Medicine: The Healing Soil

When Rutgers University needed to save some money during the war winter of 1941-42, a budget official had a bright idea: Why not fire Selman Waksman, an obscure Ukrainian-born microbiologist who was getting $4,620 a year for “playing around with microbes in the soil?” That sort of fun & games, the moneyman pointed out, had never really paid off.

Fortunately for Rutgers — and for mankind — Dean William H. Martin of the College of Agriculture saved Dr. Waksman from the ax. Within two years Selman Waksman’s “playing around with microbes” had paid off with one of the biggest jackpots that has ever gushed from a scientist’s laboratory. Dr. Waksman (rhymes with boxman) had become the discoverer of streptomycin, which ranks next to penicillin among the antibiotics and is the first of these “wonder drugs” to show hopeful results in the treatment of tuberculosis.

Today, the department of microbiology is the brightest spot on the Rutgers campus at New Brunswick, N. J., and its chairman, Dr. Selman Waksman, is one of the world’s top microbiologists. He has won for his university not only fame but fortune. Streptomycin for a 60-day course of treatment costs $60 to $80. A dozen chemical companies are turning out the new wonder drug, and for every gram (1/28 of an ounce) sold, Rutgers gets 2¢. By last week, the university’s harvest of pennies had reached more than $2,000,000.

With this money (and more still to come), Rutgers and Waksman are planning to build an Institute of Microbiology. Quiet, modest Dr. Waksman will enjoy the new equipment and the more spacious laboratories. For himself he asks little. By taking advantage of the unusually liberal Rutgers policy in such financial matters, he might have claimed all the proceeds of his discovery and become a millionaire. But he turned over his royalty rights to the Rutgers Research and Endowment Foundation with the mild observation: “Rutgers won’t let me starve.”*

Breakthrough. The exciting science of microbiology is one of the fastest advancing fronts of modern medicine. Ever since Louis Pasteur discovered that many of man’s most dreaded diseases are caused by microorganisms, scientists have searched for a drug that would kill the little villains without damaging the tissues of their human victims. A few chemical drugs were synthesized. Salvarsan, “606,” developed by Ehrlich, proved to be effective against syphilis. Much later, in 1935, came the sulfa drugs, the medical wonders of their day. But none of the chemical “magic bullets” was effective against more than a few disease organisms, and all of them were apt to have dangerous toxic effects on human tissues.

The discovery of penicillin (almost by accident) in 1928 was a conspicuous breakthrough. Britain’s Dr. Alexander Fleming noticed that the mold Penicillium notatum secretes a substance that kills certain bacteria growing on culture dishes. Later it was found that the secretion also kills many disease-producing organisms in the human body. It also does its job without any appreciable damage to human tissues. Fleming’s great discovery focused attention on the fact that some micro-organisms are powerful chemical weapons that can be used against other disease-causing microorganisms.

Bug Eat Bug. Every place that is favorable for the growth of micro-organisms (and most places are) is a churning battleground of small, fierce creatures. A pinch of moist soil weighing one gram, for instance, may contain more bacteria (up to 2 billion) than there are people on earth. Among the ordinary creatures prowl savage protozoa engulfing them one by one. There is an underworld, too, made up of submicroscopic viruses, hardly more than big molecules, which often invade the larger organisms and multiply explosively.

Across such a battleground run waves of defeat and triumph. Whole populations of thriving creatures suddenly disappear and are replaced by new ones. Small, humble organisms, which have been living a hunted existence, turn belligerent and dominate the field.

Some of the quick changes in such a “mixed culture” are due to external influences, e.g., changes of temperature or a new food supply. But often the disappearance of a certain microorganism is the result of intramural chemical warfare. It has been knocked out by some other organism, secreting a deadly compound.

Man is a part of this incessant struggle: most, if not all, of the little creatures that cause man’s diseases have enemies nearer their own size which can kill them off with chemical weapons. The warfare among the bugs* is called “antibiosis,” and the chemical weapons of war are “antibiotics.” Searchers for new antibiotics figuratively let bug eat bug; then the medical men take over the chemical weapons of the microscopic battlers and use them against the enemies of man.

What Is Life? Selman Abraham Waksman, famed U.S. expert at stirring up civil war among the bugs, was born in 1888 in the little Ukrainian village of Priluka, go miles from Kiev. His father Jacob spent most of his time making copper kitchenware in the nearby town of Vinnitsa, and young Selman was brought up almost entirely by his mother Fradia.

