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Leonard Colebrook: The real father of antibiotics?

Antibiotics have saved countless lives in the past century, and are heavily relied upon for many prescriptions for a wide variety of bacterial infections and diseases, such as pneumonia, urinary tract infections and strep throat, to name but a few. They are the first port of call for a large number of medical issues and are considered by many to be miracle drugs. This is why the man credited with the discovery of the first antibiotic has such prominence: Sir Alexander Fleming’s name is known by all, and the story of the messy scientist’s discovery of the first antibiotic, penicillin, in the squalid conditions of his disheveled laboratory is a well-known one. But have we been heralding the wrong man as the founder of this enormously important breakthrough, perhaps the most important medical innovation of the 20th Century, if not any century?

Sir Alexander Fleming, penicillin pioneer

I believe that Fleming fully deserves his fame, but there is one man that the history books overlook, a man whose work predates that of Fleming by a whole decade, a man who pioneered some of the first studies and practical uses of antibiotics. Leonard Colebrook was a bacteriologist and director of research at Queen Charlotte’s Hospital, London, from 1929. Colebrook specialised in the study of puerperal sepsis, a bacterial infection of the female reproductive tracts following childbirth or miscarriage. The main cause of this infection had been realised as group A streptococci bacteria 1, the transmission of which was largely due to a lack of basic hygiene in midwifery; in 1847, Ignaz Semmelweiss reduced the death rate of puerperal fever from nearly twenty percent to just two percent by hand washing with chlorine during childbirth procedures 2. Puerperal fever, of which puerperal sepsis is a type, led to the deaths of approximately 250,000-500,000 women in the 18th and 19th Centuries in England and Wales alone 3.

Leonard Colebrook, bacteriologist and one of the early founders of antibiotics

In 1935, German scientist Gerhard Domagk discovered that, of 26 mice infected with streptococci from human infection, only the 12 mice injected with Prontosil red dye survived. Domagk was later awarded the Nobel Prize for his work. Colebrook successfully repeated this experiment 4, but was reluctant to apply this same theory to human patients as some of the surviving mice showed kidney damage. He finally resorted to its use, however, when faced with a dying woman and no other options. Miraculously, the woman made a full recovery after treatment with this Prontosil red inoculation. The only side effect was that her skin temporarily turned blue, while the rodents’ had previously turned red instead. Colebrook began to frequently use Prontosil red in puerperal sepsis cases, treating 64 women in 1936. What’s more, he saw an astounding drop in mortality rate, from one in four in the five years leading up to the introduction of Prontosil, to just one in twenty when he began to use it 5.

French scientists then picked up the baton from Colebrook, and discovered that the reason for the incredible healing effect of Prontosil was that it was broken down to a simpler compound, sulphanilamide, upon assimilation into the body. Colebrook promptly repeated his testing using just sulphanilamide, discovering that it had the same effect as Prontosil red. Soon, sulphanilamide was being manufactured in great quantities, a whole decade before the general use of penicillin. It was used in the second world war to save hundreds of lives from infection, becoming standard issue in US soldiers’ first aid packs.

Medicine was apparently a family affair with the Colebrooks as Leonard’s sister, Dora, who too worked at Queen Charlotte’s as a scientist, also made breakthroughs. She painstakingly swabbed the hospital’s patients, their families, and staff before isolating and culturing their bacteria then making connections between the organisms. She used the links between the different bacteria samples to prove that the bacteria were evolved from one another between people, and therefore showed a clear progression of infection transmission between all individuals in the hospital. She noted that the group A streptococci bacteria from childbirth associated infections were circulating through the general population, though now causing sore throats 6, an infection known as strep throat, instead of often fatal postnatal infections. So, while Leonard Colebrook was pioneering antibiotic use, Dora Colebrook was proving and raising awareness of the risks of Hospital Associated Infections (HAIs) as we know them today. She used her evidence to stress the importance of simple hygiene such as wearing gloves and masks, washing hands and sterilising instruments in operations, and separating infected patients from those not infected.

The Colebrooks’ role in developing antibiotics might have been forgotten had Shiranee Sriskandan, an infectious disease physician and microbiologist at Imperial College London who happened to be studying group A streptococci, not salvaged a large number of the Colebrooks’ streptococcus samples from Queen Charlotte’s Hospital just before its demolition in 1998.

Streptococcus pyogenes bacteria (group A streptococcus)

Sriskandan cultured many of these samples, which were particularly exciting given their 80-year-old roots in the early founding of antibiotics and HAIs, though a large number of them were no longer viable. But with those that she succeeded in growing, she noticed that they were particularly different to any streptococci she had ever seen, with a much larger capsule surrounding the bacteria. Furthermore, this was not just a standalone case of unusual bacteria in one patient, as they were labelled as being from different patients. Genetic analysis also affirmed Dora Colebrook’s finds — the samples were genetically related.

I admire the Colebrooks greatly, and think that recognition for their incredibly valuable discoveries is long overdue. Leonard Colebrook’s selfless and modest approach to his research is perhaps an underlying reason for his lack of attention, and this makes him all the more inspirational. He used to say, “Credit should never be given to any one person. 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” 7.

I, for one, am very impressed with the quality of Colebrook’s mortar, and it looks remarkably like a brick to me.

  1.  New Scientist, Feb 2017 
  2.  Anderson, BL, April 2014, Puerperal group A streptococcal infection: beyond Semmelweis 
  3.  Loudon, Irvine, March 2000, The Tragedy of Childbed Fever 
  4.  New Scientist, Feb 2017 
  5.  New Scientist, Feb 2017 
  6.  New Scientist, Feb 2017 
  7.  New Scientist, Feb 2017