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Reductionist vs integrative approach in biology

Subhash Chandra Lakhotia

Most researchers in biology today tend to depend heavily upon molecular biological approaches to address their queries. I have commented earlier that biology teaching has also become molecular biology-centric which seems to have taken us away from a holistic understanding of biological organization. I will take this issue further.

Traditionally, biology was a descriptive discipline. Beginning around the fourth decade of last century, there has been an increasing involvement of physicists and chemists in elucidating biological principles and properties of biological molecules and following this, an experimental, and concomitant with it, reductionist approach became the new and preferred direction for biological studies. The reductionist approach has indeed been largely responsible for the astounding progress and excitement seen in biology during the past five decades or so.

However, the extreme reductionist approach and heavy reliance on the so-called molecular biology in recent years has become a negative factor and has occluded the enormously exciting view that biology presents today. Most of the current biological research of an individual is directed to obtain a deeper understanding of the functions of a given molecule or a given structure in cell or a specific phenomenon and the underlying mechanism. Thanks to the remarkable developments in technology available to biologists in recent years, such efforts are providing very excitingly detailed and precise insights into the different biological processes. However, what is now needed, and which is indeed feasible, is to remove the disconnect between individual discoveries and integrate them to meaningfully understand the phenomenon in a biological context. All that is required to achieve such integration is a little broader understanding of biology that allows amalgamation of the organismic and molecular biology. Systems biology approach is beginning to show the advantages of inter-connections. However, because of its heavy leaning on computational approaches, real-life situations are liable to be ignored.

When we look back in history of biology, we can see many examples of uncanny predictions made by classical” biologists who had an integrative understanding of diverse biological systems but little idea of the mechanistic details. Although it is generally believed that biology became an experimental science in the wake of molecular biology, some of the experimental embryology that was practiced in later 1890s would surpass many of the current cell manipulation techniques. Among the many experimental embryologists of that time, I would specially mention Theodore Boveri, whom Gilbert in his book on Developmental Biology describes the last of great observers of embryology and the first of great experimenters”. Boveri was indeed one of the first worm” developmental biologists because, working with the parasitic Ascaris, he provided a precise description of events of early cleavage divisions and how specific regions of chromatin were lost (chromatin diminution) in an orderly manner from the precursors of somatic, but not germ, cells and also experimentally demonstrated the factors that regulated the chromatin diminution events. His observations on abnormal growth of sea urchin eggs with aberrant chromosomal complement led him to find parallel in tumors; this finally resulted in his 1914 publication Zur Frage der Entstehung Maligner Tumoren” (‘The Origin of Malignant Tumours’), wherein he made seminal predictions about the basis of unrestricted growth of tumors. His predictions in 1914, without of course any background in molecular biology”, are uncannily and chillingly accurate since he predicted roles of chromosome instability, cell cycle checkpoints, oncogenes, tumor-suppressor genes, tumor predisposition etc to affect tumors (see Allan Balmain 2001 Cancer genetics: from Boveri and Mendel to microarrays. Nature Genetics 1:77 – 82). Those unaware of Boveri’s studies, would believe that we learnt all about the roles of these factors because of the molecular biological approaches in cancer research. However, while Boveri did not have the technological advantages that today’s cancer researchers have, he did have the advantage of integrative and original thinking that was not subject to the peer-reviewers’ watchful eyes”! There are many other examples where a better understanding of biological systems and the courage to come out with novel ideas led to very specific predictions that had fundamental implications and which have been understood in detail following the advent of molecular biology. Thus, the term telomere was proposed in 1930s by H.J. Muller on the basis of simple cytological observations, primarily of Barbara McClinktok, that while normal chromosome ends do not show tendency to fuse, the freshly broken chromosome ends undergo rapid fusions; therefore, the inference was that normal chromosome ends must have a special organization in the form of telomere. Realization of the DNA end-replication problem” in 1970s led to a rediscovery” of telomeres.

Unlike in the days of Boveri, Muller and others, we now have enormously rich and detailed information and equally powerful information retrieval systems. What we lack is an integrative view of the processes and phenomena that we research into. This is compounded by the lack of a formal training in organismic biology. There are many recent examples where dogmas” or fashionable areas of research that flourished following some novel observations but got demolished or lost their charm within a short time. The rapid turnover in such cases can be traced to the narrow and reductionist view of the biological systems rather than realizing the enormous diversity that the extant organisms present. 

With the flood of information that we have today, we can indeed have many more Boveris and Mullers if we enlarge the scope of our learning and thinking to encompass wider principles of biology rather than remain confined to the narrow domain of the molecule or process that one works with using more and more penetrating and precise methods. Those involved in teaching of biology and those excited young minds passionately researching into some of the fundamental biological processes, should begin to think in wider integrative manner so that the flood of information becomes a powerful tool to uncover the secrets of life’s diversity rather than merely add to the mass of information. The way we teach biology must change so that the young minds are stimulated to think integratively, while learning the reductionist approach of analysis. 

One of the reasons for a general absence of prophetic statements in current biological literature of course is the concern about the impact factor and the reviewers’ insistence on mechanistic details”, which I discussed in my earlierblogs. The impact factor and the peer-review process have their own justifications to be in place. Yet the real breakthrough in any field of science comes from novel hypotheses which stimulate new approaches and directions, rather than merely confirm what is expected. The young biologists must take advantage of the numerous possibilities by learning to take a broader and integrative view of their own observations and discoveries.