When his mother died in 1910, his strongest tie to the old country was cut. His father wanted him to go to Zurich to study industrial chemistry, but the boy had grown up in a fertile country and was fascinated each spring by the return of the generative cycle. Frequently he asked himself: What is life? How does it begin? How does it function?

Waksman first thought of studying medicine, but Russia was not the place for him to do that. With four friends from Priluka, he decided to try his luck in the U.S. The young Ukrainians landed at Philadelphia in November 1910, and Waksman went to stay with a cousin, Molki Kornblatt, and her husband Mendel, on their five-acre farm in Metuchen, N. J. He weeded the vegetable garden, fed the chickens and dug pestholes, while the Kornblatts’ children helped him improve his English. Kornblatt gave him some advice which proved decisive: go to see Dr. Jacob Lipman, another Russian immigrant, head of the New Jersey Agricultural Experiment Station at Rutgers.

Lipman argued that an agricultural school would be better for him than a medical school on microbiology. So in 1911 Waksman entered Rutgers’ College of Agriculture.

Long Road. By 1915, when he graduated, Selman Waksman already had one toe on the threshold of a great discovery: he had found in the soil a microbe which he has since named Streptomyces griseus.* He had no reason to suspect that it was a life-saving drug. A year later he wrote his master’s thesis on this and related microbes. He was on the road to streptomycin, but it would be almost 30 years before he reached the end of the road.

Meanwhile, Selman married Deborah Mitnick, a girl from the old country who had come to join her brother in the U.S. Back at Rutgers in 1918 as a lecturer in soil microbiology, after getting his Ph.D. at the University of California, Waksman worked mostly on the soil problems of farmers. But he began asking himself a question which is still far from answered: What do microbes do to the soil, to each other, and ultimately to man?

Dust to Dust. Long before Waksman began his work on soil, scientists had noted that if a diseased body is buried, the point of burial does not become a plague spot. Instead, something in the soil destroys the germs. It was proved that micro-organisms were doing the police job. But how, exactly, did one microorganism destroy another? By eating it? Beating it to the feed trough? Chemical warfare?

Says modest Dr. Waksman: “I get students from all over the world, and sometimes I learn more from the student than he learns from me.” Such a student came to Waksman in 1924 to work for his Ph.D.: a young (23) Frenchman named René Jules Dubos. Waksman turned Dubos loose on the activities of microbes in reducing plant fibers to humus.

Brilliant young Dubos went to work on a fantastic idea which, like many great ideas, was almost laughably simple: Why not feed disease germs to soil micro-organisms and see which species thrived on the diet?

Dubos took samples from patches of soil and noted which micro-organisms were present in them and how many of each kind. Then he made a brew of pneumonia bacteria and poured it on material from the patches. He repeated the experiment many times, watching for changes in the soil’s microscopic population. Some of the organisms thrived on the strange diet, indicating that they might destroy pneumonia bacteria. Dubos made cultures of the hardy fighters and tested them against various disease-causing organisms.

By this method and refinements of it, he at last found, in a sample of cranberry bog soil sent to him by Waksman, an organism from whose cultures he separated an active fraction that he named gramicidin. It killed or halted many disease bacteria, but it was dangerous for internal use.

In spite of such failings, gramicidin touched off a chain reaction. Dubos announced its discovery in 1939. A group of British researchers heard about it and recalled Alexander Fleming’s Penicillium notatum. The substance it secreted is penicillin. Ripples of excitement spread through the world’s biological laboratories.

New Direction. Waksman gives full credit to Dubos for inspiring him to change the direction of his work. The new direction was obvious: penicillin is mainly active against a particular group of bacteria. The next job was to find another substance which would be active against other bacteria—against the smaller rickettsias (which cause typhus) or the even smaller viruses which cause such diseases as polio and influenza.

Waksman and his research associates tested thousands of cultures. They could have found promising molds and other organisms in the air, in sewage or in garbage, but they went to the soil.

Time & again, Waksman and his assistants felt that success was in sight. Most of their antibiotics were poisonous. Only one of a series of six showed any promise of being useful in the human body. They tried the 1915 culture of Streptomyces griseus and it produced nothing.

