The 'white plague' wrecked lives and shattered families yet it is

virtually unheard of in this country today. This is thanks to the first

totally effective cure for TB developed by a team of Edinburgh doctors

in 1954. Chris Holme speaks to the surviving members of the group and

finds many lessons still to be learned today

IT STARTED in Scotland 40 years ago and remains probably the greatest

single achievement of the NHS, but virtually nobody knows about it . .

.An Edinburgh team found and applied the first 100% cure for

tuberculosis, the deadliest infectious disease in world history. Their

results were initially met with disbelief but their triple chemotherapy

became the standard universal treatment, saving millions of lives.

If we are now ignorant about the disease, it is because they did such

a good job at wiping it out.The reality before 1954 was different. TB

invoked far more terror than cancer. It destroyed whole families, not

just individuals.

The White Plague gnawed away at spines, and once in the blood almost

invariably killed. For TB meningitis among children there was never any

hope.Most commonly it manifested itself slowly in the lung as

consumption. Natural defences usually contained it by sealing it off in

a wax-like substance, impenetrable to any treatment and likely to remain

dormant for years before re-emerging to kill. Half of those diagnosed

would die.

Mankind had suffered the horrors of this infectious bacterium for at

least 4000 years. Numerous ''cures'' emerged and died off along with

those treated. The best regime of containment was devised by Sir Robert

Philip in Edinburgh -- fresh air, isolation of sufferers to sanitoria

and assiduous efforts to trace contacts in the community. But it was

nothing that approached a cure and when the sanitoria emptied in 1939

the bacillus was released for everyone to share.

By the end of the war five million people a year were dying from TB.

Antibiotic treatments were almost unknown, except in the USA where

efforts had been made to develop them from microbes in the soil. Albert

Schatz finally found streptomycin in October 1943 in cultures taken from

a sick chicken's throat and well-manured earth.

PAS, a derivative of aspirin discovered in Sweden by Jorgen Lehmann,

became available in 1948. The third drug, izoniazid which arrived in

1952, was largely the product of research at Bayer's Elberfeld

laboratories by Gerhard Domagk, who worked on with his colleagues

despite the daily terrors of Allied bombing.

Domagk had won a Nobel Prize for his pre-war work on sulphonamides,

the antibiotic drugs originally developed from a chemical dye. Hitler

banned him from receiving the award.

Every new drug was eagerly seized on by a desperate public, but in

each case the initial optimism died down as the bug grew resistant. This

led to a more sinister development: for years TB resistant to one or

more of the drugs was being transmitted in the population for new

sufferers to contract. The drugs were available, but no-one knew how to

use them properly, particularly for a disease notorious for its

relapses. Actress Vivien Leigh died from pulmonary tuberculosis in 1967,

ostensibly having been cured years earlier.

In Scotland there was another frightening dimension. It was the only

European country apart from Portugal where TB was rising after the war,

largely among young females. By 1953, Scottish women aged between 15 and

24 were twice as likely to die from consumption than their English

counterparts.

Although deaths from the disease were falling, new notifications were

peaking at 1000 a year in Edinburgh by 1954. There were 600 TB beds but

at least another 400 patients facing long waits for admission.

That year a team of young consultants -- Norman Horne, Ian Ross, Ian

Grant and Jimmy Williamson -- was put in charge of all services,

co-ordinating for the first time out-patient and hospital treatment.The

team was led by a diminutive but charismatic Irishman, John Crofton.

At the time, treatment was poor, organisation was appalling and the

medical hierarchy was reactionary, even by its own traditions. Viewed in

its best light this was a noble attitude of physicians protecting their

patients against false hopes. At its worst, it was gross incompetence

fuelled by ignorance, greed for treating private patients and even

calculated sadism. TB-infected women seemed to assume a ghostly beauty

with flushed cheeks, and one prominent Edinburgh consultant delighted in

going round the wards telling them ''You are all rosy apples, rotten at

the core.''

