THE stranger’s warning came to Shiranee Sriskandan by email: an irreplaceable collection of streptococcus bacteria was about to be destroyed. The samples were in a building awaiting demolition at Queen Charlotte’s Hospital in London, and if she didn’t save them, they would be gone forever. Sriskandan had no inkling of the journey through history this tip-off would set her on.
It was 1998, and – was studying group A streptococci at Imperial College London. Intrigued by the message, from a retired microbiologist, Sriskandan and her PhD student hightailed it to Queen Charlotte’s. Construction workers let them into the boarded-up building, empty except for an enormous cardboard box.
The box was full of broken sample bottles and smaller boxes. “I could see the labels. They looked like some quite alarming potential pathogens,” says Sriskandan. So she and her student donned protective clothing, extracted three or four intact boxes, put them in a big biohazard bag and made their exit. Experts were called to safely dispose of the rest.
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Inside the boxes were yet smaller ones, containing about 1000 glass ampoules labelled with codes. Digging around in the boxes some more, Sriskandan found index cards listing patients’ names – like Ada and Florence – alongside dates from the 1930s. Each card also had a code matching the ones on the ampoules, and gave the source of the sample, such as blood culture.
Investigating further, Sriskandan discovered that her rescued samples had been collected by Leonard Colebrook, a doctor at Queen Charlotte’s in the 1930s. His research had focused on puerperal sepsis: bacterial infections acquired by mothers during or after childbirth, a common and deadly occurrence at the time. Sriskandan had been unaware of Colebrook, but he turned out to be a fascinating character. He was a friend of Alexander Fleming, who discovered penicillin in 1928. Yet Colebrook’s crucial role in pioneering antibiotics is largely forgotten.
“Almost at once there was a surprising and most gratifying change”
Before 1930, about 2000 women died each year from puerperal sepsis in England and Wales. The main cause had been established as group A streptococcus, which also causes tonsillitis and scarlet fever. But doctors had no weapons with which to fight the bacteria. Then in 1935, before penicillin’s potential was realised, there was a breakthrough. infected 26 mice with streptococci from a human infection. He injected 12 of the rodents with a single dose of a red dye called . The treated mice all survived. All the untreated ones died.
After discovering Domagk’s report, Colebrook got hold of the drug and repeated the experiment. It worked, but some of the mice showed kidney damage. As a result, he was reluctant to give the drug to his patients, but faced with a dying woman and no other options, he was obliged to take the chance. While the mice had turned pink from the dye, this woman’s skin turned blue. But her high temperature returned to normal overnight, the harmful bacteria disappeared from her blood and her colour returned. The same thing happened in the next patient. “Almost at once there was a surprising and most gratifying change,” Colebrook would later recall.
By August 1936, he had given Prontosil to 64 women. In the five years before using the drug, the death rate among his patients with puerperal sepsis was 1 in 4. With Prontosil, he reported, that rate plummeted to just 1 in 20. Colebrook’s study was the first ever clinical trial of any antibiotic. It was a very big deal.
Within a year, French scientists discovered that Prontosil was broken down in the body into a simpler compound, sulphanilamide, which was curing the infections. Colebrook repeated his study with sulphanilamide and found it had the same effect. It was soon manufactured in huge quantities, predating the general use of penicillin by a decade. Sulphanilamide was widely used in the second world war to prevent and treat wound infections, saving countless lives.
Sriskandan was stunned to discover the medical history of her rescued samples, and it gave her an idea. Using modern techniques, she attempted to regrow the streptococci from the ampoules. Most were no longer viable, but she succeeded with about a dozen.
Two regrown samples looked unlike any streptococci Sriskandan had ever seen: the capsule surrounding the bacteria was much bigger than usual. She thought they must be from the same patient, but the cards showed otherwise. They were from two different women, and the samples were taken three weeks apart. It was no coincidence, though – genetic analysis of the bacteria suggested the two cases were linked.
Sriskandan was excited to have traced the progress of an outbreak that happened 80 years earlier. But what she had worked out using modern genetic techniques had already been pieced together in 1935. Leonard Colebrook’s sister Dora, also a scientist at Queen Charlotte’s, had used a much more basic – and painstaking – method to find links between cases.
Dora Colebrook was investigating how streptococcal infections were passed around the hospital. She meticulously collected samples by swabbing patients, their families and staff. To work out which bacteria were related, she grew them from the swabs, boiled the cultures and, once cool, injected them into rabbits so they produced antibodies against that particular strain. Next, she extracted these antibodies and pitted them against bacteria from other swabs. If the antibodies reacted, she knew the bacteria must be similar.
Colebrook’s work brought home to the medical community that the group A streptococci that endanger women around childbirth also circulate in the general population and cause sore throats. “They’re not special bacteria and therefore people with respiratory tract infections due to group A streptococci are a threat to women who have recently given birth,” says Sriskandan.
Colebrook stressed the importance of wearing masks and gloves in obstetrics, of sterilising instruments, handwashing and isolating people with infections. She was not the first to appreciate the risk medical staff posed to their own patients, but many still believed that women carried the bacteria before giving birth, and that cleansing the birth canal could prevent harm. Colebrook showed that the bacteria are acquired after childbirth, not before.
Reinvent the wheel
Even now, medical staff often have to relearn these lessons. In 2011, after an outbreak of group A streptococcus killed two mothers in the UK, Sriskandan was part of a team that published new guidelines on preventing such infections in hospitals. “I felt that we were reinventing the wheel because the advice about isolation of patients with streptococcal infection, about the importance of hygiene, was known thanks to Dora Colebrook.”
The 1930s bacteria that Sriskandan revived were witness to a pivotal period in the history of medicine. The first antibiotics, pioneered by Leonard Colebrook, and the establishment of good hygiene practices, spurred by Dora Colebrook, helped to turn bacterial infections from a deadly horror into a treatable affliction.
Leonard Colebrook has faded unfairly into obscurity, while his friend Fleming passed into the history books. Fleming had a story of great serendipity on his side, which his employers exploited to great effect in fundraising and PR efforts. Colebrook was altogether more modest. “Credit should never be given to any one person,” he used to say. “Medical research is like continuing the building of a wall: you only add your work on to the work others have done before you. If you’re lucky… you may be the one privileged to add a whole new brick. I hope perhaps I have added a little mortar. Only time will show whether that mortar will hold.”
And hold it has. What’s more, saved from the wrecking ball at Queen Charlotte’s Hospital, his samples have helped Sriskandan discover new insights into the long-term evolution of group A streptococcus – knowledge that could prove crucial in ongoing efforts to develop a vaccine against it.
This article appeared in print under the headline “Sibling saviours of the maternity ward”
Article amended on 10 February 2017
We have added the correct photograph of Leonard Colebrook
