Stuart Kauffman argues that physics cannot explain biology, and he is right. However, I am willing to grant him this not because his book Reinventing the Sacred makes a clear case, but because I already agreed with its central premise, which is that the reductionist approach to science — the idea that physics explains chemistry, chemistry explains biology, and so forth — has its limits. The book nevertheless provides much food for thought; indeed, its chief merit is that it makes the reader ask fruitful questions. However, it falls short of making an argument that might overturn an entrenched position.

In addition to his central theme of reductionism and what might replace it, Kauffman — a complexity theorist and professor of both biology and physics at Calgary University in Canada — has two further aims for his book. One is to present to the non-expert some fascinating areas of science such as chemical-reaction networks, evolution and graph theory. The other is more ambitious: it aims to reassess in a positive way those areas of human life normally called sacred or spiritual, but from a point of view that does not accept supernatural theism.

Kauffman is at his best when writing about what he knows: complexity theory applied to theoretical biology, and some philosophy. Complexity theory deals with systems that typically involve feedback, non-linearity and structure at many scales; such systems turn out to share patterns of behaviour. Physics has made great strides in describing deterministic behaviour on the one hand and randomness on the other, but “critical behaviour” lies right on a fascinating borderline between these two regimes, and it deserves the widespread attention that Kauffman invites.

His introduction to Boolean networks is clear and stimulating, and their application to the cell’s genetic control machinery is both beautiful and striking. While reading this chapter, it suddenly became obvious to me why a mere gene count is a completely inadequate measure of the complexity of the associated organism. The fact that the human genome is shorter than some, such as the lungfish, should not have surprised anyone.

Kauffman’s treatment of the philosophy of mind is not as careful as a technical treatise would need to be. Still, it is sound and avoids the woefully inadequate statements that have sometimes appeared in connection with neuroscience in otherwise serious scientific journals — particularly claims that demonstrating a correlation between physical brain activity and particular thoughts resolves the mind–body problem or proves the absence or presence of God.

Another strength of the book is that Kauffman maintains reasonably clear lines of demarcation between speculation and knowledge. Within that proper constraint, the text makes some bold and useful speculations, such as the idea that quantum coherence could extend far enough from the surface of protein molecules in the cell to link one protein to another via aligned water molecules. Such speculations are useful because they are both testable and (just) feasible.

Because of these strengths, I would recommend Reinventing the Sacred as a healthy read for anyone who thinks that reductionism is the whole story of science. Reductionism is a good slave but a poor master; in other words, it is the right model for almost all the science we have discovered so far, but it is not necessarily the whole story. Cracks in the reductionist edifice include quantum entanglement, emergent phenomena, criticality and the oldest one of all: human free will, without which it is debatable whether any reasoning, and therefore any science, is possible.

On balance, this is a useful book. However, it also contains some glaring errors and omissions. The chapter on the quantum brain, for example, overinterprets the concept of decoherence, misapplies the word “acausal” and misses out entanglement altogether. The book is also repetitive, and sometimes unpersuasive or overblown. Take, for example, Gödel’s incompleteness theorem, which states that any large enough, finite system of axioms and rules of deduction must give rise to propositions the truth of which cannot be decided within the system. This theorem is relevant to Kauffman’s argument because it shows that not even formal logic can be reduced to a finite number of ideas; mathematics is a rich tapestry of concepts, not a pyramid. Kauffman briefly sketches Gödel’s theorem no less than four times, but he never describes it sufficiently well for a reader unfamiliar with it to follow the argument. On the other hand, if readers are already familiar with Gödel, they do not need repeated incomplete sketches.

