GENERAL ARTICLES

DISEASE KILLER FROM THE SOIL

Scientists don’t know yet exactly how much streptomycin will do —only that it takes over where the sulfas and penicillin leave off

George H. Waltz, Jr. January 15 1946
GENERAL ARTICLES

DISEASE KILLER FROM THE SOIL

Scientists don’t know yet exactly how much streptomycin will do —only that it takes over where the sulfas and penicillin leave off

George H. Waltz, Jr. January 15 1946

DISEASE KILLER FROM THE SOIL

Scientists don’t know yet exactly how much streptomycin will do —only that it takes over where the sulfas and penicillin leave off

George H. Waltz, Jr.

TO MOST of us the word "dirt" has always carried with it the thought of filth, germs and disease. For years, in medical history, the earth that people walked on was blamed for many of the world's sicknesses. Yet from scoopfuls of this same dirt common ordinary garden soil gathered from around a small laboratory building on a university campus has come a new and potent disease~killing drug, streptomycin.

Strepl~inytin takes over where sulfa drugs and penicillin fail. In early tests it shows promise of being nn t'fiect.ive trent inent agn Inst such diseases as influenznl meningitis, urinary tract infections, tulnreinin rabbit. fever>, dysentery and similar bacterial in lect ions of the intestines. Also, it may be of value in treat inent. of bubonic plague, cholera, whooping cough, undulant fever, typhoid fever, and last, but far from least., wrlmaps certain forms of tuberculosis a disease which takes the lives of more than ,~O() Canadians and 6O,O(K~ Americans every year. ,t zt rc~nt~~ni V~i Il Wfl~ t )~(~ r~MI1lt. (~1 a

The discovery of streptomycin was the result of a long, methodical search by soil microbiologists at the Agricultural Station maintained by Rutgers University, New Brunswick, N.J. Head of this group is 57-year-okl, Russian-born Dr. Sí‘1 man A. Waksman, who came to the United States in 1910, and, after graduating from Rutgers in 1915 and obtaining his Ph.D. at the University of California in 1918, concentrated his laboratory studies on the microbes of the soil.

Two parallel facts, plus logic, intrigued Dr. Waksman into following the soil trail: one, everything buried in the soil eventually is consumed by it; two, certain fungi and bacteria placed in the soil or in stagnant muddy water die after a few days, while they will live in sterile earth or pure water. His conclusion was that the soil must contain some microbes that are antagonistic to, or kill, other microbes. Dr. Waksman reasoned that some of these soil microbes might be valuable in combating disease germs. He decided to try and find them.

Dr. Waksman’s early work convinced him that there were distinct medical possibilities among the microorganisms that inhabited soil, compost, and mud from the bottoms of swamps and ponds. Penicillin came from a soil fungus. Dr. Waksman was convinced that other equally effective disease-controlling drugs were produced by the millions of microbes that thrive in soil.

It must have seemed like an endless job. Even the tiniest pinch of dirt teems with a microbe population of assorted fungi, bacteria, and crosses between fungi and bacteria called actinomycètes—a total close to 500 millions. How to find the microbe strain in soil that would be an effective disease killer? There was no other way but by trial and

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error—a matter of screening all the soil microbes by repeated laboratory ; tests.

As part of the bait in his microbe hunt, Dr. Waksman decided to use j the Cram-negative bacteria, so called j because in order to he viewed under a i microscope they must be dyed blue with a special stain devised by a Prof.

; U, J. Cram. Neither sulfa drugs nor penicillin have any great effect on this class of bacteria. In addition to the Cram - negative germs chosen, Dr. Waksman used the bacteria that causes tuberculosis. He had a good lead to follow here. It had long been known that certain fungi and bacteria will check the growth of certain tuberculosis bacteria, but no actual chemical or drug had yet been found to control ; them.

Briefly, Dr. Waksman’s laboratory hunt was u matter of tricking the desired soil microbe into revealing itself from among the others by tempting it with bacterial food that it liked. If the microbe liked the food it would thrive and grow, while the others in the soil would not.