Then a Jersey poultryman brought a sick chicken to the poultry pathologist at Rutgers for a diagnosis. Nothing, it seemed, could have had less to do with the search for antibiotics. But in a culture taken from the chicken’s gizzard a white spot appeared which looked like a colony of Waksman’s favorite microbes. Dr. Frederick Beaudette sent it to his colleague Waksman across the campus. The culture grew well, and in growing it produced a deadly germ-killer. Once again, hopes rose.

This time, hope was rewarded. Within two days, both the chicken culture and a similar culture from heavily manured soil produced the same antibiotic. Both organisms proved to be Streptomyces griseus. The two 1943 strains* were potent, while the 1915 strain had failed.

New Hope. Waksman called his seventh antibiotic streptomycin and rejoiced in a quiet way when it worked against many germs which resist penicillin. Though more toxic than penicillin, it was not too toxic to use. Streptomycin worked in the test tube against one of the most stubborn of all disease germs: the tubercle bacillus. But so did many another substance which was of no use in treating tuberculosis in humans. Waksman did not yet dare hope that he had found a cure.

Merck & Co. (which had financed fellowships in Waksman’s department and had exclusive rights to streptomycin) soon turned out enough of the new drug for extensive tests. Almost a year after its discovery, Waksman suggested that it might have some value in tuberculosis. Successful tests on guinea pigs followed quickly, and the first tests on humans clinched it. Streptomycin was what the doctors had been looking for: the first drug to work at all against tuberculosis, which still ranks seventh among the killing diseases; between ages 15 and 35 it ranks first. For perhaps 25% of the 500,000 U.S. victims, streptomycin offers new hope.

When streptomycin began to grow into a $40 million-a-year business, it was clear that both Rutgers and Merck could be embarrassed by the exclusive arrangement between them. But Merck, too, was liberal. The company gave up its exclusive contract, but Rutgers agreed to refund the first $500,000 of royalties toward Merck’s outlay in commercializing streptomycin. More than $400,000 has already been repaid.

Added Atoms. Streptomycin does not cure all cases of tuberculosis, nor is it foolproof. In some patients it has caused such undesirable reactions as dizziness, ringing in the ears and temporary deafness. As the drug has been purified (it is now about 99% pure), these side effects have been cut down. Also, it was found in 1946 that two hydrogen atoms added chemically to the complex molecule of streptomycin ‘ produced an equally effective but less toxic variant. Called dihydrostreptomycin, the variant is now produced in two to three times the volume of ordinary streptomycin.

Dr. Waksman’s great success did not change him visibly. He continued to work, as he does today, on the crowded third floor of an old, vine-covered building. His office, about the size of a hall bedroom, is cluttered with books and scientific papers. The laboratory next door, messy-looking like all biological laboratories, is also small and cramped; no one would guess that from its windows a great light had shone.

Dr. Waksman himself is more impressive than his setting. A smallish, somewhat stocky man with a faint Russian accent and a precise way of speaking, he has the great dignity that confident small men often have. When he speaks of the new institute that his discovery will pay for, his eyes light up. He sees the whopping financial success of his work only as a means to do future service.

At Home & Abroad. The intense activity which began in Waksman’s laboratories in 1939 was matched in other labs in the U.S. and abroad. Among the first to join the hunt and bag a valuable drug was Yale University’s Dr. Paul R. Burkholder, who found antibiotic-producing lichens on the cold slopes of Mt. Washington. Later, Burkholder switched to soils and, “to avoid stepping on Dr. Waksman’s toes,” decided to try foreign soils.

From a soil sample collected near Caracas, Venezuela, Burkholder isolated a Streptomyces which yielded a valuable antibiotic called chloramphenicol.* Almost simultaneously, Midwestern researchers isolated a seemingly identical microorganism with the same properties from soil found at Urbana, Ill. Says Waksman: “The remedies are in our own backyards.” Despite Waksman’s stay-at-home views (“And,” says Burkholder, “he could be right”), Yale is sending people all over the world on soil-collecting trips.

Chloramphenicol plugged a big gap in the antibiotic field: it proved particularly deadly against the rickettsias, untouched by either penicillin or streptomycin. It gives doctors a weapon against typhus, parrot fever, and a venereal disease, lymphogranuloma, which is commonest in the Southern U.S. It also relieves and drastically shortens the course of whooping cough. By this property alone, it will save many children’s lives.

