## Baseball Cards, Gene Regulatory Networks and Chance.

One of the first skills I ever mastered, when I was about 10 or 11, was how to flip baseball cards. One kid would flip a card spinning into the air and let it come down, heads or tails. The second player would then flip one of his cards, and If he matched the result of the first card flip he got to keep both cards. If he got the opposite result, he lost his card.

You would think that card flipping would be a random game of chance, like tossing a coin or rolling dice. It wasn’t. After a great deal of practice (about ten times the amount of time I spent doing homework) I was able to flip cards in a way that gave whichever result I wanted. I was able to flip up to 50 heads in a row, and other kids could do it also.

I didn’t realize at the time, but what I had done was a very successful experiment to demonstrate the difference between deterministic chance and true stochastic randomness. Card flipping is like coin tossing, or the weather or the stock market. It is deterministic, but usually cannot be predicted or controlled, unless you know all the myriad hidden inputs that give the result. Unlike card flipping, nobody can control the result of a coin toss, not to mention the weather or the market.

We know about stochastic events in physics, the spin of electrons, the decay of radioactive atoms. But in biology what we have are a lot of deterministic but highly complex events. To some degree, all cellular processes are ruled by the chemical law of mass action, which is based on the probability that enzymes “accidently” bump into their substrates. Life found a way to work around this by having important reactions take place not in solution, but on solid surfaces, like ribosomes, or membranes, or other cellular structures.

There are plenty of chance events in biology. Mutations are the most well known, but  mutations are deterministic and not truly stochastic. They are caused by replication errors, by faulty DNA repair, and by chemical and radiation damage from the outside. It has long been known that there are hot spots for mutation, depending on type of base, and on the surrounding sequence characteristics. We don’t know enough to be able to predict mutational outcome, but that is more analogous to the butterfly effect in weather prediction, than to quantum uncertainty (which has been postulated to be a driver for mutation).

I am in the middle of a project to investigate the theory of gene regulatory networks (GRNs) courtesy of a grant from the John Templeton Foundation. Andreas Wagner, one of the leading pioneers in this field, is exploring how models of these networks, (which are groups of genes that regulate each others’ expression) function. He has found that the final phenotype of a gene regulatory network is not predictable from its original state.  In my work, I find the same thing, but surprisingly this is true even in very simple network models.

These regulatory networks are crucial to cell functioning, and probably to evolution, according to the new Extended Synthesis model. And yet, we see with GRNs  (as we do with mutations) evidence for deterministic chance.  I know that my GRN models are deterministic, because I made them. And very simple model networks do follow expected mathematical laws (on average, at least), but as network complexity increases, such laws quickly become impossible to formulate. Eventually, one sees evidence of true chaotic behavior.

In so much of biology, what we see as highly complex and random chance events, appear that way to us, because we cannot know all the contributing factors, even using simple constructed models. But, if we were God-like, things would be quite different. God is not limited by mathematics, nor by any form of ignorance of causal factors. What we see as chance, God decrees as natural law.

This is not a new idea, but it is exciting that the work many scientists are now doing on the deeper principles of biological control and evolutionary mechanisms are reinforcing that idea. I am certain that we will continue to make progress in our understanding of how God’s most marvelous creation (life) works  Perhaps we will eventually learn (again, for me) the secrets of how to flip baseball cards.

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