On Streptomycin
By HARLEY WILLIAMS
FOR the past five years the American drug, streptomycin, which is an extract of a fungus, has been used mainly in treating tuberculosis. Its unquestioned, potency produces two opposite kinds of results—cures more striking than any achieved before, and other effects profoundly harmful. The use of strepto- mycin spread over the United States like wildfire, but in this country for years it was as scarce as dollars. Now the restrictions, due partly to financial stringency and partly to clinical prudence, are at an end. Streptomycin is freely on sale. Its real value raises a complicated series of problems which will have to be solved through experience.
The discoverer of this remarkable curative agent, Dr. Selman A. Waksman, a Russian-born bacteriologist, and now head of an experi- mental station in New Jersey, is an authority on those particular forms of bacteria and fungi that grow in the soil. He became interested in the problem of finding one of them which would prove antagonistic to the germs of tuberculosis, just as penicillin is to certain other organisms. By 1944 his experiments had succeeded. Placing solutions of streptomycin in different concentrations in test tubes with colonies of tuberculosis germs, he showed clearly that the stronger the solution, the more complete was the elimination of the germ, while very powerful solutions caused it. to die out entirely. The next encounters between germ and drug took place in guinea- pigs, and, after further promising results, streptomycin was administered to actual tuberculous patients. Most of the subsequent work was carried out at the Mayo Clinic, Minnesota, and a fascinat- ing story of growing confidence and American optimism spread over the next few years.
Meanwhile the mammoth pharmaceutical trade of the U.S.A. was planning to produce the drug industrially on a very large scale. If streptomycin were to turn out as good as the early reports, the demand for it would clearly be enormous. Naturally a drug which was so lauded aroused the hopes of thousands of consumptive patients all over the world. This has always been one of the sadder consequences of each new remedy, and, ever since Robert Koch Introduced tuberculin in 1890. such " wonder drugs " have appeared every few years. Never was there anything which promised results like streptomycin. Yet each month it was more and more realised that its peculiarities are as great as its curative power.
Trials upon patients suffering from lung tuberculosis confirmed that streptomycin surpasses any other drug. Its main effect is to destroy the germ, thus giving the body a chance to heal itself. More remarkable achievements are seen in tuberculous meningitis. This serious form of the disease (affecting the delicate coverings of the brain and spinal cord) had been practically always fatal. No known chemical substance seemed to be effective in that inaccessible membrane which clothes the central nervous system. But strepto- mycin got there. Survivals from tuberculous meningitis became frequent. Yet sometimes these recoveries were not quite complete. Although streptomycin might suppress the actual germs, it could not restore nerve cells once destroyed by the disease. Suflerers from tuberculous meningitis might indeed get back their health, but a few of them remained paralysed in various ways. A few more might get better for a time, but would then relapse if the drug were not given for long enough Yet the paradox was that other patients emerged from the grip of this supposedly hopeless malady completely restaed.
Gardeners are always seeking a weed-killer that will destroy the weed without hurting the flower. The same happens in human bacteriology. It is a common experience that a drug strong enough to kill germs is able to damage the human body as well. Strepto- mycin has a toxic effect, not so much on the body as a whole as on those nerve fibres connected with our sense of balance. Patients who suffer from this form of sensitivity are unable to walk in the dark. and may feel insecure when standing upright.
These are serious drawbacks in any drug, even one so beneficial as streptomycin. To some extent they may be prevented by giving smaller doses; but this may diminish the efficiency of the treatment. For a time it was thought that a later variant of the original formula, called di-hydro streptomycin, possessed the good, without the bad, points of its relative. But now this seems doubtful. Toxic effects remain the physician's bugbear, and the patient's risk. The big American pharmaceutical corporations are now geared to a gigantic output. One such plant in Indianapolis has a frontage half a mile long, where the mould is refined in enormous containers and becomes a golden-brown liquid, which is later dried. Until this year Britain was dependent solely on such American supplies pur- chased in dollars, and, with the object of preventing waste and accumulating proper evidence of the drug's value, our Ministry of Health decided to limit the use of streptomycin to certain hospitals only. Those were the days when we heard radio appeals begging for a few grams for some desperate patient who happened not to be in one of the official streptomycin centres.
No one cares to think of a drug which is potentially a life-saver restricted either on account of dollars or red-tape. Streptomycin is used so freely in North America that it was hard to feel that British doctors should not be entrusted with its use. Today, how- ever, British manufacturers are in production, and streptomycin may be purchased anywhere, free of restrictions, simply on a doctor's certificate. It is well that people should know something about its limitations as well as its advantages. For there is still every need for caution ; this is a " wonder drug " only on condition that it is properly used. Otherwise it may be disastrous. For, in addition to the direct poisonous effects above mentioned, it has one more property, the consequence of which we cannot foresee, and which may even render streptomycin unreliable for a long- term use. In a certain number of patients the drug actually loses its power to destroy germs after about six weeks ; or, to put it the other way round, the germs become " resistant " to the killing power of the drug.
This tolerance of a germ for a drug is not a new phenomenon. Drugs indeed generally produce immunity in the body To arsznic, for instance, the body develops in the course of time its own pro- tection, so that larger and larger does can be taken with safety. But the effect of streptomycin is paradoxical. In these patients who become "resistant " it not merely ceases to kill, but it goes over to the enemy. The "watchdog turns traitor. A drug which was given to destroy germs actually develops the ability to feed them. And if such " resistant " strains of the germ are passed to other people, the range of streptomycin's impotence will be extended as more and more potential patients develop a tyre of infection which is immune to its killing power. To minimise the undesirable features it is intended that streptomycin shall be used mainly in hospitals, where the daily injections necessary can he given with regularity, where the correct dosage can be measured, the poisonous effects forestalled by laboratory tests, and where the growth of " resistant " strains can be discovered in time. Streptomycin, given at the right moment, and combined with other well-established methods of treating tuberculosis, is a life- saving weapon. Given at the wrong time, it may not merely fail to do good, but it may deny that patient, and others in the future, its life-saving power in the crucial emergency.
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