1' irst, a tiny sample of soil or compost was placed in a saucerlike covered glass dish. This contained a thin layer of agar a gelatinelike substance in which microbes feel perfectly at home. They had everything for their comfort but outside food.

Once a test plate was ready, Dr.

¡ Waksman added living cells of a j disease bacteria to the soil sample as ' the only microbe food. If a soil microbe colony grew and became larger and

larger, while the disease bacteria disappeared, it was a sign that the enlarging microbe colony was destroying the bacteria that had been added. When that happened Dr. Waksman knew he had a taker for his bait. All that remained then was to remove the disease-devouring organisms from the test plate, grow more of them, extract the germ-killing chemical, or antibiotic, they excreted, concentrate it, purify it, and test it.

It was a time-consuming job. It meant testing thousands of soil samples with foods that ran the gamut of most of the diseases caused by the Cramnegative bacteria. Dr. Waksman and his assistants, particularly Albert Schatz, had many exciting moments when they thought success was near— only to have it fade into disappointment.

One of the first bacteria-killing chemicals (antibiotics) isolated showed, without a doubt, that it was an active destroyer of just about every known disease bacteria. The soil microbe was actinomyces antibioticus and the bacteria-killing liquid extracted from it was called actinomycin. At first it looked like the real thing, but tests showed that it was almost as fatal to animals as it was to bacteria.

Another Step Forward

Actinomycin, however, was a step in the right direction. The preparation of soil-sample test plates continued. About 10,000 tries later another promising bacteria killer was isolated from a soil sample. This time the microbe’s name was actinomyces lavendulae, called that because its colony showed up as a lavender spot. The chemical it excreted was called streptothricin. It, too, was a capable enemy of many disease germs,

but although it was not fatally toxic, like actinomycin, it had a delayed toxicity that made it a poor candidate for use as a drug.

One thing, however, showed up in both of these tests. Both promising organisms so far had been actinomycètes—the soil microbes that are crosses between fungi and bacteria. From then on Dr. Waksman concentrated most of his search on actinomycètes.

Over a period of about five years he isolated thousands of strains of actinomycètes. Finally, late in 1943, from a heavily manured soil a microbe known as actinomyces griseus reared its beautiful head. The antibiotic it produced was christened streptomycin. Even in its impure laboratory form it was only slightly toxic, and although it was not as potent as actinomycin as a germ killer it was much more effective than streptothricin.

The actual testing of the medical properties and possibilities of streptomycin, Dr. Waksman turned over to experts of the Merck Institute of Therapeutic Research, Rahway, N.J.; to doctors at the famous Mayo Clinic in Rochester, Minn., and to scientists in Canadian and American universities. First tests necessarily were made in glass bottles and on microscope plates. Later they were tried on laboratory animals.

One of the first animal experiments was on tularemia (rabbit fever). JJtp until the discovery of streptomycin there had been no positive treatment or control for rabbit fever, a disease that is rare in Canada but elsewhere strikes thousands of people, particularly people who handle wild rabbits, every year. At the Mayo Clinic 60 laboratory mice were inoculated with the disease. Of the 60 half then were

given daily doses of streptomycin. In 96 hours all 30 of the untreated mice liad died, while all of the treated mice lived!

Tests on tularemia in humans have proved just as effective. Although the mortality rate from rabbit fever is relatively low, the disease has a habit of lingering on. Before streptomycin, the average rabbit fever case lasted about four months. In one recent human test case, a patient who began receiving streptomycin on the eighth day of his illness was released from the hospital as cured on the seventeenth day!

Beat Chick Typhoid

Experiments with living chick embryos showed that streptomycin gives full protection against fowl typhoid, a close cousin to human typhoid. Twenty-one chick embryos were infected with the disease. Fifteen of them also were inoculated with periodic doses of streptomycin. All six of the untreated embryos were dead at the end of four days. All but one of the treated embryos were alive and thriving at the end of 12 days!

