It is eighty years since the first effective drugs to treat tuberculosis (TB) and seventy years since the combination cure was first applied in Edinburgh. But TB still kills 1.3 million people every year across the world.
Chris Holme looks back at what went right and what went wrong and how the contributions made by women have often been marginalised or ignored…..
Sigrid and Patricia were two ordinary young women living an ocean apart who changed medicine for ever.
This was 1944, at the height of the Second World War.
Both women had advanced pulmonary tuberculosis (TB) and were close to death. They volunteered to be human guinea pigs for two experimental drugs.
TB, or consumption, had plagued humankind for millennia and had probably claimed more lives than any other disease. Robert Koch identified the bacterium in 1882, which prompted decades of scientific effort across every continent to find a cure. None came.
Then two new drugs arrived within the space of one month.
In Gothenburg, Sigrid, aged twenty-four, was diagnosed with TB after the birth of her first child Her last chance was the new drug PAS (para-amino salicylic acid). She was first given the drug orally on October 30, 1944.
At the Mayo Clinic in Minnesota, Patricia, aged twenty-two, a farmer’s daughter from Austin, Texas, was in a similarly desperate condition. She had her first injection of streptomycin on November 20.
No-one knew the correct dosages. Recovery was slow and laborious, but both women were cured and managed to return to normal life. Patricia went on to have three children.
And the world’s media had their first “miracle” drugs to beat TB.
The accounts of Sigrid and Patricia were unearthed more than 30 years ago by physician and historian Frank Ryan (Tuberculosis: The Greatest Story Never Told).
It’s not so much that women have been left out of the historiography of tuberculosis – they were never really in it from the start.
In the 19th century the image of the doomed female victim was enshrined in the heroine Mimi in Puccini’s La Bohème and Marie Duplessis, the courtesan model from Verdi’s La Traviata.
Like heroin chic in our era, it also inspired ghoulish fashion trends –thin waif-like figures with reddened cheeks, and translucent skin showing blue veins.
The reality was more horrible and prosaic. Every family knew someone who had succumbed to TB. It killed my paternal grandmother aged forty-five, six months after she gave birth to my dad. Nine children were left without a mother.
It could gnaw at the spine or spread to the brain and other organs. TB meningitis was invariably fatal. The most common form was via the lungs, condemning the wretched victim to a lingering death, often drowning in their own blood. Around half of those diagnosed would be dead within five years.
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Fear of the disease prompted Europeans to flee to healthier climes abroad, which in turn introduced it to Māori, Inuit, and other indigenous peoples hitherto unexposed to the disease.
In North America, the transcontinental railroad spawned an exodus westward of “lungers.” By 1880 one third of Colorado’s population comprised “reconstructed invalids.”
As with cancer now, TB carried enormous stigma, but unlike cancer it was infectious.
Huge hospitals – sanatoria – were built to remove sources of infection from the wider community. These offered various treatment through prolonged bed rest, nutritious food, fresh air, and in some cases surgery.
The highest luxury was offered by sanatoria in the Swiss Alps. Davos alone had forty of them. Thomas Mann chronicled daily life and death of patients in his novel The Magic Mountain published in 1924.
PAS, a derivative of aspirin (salicylic acid) was discovered by Jörgen Lehmann.
Born in Denmark, he qualified as a doctor at a time when bright researchers could still dabble in whatever area interested them.
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In 1938 he was appointed chief of a new chemical pathology laboratory at the Sahlgrenska hospital in Gothenburg. This gave him the platform to work both on the clot-busting drug dicumarol and then on PAS. His intellectual brilliance was matched by eccentricity, like riding his black bicycle along the Sahlgrenska’s long corridors.
Delivery of scientific journals to Sweden was disrupted during the war, but Lehmann received a letter in 1940 from his American friend Frederick Bernheim which triggered his interest in the aspirin molecule and how it might be modified into a compound that stopped TB germs from growing.
Ferrosan, a small drug company in Malmo, was able to manufacture it, as it had dicumarol. PAS was born.
