Abstract
We appreciate the scholarly contribution of Dr. Kimelberg, although we do not share his pessimistic view about hypothesis-driven research, nor do we embrace his position upon how research should be conducted. Of course, we do not believe in the supremacy of one form of scientific enquiry over the others, even when promoted by a giant such as Isaac Newton. We rather prefer the pluralistic view that there are many different ways to probe the mysteries of nature, all of them being equally valuable. Some researchers like to collect data, others prefer to formulate hypotheses and try to confirm or infirm them. Some individuals formulate theories, leaving the task to skilled experimentalists to find out whether data support proposed models. Finally, for many of us, several of these different strategies might be used at one point or another during our work. It is important to recognize that all of these approaches (or stages toward a coherent explanation of natural phenomena) play an important role in the progress of science, and even if one were to have the stature of Newton in his or her field, it appears presumptuous to recommend to future generations of scientists to favor one particular mode of investigation. The development of modern physics is there to remind us that it was fortunate that some individuals could escape the Newtonian vision of the world and formulate their own models, sometimes out of very little data, to be proven experimentally only decades later. As nicely summarized by Changeux (2004), the debate between empiricists and rationalists started by Aristotle and Plato, and then pursued by Bacon, Locke, and Hume on the empiricist side and by Descartes and Kant on the rationalist side, to name a few, is still ongoing. According to empiricists, theory should come only after the facts. The rationalist view calls for an anticipatory role of theory (models), which in this way can structure and orient experimentation. Changeux goes on to argue that the two approaches may reflect two modes of functioning of the brain, which are influenced by the sociocultural environment.
In biology, studies performed upon in vitro preparations have demonstrated their capacity to provide tremendous insights about the cellular and molecular mechanisms operating in various tissue, including the central nervous system. The formulation of hypotheses based upon in vitro data represents the best way such insights can be rigorously expressed and disseminated in the scientific literature to be tested by many researchers with different approaches. Of course, we agree with Dr. Kimelberg that it is important to obtain at some point a validation in vivo of hypotheses developed on the basis of in vitro studies. This is precisely what we have done for the lactate shuttle model that was elaborated and refined on the basis of a series of in vitro experiments (Bouzier-Sore et al., 2003;Brunet et al., 2004;Chatton et al., 2003;Debernardi et al., 2003;Pellerin and Magistretti, 1994, 1996, 1997;Pellerin et al., 1998a;Pierre et al., 2003), whereas some aspects were subsequently tested ex vivo and in vivo (Bittar et al., 1996;Cholet et al., 2001, 2002;Pellerin et al., 1998b;Pierre et al., 2000, 2002;Voutsinos-Porche et al., 2003). In fact, it is doubtful that in vivo experiments would have been performed without the insight provided by in vitro studies. Considering the number of interesting findings that have been made so far and the perspectives opened by the aforementioned hypothesis with new experiments being pursued by different laboratories, we can (still) predict a bright future to hypothesis-driven research. In this regard, it is instructive to consider Louis Pasteur's statement (1880): “The illusions of the experimenter form a great part of his power. These are the preconceived ideas which serve to guide him. Many of these vanish along the path which he must travel, but one fine day he discovers and proves that some of them are adequate to the truth. Then he finds himself master of facts and new principles, the applications of which, sooner or later, bestow their benefits.”