Physicist Nigel Goldenfeld hates biology: “At least not in the form in which I was taught it in school,” he says. “It was like a rambling set of facts. There was practically no precise quantitative analysis. This attitude might surprise anyone who looks at the many projects Goldenfeld's lab is working on.
He and his colleagues monitor the collective and individual behavior of honeybees, analyze biofilms, observe genes jumping, assess the diversity of life forms in ecosystems, and explore the relationship of microbiomes.
Goldenfeld is the head of NASA's Astrobiology Institute for General Biology, but he does not spend most of his time in the physics department at the University of Illinois, but in his biological laboratory on campus in Urbana-Champaign.
Nigel Goldenfeld is not the only physicist trying to solve problems in biology. In the 1930s, Max Delbrück changed the concept of viruses. Later Erwin Schrödinger published What is Life? The physical aspect of a living cell”. Francis Crick, a pioneer in X-ray crystallography, helped uncover the structure of DNA.
Goldenfeld wants to benefit from his knowledge of condensed matter theory. In studying this theory, he simulates the development of a sample in a dynamic physical system in order to better understand various phenomena (turbulence, phase transitions, features of geological rocks, the financial market).
An interest in the emergent state of matter led physicists to one of the greatest mysteries of biology - the origin of life itself. It was from this task that the current branch of his research developed.
"Physicists can ask questions differently," Goldenfeld is convinced. “My motivation has always been to look in biology for areas where such an approach would make sense. But to succeed, you need to work with biologists and, in fact, become one yourself. Physics and biology are equally needed."
A representative from the magazine Quanta spoke with Goldenfeld about collective phenomena in physics and the extension of the synthetic theory of evolution. They also discussed the use of quantitative and theoretical tools from physics to lift the veil of mystery that surrounds early life on Earth and the interactions between cyanobacteria and predatory viruses. The following is a summary of this conversation.
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Physics has a basic conceptual structure, while biology does not. Are you trying to develop a general theory of biology?
“God, of course not. There is no single theory in biology. Evolution is the closest thing you can bring to it. Biology itself is the result of evolution; life in all its diversity and without exception has developed as a result of evolution. It is necessary to truly understand evolution as a process in order to understand biology.
How can collective effects from the field of physics complement our understanding of evolution?
When you think about evolution, you usually tend to think about population genetics, about the repetition of genes in a population. But if you look at the Last Universal Common Ancestor (the ancestor organism of all other organisms, which we can trace through phylogenetics), you will understand that this is not the very beginning of the origin of life.
Before that, there was definitely an even simpler form of life - a form that did not even possess genes when there were no species yet. We know that evolution is a much broader phenomenon than population genetics.
The last universal common ancestor lived 3.8 billion years ago. Planet Earth is 4.6 billion years old. Life itself has traveled from inception to the complexity of the modern cell in less than a billion years. Probably even faster: since then, relatively few developments have occurred in the evolution of the cellular structure. It turns out that evolution has been slow over the past 3.5 billion years, but very fast in the beginning. Why has life developed so rapidly?
Karl Woese (biophysicist, died 2012) and I believed that initially the development took place differently. In our era, life evolves through "vertical" inheritance: you pass on your genes to your children, they, in turn, to their children, and so on. The "horizontal" transfer of genes is carried out between organisms that are not connected with each other.
This is now happening in bacteria and other organisms with genes that are not very important in cell structure. For example, genes that give resistance to antibiotics - thanks to them, bacteria acquire protection from drugs so quickly. However, in the early phases of life, even the basic mechanism of the cell was transmitted horizontally.
Previously, life was a cumulative state and was more a community closely knit by gene exchange than just a collection of individual forms. There are many other examples of collective states, such as a colony of bees or a flock of birds, where the collective seems to have its own personality and behavior, arising from the elements and ways in which they interact. Early life was communicated through gene transfer.
How do you know?
“We can explain such a rapid and optimal development of life only if we allow the effect of this“early network”and not the [family] tree. About 10 years ago, we discovered that this theory applies to the genetic code, to the rules that tell the cell which amino acids to use to make protein. Every organism on the planet has the same genetic code with minimal differences.
In the 1960s, Karl was the first to come up with the idea that the genetic code we possess is as good as possible to minimize errors. Even if you get the wrong amino acid due to a mutation or a mistake in the cellular transport mechanism, the genetic code will pinpoint the amino acid you should receive. So, you still have a chance that the protein you produce will function and your body will not die.
David Haig (Harvard) and Lawrence Hirst (University of Bath) were the first to demonstrate that this idea can be qualitatively evaluated using the Monte Carlo method: they tried to find out whose genetic code is most resistant to this kind of error. And we ourselves became the answer. This is truly a startling discovery, but not as widespread as it should be.
Later, Karl and I, together with Kalin Vestigian (University of Wisconsin at Madison), performed virtual simulations of groups of organisms with many artificial, hypothetical genetic codes. We created computer virus models that mimicked living systems: they had a genome, expressed proteins, they could reproduce themselves, survive selection, and their adaptability was a function of their own proteins.
We found that not only their genomes evolved. Their genetic year also evolved. When it comes to vertical evolution (between generations), the genetic code never becomes unique or optimal. But when it comes to the "collective network" effect, then the genetic code is rapidly evolving into the unique optimal state that we observe today.
