In 1954, Stähelin successfully applied for a 12-month postdoctoral fellowship sponsored by the Swiss National Foundation (SNF) to work on a project on phagocytosis inspired by Emanuel Suter (then at Harvard, later second Dean of the University of Florida Medical School).
Teniposide and etoposide were found by Stähelin to have a new mechanism of action: they blocked the entry of cells into mitosis (with arrest in late S or G2 phase), in contrast to SP-G and SP-I, which were spindle poisons.
Etoposide is still considered a potent, well-tolerated combination partner in innumerable hematologic and solid tumor treatment schedules, including those for malignant lymphomas and lung cancer.
[7][8] Stähelin was also instrumental in the discovery process of several microbial products inhibiting cell proliferation, including cytochalasin B, brefeldin A, verrucarin A, anguinine and chlamydocin, which have played an important role in basic cancer research.
The "Stähelin Screen" was rapidly and very successfully adopted by the Japanese pharmaceutical company Fujisawa (now Astellas), which subsequently discovered tacrolimus (FK-506, Prograf), the second clinically used calcineurin inhibitor.
On receiving the American Association for Cancer Research Bruce F. Cain Award jointly with his colleague A. von Wartburg in 1990, Stähelin wrote: "...there are an astonishing number of coincidences between etoposide and cyclosporine.
The first coincidence was that etoposide and cyclosporine were both found and developed on the chemical and biological side by the same groups, those of the present authors and their specific biological effects were discovered by one of us; second, both compounds were approved by the United States Food and Drug Administration on the same day in November 1983, although they had been submitted by different companies; furthermore, both drugs act via an effect on an intranuclear isomerase, topoisomerase II, and peptide cis-trans-isomerase, respectively; both compounds are potent immunosuppressants; etoposide as well as cyclosporine are used in the treatment of leukemias or other malignancies; the latter after bone marrow transplantation to prevent graft-versus-host disease, the former also being used in conjunction with bone marrow transplantation; sometimes, the two compounds are used concomitantly, exploiting the capacity of cyclosporine to reduce certain types of multidrug resistance or to modify immunity against tumors cured by etoposide; in the development of both drugs, galenical problems arose, related to poor water solubility and absorption from intestinal tract, and experience gained with etoposide in this area was crucial for overcoming, several years later, difficulties of a similar type with cyclosporine.
It is left to the reader to make assumptions about the heuristic aspects of these surprising coincidences..."[12] Married to a distant cousin (Irene Staehelin, who is also a member of an old Basel family dating back to 1520) and the father of four adult children, Stähelin retired in 1990.