The Role of Hypotheses in Current Research, Illustrated by Hypotheses on the Possible Role of Astrocytes in Energy Metabolism and Cerebral Blood Flow: From Newton to Now

Abstract

Scientists currently strive to obtain reliable data on the properties of astrocytes in situ, and pari passu to define what the term astrocyte should encompass. As is the current fashion, they are also required to propose in a formal sense hypotheses for astrocytic function that serve as guides for such research. It has become the fashion to raise up “hypothesis-driven” science and denigrate descriptive science that lacks this formal introduction as merely cataloguing. Terms such as “fishing expedition” are often used pejoratively to describe scientific studies that are viewed as simply collecting data with no end in view. This seems as though it would be rather rare and would anyway describe the efforts of a rather inexperienced angler who does not have sufficient experience and skill to determine the types of fish that are likely to be caught where he or she is planning to fish. There is no dispute as to whether the postulation of hypotheses will lead to experiments. The real question, however, is whether always starting with hypotheses leads to more discoveries and a better-organized, more reliable database. To be consistent, this would have to be resolved scientifically; to test this hypothesis in the usual carefully controlled fashion with defined measures of whether so called hypothesis-driven science provides better data or more insights than so called non– hypothesis-driven science. It would be a simple exercise for the research professional to restate this question in the form of a hypothesis and develop a research plan to address it. To put it into practice, however, will rapidly lead to complications. For example, we would first need to define what non–hypothesis-driven science actually is and how it differs from the hypothesis-driven science. The lack of a formal hypothesis does not mean there is not some end in view. It may simply be that in the hypothesis-driven variety we take a positive view that we can guess pretty well what the mechanism or relation is, whereas in the latter case, we leave the question open and will come to this later because we believe we don’t have enough data to form a sensible hypothesis. I would hope that an individual scientist’s opinion, as an expert in his or her field on this issue, would be respected and not dismissed out of hand. You obviously need a background of reliable observations (that is, facts) to propose a hypothesis, and it may well not be clear to another observer when you are ready to propose it. The criticism on a case-by-case basis would be that any reasonable scientist, given the state of knowledge, should be able to come up with a reasonable hypothesis for the area of study under question. This is, in practice, unpredictable and when successful is referred to as scientific intuition. I will assume that everyone agrees that randomly obtained data, however reliable, with no question in mind (although by chance it may come up with important data leading to insights) is not acceptable because it is simply too much of a gamble, and this leaves one very uncomfortable. The two astrocyte-related hypotheses that I will cover to illustrate the problems of this common current practice are as follows: 1) that glucose enters the CNS via the astrocytic processes where it is converted by aerobic glycolysis to lactate which then serves as the principle source of energy for neurons (Magistretti et al., 1994; Pellerin and Magistretti, 2003; Voutsinos-Porche et al., 2003), and 2) that the processes of astrocytes that surround blood vessels at the levels of the arterioles affect smooth muscle contractility and therefore blood flow by releasing vasoactive agents. (Anderson and Nedergaard, 2003; Simard et al., 2003; Zonta et al., 2002). In a recent commentary regarding their well-known astrocyte-neuron lactate shuttle hypothesis (ANLSH), Received January 8, 2004; accepted June 9, 2004. Address correspondence and reprint requests to Dr. Kimelberg, Neural and Vascular Biology Theme, Ordway Research Institute, 150 New Scotland Ave., Albany, NY 12208; e-mail: hkimelberg@ ordwayresearch.org Journal of Cerebral Blood Flow & Metabolism 24:1235–1239 © 2004 The International Society for Cerebral Blood Flow and Metabolism Published by Lippincott Williams & Wilkins, Baltimore