Infections of the urinary tract are particularly sensitive to the powers of streptomycin. This first was proved by Dr. P. H. Greey of the University of Toronto’s Banting Institute, working through the National Research Council and in collaboration with the staff of Christie Street Military Hospital in Toronto. His findings in use of the drug on paraplegics later were verified by the U. S. Army Medical Corps. Chronic urinary infections that previously had been resistant to any kind of treatment yielded to the new drug.

One of the great questions about streptomycin is the extent of its power to combat the bacilli that cause tuberculosis. A few months ago, again at the Mayo Clinic, a group of guinea pigs were inoculated with overdoses of human tuberculosis bacilli. As in all previous tests, half of the animals were given streptomycin daily, the other half were not treated. After 60 days laboratory examination showed that the untreated guinea pigs had all the symptoms of advanced tuberculosis.

There was no doubt about its activity | in their lungs, liver and spleen. The j streptomycin-treated animals, on the other hand, presented an entirely different picture—there were few signs of tuberculous lesions. In most cases no trace of the disease could be found.

Tests on tuberculous patients in hospitals are now in progress, but Dr. Waksman, cautious as all careful scientists are about a new discovery, warns: “It must be emphasized that

the information available is much too limited in scope at present for serious consideration of the effectiveness of streptomycin in treatment of tuberculosis. To date sufficient information has not been accumulated.”

Although at first it was believed that streptomycin might he slightly toxic to humans—causing headache, slight nausea, skin rash, pains in the joints, and sometimes vomiting, all of these reactions were traced to the impure, experimentally produced form of the streptomycin that was used. When pure crystalline streptomycin is used none of these aftereffects appears. Streptomycin is not absorbed nor destroyed in the intestines and, unlike penicillin, it is not affected by the acids in the stomach.

It’s Scarce Now

At the present time a production bottleneck is the main stumbling block in the way of further knowledge regarding the drug. The small output of the main streptomycin source—one experimental pilot plant operated by Merck & Co. has been able to do little more than meet the needs of individual researchers and a small fraction of the requirements of the U. S. Army and Navy. Military demands alone have been for an average of 55 billion units of streptomycin a month, while the current experimental production has seldom been more than 3}/¿ billions a month. The normal human dosage now being tried varies between one million and five million units a day per patient. Quantity production naturally will bring down the cost of the drug to within reach of the average patient, hut today—if you could walk in and

buy it—a dose of one million units would cost in the neighborhood of $50!

To help meet some of the demand, Merck & Co. has begun the construction of $3% millions worth of streptomycin “factories” in Elk ton, Va., and Rahway, N.J. Another pilot plant just started by the E. R, Squibb & Co. is the forerunner of another $3 millions production unit, and a dozen other pharmaceutical companies have similar operations in the planning stage.

Commercially, the microbe that produces streptomycin must be grown in wholesale quantities large vats replace the laboratory culture plates, and a nutrient broth of meat extract, glucose, peptone, salt, and water replaces the thin layers of agar medium. The problem is similar to that of the large-scale production of penicillin it is time consuming and the daily yield of tin; drug is small.

Finished Product

When the microbe cultures have reached their full maturity and activity

generally a matter of several days— the fluid containing streptomycin is filtered off, concentrated, purified and dried. The result is a fine white crystalline powder that is soluble in water. It can be administered as a pill or it can be injected into the veins as a liquid. In pill form it does not enter the blood.

Conservative estimates indicate that some streptomycin for civilian use will be available during the first six months of 1946. Until a good supply is available, and the drug can be tried on a large scale, it will be impossible to evaluate its over-all effectiveness and use. It took more than a year for doctors to scratch the full capabilities of penicillin; and streptomycin, in spite of its speedy laboratory development, will go through the same or longer clinical trial period. In comparing the two drugs it must be remembered that penicillin is particularly effective against the acute or “explosive” types of diseases and infections. Therefore its results were immediately recognized. Streptomycin, on the other hand, is aimed at the chronic ailments, illnesses that take long and extended treatment before they respond. There is also possibility that the two drugs may be used together to clear up complex infections which neither one could combat alone.

