Throughout history, tuberculosis has been the deadliest scourge of mankind; in Europe, it reached its greatest severity in the mid-nineteenth Century as a consequence of the dramatic socio-economic changes caused by the industrial revolution. By this time, it was the commonest cause of death in Britain. Thereafter, a slow decline occurred, presumably due to gradual improvements in nutrition and living conditions.
This slow improvement continued into the 20th Century, although with significant reversals during the First and Second World Wars. Following the Second World War, there was a rapid decline in incidence and mortality throughout Europe, except in Scotland and Portugal, where the situation continued to worsen. As far as I can ascertain, no one has ever satisfactorily explained this phenomenon.
For someone like myself, working in chest medicine, it was only too obvious that many lives were being lost and many families blighted by the ravages of this disease. Many of the victims were young persons, especially females who had their whole lives ahead of them. Tuberculosis cast a deep shadow across the land, not only because of its high mortality, but because of the serious stigma attached to it. Individuals and families were loath to talk about it or even admit to having had the disease. It was thus a harrowing experience to have to tell a young person that the diagnosis was tuberculosis. Even more painful was having to tell the parents of a child that their offspring had tuberculous meningitis, which was inevitably fatal, usually within a matter of days or weeks.
There were, of course, some treatments for pulmonary tuberculosis, the standard being bed rest and fresh air, which were expected to maximize the patient’s immune system and eventually lead to cure. This was effective in a proportion of cases. Then there was "collapse therapy" in which the diseased lung (or part thereof) was artificially "put to rest" and thus helped local healing forces. It is impossible to estimate how many cases were arrested by this type of treatment since no controlled trials were ever carried out. Collapse therapy was however very widely practiced in the first half of last Century. There seems little doubt that some apical cavities were closed by the procedure known as thoracoplasty in which a number of upper ribs were removed and the lung apex was freed by dissection so that the cavity was compressed from above as well as laterally. This was a rather mutilating operation, and often had to be done in two stages. The most popular collapse measure was artificial pneumothorax in which air was introduced into the pleural cavity and the lung thus allowed to shrink in size. Another reversible process was artificial pneumoperitoneum in which air was pumped into the peritoneal cavity thus pushing up the diaphragm. This was usually accompanied by crushing the phrenic nerve on the more affected side in order to paralyse the diaphragm on that side. Refills of air had to be given every week and each chest clinic had "refill sessions", often in the evenings or at week-ends. Thirty or 40 patients would attend each session. These procedures probably did benefit some patients, but when things went wrong, it could be very serious, e.g. if an artificial pneumothorax became infected it was a most unpleasant affair and patients could have prolonged effects, often ending in death from empyema.
Ever since Koch in 1882 demonstrated that tuberculosis was an infectious disease caused by Mycobacterium tuberculosis, there had been hope that eventually a drug would be found which would kill this infecting organism (or at least inhibit its growth). This hope was raised by Ehirlich’s discovery of Salvarsan as an effective treatment of syphilis, and although this drug often had serious side effects, it was the first "magic bullet" in the development of modern chemotherapy. In 1935, Domagk in Germany produced the first sulphonamides, which revolutionised the treatment of many common infectious diseases, including those due to the haemolytic streptococcus and later pneumococcal pneumonia (which often had a 50% mortality rate).
Then came Fleming’s discovery that a mould called Penicillium notatum could inhibit a wide range of organisms including staphylococci, streptococci as well as meningococci and gonococci. By 1940, penicillin was in commercial production, and the search was on for an antibiotic effective against TB. In 1944, Schatz showed that Streptomycin derived from a soil fungus called Actinomyces griseus could inhibit the growth of M tuberculosis in the laboratory.(1) Within a remarkably short time, workers in America (2) showed that Streptomycin could have beneficial clinical effects in human tuberculosis an in 1948 the MRC published the results of a double blind trial of Streptomycin patients with "acute progressive" pulmonary TB. Patients were randomly allocated to "bed rest only" or "bed rest plus Streptomycin", and it was demonstrated clearly that the course of the disease was favourably influenced by Streptomycin; some cases showed sputum conversion and reduction in size of X-ray lung shadows.