Crofton and Grant had been junior colleagues at the foremost English

chest hospital, the Brompton in London. Crofton supervised the first

Medical Research Council trials of streptomycin while one of Grant's

tasks for his consultant was to stand out in the Fulham Road for a black

market delivery of the drug for his boss's private patients. Little good

it would do many of them.

Grant then moved to the City Hospital in Edinburgh, where the serious

and hopeless cases were sent. ''The TB problem in Edinburgh was

absolutely shocking. There was an Irish family of about six in the

hospital. The daughters were strikingly attractive but they were all

wiped out within three years,'' he said.

Surgical treatment -- artificial pneumothorax whereby the lung was

collapsed, or thoracoplasty where ribs were removed to gain access to

the chest -- was fraught with danger and frequently ineffective.

Williamson recalls: ''It was a pretty trying business. Very often at

that time some patients got better in spite of, rather than as a result

of what you did.

''It was very distressing because before effective chemotherapy, you

would see these very healthy young women, then x-ray them and find their

lungs in a mess and you knew a high proportion of them were going to

die.''

As a junior doctor at Hairmyres Hospital in Lanarkshire, he treated

George Orwell, who obtained supplies of streptomycin from New York

through his publisher, David Astor. ''I didn't actually realise he was a

celebrity,'' Williamson recalls. ''He was just an ordinary patient, a

tall thin chap who seemed to spend all his time at the typewriter,

working on what was to be 1984.''

Orwell developed a huge allergic reaction to the drug and died two

years later in 1950. As with Robert Louis Stevenson, Walter Scott, Emily

Bronte, John Keats and an endless list of writers, his TB fashioned his

work. Its deadline was short and literal.

Faced by all this frustration and failure, the Edinburgh team set

about its work.The basic theory they developed was simple. Intuition and

past experience told them single drugs were no use individually and

indeed positively harmful. Combinations of two were better but still had

failures. It seemed a good idea to hit the bacillus with all three drugs

at the same time: kill it, kill it again and then kill it when it was

dead just to be sure. If it was resistant to one drug, the other two

would still get it.

Applying the theory in practice was infinitely more complex. The key

to its success was the meticulous monitoring of treatment by two

bacteriologists, Archie Wallace and Sheila Stewart.

Every Tuesday night after work the whole team would meet to discuss

the progress of each patient. Soon they established that all failures

were due to bad treatment or not sticking rigorously to the dose for the

required period, usually 18 months.

The painstaking laboratory work by Wallace and Stewart also revealed a

crucial flaw in the standard MRC test used for detecting streptomycin

resistance. It was not sensitive enough and was later replaced by the

Edinburgh model.

''But for John Crofton, none of this would have happened. We were just

lucky to be in his unit,'' Stewart said. ''We worked very hard but it

never seemed like that because he was working harder. It was a very

exciting time.''

Crofton was the organisational genius, drawing out the talents of his

colleagues and diplomatically smoothing any ruffled feathers. Informal

monthly lunches were held with the Medical Officer of Health and

representatives from GPs and the x-ray service to co-ordinate strategy.

Equally vital was the support from nurses, health visitors, hospital

social workers and administrators. Patients were people and treatment

was no longer determined by money. Crofton set the tone: standing up to

welcome each new patient by name with a handshake. Once cured, they

still carried the social stigma of TB. He would write personal letters

on their behalf to get them jobs.

Unmistakeable evidence soon started emerging that the system worked.

Williamson and his colleagues were taken aback: ''We very rapidly

realised that what we were doing was revolutionary. We were pretty well

curing everybody that came our way and that had never happened before.

''We were also doing quite a lot of surgery, taking out a lobe which

had been badly infected and not finding any tubercle bacilli in it. That

was a dramatic indication that things were going even better than we had

anticipated.''

Routine surgery was then abandoned as unnecessary, as were months of

bed rest. New patients were given the triple chemotherapy at the outset

and the cure rate was virtually 100%. The team also managed to recover

half of the serious cases presenting with acquired drug resistance.

The waiting list disappeared within a year and in the three years to

1957, the incidence of and mortality from TB was more than halved in

Edinburgh, a feat unmatched anywhere before or since.

