The first evidence in favor of the physical theory of the origin of life

Take chemistry, add energy, and get life. The first tests of the provocative hypothesis of the origin of life put forward by Jeremy England have been carried out, and they show how order can arise out of nothing

Biophysicist Jeremy Ingland excited the public in 2013 with his new theory , making the origin of life an inevitable consequence of thermodynamics. His equations imply that under certain conditions groups of atoms naturally rearrange themselves to spend more and more energy, contributing to the continuous dissipation of energy and the emergence of "entropy" or disorder in the Universe. Ingland says that this restructuring effect, called adaptation by scattering, stimulates the growth of complex structures, including living organisms. The existence of life is not a mystery and not luck, he wrote in 2014 , it follows from the basic physical principles and "should be as unsurprising as the stones rolling from the mountain."



Since then, England, a 35-year-old associate professor at the Massachusetts Institute of Technology, has been testing aspects of his idea in computer simulations. Two of the most important of his works were published in July 2017 - the most interesting result appeared in the journal Proceedings of the National Academy of Sciences (PNAS), and the second - in Physical Review Letters (PRL). The results of both experiments, apparently, confirm Ingland's main statement about adaptation under the influence of scattering, although the possibility of their application to real life remains in question.



“This is obviously a groundbreaking study,” said Michael Lässig , a specialist in statistical physics and quantitative biology from the University of Cologne in Germany, about the work from PNAS written by Ingland and the MIT postdoc, Jordan Horowitz . Lassig writes that this is “an example of studying a given set of rules in a relatively small system, so it is too early to say whether it will be possible to generalize it. However, the obvious interesting question is what it means for life. ”



The work deals with practically important details of cells and biology, and describes a simplified, simulated system of chemical compounds, in which, nevertheless, the spontaneous emergence of an exceptional structure is possible - this phenomenon Ingland considers to be the driving force behind the emergence of life. “This does not mean that you are guaranteed to receive this structure,” explains Ingland. The dynamics of the system is too complex and non-linear to predict results.



The simulation involves soup from 25 chemical compounds that interact with each other in a huge number of ways. Energy sources force some of these reactions to take place, as sunlight triggers ozone production in the atmosphere, and adenosine triphosphate chemical fuel drives the processes in the cell. Starting with random initial concentrations, reaction rates and “forced landscapes” [forcing landscapes] - rules that tell which reactions receive external forces and which — a simulated network of chemical reactions develops until it reaches a final, stable state, or “fixed point” ".







The system often calms down in equilibrium with a balanced concentration of chemicals and reactions, with equal probability going in both directions. The desire for equilibrium, for example, a cup of coffee cooling down to room temperature is the most familiar result of the second law of thermodynamics , postulating that energy is constantly spreading, and the entropy of the Universe is constantly increasing. The second law works because energy has more ways to distribute between particles than to concentrate in one place, therefore as the particles move and interact, the distribution of energy between them is more likely.



But for some initial conditions, the network of chemical reactions in the simulation develops quite differently. In these cases, it evolves to fixed states that are far from the equilibrium point, where it begins to actively drive reaction cycles, taking the maximum available amount of energy from the environment. These cases can be considered "examples of fine adjustment" between the system and the environment, as Horowitz and Ingland put it, when the system finds "rare states of extreme thermodynamic coercion."



Living beings also maintain stable states of extreme coercion: we are super-consumers, burning huge amounts of chemical energy through reactions in cells, thereby increasing the entropy of the Universe. The computer emulates this behavior in a simpler and more abstract chemical system, and shows that this state can appear “right away, without a huge waiting time,” says Lassig, which shows the availability of these points in practice.



Many biophysicists believe that in the history of life there could be something similar to what Ingland describes. But did he find the most important stage in the origin of life, depends on what is the essence of life? Here opinions differ.

Form and functioning

Ingland, a comprehensively gifted person who worked at Harvard, Oxford, Stanford and Princeton before coming to MIT at 29, believes that the essence of living things is the exceptional arrangement of their constituent atoms. “If we imagine that I randomly mix the atoms of a bacterium — I take it, mark it, and mix it in space — I’ll probably get some garbage,” he wrote earlier. “Most of the combinations of atoms will not turn into such a metabolic power station as a bacterium.”



A group of atoms is not easy to access chemical energy and burn it. To accomplish such a task, atoms must be lined up in a very unusual structure. According to England, the existence of a relationship of form and function "implies that the environment poses a problem that the resulting structure solves."



But how and why do atoms take on a certain form and function of a bacterium, with its optimal configuration for the consumption of chemical energy? Ingland believes that this is a natural consequence of thermodynamics for systems that are far from the equilibrium point.



The physical chemist, Nobel Prize laureate Ilya Prigogine , dealt with similar ideas in the 1960s, but his methods were limited. Traditional thermodynamic equations work well only for studying systems that are in a state close to the equilibrium state, such as a slowly cooled or heated gas. Systems fueled by powerful external energy sources have much more complex dynamics and are much more difficult to study.



The situation changed in the late 1990s, when physicists Gavin Crookes and Chris Yarzinsky [Gavin Crooks and Chris Jarzynski] derived " fluctuation theorems ", which can be used to calculate how direct physical processes occur more often than inverse. Theorems allow researchers to study the evolution of a system, even far from equilibrium. Ingland's new approach, according to Sarah Walker , a theoretical physicist and specialist in the origin of life from the University of Arizona, is to apply fluctuation theorems to "problems associated with the origin of life." I think he is the only person of them who does it quite thoroughly. ”



Coffee cools due to the fact that nothing heats it, but Ingland’s calculations suggest that atomic groups fed by external sources of energy may behave differently. They seek to connect to these energy sources, leveling up and switching places so as to better absorb energy and dissipate it in the form of heat. He further showed that this statistical trend towards energy dissipation can support self-reproduction (as he explained in 2014, “making yourself copies of yourself is a great way to dissipate more energy). Ingland believes that life, and its extraordinary combination of form and function, is the result of adaptation, fueled by the desire for dispersion and self-reproduction.



