Why biology is more than genetics and biochemistry?

The caption is the subtitle of a talk given by Eric Siggia. If ever there is talk that is deeply influential to me, I bet it is this one. If ever there is a single quote that keeps me contemplating for long and (maybe in the years to come), it is this quote.

When I was a second-year undergrad, I was obsessed in natural history, studying insects all the time. I was committed to study ecology then. Later, when I was in my third year, I met Chung-I Wu, who told me that genetics, which attempts to link phenotypes with genotypes, is the most fundamental subject in biology. I took it as true and decided to be a geneticist instead.

The birth of genetics surely marks a big leap in the history of biology. The later discovery of DNA as the genetic material is even exciting, indicating that the remarkable diversity exhibited by the organisms inhabiting this planet, from bacteria to plant, from fungi to vertebrates, share the same form of code of inheritance, and it is the change of this code that leads to the change of life form, hence the diversity. What a beautiful unity biology has achieved thus far!

The physicist and Nobel laureate Jean Perrin once said that the essence of scientific progress is to be able "to explain the complex visible by some simple invisible." Under such an insightful distillment, disovering DNA as the genetic material is surely a feat of scientific progress. The principle of natural selection brought up by Charles Darwin is undeniably another milestone of this kind, which is able to explain the diverse phenomena in biological world by a simple rule.

However, links between DNA and phenotypes, as genetics studies, are neither invisible nor simple. For the visibility, we know for sure there are macromolecular interactions in action down beneath the cell membrane; we can see them either through advanced microscopes directly or via experiments indirectly. For the complexity, generations of biochemists, cell biologists, and most importantly, geneticists, dedicate themselves to unveil the links, but, a bit discouragingly, we still don't know much about how genes conspire to produce phenotypes, especially when it comes to complex traits in higher eukaryotes.

For long it has baffled me that a great amount of graduate students are willing to spend their entire degree research on a couple of proteins and their interactions. An even more brash thought is, even they have discovered many important pathways, so what? It certainly sounds arrogant for the time being, when we are still naive about the physical basis of life and are making efforts to discover them. However, if we take understanding how life really works as our ultimate goal, I would think discovering some pathways can be, at best, some minor, if not trivial, success.

If one seeks to know how life really works, s/he is actually asking why, instead of how (as genetics/biochemistry/... pursue). In my opinion, knowing the answer to the why questions represents a big conceptual progress, while knowing to answer the how questions is not now.

That is why I have been thinking about moving to the bacteria/virus/yeast systems, after thinking about being a fly evolutionary geneticist for years. I think there is a spectrum of model organisms in biology. One one end is mammals like rats, which are extremely complex yet very similar to human so that studies of them can have promising applications in medicine, pharmacology, etc. On the other end are those microbes, which have beautiful simplicity, have been subject to most thorough studies and are the most probable for quantifications. If any true insight of the working of life can emerge, it most likely comes from them.

Biology is now in an era of rapid expansion, with many researchers with different backgrounds entering it each year. Among the other disciplines, I think engineering is the most useful as a tool and perspective for biologists. While scientists discover features and rules of natural systems, engineers invent systems with desired features under the same set of rules. Their perspectives are reverse and hence potentially complementary. At some points it may be rewarding to think in an engineering way of biological systems, and we may break a crack on the why questions.

Life is short. Besides doing what one is capable of, s/he should be more encouraged to do what s/he likes. Having a natural tendency of exploring things at a fundamental level, I look forward to such a move. It will be tough, but I just like it.