Evolutionary Biology, Cell-Cell Communication, and Complex Disease

Even in this advanced age of genomics, the evolutionary process of unicellular and multicellular organisms is continually in debate. Dr. John S. Torday, one of the two authors of Evolutionary Biology, Cell-Cell Communication, and Complex Disease took the time to briefly discuss his book with us. Coauthored by Dr. Virender K. Rehanwhich, Evolutionary Biology hones in on the “why and how” of evolution by focusing on the cell as the smallest unit of biologic structure and function.

  • What made you originally decide to write Evolutionary Biology?

The writing of the book was prompted by a variety of factors. First, evolutionary-developmental biology was not taking advantage of the standard cell-molecular experimental methods of developmental biology. Second, the Human Genome Project was not catalyzing biomedical research, as was expected, for lack of an ‘algorithm’ by which to readily convert genes into phenotypes; since evolutionary-developmental biology is predicated on that process, the problem had to be addressed. Third, because lung developmental biology—the most successful scientific endeavor to translate basic science into clinical practice to date—was largely driven by the serendipitous discovery that hormones regulate this process. There is too much serendipity and anecdotal thinking in biology and medicine for lack of a unifying theory, and since ‘evolution is all of biology’ (Dobzhansky), that seemed the logical place to look.

  • Have you gained any insights from writing the book?

The key concept in the book is that evolution is a process that can be reduced to cell-cell signaling. By doing so, evolution becomes mainstream to all of biology, no longer requiring metaphoric thinking and expression to understand it. On the contrary, it makes evolutionary biology more accessible to mechanistic hypothesis testing using molecular tools. That is significant because as a result, evolutionary biology will now and forever be seen as relevant to the other biologic disciplines, and to medicine.

  • In a few short sentences, can you summarize the shortcomings of using a symptom-based, descriptive approach to studying complex disease?

In the age of managed care, Big Pharma and medicine are in the business of making the symptoms of disease go away and ‘living with chronic disease’. On the other hand, we in biomedical research are dedicated to understanding the ultimate cause of diseases, and eradicating them. To do otherwise would be to allow the underlying causes of disease to persist and spread ever-further in the population. Given that, we may ultimately fail to effectively treat disease for lack of resources and of will.

  • Historically, a gap has existed between the research produced by evolutionary biologists and applications in clinical medicine. Has any recent progress been made to bridge that gap?

The recapitulation of developmental biology as an important concept in evolutionary biology has created the opportunity to understand the mechanisms for the histories of organisms, both immediate (development) and long-term (evolution). The developmental approach was dropped in the late 19th century in favor of genetics. Now, armed with the tools we need to do so, we have come full circle to solve the mystery of evolution using developmental genomics. This effort has been bolstered by the Barker Hypothesis, which addresses the fetal origins of adult diseases, merging evolution, development and pathology mechanistically.

  • The publication of the Human Genome in 2000 was a huge stepping-stone toward using genetic information to diagnose, treat, and prevent disease. What do you think will be the next big breakthrough?

The Human Genome is metaphorically characterized as the ‘book of life’, but it has no characters or plot. It’s just a compendium of human genes. We need an algorithm that readily translates genes into phenotypes, and visa versa. This would be the biologic equivalent of the Periodic Table of Elements, as described in Evolutionary Biology, Cell-Cell Communication and Complex Disease.

  • You both work in Pediatrics. What is the most unusual thing you have ever had to do in your line of work?

Understanding the relevance of endocrinology to normal lung development. It is counterintuitive, yet it has largely formed the basis for the practice of Maternal-Fetal Medicine and Neonatology.

  • What is the most important piece of advice you can offer to students interested in studying disease from either a research or clinical perspective?

To delve as deeply as possible into the problem, unencumbered by traditional thought, because we are constantly reasoning after the fact in biology and medicine. The phenotypes we ponder are adaptations and maladaptions that emerged from the Cambrian Burst several million years ago.

  • Who are your scientific/intellectual heroes?

Iconoclasts like Copernicus, who first said that the earth rotates around the sun, and mentors like J.S.L. Brown, who discovered cortisol, C.J.P. Giroud, who discovered the ‘functional zonation of the adrenal gland’, Jack Gorski, who discovered the steroid hormone receptor, and Mary Ellen Avery, who discovered that Hyaline Membrane Disease is due to lung surfactant deficiency, not the other way around.

  • Why does biology lack a central theory?

Because we haven’t figured out the “why” and “how” of Evolutionary Biology, which is the mechanistic basis for biology.

  • Why is medicine largely non-predictive?

Because it is based on biology, which is similarly non-predictive.

  • Are humans a unique life form?

Since evolution is emergent and contingent, there may be life forms on other planets, but they will not look or act like we do, yet the basic self-organizing principles of cell biology and homeostasis will apply. Understanding that evolution is based on such first principles will enable us to appreciate such life forms, much as evolutionary biology has taught us how we are related to the other life forms on Earth.

Read excerpts from Evolutionary Biology, Cell-Cell Communication, and Complex Disease and find out more about the book at wiley.com.

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