Moreover, the central argument is unconvincing when the book implies that a case has been proven when it has not. Concerning the animal heart, for example, an early chapter promises “the organization of the heart arose largely by natural selection, which, as we will see, cannot be reduced to physics”, and in due course some relevant evidence is given. However, when later the text says things like “…as we have seen, this cannot be reduced to physics”, it leaves the reader feeling that something was missing in the middle. The evidence offered is that the emergent complexity of the biosphere may exceed the capacity of any compact description available beforehand to capture it. This and other arguments provide telling evidence for the case against reductionism, but it is, I think, premature to claim that we can prove the case sufficiently well to make reductionism clearly untenable.

The single greatest problem with this book is not in the science, however, but in the reasoning about the sacred. I am encouraged that Kauffman is willing to address questions of meaning and purpose, and his approach is surely preferable to pseudo-scientific statements along the lines of “the purpose of human life is to replicate genes”. His aim is valid and worthy: to draw people together around shared values. With a view to this, the book argues for a kind of pan-theism in which the word “god” is applied to the emergent creativity that exists in the universe.

Kauffman is welcome to promote this idea, but he should recognize that this type of thinking has a very long history and its shortcomings have been carefully thought through. For example, it does not adequately address our most basic hunches, such as the value of individual people above grand impersonal systems, and the need for justice or forgiveness. I would encourage him to explore instead those threads of religious thinking that are willing to seek answers beyond physicality, but that take physical evidence seriously.

In July 1997 Adrian Parsegian, a biophysicist at the National Institutes of Health in the US and a former president of the Biophysical Society, published an article in Physics Today in which he outlined his thoughts about the main obstacles to a happy marriage between physics and biology. Parsegian started his article with a joke about a physicist talking to his biology-trained friend.

Physicist: “I want to study the brain. Tell me something helpful.”
Biologist: “Well, first of all, the brain has two sides.”
Physicist: “Stop! You’ve told me too much!”

Parsegian went on to list a few areas in biology where input from physicists is particularly welcome. But his main conclusion was that physicists must really learn biology before trying to contribute to the field. He also warned that it may not even be enough for a physicist to have a biologist friend to act as an “interpreter” to translate a problem into the language of physics.

Despite being gentle and elegantly written, the article provoked a stormy reaction from Robert Austin, a physicist at Princeton University, who accused Parsegian of forbidding physicists from tackling the big questions in biology. My view lies somewhere between those of Parsegian and Austin, and, in my opinion, the relationship between physicists and biologists has improved on some fronts in the 12 years since Parsegian’s article first appeared. However, I believe that those relationships are still being poisoned by a number of misguided beliefs that are preventing physicists and biologists from working closer together.

More than beliefs?

Back in the early 1970s, when I was a first-year PhD student at the Frumkin Institute in Moscow, I used to attend theoretical seminars chaired by Benjamin Levich — a former pupil of Lev Landau — who was widely regarded as the founding father of physical-chemical hydrodynamics. Whenever an overly enthusiastic speaker would tell us with 100% confidence how, say, electrons and atoms behave in a solvent near an electrode, Levich would spice up the seminar by joking “How do you know? Have you been there?”

Almost four decades on, physicists now have plenty of experimental tools to “go there”. For example, modern X-ray synchrotron sources allow researchers to look at how crystals form, to discover how biological samples mutate and even to pinpoint where ions adsorb on DNA; while techniques such as the fluorescence imaging with nanometre accuracy (FIONA) allow the motion of proteins such as myosin or kinesin to be traced in real time. But although these techniques often produce fascinating results, they may not be enough without a deep theoretical analysis of what one is actually “seeing”. So, the first of these misconceptions is that “seeing is believing”. A pretty picture may have a beguiling charm, but on its own it is not enough.

The second belief hampering collaboration is that the formalism of a biological theory must be simple — it should not contain more than exponential functions and logarithms (no Bessel functions, please!). Otherwise, the job should be left for computers to do. This point of view was advocated by Rob Philips of the California Institute of Technology, who came to his new love — biology — from solid-state theory. I strongly disagree with that view, however, and I used to argue with him about it when we were both on sabbatical at the Kavli Institute for Theoretical Physics in Santa Barbara. As I used to point out, James Watson and Francis Crick could never have deciphered the structure of DNA from the X-ray scattering patterns obtained by Rosalind Franklin and Maurice Wilkins had they not had the mathematical tools developed by Crick, William Cochran and Vladimir Vand a year earlier (1952 Acta. Crystollograph. 5 581). Indeed, Bessel functions were at the heart of that analysis.