These results however were fairly modest and, most disappointingly, many organisms had become resistant to Streptomycin at three months. The conclusion was that Streptomycin had a bacteriostatic effect upon M. tuberculosis and could benefit some patients. A most important aspect of this trial was that it established for the first time the necessity to subject therapeutic interventions/measures to the strictest form of random controlled experiments. This work by Bradford Hill (and later Ian Sutherland) dramatically changed the nature of medical research; this crusade for more rigorous conduct of trials of therapeutic measures was taken up by the late Archie Cochrane, and has resulted in the setting up of the Worldwide Cochrane Collaboration.
My first acquaintance with Streptomycin was in 1948 when I was junior doctor at Hairmyres Hospital; one of the patients was George Orwell who had bilateral apical "chronic" tuberculosis with a cavity in the right lung. He was treated with bed rest, artificial pneumopertioneum and R.phrenic nerve crush. Modest improvement occurred. Then Mr. Bruce Dick (thoracic surgeon in charge) heard about Streptomycin and sought a supply for Orwell. It was impossible to purchase this drug in the UK at this time because it had to be paid for in dollars, but this difficulty was overcome by arranging for his publisher in New York to send a supply (this action was cleared with Aneurin Bevan the Health Minister).
Orwell was writing ‘Nineteen Eighty Four’ at this time and my memory of him is of constant typing in bed almost always with a hand rolled cigarette between his lips. He was given 1g of Streptomycin daily and appeared to be making some clinical response, but after a few weeks he developed a severe allergic reaction with dermatitis and stomatitis.(See footnote) He wrote an excellent description of this in his notebook,(4) he could not receive any more of this drug, but he readily agreed that we should offer the remainder to another patient (who did well).
After this rather alarming introduction to the chemotherapy of tuberculosis, I continued my training in chest medicine, and in April 1954 I joined the Edinburgh team as consultant and medical superintendent of the Royal Victoria Dispensary, which was then the central chest clinic for the City. This Dispensary was the direct descendent of the original one founded by Sir Robert Philip in 1887 only five years after the discovery of the infectious nature of TB. The Dispensary was the central part of Sir Robert’s scheme for the control of tuberculosis and provided diagnostic and treatment facilities, together with important preventive measures such as education (for example safe sputum disposal) and most important, contact tracing. These policies were soon adopted throughout the UK (and indeed Worldwide). Philip became the first Professor of Tuberculosis and still occupied that Chair at the time of his death in 1938.
Long before his death, however, damaging schisms had occurred in what had originally been a closely integrated service providing preventive and outpatient services as well as in-patient care; in 1914, the local authority began to take over the functions of the service built up by Sir Robert and in due course a City TB Officer was appointed. This must have been upsetting for Philip, who was accustomed to having his own way. The result was that out-patient services were run by one team of doctors and in-patients were under the care of other teams, and what had been a closely co-ordinated service became seriously divided.
Charles Cameron was Philip’s successor in the Chair after the Second World War, and he and Dr. Elder (my predecessor as medical superintendent of the Dispensary) eventually produced a report which contained the following ridiculous statement:
"The man (sic) responsible for the detection of tuberculosis and all its problems can find little time for the treatment of the individual patient which is becoming more and more specialised. If he does one properly he has no time for the other."
This remarkable arrangement meant that a patient would be supervised by dispensary doctors but if admitted to hospital would be managed by another team and, when discharged, would revert to the care of the Dispensary team. Dr. Elder retired at the end of 1953 and I replaced him in the following April. I was the last of the five consultants to be appointed, the others being Ian Grant, Norman Horne and the late Ian Ross. Our dynamic leader was John Crofton, who had succeeded Cameron in the Chair in 1952. We had remarkable support from Dr. Archie Wallace, who was our bacteriologist and provided an extraordinary service, which I must confess I took largely for granted. In retrospect, I realise that we could never have achieved what we did without his unstinting efforts in the laboratory.
