A new forum for Physics and Biology in Cambridge

The Theory of Living Matter is a new discussion group in Cambridge led by young physicists from the Theory of Condensed Matter (TCM) group in the Cavendish (Cambridge). The idea behind the group (www.tcm.phy.cam.ac.uk/tlm/) is to promote interactions between theorists and experimentalists in the realm of the biological questions and serve as a forum and a local hub for this topic. There have been two meetings to date with a fair amount of success.

This is a very good time for physicists to get into Biology and for biologists to deal with physicists. The main reason for this is that there is data and that therefore theory need not be some abstraction that describes a reality which does not exist; this has happened several times before and a good example is the surge of mathematical biology in the 60s and 70s which, deservedly, did not go very far because there was little to model or theorize about. Nowadays it is different, There is a huge amount of information or data (depending on who you talk to) waiting for an explanation, for a framework, for a model. Physicist (and mathematicians and engineers in the same group) are talking to biologists but for these two cultures to partner successfully there have to be some rules and here I would just like to provide some thoughts from my own experience over the last ten years.

For biologists, the most important point might surprise us (I am a biologist) and is encapsulated in two statements that an eminent biophysicist made to me many years ago and changed my view of Biology. They are obvious. We need to learn to measure and also appreciate the differences between averages and distributions. The first one is very important and might sound odd: physicists telling us that we need to measure? Physicists suggesting that we do not know how to do an experiment? Don’t we spend our lives doing experiments? Well, yes. But I am afraid that in the days of kits and, sequencing by post and high throughput-anything, our ability to make accurate measurements that give information has dwindled. I would even argue that our ability to even have our experiments driven by hypothesis is a thing of the past. Well, yes, this happens more in some disciplines than others but it is a trend. There are two exceptions. One is cell biology where a large influx of physicists over the years has created a good culture of measurement, hypothesis and quantitative science. The other one is, of course, evolutionary biology which today lives a Renaissance because of the abundance of data to check theories and test models. But in genetics and molecular biology things have drifted and for the most part we design experiments not with the idea of obtaining a measurement but with that of obtaining a result. This, of course does not apply to everybody but……….It is interesting that in many places computational biology is understood as advanced bioinformatics. So, it is indeed important that when we (biologists) design experiments we have a question in mind and ensure that we aim to get a measurement, a number.

The second point, the difference between averages and distributions, is trivial for those in the physical sciences and yet, it is totally unappreciated by the biologists; though I shall admit that this is slowly changing. A great deal of Biology is based on average values. A phenotype is an average value and this is what we use as reference in many different situations. Where before we had just an image or, as they say, a ‘representative image’, nowadays we often have some values, charts, with error bars which is, still, an average. This might work in some instances but we should think about whether it is the appropriate measure of what we need or not. Distributions are far too often neglected ignoring that it is here that lies the information. There are variables which under different circumstances have the same mean which results from different distributions; it is the distribution that matters, The trivial case here is cell division: a survey of a population in culture would show some cells dividing and some cells not dividing which would suggest that, on average, a cell divides 0.5 times. This makes no sense: the distribution and not the mean is the information here.

The importance of these two pieces of advice or realizations is that as we go beyond hunting genes and linking them to phenotypes, we are starting to see that cells, really the product of gene interactions, produce numbers and we need to understand those numbers. As any physicist knows, seeing the distribution associated with a variable is a way to get into the mechanism (in the sense a physicist uses this word: a causal explanation for an observation rather than Figure 8).

And while we are talking about physicists I also have something to say to them as to how to deal with biologists. A renown physicist doing biology starts many of his talks stating that he is a theorist and that without data he is disabled. As if experimentalists could live without data! As if we, biologists, just would like to potter around and this were the aim of our toilings!  Experimentalists are also theorists and this is something that any physicist, particularly theoretical physicist needs to appreciate when interacting with Biology. When an experimentalist probes into Nature, is not just pottering around, we are testing a hypothesis and sometimes a theory. Theoreticians running into Biology should bear this in mind. A physicist will be better prepared than a biologist to understand a measurement, maybe even to design an experiment, but there will be a need to understand that biological systems are not physical systems (‘From molecular to modular cell biology.’
Hartwell LH, Hopfield JJ, Leibler S, Murray AW. Nature. 1999 ). The differences will drive a physicist mad but if understood properly will bring some joy. And by the way, if you are a physicist getting into Biology, get as close to experiments as possible and even dip your fingers and your mind into an experiments. R. Feynman and F. Crick did it. Feynman worked for a while (well, a few weeks) in the lab of Delbruck in Caltech. At the time the hot topic was the genetic code and, as it happens, Feynman isolated some of the first intragenic suppressors. But Biology did not grab Feynman: too much variability, too early for predictions and calculations. The one who got hooked was F. Crick and you can see how and why in his book “What a Mad Pursuit’ where you can see his sharp mind in action and find much that is good about the role that physicists should play in Biology.

As a local, I am very pleased about the development of the Theory of Living Matter forum. Anything that is done to bring the ideas and methods of the physical sciences into Biology is a good thing but, more importantly, it is something much needed at the moment.