However, even with the use of fluctuation theorems, the conditions on the early Earth or in the cell will be too complicated for predictions to be made based on these principles. Therefore, ideas need to be tested under simplified conditions simulated on a computer in an attempt to get closer to realism.



For PRL, Ingland et al., Tal Kachman and Jeremy Owen from MIT, simulated a system of interacting particles. They found that the system increases the absorption of energy over time, forming and breaking bonds in order to better resonate with its driving frequency. “This is in some sense a simpler result” than the work for PNAS, which involves a network of chemical reactions, says Ingland.



In the second work, he and Horowitz created difficult conditions in which special configurations of atoms would have to be connected to available energy sources, just as the special configuration of the bacteria atoms allows it to metabolize. In the simulation, external sources of energy fueled certain chemical reactions in the reaction network. The activity of such stimulation depended on the concentrations of various chemical compounds. With the course of reactions and increasing concentrations, the power of stimulation could change dramatically. Such harshness made it difficult for the system to “find combinations of reactions capable of optimally extracting available energy,” explains Jeremy Gunawardenna , a mathematician and systems biologist at Harvard Medical School.



And yet, when researchers allowed a network of reactions to evolve in such an environment, it became finely tuned to this environment. The random set of initial conditions evolved and assumed rare states of vigorous chemical activity and extreme support four times more often than expected. And when such results came, it happened very sharply. In this case, the systems passed through cycles of reactions and dissipated energy in the process, which, from the point of view of Ingland, is the simplest relationship between form and functionality necessary for the emergence of life.

Information processors

Experts say that the next important step for Ingland and his colleagues will be scaling the networks of chemical reactions in order to see whether there is a dynamic evolution with them to rare fixed states of extreme support. They may also try to make the stimulation less abstract by bringing chemical concentrations, reaction rates and support conditions to those that could exist in tidal creeks or near volcanic tubes in the primary broth of the early Earth (but reproducing the conditions from which life actually arose these are mainly guesses and assumptions). Raul Sarpeshkar , a professor of mechanical engineering, a physicist and microbiologist at Dartmoor College, said: “It would be nice to get specific physical information on these abstract constructions.” He hopes to see how these situations will be reproduced in actual experiments, perhaps with the help of biology-related chemical compounds and energy sources, such as glucose.



But even if it is possible to see the conditions with a fine adjustment, very much resembling the conditions that are supposed to give rise to the birth of life, some researchers believe that Ingland's dissertation describes the “necessary but not sufficient” conditions to explain the emergence of life, as Walker says. They cannot describe what some consider to be the true sign of biological systems: the ability to process information. From the simplest chemotaxis (the ability of bacteria to move towards nutrient concentrations or from toxic compounds) to human intercourse, life forms accept and respond to information about their environment.







Walker believes that this distinguishes us from other systems that fall within the scope of Ingland's theory of adaptation under the influence of scattering, such as the Jupiter's Great Red Spot . “This is a non-equilibrium scattering structure that has existed for at least 300 years, and it is very different from the non-equilibrium scattering structures that exist on Earth today and have evolved billions of years,” she says. Understanding what makes life stand out among such structures “requires an explicit definition of information beyond the limits of the dispersion process”. From her point of view, the ability to react to information is the key to this: "We need a network of chemical reactions that can get on their feet and get away from the environment in which they originated."



Gunawardena notes that in addition to the thermodynamic properties and processing capabilities of information existing in life forms, they also store and transmit genetic information about themselves to their descendants. The origin of life, he says, is “not just the emergence of a structure, it is the emergence of a certain dynamic, a Darwinian sense. This is the emergence of reproducing structures. And the ability to influence the properties of these objects on the playback speed. When you fulfill both conditions, you will find yourself in the situation of the beginning of the Darwinian evolution, and biologists believe that this is the whole point. "



Evgeny Shakhnovich , a professor of chemistry and chemical biology at Harvard, who led Ingland's research, clearly shares the work of his former student and questions of biology. “He started his scientific career in my laboratory and I know how capable he is,” says Shahnovich, “but Jeremy’s work presents potentially interesting exercises in the non-equilibrium statistical mechanics of simple abstract systems.” All claims that they are related to the origin of life, he adds, "are pure and shameless speculation."



Even if Ingland is on the right track from the point of view of physics, biologists need more specific things - for example, the theory of which primitive protocells first live cells came from and how the genetic code appeared. England agrees that his discoveries have no answer to these questions. “In the short term, they tell me little about the work of biological systems, I don’t even declare that they will tell me about where the life we ​​know came from,” he says. Both questions are a “depressing mess”, based on “fragmentary evidence”, from which he “intends to stay away”. He simply suggests that in the first-life toolkit “perhaps there is something that can be obtained for nothing and then optimized using the Darwinian mechanism”.



Sarpeshkar, apparently, regarded the adaptation under the influence of scattering as the first act of the history of the origin of life. “Jeremy shows that if you are able to extract energy from the environment, order will spontaneously appear and self-adjust,” he says. He notes that living organisms perform far more activities than the chemical network of Ingland and Horowitz. "But we are talking about how life first appeared - how order could come out of nothing."