Arrowsmith, Clinical Trials, Compassionate Use and Phosphethanolamine

I came across an interesting article in a recent Nature (Ledford, H., Brazilian courts tussle over unproven cancer treatments, Nature 527, 420-421, 2015). This article describes phosphoethanolamine which has been shown to have in vitro activity in killing tumor cells by investigators at the University of São Paulo.  There is immense demand for this experimental drug which has not been shown to be effective in humans and the issue is in the Brazilian courts.  Access to unproven drugs appears to be an increasing problem with public demand for drugs which have not been subjected to evaluation by clinical trials. However, use of an experimental drug outside of the current clinical trial framework does present problems for a potential trial sponsor.  Several years ago, an issue of compassionate use resulted in death threats and eventual resignation of the company president here in the Research Triangle in North Carolina.   While we tend to think that issue of compassionate use is a current problem with no history, Martin Arrowsmith had the same ethical issue with a vaccine trial in the book by Sinclair Lewis in 1945.  It is of no small interest that Arrowsmith was using-phage based technology which is seeing a bit of a renaissance. Arrowsmith also faced the issue  of trying to do good science in a challenging environment.  I  spent two of the best years of my professional life at the Rockefeller University and became acquainted with Martin Arrowsmith as an urban legend.  There was a relationship between Lewis and the Rockefeller Institute (as it was in the 1920's) through Paul  de Kruif but it is not apparent that the Rockefeller was a model for the McGurk Institute in Arrowsmith.  Rosenberg has an excellent analysis of this relationship (Rosenberg, C.E., Martin Arrowsmith: The Scientist as Hero, American Quarterly 15, 447-458, 1963 which was reprinted in a later collection of critiques of Arrowsmith (Twentieth Century Interpretations of Arrowsmith, ed. R.J. Griffin, Prentice-Hall, Englewood Cliffs, New Jersey, USA, 1968).   Regardless, Arrowsmith has much to tell us in the current time about the development of drugs and the challenges facing scientists in a tech-driven era.