I recently needed to do a thing talking about what’s exciting in various different fields of physics, which led me to ask a colleague “What’s the most exciting stuff in biophysics these days?” One of his answers about cool new stuff led me to look back at some very old work, and it’s fascinating to see how the recent work parallels and complements the old, and fills in some of the spaces.
In recent years, Richard Feynman gets a lot of credit (maybe too much credit) for launching the fields of nanotechnology and quantum computing thanks to pieces he wrote in a kind of offhand and speculative way about fields that were sort of off to the side of the research he’s best known for. This is often held up as evidence of Feynman’s singular genius, but in fact poking at other fields in physicist-y ways that turn out to be productive is a fairly general behavior of physicists.
One of the best examples is the old work I was reminded of when I talked to my biophysicist colleague. In 1943, the Austrian physicist Erwin Schrödinger was working in Dublin, having been personally recruited there by Eamon de Valera to help found an Institute for Advanced Studies. Schrödinger was famous for his development of the quantum wave equation that bears his name, but had become disenchanted with the philosophical implications of that theory; his (in)famous cat gedankenexperiment was something of a parting shot on his way out of the field. He pursued other interests for the remainder of his career, most of which didn’t amount to much, but one odd side trip ended up being surprisingly important.
In February of 1943, Schrödinger delivered a course of public lectures in Dublin to an audience of several hundred (this probably tells you something about the entertainment landscape in WWII-era Ireland…), on the question “What Is Life?” This was successful enough that it was later published as a (short) book, adding the subtitle “The Physical Aspect of the Living Cell.” The lectures and book represent the attempt of a self-describe “naïve physicist” to understand the basic processes and properties of life in terms of fundamental physics principles.
This is a very physicist-y kind of thing to do, and Schrödinger is a clear and charming narrator as he goes through this approach. It’s notable for two clever lines of argument in the earlier chapters. The first has to do with scaling, specifically the question of why living things are so large compared to atoms. This is one of those questions that probably only occur to philosophers, theoretical physicists, and profoundly stoned college students, but Schrödinger notes that there’s actually a sensible physics answer: life relies on having various physical and chemical processes go forward in a reliable way, but quantum physics tells us that the states of atoms are fundamentally probabilistic. The way to reconcile these, it turns out, is to have huge numbers of atoms.
This is an example of something I wrote about a couple of years ago, and bang on about in my modern physics class: infinite numbers are much easier to deal with, physics-wise, than numbers you can count on your fingers. Schrödinger’s scaling argument makes a nice way to see this– if you have only a couple of atoms, you can’t say with any confidence when any of them will undergo any particular process, but if you have millions of them, you can make very solid statistical predictions about what fraction of those atoms will do that thing they do in the next short interval of time. Those behaviors are still statistical– you can’t say which atoms will react– but extremely reliable, in a way that the more quantum behavior of smaller numbers of atoms is not. Thus, to get the reliable laws they need to operate, living things should necessarily be pretty big compared to the scale of atoms.
The second argument has to do with information storage and retrieval in living things. Schrödinger notes that making something as complicated as a new cell requires a great deal of information about how molecules should be put together to make all the various bits of a living thing. This needs to be stored in a pretty compact way– small compared to a cell (but still involving many atoms)– and also needs to be fairly permanent in order for heredity to work as observed in nature. Going back to the quantum and statistical nature of thing, he argues that this points to a complex molecule– an “aperiodic crystal” (which has some potential as a band or album name)– as the storage medium, as the energy needed to re-arrange a molecule makes it exceedingly unlikely that this will happen spontaneously.
There’s a decent argument to be made that nothing in “What Is Life?” is actually ground-breaking, science-wise, and indeed Schrödinger openly acknowledges that he’s drawing on earlier work by Max Delbrück. It’s a very clear and cogent presentation of the core argument, though, and that has a good deal of value in inspiring young scientists to pursue similar inquiries. Both James Watson and Francis Crick, who later shared a Nobel Prize for discovering the structure of DNA, credited Schrödinger’s book as an influence pushing them toward biophysics.
Of course, being a very old work, Schrödinger’s “What Is Life?” has some flaws. In particular, it gets a little squirrelly in the last couple of chapters, where he turns to considerations of entropy. Entropy is, famously, a measure of the disorder of a system, which can be given a precise technical definition in terms of statistics. That disorder always increases over time, the famous Second Law of Thermodynamics (which is itself a statistical result, as discussed a bit in this book review).
The action of living things, though, seems to run counter to the increase of entropy– the growth and reproduction of cells, for example, certainly looks like making matter more orderly, not less. Schrödinger goes on at some length, much less cogently than in the earlier sections, about “negative entropy,” and the possibility of some new physical principle applying to living things. This was influenced in no small part by his interest in Vedic philosophy, but significantly undermines the ending of the book.
A more coherent explanation of the entropy issue Schrödinger fumbles involves recognizing that the seemingly anti-entropic behavior of life is really only a problem if you make the mistaken assumption that you’re dealing with a system in which there’s no energy input. That’s very clearly not the case for real-life situations involving, well, life– the operation of life is all about extracting energy from a larger environment, and using that energy input to do stuff.
A proper consideration of this scenario requires a more sophisticated approach to entropy, and that’s what my biophysicist colleague pointed me to. Specifically, the lab of Jeremy England at MIT, where they’re applying ideas from non-equilibrium thermodynamics to understanding the action of living objects. A lot of this is very much in the spirit of “What Is Life?”, though, you know, more modern and nuanced in its handling of the entropy question.
This parallel occurred to me specifically regarding a paper from 2013 on self-replication. Reproduction is one of the signature behaviors of living systems, and one that provides a nice way to see a connection to entropy, because it’s irreversible. That is, we regularly see living cells split in two, but never see two cells merge into one, which strongly suggests that the entropy of the two-copy system must be higher than that of the original single cell. And, indeed, when they do a detailed analysis of the process of a self-replicating system extracting energy from its environment and using that to make a copy of itself, they can show how much the entropy increases, and how much heat must be generated, and so on. Using some fairly minimal assumptions about what’s involved in the process, they can estimate various quantities and reproduction rates, and get numbers that are pretty close to what we see in real systems.
This is probably the most physicist-y approach to biology possible– skipping lightly past all the messy details of biochemistry to deal in high-level abstractions– but it works impressively well. And they’ve continued this general line of attack, looking into what statistical mechanics and thermodynamics can tell us about the minimum requirements for life-like behavior– self-replication, adaptation, etc.– to emerge from simple systems interacting with large environments. This kind of thing, as abstract as it may seem, has profound implications for models of how life initially emerged on Earth, and potentially elsewhere in the universe.
So, in the end, I do agree with my colleague that this is cool and exciting work in biophysics. And part of what makes it so interesting is the way it resonates with work from three-quarters of a century ago.