Comments on Scientific Process in Clinical Research

COMMENTS ON SCIENTIFIC PROCESS IN CUNICAL RESEARCH BARUCH S. BLUMBERG* Introduction Active scientists in the productive periods of their careers usually do not have time for, or interest in, the study of scientific method. Thinking about the methods of science, it is perceived, is an alternative to collecting data or doing experiments. Philosophy of science is usually an activity of philosophers or of scientists who, at a relatively early period in their careers, take a philosophical path. In clinical research, in particular , writing about philosophy, history, or method is usually taken as an indication that the productive life of the scientist is completed, although it is fair to say that this is not always true. In this paper, I plan to present information derived mostly from the investigations done in our own laboratory since the early 1960s which resulted in the discovery of Australia antigen, its identification with hepatitis B virus, and the association of this virus with acute and chronic hepatitis, chronic liver disease, and primary cancer of the liver. Our work has usually been planned in a formal manner: statement of hypothesis, study design, data resulting from the investigation, a decision if the hypothesis had been supported or rejected, and new or modified hypotheses generated by the new data. A very large diagram showing the interrelations between all the studies based on this hypothesis-deduction-induction structure has been prepared. From this, it has been possible to make observations on scientific process, and some This work was supported by USPHS grants CA-06551, RR-05539, and CA-06927 from the National Institutes of Health and by an appropriation from the Commonwealth of Pennsylvania. Material in this paper was used in the Scharf Memorial Lecture given at Gettysburg College, Gettysburg, Pennsylvania, on December 2, 1977, and was also included in the President's Lecture Series of the University of Pennsylvania, Philadelphia, Pennsylvania, on December 8, 1977. The paper was written at the Center for Advanced Study in the Behavioral Sciences, Stanford, California, summer 1978. ?Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.© 1980 by The University of Chicago. 0031-5982/81/2401-0204$01.00 Perspectives in Biology and Medicine · Autumn 1980 \ 15 of these may apply to other investigations. However, the material to be discussed is primarily derived from our particular experience, and I must, at the outset, apologize for this parochiality. To my knowledge, the methods we used do not contain any original developments, and it also is important to stress that this is not meant to be a primer for scientific process. Process is a very personal matter, and most scientists prefer to develop their own style. Observation, Hypothesis, Deduction, Induction A diagram of the general methods used is given in figure 1. One or more observations are used to generate a hypothesis. A hypothesis need not be based on observation but can be derived from theory or from the observations of others. However, in the long run we have found that hypotheses derived from nature are as interesting and imaginative as those drawn from other sources, with the additional advantage that they are more firmly rooted in reality. This brings to mind a description (by his biographer, Stanley Vestal) of the mental processes ofJim Bridger, the American pioneer, explorer, and "mountain man," emphasizing the imaginative possibilities of real life: "he used a more exacting type of imagination—that imagination which identifies itself with reality, lovingly exploring every nook and corner of things that are . . ." [I]. In using the inductive method, data are first collected and from these a hypothesis is made. In deduction, the hypothesis is made first and then I OBSERVATION | HYPOTHESIS 1 STUDY DESIGN I DATA I I DATA I [ DATA SUPPOB «EJECT I HYPOTHESIS 3 HYPOTHESIS 2 STUDY DESIGN STUDY DESIGN isZ SUPPORT REJECT I nypornEsis ? I I nmmtcsis 5]| HworoËsis 6*1|wron€sis 7]| nmmeis g] Fig. 1.—Diagram of the succession ofobservation, hypotheses formation, and deduction in scientific process. 16 I Baruch S. Blumberg ¦ Scientific Process in Clinical Research data are collected to test it (essentially an attempt is made to rule it out). A hypothesis is a declarative statement about a state of nature...