TB --and Hope

Never in the agelong history of tuberculosis had there been such excitement about a new treatment for the white scourge. The tabloid New York Post used most of its front page to proclaim in two-inch type: WONDER DRUG FIGHTS TB. The New York Times gave the story top of Page One. In Staten Island's Sea View Hospital, patients who had taken the drugs danced in the wards, to the delight of news photographers. At Tuba City, in the Western Navajo Reservation of Arizona, Indians powwowed solemnly about the progress toward recovery that a 17-year-old Navajo girl was making. Around the world, physicians and patients wondered what it would all add up to in the end.

They will have to wait quite a while for an answer.

Parallel Lines. A few years ago, researchers of Hoffmann-La Roche, Inc. in Nutley, N.J. began testing a series of chemicals that might be useful against TB, and wound up with a group similar to nicotinic acid (part of the vitamin-B complex). Without knowledge of this, chemists of E. R. Squibb & Sons were doing a parallel job. Both groups settled on the hydrazide of isonicotinic acid as the best.

This compound, which Hoffmann-La Roche called Rimifon (and Squibb called Nydrazid), killed tubercle bacilli in test tubes. Lots of things do that. It also seemed to cure tuberculosis in mice without killing the mice. That was promising. It did the same for a rhesus monkey. Rimifon seemed safe enough to be used on human patients. Last June, doctors at Sea View Hospital started giving it to volunteers from among the 1,500 patients.

To be eligible for the tests, the patients had to have advanced tuberculosis of both lungs, usually with a persistent cough producing a lot of sputum loaded with tubercle bacilli. Of the first 92 patients, 44 had fever. Many had lost weight until they were living skeletons, with no appetite and no ambition. All had reached the point where no other drug or treatment seemed to help them.

Eleven Eggs a Day. Rimifon and a related product called Marsilid produced results that were obvious to the eye. All 44 patients with fever had a temperature drop to normal within two weeks, most of them within one week, some in a single day. Patients who had picked apathetically at their food became ravenous; they called for third and fourth helpings of cereal, and many worked up from one egg at breakfast to five. One old man got his ration up to eleven.

Weight gains were amazing. All 92 patients in the series showed some gain; several gained up to 50 pounds in three months. At first, the doctors were worried that the added weight might show up as an unhealthy accumulation of water, but with minor exceptions this did not happen. Patients who had been bedridden for months felt so much stronger that they got up and wandered around the wards.

With the limited lab facilities of a city hospital, the doctors at Sea View were trying to evaluate the medical progress of their patients when Squibb & Sons gave their Nydrazid to doctors at New York Hospital. There, though patients with advanced TB were scarce, the lab facilities were enormous. Dr. Walsh McDermott began elaborate biochemical tests on Nydrazid and soon made an important discovery: although it is swallowed as a pill (smaller than an aspirin tablet), the substance soon appears in the spinal fluid in "beautiful concentration." This meant that it might be extremely useful for tuberculous meningitis. Other tests recommended Nydrazid for miliary tuberculosis (throughout the body).

The Patient Navajo. Another shipment of Nydrazid was sent to Tuba City, where Dr. Charles Clark found, among the unhappy Navajos, all too many cases of both meningeal and miliary tuberculosis. A 17-year-old girl (a miliary case), admitted with a fever of 103DEG and so weak that she could not walk alone, was fever free within a week and soon coughed no more sputum. Now she is up & around.

On New Year's Eve Dr. Elmer Sev-ringhaus of Hoffmann-La Roche dropped in to see Dr. McDermott of New York Hospital and tell him about Rimifon. It was soon clear that Rimifon was chemically the same as Nydrazid, and a week later Squibb and Hoffmann-La Roche got together to plan further testing of the drug and arrange a request to the Food & Drug Administration to have it released for general use by physicians. That release cannot be given until May or June; by then, both companies will be ready to market the drug in wholesale lots (it is easily made from coal tar). Probable price: about 75^ for a day's dosage.

Lesson of History. Before the FDA acts, it will want to know whether the new drugs, given over long periods, will prove too poisonous for the patient to tolerate. Doctors want to know much more. Will the germs learn to resist the new drugs and live with them, as they often do with streptomycin? If a patient's sputum is free of germs a month after treatment is started, will it still be clear a year later, or will he suffer a shattering relapse?

Even harder to answer is whether the new drugs halt the disease long enough for the body to repair long-standing damage, especially in the lungs. So far, even with X rays, the answer is only hesitant: the drugs seem to restore the patient so that he should be better able to stand drastic surgery. And in many cases, surgery will still be necessary. So will bed rest and sanatoria. It is far too soon to talk about tearing down the hospitals.

It will take six months for doctors to render a confident verdict on Rimifon, Marsilid and Nydrazid. Meanwhile, there is a sobering lesson in the history of anti-TB drugs: dozens have come and all but one "wonder drug" (streptomycin) have gone, but TB remains.

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