Sir John Crofton dies at 97; doctor pioneered combination therapy to treat tuberculosis

Sir John Crofton, a physician who is credited with saving millions of lives by pioneering the use of cocktails of antibiotics to treat tuberculosis -- a concept that has subsequently been applied to treating a variety of other diseases, particularly cancer and AIDS -- died Nov. 3 at his home in Edinburgh, Scotland. He was 97.

A specialist in diseases of the lungs, Crofton later turned his attention to battling smoking at home in Scotland and around the world, co-founding ASH-UK (Action on Smoking and Health) and ASH-Scotland. His inexpensive books on tuberculosis and smoking have become field manuals for battling lung diseases around the world.

When Crofton joined Royal Brompton Hospital in London in 1947, tuberculosis was a common and frequently fatal disease that was virtually untreatable. The only approach available was commitment to an isolated sanitarium, where the patients could rest, breathe fresh air and eat well. Surgery often was performed to remove severely diseased portions of the lungs.

Crofton was appointed to a team formed by Britain’s Medical Research Council to investigate the treatment of TB with a recently discovered antibiotic called streptomycin -- which was available in the United Kingdom in only limited quantities because of that country’s impoverishment after World War II. Treatment was urgent because there were more than 50,000 TB cases in the country.

The team compared the drug to the sanitarium treatment and found that it initially reduced deaths. After three to four months, however, the TB bacilli developed resistance to the drug and the disease resumed its normal course.

Crofton and his team then showed that the development of resistance could be delayed by combining streptomycin with another new antibiotic, para-aminosalicylic acid, commonly known as PAS.

After Crofton was appointed chairman of the department of respiratory diseases at the University of Edinburgh in 1951, he took the unprecedented step of adding a third new drug, isoniazid, to the mix, and that proved to be the key. His team developed a protocol in which all three drugs were administered initially. After several months, the patient stopped taking streptomycin to minimize loss of hearing, a common side effect of the drug.

When patients took the drug religiously, resistance did not develop and 100% of patients were cured in a few months. The team also showed that the treatment was just as effective when given on an out-patient basis as it was when used in the hospital, which proved to be a major benefit to the working class, who were thus able to maintain an income while under treatment. Within six years, Crofton and his colleagues were able to eliminate 90% of the hospital beds in Edinburgh devoted to TB.

At the annual meeting of the British Medical Assn. in 1958, he announced his first results with 63 patients who had taken the drugs for 18 months, but his report was met with widespread skepticism because of the difficulties other researchers had encountered in treating TB.

To prove the cocktail’s efficacy, Crofton helped organize a 23-country trial of triple therapy, which was one of the very first international collaborative trials for any disease.

The trial was a great success. Failures were found to be the result of physicians breaking the treatment protocol. The method was quickly adopted and is still the regimen of choice, although the identities of the drugs used has changed over the years as new antibiotics have been developed.

As chairman of the scientific committees of the International Union Against Tuberculosis and Lung Disease, Crofton also spearheaded the first international study of the prevalence of drug resistance, an international trial of the reliability of X-ray diagnosis for TB and another for sputum diagnosis, which proved to be the preferred method.

John Wenman Crofton was born March 27, 1912, in Dublin, the son of a general practitioner. His earliest memory, he recalled, was hearing bullets hitting the ceiling of his nursery during the Easter Rebellion of 1916. He was educated at Sidney Sussex College at Cambridge and St. Thomas’ Hospital in London, qualifying in medicine in 1936.

His further studies were interrupted in 1939 by the war, and he served as an army physician in theaters throughout Europe, the Middle East and North Africa, honing his surgical skills. A visit to the Auschwitz concentration camp near the end of the war marked “the only time in my life when I could not sleep at night,” he told friends.

In Egypt, Crofton ran a typhoid ward for 18 months under the command of Dr. John Guyett Scadding, an expert on respiratory diseases from Royal Brompton, forming a friendship that would later serve him admirably.

After the war, Scadding returned to the hospital and invited the unemployed Crofton to join him as an unpaid clinical assistant. Crofton soon was appointed to a senior teaching position.

After his Edinburgh studies on TB treatment, Crofton was elected to the Royal College of Physicians -- at 39 the youngest ever so honored.

A tireless advocate for TB research and treatment, Crofton traveled the globe teaching young doctors and lecturing on the benefits of drug-cocktail therapy. Later, those trips also promoted anti-smoking campaigns.

When New York City Mayor Michael Bloomberg decided to spend $200 million of his own money in developing countries, he consulted Crofton, who advised him to fight smoking, focusing on high-incidence countries and a major effort in the media -- suggestions that Bloomberg adopted.

Crofton was knighted in 1977, the year he formally retired from Edinburgh, but he kept working and traveling, spreading the gospel of respiratory health.

A skillful and dedicated climber, Crofton scaled mountains around the world. In 1933, he was credited with the first ascent of a difficult rock-climbing route on Garbh Choire of Beinn a’Bhuird in the Scottish Cairngorms, still known as the Cumming-Crofton route.

Crofton is survived by his wife of 64 years, Eileen; two sons; three daughters; 11 grandchildren; and two great-grandchildren.

thomas.maugh@latimes.com