A fungus from Norwegian soil
In 1971, researchers at the pharmaceutical company Sandoz in Basel, Switzerland were screening soil samples collected from various locations around the world, including Norway and Wisconsin, for fungal strains that might produce useful natural compounds, a routine practice for pharmaceutical prospecting at the time. Among the fungi identified was a strain, later classified as Tolypocladium inflatum, brought back from Norwegian soil by a travelling employee, which produced a family of related compounds the company began investigating primarily for antifungal activity, the property that had originally attracted attention to fungal natural products of this general kind.
An antifungal compound that suppressed immunity instead
The compound’s real significance emerged from a different line of testing entirely. On 31 January 1972, using a screening test designed at Sandoz, Jean-Francois Borel found that one of these fungal compounds, which would later be named cyclosporine, suppressed immune function rather than acting mainly as an antifungal agent, an unexpected result given what the screening programme had originally been built to detect in the first place. That discovery redirected the compound’s development away from treating fungal infection and toward an entirely different medical application: controlling the immune system’s response to foreign tissue.
Blocking one signal in the immune system
Cyclosporine works by binding to a protein called cyclophilin inside cells, and the resulting complex blocks an enzyme, calcineurin, that would otherwise switch on the genes needed to activate a class of immune cells called T-cells. By interrupting this one specific step rather than suppressing the immune system indiscriminately across the board, cyclosporine dampens the immune response responsible for rejecting a transplanted organ while leaving other immune functions comparatively less disrupted than earlier, cruder immunosuppressive treatments had managed, a more targeted mechanism that made it considerably more useful in transplant medicine going forward.
From kidney to liver transplants
Clinical testing moved quickly once the immunosuppressive property was identified: British surgeon Roy Calne demonstrated cyclosporine’s effectiveness in kidney transplants from 1978, and Thomas Starzl performed the first successful liver transplant using the drug on 9 March 1980, results that, in Starzl’s own account, substantially expanded what organ transplantation could achieve by improving rejection control well beyond what had previously been possible. The United States Food and Drug Administration approved cyclosporine on 2 September 1983, and it became a standard immunosuppressant across kidney, liver, heart and other organ transplants in the years that followed.
A drug with its own costs
Cyclosporine’s benefits came with acknowledged costs. Common side effects include raised blood pressure, headache, kidney dysfunction, excessive hair growth and gum enlargement, alongside less common problems such as peptic ulcers and elevated cholesterol. The rise in blood pressure has a specific cause: the drug narrows blood vessels within the kidneys while prompting the body to retain more sodium, which is why the lowest dose that still controls rejection is generally preferred. Cyclosporine is also classified as a Group 1 carcinogen by the International Agency for Research on Cancer, with documented associations to skin cancer and lymphoma among long-term patients. These risks did not undo its overall value in preventing organ rejection, but they meant cyclosporine required careful, ongoing clinical management rather than a simple, side-effect-free solution.
A discovery whose credit was contested
The discovery is worth understanding alongside a detail that complicates its tidy attribution to Borel alone: credit for identifying cyclosporine’s immunosuppressive properties was later disputed between Borel and Hartmann Stahelin, the Sandoz colleague who had helped design the screening programme that produced the result, each with a claim to a central role in the finding. That dispute does not change what cyclosporine achieved for transplant medicine, but it is a useful reminder that even well-documented, well-dated discoveries can carry an unresolved question about whose insight actually mattered most, a question the historical record does not always settle cleanly.
