovery and breakthroughs which had a profound effect upon the medical world and human health. In spite of setbacks which would destroyed a lesser man, Waksman demonstrated a true microbiologist's love and faith until the end.
One of the authors had the chance to meet him during the late sixties. His warm and brilliant thoughts impressed him profoundly. Waksman was also an extreme hard worker. He worked day and night, during the travel or at home. He wrote more than thirty books. His devotion to science and also to his teachers was a profound impression of this great microbiologist.