Monday, December 27, 2004

Turning points in biology

Over the years, I've read a lot of books about the "history" of physics and mathematics ["Men of Mathematics", by ET Bell, is a great book, btw] ie who the major figures were and what their discoveries/contributions were. That's given me some context so that when I read a math/physics textbook I have an idea of where the material I'm reading originated. As part of my "re-education", I've been trying to do something similar for biology, getting to a historical understanding beyond "Crick and Watson discovered the double helix structure of DNA".

One of the interesting bits I've come across is that a lot of the "founding fathers" of modern molecular biology were actually physicists by training who converted over to biology. Examples include:

-Leo Szilard came up with the initial idea of an atomic chain reaction which led to the atomic bomb, and then went on to contribute to the analysis of gene regulation in bacteria
-George Gamow, one of the originators of the "big bang" theory of the creation of the universe, proposed a code explaining the relationship between the sequence of bases in DNA and the amino acids in proteins. The code was wrong, but he was the first person to propose it, days after Watson and Crick announced their discovery.
- Erwin Schroedinger, one of the giants of quantum physics, wrote a book called "What is life ?" which apparently served to attract lots of young physicists to biology.
- Max Delbruck got his PhD in theoretical physics, was attracted to biology by some of Niels Bohr's thoughts on the subject and then became the unofficial leader of the "phage group", a well-known group of scientists who worked on bacteriophage ie viruses that infect bacteria.

The book I'm currently reading, "A History of Molecular Biology", by Michael Morange, has an interesting theory, attributed to Francois Jacob, about why so many physicists moved over to biology. The gist of it is that before WW II, some young physicists felt like physics was at a point where it was mostly a matter of refining existing models/theories, and required large collaborative efforts. In addition, during the war, many physicists were drafted to assist their countries' war efforts and came away feeling a bit sullied by the fact that their efforts contributed to killing people. In contrast, biology appeared far away from political and military uses, and a field which had lots of open fundamental questions and thus room for revolutionary contributions by individual scientists. Over time, though, the number of physicists [and other kinds of scientists, like chemists] switching over to biology slowed down, because the profile of biology had become high enough that young people interested in science headed straight for biology instead of 'detouring' through another science.

So, in summary, there was a curious sort of "inflection point" in biology in the 30's and 40's, when a lot of scientists from other disciplines switched into biology. It feels like we're at a similar inflection point right now, with biology benefitting from the interdisciplinary efforts of people originally trained in "computational" subjects like physics, mathematics, computer science etc. I think some of the causes are the same. Biology is once again a "hot" subject, with lots of excitement about the possibilities for biologically-based technological advances, attracting folks from other disciplines who like the idea that their expertise can be put to good use in investigating biological phenomena. I also expect that, over time, the number of people who are explicitly changing tracks will once again decrease, as more universities introduce interdisciplinary educational programs that combine biology with math/engineering/computer science [ie Bioengineering and Computational Biology departments and majors] that allow people to integrate different disciplines right from the start, rather than having to do it later in their careers.

When the first "cross-over" occurred, part of the hope was that the tools of quantum physics could be applied towards understanding biology, ie that biology could become a more quantitative science, but this effort met with limited success. My impression/suspicion is that the idea was simply ahead of its time in that we didn't know enough about the actual molecular mechanisms at play, and didn't have the right experimental tools, to really be able to apply computational methods. In any case, what's happening today is a resurrection of this desire to "quantify" biology. There is an increasingly widespread belief that biology will benefit from the application of computational methods, in the form of mathematical models of biological processes, computer-based analysis of data etc. This time, I think we have a much better shot at being successful -- we know a lot more about certain areas of biology and have much better experimental techniques and tools than were available 60 years ago. So, from a "pure research" perspective, biology is well on its way to becoming more quantitative. However, the jury is still out on how long it'll take before some aspects of these computational approaches become relevant to industry.

What I find most exciting about all this is that I feel like I'm getting a chance to participate in a period that will [hopefully =)] be viewed as a turning point in biology in the coming years, a period when our understanding of, and ability to manipulate, biological systems started to increase exponentially. Quite apart from my inherent interest in the subject matter, the notion of being present at a crucial point in history is, in many ways, what consoles me when I consider that I gave up an insanely cushy corporate job for the grind and relative poverty of graduate school and, in many ways, having to start all over again.

Ask me again in a few years how that's working out for me ;-)

- Francis Crick was also a physicist by training before turning to biology.
- I was under the impression that notions like "information content", "programs", "feedback loops" etc that are commonly associated with engineering/computer science were relatively recent ways of looking at biology. Apparently, though, these viewpoints been around since the 40's, so I'm left wondering what caused their new rise to prominence.


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