The problem was that nobody believed them, particularly in America and

even, for some time, in nearby Glasgow. The team was accused of fiddling

the figures. An open invitation was made for any doctor to examine any

of the case records, but no-one took it up. As Norman Horne recalls:

''We were well aware that other physicians throughout the country were

loathe to believe it, understandably, because it was almost unbelievable

that it could be so successful.''

For the usually ebullient Crofton, these weren't the brightest days:

''We had to keep our courage up. Even the MRC didn't believe us.''

His riposte was ingenious. Two bacteriologists at the Pasteur

Institute in Paris, Noel Rist and Georges Canetti, did have faith in the

Edinburgh work. Together they arranged the first international

co-operative trial of any treatment -- ostensibly for failures in TB.

However, the Edinburgh method was used as the standard protocol for

the trials. Thus it was introduced via the back door to Europe's leading

hospitals where doctors could see it working on their patients. It

rapidly became the gold standard therapy and is still used today, albeit

with different drugs over a six-month period.

Back in Edinburgh in 1958, mass radiography was introduced to root out

the remaining TB in the tenements. It covered 80% of the population and

along with BCG vaccination is what most people remember about the TB

campaign.

But vaccination had its limitations and there was no point screening

for new cases if there was no effective treatment. The new cure itself,

in fact, proved the best form of prevention. Destroying TB in individual

patients stopped new infection in others.

By 1960 the Edinburgh TB team had been so successful they had made

themselves redundant. They had dreamed about controlling the disease in

Edinburgh within 20 years. They actually managed it within six.

All seven of them either carried on with research or else switched to

other interests. Williamson carved a new and distinguished career in

geriatrics and Grant in asthma, establishing the self-referral clinic in

Edinburgh, later copied throughout Britain.

Crofton, knighted in 1977, helped set up ASH with his wife, Eileen,

and has has continued to campaign tirelessly against TB. He outlined a

blueprint in 1960 for the international control of the disease which

proved prophetic in its warnings of complacency.

Sporadic success in some countries has been outweighed by politicial

indifference, lack of resources and continued bad treatment.

This still rankles with Crofton and Horne, co-authors of a new and

much translated book distributed free to Third World health workers and

which may yet help turn the tide.

''The main lesson from our group 40 years ago is that if you employ

the drugs in proper combinations and if the patient co-operates, you can

get almost 100% success,'' said Horne.

''The problem is that people try and use short cuts and wrong

combinations and they wonder why they do not work. It is a matter of

great regret that people failed to learn that salient lesson.''

The Edinburgh treatment remains the cornerstone of the World Health

Organisation's strategy against TB. The bacillus found a new friend in

the HIV virus which in compromising immune defences has opened the

floodgates to new pandemics which now cover Africa and many parts of

Asia.

There are now, thanks to the increase in population, more TB cases in

the world than 40 years ago. It still kills three million people a year

and the World Bank has identified TB treatment as the single most

cost-effective health intervention available in the world.

In developed countries, New York provides a graphic example of the

perils of deviating from the Edinburgh protocol. Only now has it managed

to get a grip on an epidemic caused by poor public health controls.

Patients with HIV and TB were discharged from hospital and left to

take required drugs at home. They didn't complete the courses and

various resistant strains of the disease emerged with a vengeance.

There are much broader lessons from the Edinburgh team which the NHS

in the 1990s is still struggling to learn.

It was years ahead of its time in demonstrating the best of Scottish

medicine: rigorous self-audit, immediate application of research to

treatment, regarding patients as people and gearing the to their needs

through appointments times and evening clinics for those at work, and,

above all else, close teamwork for the common good.

It remains to be seen if such beneficial collaboration can be repeated

in the new NHS, deliberately disintegrated into competing sectors.

The lasting legacy in Britain is that the disease has been effectively

eradicated. TB notifications in Scotland fell last year and are largely

confined to the elderly who would have contracted it 60 or 70 years ago.

There can be complications from infections coming from overseas, but

cases arising in this country are invariably treated by first-line drug

therapy.

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