The third belief is that biologists will never read scientific papers containing mathematical formulas. As Don Roy Forsdyke, a biochemist at Queen’s University in Ontario, Canada, once told to me, “The biological literature is vast. Biologists have too many papers to read and too many experiments to make. They will leave aside any reading that looks difficult.” If this is true, and I think it is, physicists are in big trouble.

This brings us neatly to the next belief, which is that it is impossible for physicists to publish a serious theoretical paper in a biological journal. Theorists need mathematical derivations to validate their findings, but any paper containing derivations will be rejected. If you then publish the article in a physics journal, it will not be read by those to whom it is addressed. Actually, good papers of that kind are still sometimes published and read, but this remains a difficult issue.

DNA revolution

Physicists want to simplify and unify things, as much as possible, whereas biologists resist the reductionist approach and are happy with diversification and complexity. So, the biologists’ fifth belief is that physicists are too ignorant about diversity to offer them anything useful. Biologists admit that physicists can provide, say, a new spectroscopic technique or apparatus for measuring forces, but that is about it. In their view, biology should be left to the professionals.

The final belief is that biologists think physicists made one big breakthrough — elucidating the structure and function of DNA — but that a similar revolution is unlikely to ever happen again. However, the key to that discovery was the “chemistry” between Watson (a biologist) and Crick (a physicist), which helped them to find a common language and gave rise to the idea of DNA replication and the subsequent principles of molecular biology.

I believe that we can expect other breakthroughs of this sort because physics and mathematics have a long history of revolutionizing not only science but our lives too.

Meaningful collaborations

In spite of all this, my feeling is that physicists and biologists are getting on better. For example, last month, together with Parsegian and Wilma Olson of Rutgers University, who is another former president of the Biophysical Society, I organized a conference entitled “From DNA-Inspired Physics to Physics-Inspired Biology”. Attended by some 140 researchers, the meeting was held at the International Centre for Theoretical Physics (ICTP), in Trieste, Italy, and sponsored by the ICTP and co-sponsored by the Wellcome Trust. But the conference was not just for physicists interested in biology. It was also aimed at biologists who were interested in learning what new physical methods and existing knowledge could offer them, as well as pinpointing for physicists the subjects that biologists think could benefit from input from physics.

The conference included over 60 talks — demonstrating the interplay between physics and biology — on everything from DNA mechanics, structure, interactions and aggregation to DNA compaction in viruses, DNA-protein interaction and recognition, DNA in confinement (pores and vesicles) and smart DNA (robotics, nano-architectures, switches, sensors and DNA electronics). More details are available online.

Taking Rutherford’s famous saying that there is physics and everything else in science is stamp collecting, Paul Selvin, a physicist at the University of Illinois, recently said that if Rutherford were alive today, he would have said that “all science is either biology or tool-making for biology or not fundable”. Today, in general, the arrogance is rarely on the side of physicists. But to overcome the barrier of scepticism, physicists need to demonstrate (or, even better, inspire biologists to show) that insights from physics do not just apply in model systems in the lab but work equally well inside the real world of the cell.

Crick not only had a great mind and was very serious about biology but he was also lucky to meet the right collaborator in Watson. Many of us seeking to do important work in biology will not be able to do so alone unless we too find the right match. The future is far from hopeless — and meetings such as the one held in Trieste last month may well make the difference. As the Cambridge physicist Stephen Hawking once said, “The greatest discoveries of the 21st century will take place where we do not expect them.” Likewise, I am convinced that great surprises and discoveries in biology will come from physics.