These findings, and questions about how life could have acquired these genetic codes so quickly, suggest that we should be seeing signs of horizontal gene transfer earlier than in the Last Universal Common Ancestor, for example. And we see them: some of the enzymes that are associated with the main mechanism of cell translation and gene expression show strong evidence for early horizontal gene transfer.
How could you rely on these conclusions?
- Tommaso Biancalani and I (now at MIT) conducted a study about a year ago - our article was published about him - that life automatically turns off horizontal gene transfer as soon as it became complicated enough. When we simulate this process, it basically shuts down by itself. Attempts are made to perform horizontal gene transfer, but almost nothing takes root. Then the only dominant evolutionary mechanism is vertical evolution, which has always been present. We are now trying to do experiments to see if the kernel has completely made the transition from horizontal to vertical transmission.
Is it because of this approach to early evolution that you said that we should speak differently about biology?
People tend to think of evolution as synonymous with population genetics. I think this is, in principle, correct. But not really. Evolution took place even before genes existed, and this cannot be explained by statistical models of population genetics. There are collective ways of evolution that also need to be taken seriously (for example, processes like horizontal gene transfer).
It is in this sense that our understanding of evolution as a process is too narrow. We need to think about dynamic systems and how it is possible that systems capable of developing and reproducing are capable of existing at all. When you think about the physical world, it is not obvious why you just don't do more dead things.
Why does the planet have the ability to support life? Why does life even exist? The dynamics of evolution should be able to resolve this issue. It is noteworthy that we do not even have an idea on how to resolve this issue. And given that life began as something physical, not biological, he expresses a physical interest.
How does your work on cyanobacteria fit into the application of the theory of condensed matter?
- My graduate student Hong-Yang Shi and I modeled an ecosystem of an organism called Prochlorococcus, a cyanobacterium that lives in the ocean and uses photosynthesis. I think this organism may be the most abundant cellular organism on the planet.
There are viruses, "phages" that prey on bacteria. A decade ago, scientists discovered that these phages also have genes for photosynthesis. You don't usually think of a virus as someone who needs photosynthesis. Then why do they carry these genes?
“It seems that bacteria and phages do not behave exactly like a predator-prey model. Bacteria do benefit phages. In fact, bacteria could prevent phages from attacking them in various ways, but they don't, at least not entirely. Phage photosynthetic genes originally came from bacteria - and, surprisingly, the phages then transferred them back to the bacteria. Over the past 150 million years, the genes for photosynthesis have moved between bacteria and phages several times.
It turns out that genes develop much faster in viruses than in bacteria, because the replication process for viruses is much shorter and more likely to make mistakes (replication is the process of synthesizing a daughter molecule of deoxyribonucleic acid on the template of the parent DNA molecule - no more).
As a side effect of phage hunting for bacteria, bacterial genes are sometimes carried over into viruses, where they can spread, develop rapidly, and then return to bacteria, which can then benefit from it. Therefore, phages were beneficial to bacteria. For example, there are two strains of Prochlorococcus that live at different depths. One of these ecotypes is adapted to live closer to the surface, where the light is much more intense, and the difference in its frequencies is greater. This adaptation may be due to the fact that viruses have evolved rapidly.
Viruses also benefit from genes. When a virus infects a host and replicates itself, the number of new viruses it creates depends on how long the captured cell can survive. If the virus carries the life support system (genes for photosynthesis), it can keep the cell longer in order to make more copies of the virus.
A virus that carries genes for photosynthesis has a competitive advantage over one that does not. There is breeding pressure on viruses to transfer genes that benefit the host. You would expect that because viruses mutate so quickly, their genes will quickly "degrade". But as a result of calculations, we found that bacteria filter "good" genes and transfer them to viruses.
Therefore, this is a cute story: the interaction of these bacteria and viruses resembles the behavior of a substance in a condensed state - this system can be modeled to predict its properties.
We talked about a physical approach to biology. Have you seen the opposite when biology inspired physics?
- Yes. I am working on turbulence. When I return home, it is she who keeps me awake at night. In an article published last year in Nature Physics, Hong-Yan Shin, Tsung-Ling Sheng and I wanted to explain in detail how a fluid in a pipe goes from a plastic state, where it flows smoothly and predictably, to a state of turbulence, where its behavior is unpredictable. and wrong.
We found that before the transition, turbulence behaves like an ecosystem. There is a special dynamic regime of fluid flow, similar to a predator: it tries to "eat" turbulence, and the interaction between this regime and the resulting turbulence leads to some of the phenomena you see when the fluid becomes turbulent.
Ultimately, our work assumes that a certain type of phase transition occurs in liquids, and this is what experiments confirm. Since the problem of physics turned out to be suitable for solving this biological problem - about the relationship between predator and prey - Hong-Yan and I knew how to imitate and simulate a system and reproduce what people see in experiments. Knowing biology really helped us understand physics.
Are there any limitations for the physical approach to biology?
- There is a danger of repeating only what is known, so you cannot make any new predictions. But sometimes your abstraction or minimal representation gets simplified and you lose something in the process.
You cannot think too theoretically. You should roll up your sleeves to study biology, be closely connected with real experimental phenomena and real data.
That is why our work is carried out in conjunction with experimenters: together with colleagues, I collected microbes from the hot springs of Yellowstone National Park, watched the “jumping” genes in living cells in real time, sequenced (sequencing - determining the amino acid or nucleotide sequence - approx. - intestinal microbiome of vertebrates. Every day I work at the Institute of Genomic Biology, although physics is my "native" field.
Jordana Cepelewicz
The translation was carried out by the project New