The potential usefulness of streptomycin by no means ends with human ailments. When mass production has reduced the cost it offers to farmers and I cattle raisers the possibility of controlling many of the infectious animal diseases that take a high dollar-andcents toll from poultry and livestock producers every year.

Bang’s disease, the animal equivalent of ondulant fever in humans, is an important example. Bang’s disease has cost cattlemen millions of dollars, and up until now there has been no cure or effective preventive measure. Thousands and thousands of cattle have had to be destroyed to stop the spread of the infection. Streptomycin, however, attacks the Brucelle abortus, which causes Bang’s disease, just as it attacks nearly all organisms that fall into (he Gram-negative class.

By the same token, the calf disease known as “white scours”; aertryke which affects pigeons, chickens, ducks, and turkeys; “keel” which plagues duck raisers; hog cholera; and the “white diarrhea” of young chicks are all caused by intestinal organisms that can be overpowered and controlled by streptomycin. The new drug may well prove as important to the farmer as to the doctor.

Flag From French Canada

Tonight I bought your very interesting magazine at Sillery Jet., and noticed on page 64 (Backstage at Ottawa) a version about the flag that has been placed in the window of our drugstore.

May I present my design, that you are talking about, for more criticism if possible. I take this opportunity to give you a general analysis of this presentation:

Red Color: English element, is

placed near the staff because we are under English domination.

Blue Color: French element, placed in diagonal way, to match with the red color.

White Cross: Union of all races in

Canada. This sign is the only pacific and international symbol, with the

neutral color, to represent and make the union of all races.

Maple Leaf: The national emblem

of Canada, recognized at the Society of Nations in Geneva after the war 1914-18.

With nine lobes: The typification of the nine provinces, if you prefer we have also the nine points. P. A. Rov, Quebec City.

Likes Band Cover

The picture of the “Town Band Practice on your Maclean’s Magazine Nov. 1 issue is really wonderful!!— (Mrs.) E. M. Padmore, Liverpool, N.S.

In Russia’s Defense

As is very often the case, Beverley Baxter in his London Letter of Nov. 1 takes a crack at Stalin and the Russians. I believe such journalists as he and Dorothy Thompson are doing much to wreck the making of world peace.

Baxter writes, “So Stalin, who signed a pact of alliance with Poland in 1941, canes up his ally in 1945.” Is this a fair statement of what Stalin has done in Poland.’ Let s get the facts. Russia fought with us in 1914-18, as an ally, until defeated by Germany, then after the armistice the so-called democracies carved slices from Russian territory to form the Baltic States and to enlarge Finland and Poland, and what Russia now takes back is the territory that was taken from her by force after the last war, and Beverley Baxter calls that carving up Poland. I would say that it is reclaiming what Poland with our help carved from Russia after the first world war. Even then Poland was not able to hold it but lost it to Germany and Russia took it back.

If we are going to have peace, we best look at Russian viewpoints and not overlook our own failings.— J. W. Hutchison, Sr., Spalding, Sask.

The Farmer Speaks

I have been reading about these strikes and labor troubles we have been experiencing in this country, and it has stirred me to wrath; as a farmer I would like to express my opinion from the farm viewpoint.

Labor? We have been hearing for 100 years of Labor’s rights, now let us hear of Labor’s obligations. Labor has gained social security to an extent greater than any other class, and at the public expense, so Labor must fulfill its function in the national economy; it must work. Labor has forfeited the right to absenteeism and strikes. Any man, either company official or union leader, who calls either lockout or strike or slowdown should be subject to a penalty of a penitentiary term at hard labor; the rank and file who follow such a leader should he deprived of their various forms of social security for definite periods of time in accordance with the seriousness of their actions. Again I say Labor cannot have its cake and eat it too. Labor has gained its rights — now it must perform its obligations. ; (