Streptomycin arrived via different route at Rutgers University in New Jersey where Selman Waksman was exploring soil samples for potential drugs to be developed with the pharmaceutical giant Merck. A PhD student, Albert Schatz, discovered streptomycin.
Stung by the disbelief with which Swedish TB physicians greeted PAS, Lehmann did not publish his findings until January 1946.
The first scientific paper on laboratory results of streptomycin had appeared two years earlier. Its co-authors were Waksman, Schatz, and Betty Bugie, one of several women who contributed to its development.
This was her first and last appearance. At this time institutional sexism was pervasive in most professions when marriage, or even the prospect of it, killed women’s careers. They were expected or required to resign.
Bugie could have been named on the patent for streptomycin but was left out because Waksman predicted she would “just get married.”
There were more egregious examples. Kathleen Drew-Baker lectured in botany at Manchester University until her dismissal in 1928 after marrying a fellow academic.
She continued her research into seaweed at home and in 1949 published a landmark paper in Nature which caught the attention of Segawa Sokichi of Kyushu University in Japan. This provided the basis of the process for commercial harvesting of nori, an essential ingredient for sushi. There is statute in the city of Uto and an annual festival in her memory.
Old attitudes died hard and sometimes misogyny descended into sadism. One Edinburgh TB physician delighted in telling young women on his ward “You are all rosy, red apples, rotten to the core.”
History has also tended to ignore the role of nurses who did all the work of tending to TB patients. This was – and still is – immensely challenging but undervalued and overwhelmingly carried out by women.
Some balance has been restored by Maria Smilios with her book (Black Angels) which chronicles the struggles of African American nurses at the Sea View sanatorium in New York against both TB and racism.
TB also took its toll on young nurses arriving at TB sanatoria from remote parts of Scotland and Ireland with no naturally acquired immunity to the disease. The BCG vaccine was finally rolled out in Britain after decades of dithering.
More controversy surrounded the new TB drugs when the 1952 Nobel prize for medicine was awarded to Waksman alone, excluding both Lehmann and Schatz.
The British Medical Research Council (MRC) conducted a series of studies to evaluate streptomycin and PAS. This helped engineer what became evidence-based medicine, using objective assessment provided by randomised trials.
A third drug, isoniazid, arrived in 1952. In Edinburgh, Professor John Crofton brought in a new team of consultants. From 1954 they started using all three drugs from the outset rather than consecutively, and meticulously monitored each patient’s progress.
This stopped the development of drug resistance, and the Edinburgh method became the gold standard for curing tuberculosis.
Next came the mass x-ray campaigns in Glasgow, Edinburgh, Aberdeen, and Dundee to root out latent TB in the cites.
But eighty years on from Sigrid and Patricia’s experiences, and despite newer drugs, TB is still killing 1.3 million people every year.
It was dogged by problems from the outset – indiscriminate and ignorant prescribing compounded by patients not completing treatment which often lasted months.
Like TB itself, efforts to control the disease have also suffered relapses – one step forward then two steps back. New York found this out in the early 1990s when drug resistant TB returned and a much-weakened public health infrastructure could not cope.
HIV allowed dormant TB to reactivate and become the leading cause of death in sub-Saharan Africa.
It still kills in richer countries. Arifa Akbar’s poignant memoir (Consumed) of her sister Fauzia chronicles her death in a London hospital from undiagnosed TB.
However, lack of access to treatment in poorer countries remains the biggest obstacle to progress. The MRC organised further studies across Asia and Africa to find the best affordable treatments.
A trial in Madras (Chennai) in 1959 involving 180 of the poorest slum dwellers, showed that patients recovered just as well from home treatment as those in sanatoria.
The lesson for the entire world was that TB sanatoria were no longer needed. As a result, billions of dollars were wiped off the health budgets of affluent countries.
This is something world leaders might chew over when they next meet at Davos which in the 1970s reinvented itself as a luxury conference resort.
For a disease largely caused by inspiration, there is plenty of room for inspirational leadership.
But don’t hold your breath.
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