Our immediate challenge was the waiting list for hospital admission, which numbered about 400. Under the previous regimen when a vacancy occurred, Dr. Elder was notified and he would decide which patient was to be admitted. Our first action was to divide the City into five sectors and each of these was served by teams headed by one of the consultants; we all had our own beds in various hospitals, and we all had our own waiting lists on which patients were classified according to clinical urgency based upon severity of disease, potential for spreading disease (sputum smear positive, culture positive, culture negative) and "social" priority (presence of children in house, poor housing/overcrowding, etc.). Hence, when a consultant had an empty bed, he would readily know which patient should be admitted.
Meanwhile, chemotherapy of tuberculosis was advancing rapidly. First came Para-amino Salicylic Acid (PAS), which was pioneered in Sweden by Lehman.(5) This drug possesses modest bacteriostatic properties, but had to be taken in rather large quantities of 5g. four times daily and was unpopular with patients. It was very widely used, often rather indiscriminately, and it was soon found that drug resistance was very common. Great excitement was generated when it was found that new cases treated with combined Streptomycin and PAS did not develop resistance. Of course, if a patient had already received single drug treatment, change to combined therapy would not necessarily prevent resistance.
Then Domagk (of sulphonamide fame) produced another therapeutic triumph in the shape of Isoniazid, which was soon shown by American doctors to have a dramatic and rapid effect in pulmonary TB X-Ray appearances improved, cavities closed, sputum became negative and the patient’s general condition became much better. Once again, however, drug resistance became a big problem and this drug that seemed "nearly perfect", (cheap, easy to take, very few side effects) once again seemed a disappointment.
However, we now had three effective anti-TB drugs, and by 1954, it was apparent to my colleagues that the only sensible policy was to treat each new case as if the bacteria were resistant to at least one of these drugs (either from previous single drug therapy or because of infection with resistant strains acquired from another patient). All new patients were therefore to receive triple therapy until such time as resistance tests revealed that no resistance existed.(8) This was the situation which existed in 1954/55, and it was really exciting to discover that, for the first time in history we could virtually guarantee that all patients could be cured, even those with severe and advanced disease. Very soon, collapse therapy and resection of diseased lung tissue were no longer necessary, apart from the few cases with resistant strains
This remarkable achievement was unfortunately not immediately accepted by colleagues both in the UK and abroad. John Crofton did his utmost to communicate the fact that almost 100% of patients could be cured by correct use of chemotherapy, and eventually the International Union Against Tuberculosis was persuaded to organize a multi-centre trial of this regime and this confirmed the success of the Edinburgh results.(7,8)
At this stage, there undoubtedly existed a chance to conquer tuberculosis Worldwide by launching campaigns using optimum chemotherapy. These prospects were greatly enhanced by studies in the Third World where it was shown that even in the slums of Madras, it was possible to treat tuberculosis successfully in the patient’s home and avoid hospitalisation altogether. However, it was not to be; due to doctor errors, lack of financial support by national and international agencies and poor patient compliance, drug and multi-drug resistant strains have become much more prevalent and the final blow has been the advent of AIDS and associated HIV infection, especially in developing regions.
This abysmal failure has been dramatically chronicled by Chris Holme, the Health Correspondent with The Herald.(9) He has made an excellent study of the history of tuberculosis and this lost opportunity. However, back in Edinburgh we continued the battle and within a year there was no hospital waiting list, although new cases were still plentiful. The Scottish Mass X-ray Campaign began in 1957, with the objective of identifying the undiagnosed cases in the main cities. In March 1958, 84% of the adult population of Edinburgh was X-rayed. This Edinburgh campaign was co-ordinated by a "technical Committee" (of which I was Chairman). The Scottish Health Department, the City of Edinburgh Public Health Department, were represented, and we had as a member the Editor of a Scottish daily newspaper. In four weeks, 423 patients were diagnosed as having active pulmonary TB; most were early cases and received chemotherapy at home.(10) After this, notification rates fell rapidly and within a few years, Edinburgh had one of the lowest mortality and incidence rates in Europe, a marked and welcome change from the post-War Scottish epidemic referred to above. With the disappearance of hospital waiting lists, TB beds fell vacant and some were allocated to the next important under-resourced part of the Health Service, viz the geriatric service.
By the end of 1958, I decided to seek new challenges and so I became a geriatrician, but that is another story!