As time goes by and irresponsible strikes inconvenience and hamper the people of this country, and cost them money, many more will come to my way of thinking. The part is not greater than the whole, as our union leaders are due to find out, to their sorrow.—Another Hayseed, Glengarry, Ont. __

“Damage Unlimited”

Many farmers of western Canada were not surprised to read in the article published in a recent issue of Maclean’s, under the title “Ducks Unlimited,” that the duck population has been enormously increased in the last few years. We should know, because we are the ones that supply the feed, and I can assure you not willingly; our names are not on the list of donations to “Ducks Unlimited,” but thousands .should be. The damage in loss of grain in this district in the last two years particularly has been enormous every day for weeks while our grain has laid m the field in stooks and swath, and most of it is swathed now. The air has been black with thousands of ducks which settled on the grain in swarms at times so thick that it would look like a piece of plowing instead of grain.

In the last two years my wheat has suffered heavily. As I drove around the field with the combine, “picking up” the swath, I could see all the empty heads showing up, and. underneath, the ground was littered with grain thé ducks had knocked out.

The damage is assisted by the hunters who then wander indiscriminately through private property, tramping around on the grain and often piling up bunches of the swaths for “fox holes.”

In a Calgary paper there was an

account of a case where 10 men went into a field of swathed wheat and in a short time shot down 110 birds. As the paper said, the sky was black with ducks; you couldn’t miss.

The same paper in large front-page headlines referred to a meeting to be held by a farm organization to discuss the matter because of the large number of complaints made by farmers.

For years now the Provincial Government has paid out large sums through the school districts for the collection of crows’ and magpies’ eggs and feet, and also gopher*tails. At the same time gopher poison has been distributed. The loss and damage by these pests have been infinitesimal compared with that caused by the ducks the last two years.

It is not very comforting to a farmer to see his year’s harvest lying out through weeks of rain and snow (and there are hundreds of acres still out on Nov. 4), while “Ducks Unlimited,” with Government approval, spend thousands of dollars to increase the number of ducks for hunters’ amusement, to such an extent that they become the worst pest we have had to contend with. — H. R. A. Clark, Bowden, Alta.

For Canadian Culture

Canada, as a great nation, has but one rival — the United States. The fact is apparent, the reason simple. We have no culture that is truly Canadian. True, we have culture, but it is borrowed and lacks Canadianism. Why?

Culture is the reflection of a person’s thoughts and emotions. If any man’s feelings are strong enough, and they receive the necessary encouragement, culture is the inevitable result. Canadians, I am sure, have within them enough feeling to create a most interesting and completely different culture. Canadian history is colorful

and Canada’s contribution to international advancement in the past few years has been outstanding. Therefore a Canadian culture must result. However, it has been retarded by persons who are pessimistic toward anything new, particularly Canadian, in cultural lines. Let us who believe in Canada go forward and show the world that our country can produce a culture that can keep pace with our other outstanding features.

For a Canadian culture will increase our patriotism, and unite the many different people of our country and tend to make them finer and more contented Canadians.—Roger Wynn Koro, Edmonton, Alta.

“Union Shop”

In your Nov. 1 issue of Maclean’s appears the article: Is the Union Shop Democratic? Professors Cameron and Curtis answer by saying “NO.”

May I now ask these gentlemen that if, in their opinion, this is right, would they then claim it also to be undemocratic to have a medical union, such as the Medical Association? Here, too, no medical man can practice unless he joins the Association and charges the fees as set forth by the Association. Next we can go on to the manufacturers of farm implements, who have their union by agreements that each and every one shall put implements in the market at one and the same price, no doubt the largest company holding the club. One could go on and on. If today, Mr. Editor, Labor no longer operates under democratic rule, it is only because Management was no longer democratic, and it is for this reason that people today are leaving the old political Parties, as they have long ago forsaken democracy.

Now, Mr. Editor, let us see how democratic you are by either printing this letter or leaving it out. — J. A. Miner, Spruce Lake, Sask.