Gold Dust. In American Cyanamid Co.’s Lederle Laboratories at Pearl River, N.Y. another Streptomyces was found to secrete a gold-colored, germ-killing substance. Dr. Benjamin M. Duggar, the discoverer, called this antibiotic aureomycin. First used on human patients at New York’s Harlem Hospital by Dr. Louis T. Wright, the “gold dust” worked wonders for victims of lymphogranuloma. Like Chloromycetin, it deals with many of the rickettsias. In treating brucellosis (undulant fever), aureomycin is likely to replace the streptomycin-sulfadiazine combination much used at present.

This year (TIME, April 4), Dr. Waksman announced that he and an assistant, Hubert Lechevalier, had isolated another antibiotic from a soil microbe which Waksman named Streptomyces fradiae in honor of his mother. The drug, neomycin, is as effective as streptomycin against tubercle bacilli in the test tube, and Waksman hopes that it can be combined with streptomycin in treating tuberculosis.

There is need for such a combination because streptomycin, more than any other of the antibiotics, tends to develop resistant strains of germs. Some strains learn to live with it, even becoming dependent on it—as if a rat began to fatten on rat poison. The resistant strains can be highly dangerous; if they infect another victim, he cannot be cured by streptomycin or anything else yet known.

The Fat Farmer. It is still too early to put neomycin among the widely useful antibiotics because of possible harmful side effects such as kidney damage. But it has already been used with success as a last desperate measure. Just before Labor Day, a fat but unhappy farmer was admitted to Pennsylvania Hospital in Philadelphia. He had a deep-seated infection caused by a common microbe, Aerobacter aerogenes, which is usually a pushover for penicillin or streptomycin.

But the farmer’s germs were a special strain. They had licked their weight in penicillin, and come back to knock out streptomycin, chloramphenicol and aureomycin. Unchecked, they were a sure bet to kill the farmer. Dr. Garfield G. Duncan pitted the tough germs in a test tube against neomycin. The drug murdered them.

Then Dr. Duncan tried Waksman’s supposedly dangerous drug on the patient. Within a few hours the infection was licked, and a few days later the fat farmer walked out, pain-free for the first time in years. Says Dr. Duncan: “There may not be many cases like this, but if we can save only one or two patients a year with a drug like neomycin, that drug has justified its existence.”

Select Club. Dr. Waksman lives in the same modest six-room house that he has lived in for 25 years. He manages to make clothes look shapeless and still wears high-laced black shoes. His only son, Byron Halsted Waksman (30, and an M.D.), is on the staff of Massachusetts General Hospital in Boston. Dr. Waksman and his wife often go to concerts in New York (Mrs. Waksman likes the more serious works; he likes “musical music”).

During his last trip to his native Russia in 1946, Waksman was treated royally by the Russians and made a member of the Academy of Sciences of the U.S.S.R. With this honor went a 15,000-ruble prize, but Waksman could not take the money out of Russia. So he bought a rather formidable painting of a north Russian landscape by Beruleia-Berulia, which now hangs in the living room. The firmly fixed price was 18,000 rubles, but the Russians agreed to knock off 3,000 rubles if allowed to keep the frame.

While Waksman waits to set up his institute with streptomycin money, the search for better antibiotics goes on. The requirements for a new antibiotic seeking membership in the select club are getting stiffer all the time. Explains Waksman: to qualify, a new drug must kill some kinds of germs more effectively than any drug now known; it must work well in the body and not damage the body; it should be stable and soluble in water.

The biggest class of germs against which no drug (antibiotic or otherwise) has been found effective: the viruses. Rutgers has just added a virologist, Dr. Vincent Groupe, to Waksman’s staff. Thus far, Groupe can report no progress, but neither can other virologists; the job may take years. But Waksman is sure that some day, somewhere, something will be found to ease the horror of poliomyelitis and the nuisance of the common cold. That something may well be an unknown microorganism fighting its battle in the soil.

*It won’t: his salary is now $10,000, and he may get a percentage of the gross take. *Microbiologists would prefer that laymen call each organism by its right name, but in the privacy of their own laboratories, they often call them all “bugs.” *From the Greek for “white twisted fungus.” *With nearly all microorganisms, a species is made up of many strains which may differ as much as a German shepherd differs from a Pekingese in the dog species. *Marketed by Parke, Davis & Co., which financed Burkholder’s work, under the trade name Chloromycetin (pronounced Chloromy-.ree-.tin).