More on Biological Theory

I have studied many things in my long career in biological research. Most of my work was on applied biology. I worked, published papers, and got grants in environmental health sciences, toxicology, cancer research, molecular epidemiology, population genetics, gene-environment interactions, genetic susceptibility, metabolic gene polymorphisms, and others. I achieved a brief and modest degree of recognition in the field of molecular carcinogenesis in the early 1990s, and again in the field of human genetic susceptibility to environmental disease in the 2000s.

But during this entire 40-year career in research (this year marks the 40th anniversary of my Ph.D. in Biochemistry), I was always most interested in something quite different: theoretical biology.

I was told by a senior researcher once that theoretical biology is an oxymoron. Biologists don’t do theory.  There is a Journal of Theoretical Biology, in which I have published a few articles, but the journal has always had a low citation index (it’s now about 2, but used to be below 1), and my papers there are among the least cited of any of my papers.

My favorite paper, the one I think is the best paper I ever published, is called

Fractal Properties of the Human Genome. J. Theor. Biol. 230:251-260, 2004. This paper has been cited 20 times, which isn’t bad, but not great for a 12-year old paper. The first two or three years after it was published, it got no citations at all. I published 7 research papers in 2004, with an average citation count of 48. The fractal paper has the lowest number of citations in the group for that year.

I have blogged on this topic before (see Biology, the Lawless Science). Of course it isn’t news that biologists don’t like theory, nor that they don’t understand the value of theory. And theoretical biology is hard. Many papers in the field are from mathematicians who want to apply their favorite models to biological issues, and their papers are not accessible to ordinary, non-mathematically minded mortals.

But the good news, at least for me, is that some of this anti-theoretical bias in biology might be starting to change. There are some fields, like evolutionary biology, where new models and new theories are emerging, although nothing like a universal law has yet been brought forth.

I have mentioned my own work when I started this blog. I thought it would be a good idea to try to derive some basic laws or principles for the way that gene regulatory networks (GRNs) operate. GRNs have become recognized as potentially key features of evolutionary progress. Such networks can be represented by mathematical arrays or matrices of gene interactions, and should therefore be highly susceptible to theoretical analysis. And many scientists have been working in this area. Andreas Wagner, whose book The Arrival of the Fittest made a big splash in the modern field of extending the evolutionary synthesis beyond neo-Darwinism, bases much of his argument on his findings of how robust regulatory networks can lead to innovations in evolution.

I have also made some modest findings in this field on a simpler level, but they are interesting and I am writing them up for publication in the scientific literature. If and when these papers are accepted I will post some of that work here.

Throughout my career, I have published a lot of findings, results, even some ideas and concepts. But I would be really thrilled to be able to find some kind of fundamental law that can explain any aspect of that marvelous, astounding and absolutely unique thing we call life. We’ll see.

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4 Responses to More on Biological Theory

  1. Jon Garvey says:

    Hi Sy

    Indeed there must surely be order in something like the genome that operates semantically, rather than having to just say “stuff happens despite the disorder”. At the same time time, the endless variety of life tells one there’s more going on that, say, in the structure of crystals.

    So I suppose the goals have to be something akin to linguistics – great insights into the universality of the characteristics of the human mind, and (as Chomsky found) significant general lessons about Life, the Universe and Everything. But it wouldn’t attempt to explain why King Lear isn’t Hamlet, or the overall trajectory of human language evolution.

    In other words, perhaps it will bear more fruit for the kind of science that seeks knowledge as philosophia (thinking God’s thoughts after him) than the “baconian” aim of getting nature sussed before setting it to the treadwheel of human need.

    It’ll certainly be intriguing to see what your work unveils.

  2. SheilaDeeth says:

    You had me at mathematical arrays. It’s interesting that the more we simplify what we think we know, the more we find there are mysteries lurking behind it. It seems like your theoretical papers have been sneaking a peak at ideas just beginning to rise to the surface. I love your convey the thrill of science!

    • Thank you Sheila. That “sneaking a peak” is a perfect description of whatever it is that I am probably doing. It’s all so early in the game yet, that I would normally hesitate before even talking about it. But, one of the things I promised to do in my grant request was to spread the work on what I am doing, so this is the beginning of that. I will go into much more detail, once papers are accepted. (Pray for that). Peace.

  3. Jon
    Interesting point. I would very much like to go there, (toward philosophia) but I need to tiptoe slowly in that direction. At least for now. I want to publish whatever I find in the scientific literature (one paper almost ready to go out) and as you know, and as we discussed before w/r/t the whole “creator” in the literature drama, one cannot be too un Baconian in that world. But there are other ways to approach things. A. Wagner wrote a book, others use other venues for going after God’s thoughts. I have this blog, I can comment on The Hump of the Camel (readers who dont know about Jon’s wonderful blog, please check it out), and other venues. So my hope is to be able to keep “un piede in due mondi” as the Italian saying goes (A foot in two worlds). We’ll see how well that works.

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