IT’S not a virus, but spreads like one. For several millennia, it has been a constant threat to humankind. It still kills hundreds of thousands of people every year across the globe. We know it as tuberculosis, but it used to be called consumption, because it appeared to consume its victims from the inside.
This is what the World Health Organisation (WHO) says of TB: “About one quarter of the world’s population is infected with tuberculosis (TB) bacteria. Only a small proportion of those infected will become sick with TB. People with weakened immune systems have a much greater risk of falling ill from TB. A person living with HIV is about 20 times more likely to develop active TB.”
The latest WHO fatality figures are as follows: “In 2018, an estimated 10 million people fell ill with TB worldwide – 5.7m men, 3.2m women and 1.1m children. There were cases in all countries and age groups. A total of 1.5 MILLION (my caps) people died from TB in 2018, including 251,000 people with HIV. Worldwide, TB is one of the top 10 causes of death and the leading cause from a single infectious agent (above HIV/AIDS).”
The WHO adds a simple line: “But TB is curable and preventable.”
It used to be like Covid-19. Feared and despised, yet with a pervasive penetration into all classes of society, though as always, the poor and deprived suffered the most.
By the dawn of the 19th century, TB had killed one seventh of all people who had ever lived. It had no cure and no vaccine, yet developments in the late 19th century, such as Robert Koch’s discovery of the infectious agent and his fellow German scientist Wilhelm Conrad Rontgen’s discovery of x-rays held out the chance of a cure. Koch told the world on March 24, 1882 of his discovery of the Microbacterium that causes the disease, and today is the 138th anniversary of that declaration – and it’s why March 24 each year is World Tuberculosis Day.
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The sanatorium movement greatly improved the treatment of TB, but people came to loath the idea of going into a sanatorium, many of which were located abroad as good weather and high altitude were seen by some physicians as necessary for treatment. A patient able to spend many months in a sanatorium had a chance to be cured, but not too many people could do that.
In July 1921, two French bacteriologists, Albert Calmette and Camille Guerin, carried out their first use of the vaccine named after them, bacille Calmette Guerin or BCG, on a human. It went on to become the vaccine of choice and remains so in many countries with a high incidence of TB. Still, there was no cure until Sir Alexander Fleming discovered penicillin and antibiotics such as streptomycin were developed, though in truth the incidence of TB in developed countries was declining in any case due to higher living standards and improve public hygiene.
Even in the early 1950s, TB was still seen as a killer disease – George Orwell (Eric Blair) died of complications arising from it on January 21, 1950. He was just one of tens of thousands who died of TB that year, in an era when it was seen as shameful to catch the disease because it was so associated with poverty.
Deliberately collapsing the affected lung was a standard treatment when, in the immediate post-war years, pulmonary TB, the most common killer version of the disease, killed 50% of sufferers within five years of contracting it. TB meningitis meant certain death.
At that point, Scotland intervened. Rather, I should say, Ireland and Scotland. And the result seemed like a miracle and may hold clues as to how we deal with Covid-19.
John Crofton was born in Dublin in 1912. He was of Anglo-Irish ancestry and his family were well off as his father was a physician and medical researcher who had practices both in Dublin and London.
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He attended Tonbridge public school in Kent before studying medicine at Cambridge University. While a student, he became a keen climber and made many trips to Scotland – where the Cumming-Crofton route on Mitre Ridge in the Cairngorms is named after him after his successful first exploration of the route.
During his war service in the Royal Army Medical Corps, Crofton served under Lieutenant Colonel Guy Scadding, who had been a young consultant in London in a teaching hospital and had a particular interest in respiratory diseases. While serving in Egypt, Crofton contracted typhoid but survived. Perhaps that near thing inspired his dedication to finding cures for infections diseases.
After demob, Crofton married his wife Eileen and went to work for Scadding and the Medical Research Council, specialising in TB and other respiratory diseases. He took part in the first controlled trial of streptomycin, before Edinburgh University offered him the post of professor of tuberculosis.
Across Europe, rates of vaccine and successful treatment of TB were on the increase, but not in Scotland. Working at Southfield Sanatorium in Liberton, Crofton was upset at the awful situation facing the people of Edinburgh as he took up his post in 1952.
He said in an interview many years later: “I inherited not only the 400 beds designated for tuberculosis at the hospital, but a waiting list of several hundred people.
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“It was a grim situation not helped by the fact that there was one set of doctors handling outpatient diagnosis and another set dealing with the patients. I thought this was a bad thing from the point of view of continuity of care. There was also a problem with doctors in the hospital being able to pass patients they considered incurable back to the outpatient doctors.
