The fungus that makes transplants possible – Quartz –

The fungus that makes transplants possible – Quartz


Fifty years ago today (December 3), Denise Darvall, a South African woman in her 20s, died in a car accident. His death was tragic, but it had a positive side: it catalysed one of the most important medical advances in modern history.

Christiaan Barnard, senior cardiothoracic surgeon at the Groote Schuur Hospital in Cape Town, had been practicing heart transplants for years in dogs. When Darvall entered the hospital, Barnard had a patient, Louis Washkansky, who was dying of diabetes and heart failure.

When the doctors who tried to save Darvall's life noticed, after his death, that his heart was healthy, and that he had the same blood type as Washkansky, Barnard jumped into action. In a span of five hours, he made history when he completed the first successful human heart transplant.

"On Saturday, I was a surgeon in South Africa, very little known, and on Monday, I was known worldwide," he said, according to PBS.

Surgeons around the world were hopeful that development would soon lead to thousands of lives saved. But his patients were still dying; Even after successful surgeries, their bodies would not accept their new organs. Although there were drugs that could suppress the immune system, they were so powerful that transplant recipients could not fight off any infection; Washkansky himself died of pneumonia only 18 days after receiving his new heart. After all these failures, the number of heart transplant surgeries plummeted from 100 in 1968 to only 18 in 1970.

Two years after the first heart transplant and about 9,400 miles (15,000 km) from South Africa, Swiss microbiologist Jean-Francois Borel was taking vacations (paywall) in Norway. His employer, a biomedical company called Sandoz Laboratories (now owned by the pharmaceutical giant Novartis), encouraged employees (pdf) to take soil samples when they traveled, hoping that one day they would run into a possible new drug. [19659002] The Norwegian soil sample from Borel proved to be the key to the problem of heart transplantation. Back in the laboratory, he discovered that the soil contained pieces of a mold of natural origin called Tolypocladium inflatum. The species was found to be an abadual form of a known fungus called Cordyceps subsessilis. In his badual state, C. subsessilis is a parasite that appropriates the muscles of beetles and does not have much value for human health. In its abadual state, however, T. inflatum produces a group of compounds called cyclopeptides that Borel discovered, by testing in laboratory mice, that seemed to suppress the exact immune cells involved in the rejection of organ transplantation .

From there, Borel's fungal discovery had to clear up a couple more research obstacles before approval. After four years working to convert the compounds into useful human drugs, in 1973 Sandoz almost abandoned the compound's research after the company estimated it would have needed another $ 250 million to submit the drug to clinical trials required by the FDA (more of $ 1.3 billion in 2017 dollars). At that time, the market for immunosuppressive drugs for transplant patients was very small. The transplants were unpopular, due to their poor long-term results … because the field lacked effective immunosuppressants.

Fortunately, scientists at the British Society of Immunologists convinced Sandoz that these peptides could treat common types of inflammatory diseases such as rheumatoid arthritis. what made them a better bet to recover the anticipated costs of research and development. In 1983, the US Food and Drug Administration. UU Approved (paywall) ciclosporin with the name Sandimmune.

"Cyclosporine was revolutionary," says Howard Eisen, a cardiology surgeon at the Faculty of Medicine at Drexel University. It works by limiting only the immune cells that would attack the new organ, leaving the rest of the immune system intact. It also keeps chronic inflammation at bay. With ciclosporin, patients with transplants really had the opportunity to live with their new hearts. Shortly after the approval of the drug, transplants skyrocketed and, as of June 30, 2016, more than 135,000 successful heart transplants had been performed, according to the International Society for Heart and Lung Transplantation.

The medication was never perfect: at the originally prescribed doses, cyclosporine severely damaged kidneys and was found to be a potential carcinogen, says Ellis. Currently, all recipients of transplants are given a combination of three separate immunosuppressant drugs, including a lower dose of cyclosporine, to mitigate these side effects. That said, the development of cyclosporine was a game changer. Without their discovery, additional advances in the field of heart transplantation would probably have been slower or never occurred. Although its origins are humble, the impact of the drug has been extraordinary.

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