Chemiotics: Causality in the cell and how puppies give us hope

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Posted on behalf of Retread

This post is pretty philosophic, but it discusses some issues raised by the previous post that shouldn’t be ignored. Future posts will be far more chemical.

Do we have any hope of constructing a nice chain of causality for what happens when we throw epidermal growth factor (EGF) at a Hela cell (described in the last post) — e.g., the EGF receptor activates kinases 1 through N, each of which phosphorylates substrates (some of which are other kinases) which eventually phosphorylate the 924 sites on the 2,244 proteins (and in the correct temporal order to boot). I don’t think there are enough researchers to do it, or labs to hold them. Even worse, if the results were available, I don’t think our minds are strong enough to grasp them.

A big stumbling block would be the multiple degrees of feedback present even with something as simple as phosphorylation and dephosphorylation. Simple ideas of causality and control vanish with feedback (see two posts back — “The Decline of Master Gland…”). Causality is inherently a linear, sequential idea. Even chaos theory is basically causal, although predictability goes out the window.

That’s not to say our brains don’t do incredibly complex things such as just recognizing people. You never see anyone at exactly the same angle, under the same light, with the same background. People are usually moving, attired differently, etc., etc… Yet our brains in some way compute an invariant that computer science can only dream about permitting instant recognition. As people move about and you interact with them, zillions of new sensory inputs must be absorbed, transformed and matched to the same invariant. Since we do all this unconsciously, we don’t think anything of it.

Yet we don’t do very well predicting events where feedback is involved (like the stock market where most people lose). Perhaps the next step up in human intelligence is the ability to perceive the various forms of multiloop feedback, the way we recognize faces and people.

Could our brains change that fast? Possibly. Consider the man’s best friend vs. the chimp. [Science vol. 298 pp. 1634–1636 (2002)] Chimpanzees are terrible at picking up human cues as to where food is hidden, even when the cues are as obvious as pointing to the food container. Even chimps that eventually perform well, take dozens of trials or more to learn what the cues mean. I find this surprising.

However, puppies (raised with no contact with humans) do much better at this than chimps — anyone owning a dog knows they can read us like a book. Wolf cubs don’t do better than the chimps, even cubs raised by humans. This implies that during the process of domestication, dogs have been selected for a set of cognitive and social abilities that allow them to communicate with us. Domestication has only gone on for 10,000–15,000 years (the dawn of agriculture). I find it absolutely incredible that we could have changed the dog’s brain in what is basically a microsecond in evolutionary time. Yet we did. Hopefully our brains are as plastic.

Not to be too depressed by this. There clearly are single chains of causality in the cell and chokepoints which we can find and modify. Consider Gleevec. Success stories like this provide employment for legions of chemists.

Stu Cantrill

Chief Editor, Nature Chemistry, Springer Nature