Tuesday, 18.05.2021

Pierre Baumann and Francois Ferrero: An official inquiry of the clinical research activities (1946-1972) of Roland Kuhn (1912-2005)  

Barry Blackwell’s comments

 

        This is a synopsis of a summary in English based on a book in German about the clinical research activities of Ronald Kuhn (1946-1972) at the 700-bed Münsterlingen Psychiatric Hospital where Kuhn was Medical Director between 1970 and 1979; he was between 34 and 38-years-old during that period. He died in 2005 at age 93. 

        The “summary” was written by Pierre Baumann and François Ferrero and appeared on inhn.org on December 19, 2019. All quotations below are from that post.

        Triggered by newspaper articles and complaints by former patients and nurses between 2013 and 2015, the enquiry began in 2015 and concluded in September 2019, long after Kuhn’s death. Only three of the original auditors of the German report were editors, two were historians of psychiatry (Professor Meier and Dr. Konig), the other was a historian of accounting (M. Tornay). The identities and clinical expertise of the other five appointed auditors, not authors, are not identified nor is their reason for abstaining.

        The substance of the report is based on witnesses, the archives of the Münsterlingen Hospital, pharmaceutical manufacturers (including Ciba and Geigy), the FDA of Switzerland and Kuhn’s private archives (45 meters in length).

        According to the report, 120 drug compounds were investigated overall, but actual clinical studies were available for only 67. Kuhn mentioned 3,000 patients but documents existed for only 1,100 patients identified by name. Pharmaceutical companies sent “at least” 3 million drug doses to Münsterlingen but also to a “wide network of inpatients and outpatients and practitioners from many other hospitals, institutions and offices.”

        Patients were not selected by gender or social status, but children and adolescents from “orphanages and other institutions” were included. Chronic and severely ill patients “were preferentially recruited by Kuhn to test new compounds.”

        Although Kuhn was aware of standard double-blind, placebo controlled studies at the time, he shunned them, proceeding “according to an exploratory procedure.” Kuhn considered numbers, statistics and graphic presentations inappropriate, preferring an “unsystematic methodology… welcomed by the pharmaceutical industry and manufacturers that allowed him to carry out long term studies using his approach.”

        Kuhn alleged patients were “continuously observed and monitored, but this is likely impossible because the size was insufficient to record all observations and carry out the necessary exams.”

        “The report mentions 36 patients died… they were very rarely informed about the nature of the substances they were taking and rarely participated voluntarily in a study. He very rarely informed patients spontaneously, but rather they had to ask for information.”

        The report does not give many details about the state of research performed by pharmaceutical companies, with no mention of toxicity or Phase I clinical trials. Kuhn was “lauded as a rapid investigator to carry out toxicological studies performed on chronic patients, (again likely against their knowledge or consent).” Many compounds “were not tested for their therapeutic effect but for clinical effects and chemical structure to aid in development of future agents.”

        “Kuhn was looking for international recognition that would come largely in the form of substantial financial support.” The report estimates this amounted, in today’s standards, to $1.8 million. “Kuhn argued he did not perform these tests in regular working time and that the Canton saved costs as the medications were freely provided by the pharmaceutical companies.”

        Drugs tested included imipramine and those with similar structure. In 1956 alone eight such compounds were tested but none commercialized. “Kuhn even asked to stain a new drug the same color as a previous one to improve compliance; if necessary those hesitating to take drugs received them in drinks.”

 

Reviewer’s Comments

        In 1970, together with Frank Ayd, we organized an International Conference at the Taylor Manor Hospital in Baltimore on “Discoveries in Biological Psychiatry” to which all those clinicians and scientists involved were invited. Each received the First Annual Taylor Manor Award. The proceedings were published and are still available (Ayd and Blackwell 1970). Ronald Kuhn was among the recipients and gave a sophisticated scientific account of his discovery of imipramine, equal in quality to all the other presentations.

        Regardless, this new material is deeply disturbing and potentially damning to Kuhn’s reputation. It also raises credible concerns. It is abstracted from a book in German, not yet translated into English. Thus the conclusions and inferences derived in the synopsis cannot be verified but are potentially damaging and destructive to a person unable to reply or rebut them. An added concern is that five of the original eight auditors did not subscribe to the book and the remaining three are all historians, one an accountant. The level of clinical and pharmacological input into the review process remains unclear.

        Another concern has to do with the post-World War 2 political climate in Germany, perhaps tainted by guilt aroused about Nazi atrocities during the Nuremberg trials and development of the Nuremburg Code for Ethical Human Experimentation. Was there a climate conducive to scapegoating?

        Finally, it is unclear to this reviewer why “It is urgent that the international scientific and medical community is rapidly informed.” Surely, there is a countervailing ethical obligation to pursue the facts and allegations until they are scrupulously verified.  

 

References:

Ayd F, Blackwell B. Discoveries in Biological Psychiatry. J. B. Lippincott; First Edition. 1970.

Baumann P, Ferrero F. An official inquiry of the clinical research activities (1946-1972) of Roland Kuhn (1912-2005). Pierre Baumann and François Ferrero: The Report of the Official Commission. inhn.org.perspective. December  26, 2019.

Kuhn R. The Imipramine Story. In: Ayd FJ, Blackwell B, editors. Discoveries in Biological Psychiatry.  Philadelphia/Toronto; JB Lippincott, 1970; 205-17.

 

April 30, 2020