John Crofton, 97, pioneer in the cure for tuberculosis

The Royal College of Physicians of Edinburgh announced his death.

Dr. Crofton started his research in the late 1940s, just as the first antibiotics were entering clinical practice, carrying with them the hope of conquering a disease for which helpless physicians had little to offer besides bed rest. The disease killed half the people who contracted it.

But the mutable tubercle bacillus proved an elusive target, becoming resistant to each successive drug tried. Increasingly, researchers came to believe that drugs alone would never cure tuberculosis.

Building on evidence that a two-drug combination reduced the development of resistant strains, Dr. Crofton started using three antibiotics at once to treat patients in Edinburgh during a tuberculosis crisis, reasoning that a multipronged attack would overcome the problems of resistance.

In 1958, at the annual meeting of the British Medical Association, he announced that his regimen had cured tuberculosis in the 63 patients who adhered to it for at least 18 months. But his triumph was met with skepticism until a multinational clinical trial confirmed his results.

Dr. Crofton’s multidrug approach remains the standard for treating tuberculosis and has provided the template for combination therapies to combat grave diseases like cancer and AIDS.

“He was a giant,’’ said Dr. Jacques Grosset, a professor at the Center for Tuberculosis Research at Johns Hopkins University in Baltimore who lost a portion of his lung to tuberculosis.

“John Crofton understood that using three drugs at the same time would increase their potency, something lab researchers like me did not understand. It was a big, big revelation.’’

John Wenman Crofton was born in Dublin, the son of a physician.

He earned bachelor of medicine and doctor of medicine degrees from Cambridge University and pursued further training at St. Thomas Hospital in London.

In 1939, during World War II, he entered the Royal Army Medical Corps and served in field hospitals in France, Germany, and the Middle East. On a posting to Egypt, he ran a typhoid ward for 18 months under the command of Dr. John Guyett Scadding, a British specialist on respiratory diseases.

The men became friends, a relationship that would soon shape Dr. Crofton’s career.

After the war, Scadding rejoined the staff of Brompton Hospital in London and invited Dr. Crofton, who was then unemployed, to work with him as an unpaid clinical assistant. Dr. Crofton was soon appointed to a registrarship, or senior training position, at Brompton.

In late 1946, at Scadding’s suggestion, Dr. Crofton joined a research team that was being formed by Britain’s Medical Research Council to test the effectiveness of a new antibiotic, streptomycin, against tuberculosis.

A Rutgers University scientist had isolated streptomycin from two soil fungi in 1943, and the antibiotic appeared to be effective against tuberculosis in guinea pigs and in some highly publicized cases of patients who had received the drug. But streptomycin was expensive, and only a limited quantity was available in impoverished postwar Britain for testing on patients. Dr. Crofton’s role was to coordinate the trials at Brompton Hospital.

The British study randomly assigned 107 patients to a control group that received only bed rest or to a treatment group that received daily injections of streptomycin in addition to bed rest. The drug reduced deaths from tuberculosis at first, but the victory was brief. After three to four months of treatment, tubercle bacilli became resistant to streptomycin, and the disease resumed its course.

The study, although a huge disappointment, spurred Dr. Crofton to continue working on tuberculosis treatment and gave him the clinical research skills to find an approach that worked.

In 1952, he was appointed chairman of the department of respiratory diseases and tuberculosis at the University of Edinburgh, amid a tuberculosis epidemic in Scotland. Three years earlier, researchers in Britain reported that combining streptomycin with a newer medicine, para-aminosalicylic acid, could reduce the development of drug resistance. To this mix, Dr. Crofton added isoniazid, a new drug that became available shortly after his arrival in Edinburgh.

The third drug was the charm. Through careful monitoring, he devised a regimen that called for starting patients on all three drugs and then stopping streptomycin, which can cause hearing loss, after several months. For more than a decade, until it was replaced by a cocktail of newer and more powerful drugs, Dr. Crofton’s three-drug regimen was the standard treatment for tuberculosis.

“The treatment principles he developed are the ones we are using today,’’ said Dr. Mario C. Raviglione, director of the World Health Organization’s Stop TB department. “They are the model for cancer and for HIV. His legacy is quite significant.’’

Dr. Crofton was knighted in 1977, the year he retired from the University of Edinburgh. In the mid-1990s, as an adviser to WHO, he helped write the organization’s tuberculosis treatment guidelines.

He leaves his wife, Eileen; three daughters, Pamela Feaux de la Croix of Germany and Alison Kilpatrick and Patricia Raemakers, both of Scotland; two sons, Dr. Richard Crofton of Scotland and Ian Crofton of England; 11 grandchildren; and two great-grandchildren.