“In other words, they were able to get rid of their failures. I thought that if they had to keep their failures, they would make more of an effort not to have failures in the first place.”
Crofton instituted a regime where patients were under observation and monitored most of the time, he being aware that many patients were unable or unwilling to take their medicines at the correct times.
Having sorted out the professional care, Crofton went on the attack against the disease itself. He soon concluded that the epidemic in Edinburgh – there were 1000 new cases of TB in the city in 1954 – was due to the disease becoming resistant to the drugs that were being used to treat it.
The drugs such as streptomycin and PAS (para-aminosalicylic acid) worked well in the test tube but failed to cure the patients, and that was the cue for Crofton to begin experimentation. It’s fair to say some of his colleagues were not fully supportive of this Irish Englishman who had come north to sort things out, but Crofton was a leader of men and women and soon won them round.
A new drug, isoniazid, appeared on the scene and Crofton and other TB doctors worried about how it would work in relation to PAS and streptomycin. Even after extensive testing, they were worried the new drug could have an adverse of the medication they were prescribing – which, don’t forget, was failing many patients due to drug resistance.
Then Crofton had a lightbulb moment. What if all three drugs were used simultaneously?
In what would be a phenomenal scene in a movie, Crofton and his colleagues had a group of patients injected with the three drugs. He would later say that some of the patients were on the verge of death, but then something quite extraordinary happened.
Within days, and even hours in some cases, the patients began to respond, and at the end of the trial the cure rate was 100%.
Then those pesky human beings began to mess things up. Crofton explained: “We were curing nearly everyone we treated. For the first time, 100% cure was a reasonable goal; in the past it had only been 50%. New cases dropped by 59% in the three years from 1954.
“Treatment was effective, but it was still a challenge to get patients to take the drugs. Patients took all three drugs when they were terrified of the disease, but as soon as they showed improvement, they stopped. We did urine tests on patients whose sputum had been declared negative and who had been discharged home with instructions to continue chemotherapy. Of 100 sampled, 25 patients showed no trace of having taken the drugs. So we initiated a routine of regular urine testing and follow-up with patients who were not taking the drugs.”
The combination of the triple drug cocktail and rigorous testing became known as the Edinburgh Method. Bizarrely, other countries were sceptical about the method, until Crofton came up with the idea of a large international trial.
He takes up the story again: “We initiated a trial in some 23 countries, choosing influential centres where, if they got good results, other people would take up the treatment. Due to scepticism about our method, we called it ‘a study of the causes of disease in far advanced pulmonary tuberculosis’. We specified in the protocol that the cases could be moribund, very advanced and very bad, and that all the patients would have all three drugs.
“It worked out as we had hoped. While one or two moribund patients died a week or two after they came into the trial, all the other treatment failures were because the doctors had failed to adhere to the protocol. So at last, we had acceptance.”
Indeed he did. Watching people on the cusp of death returning to full health convinced even the most sceptical medics, and the Edinburgh Method was adopted around the world.
For the first time in human history, there was a cure for tuberculosis – and it was pioneered right here in Scotland by a combination of dedication and commitment, some out of the box thinking, and the courage to take a long term view of an epidemic and working to cure it over time.
As I have written before, I long for Scotland to be independent so that we can dedicate our resources not to harbouring weapons of mass destruction that can never be used, but to finding a cure, a panacea, for cancer and the other diseases that blight the world. Follow the example of Crofton and his Edinburgh Method colleagues, and we may even be first to find a cure for Covid-19.
John Crofton was knighted for his work. Having been Dean of Medicine and Vice-Principal, after retirement from the university he became a fierce campaigner against smoking and he also advised WHO on the growing problem of drug resistance. Tuberculosis became a real issue for many governments across the world because of drug resistance, and the United Nations now has an End TB strategy which Crofton’s work did much to influence. He died in Edinburgh, which honoured him with the Edinburgh Medal in 1995, in 2009, aged 95.
Typically, in a WHO bulletin interview printed in 2009, Crofton insisted that his fellow pioneers of the Edinburgh method should be acknowledged: “I worked very closely with both senior and junior colleagues, who made at least as much of a contribution as I did. In my old age I have been flattered to receive a good deal of credit for my work in tuberculosis, and I feel that I have had too much credit and some of my colleagues not enough.”
We could do with Sir John Crofton and his ilk in these dark days, but his story and Scotland’s medical history shows there is always hope even in the face of an awesome invisible enemy.
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