​The so-called "bold new theory of everything" is a new paradigm? Or a false proposition?

This universal theory that attempts to unify physics and biological selection has caused an uproar in the academic community since its appearance in Nature magazine. Some people think it is an innovative unified framework, while others think it is a misunderstanding and exaggeration of existing knowledge. Which side do you stand on?

Written by | Xiaoye

What are scientists doing? Revealing the mysteries of life on earth, exploring the evolution of stardust in the sky, and unraveling the principles of everything... As we all know, since the beginning of the last century, physicists have been pursuing whether they can use simple theories to describe all physical events that occur in the universe.

One hundred years later, scientists continue to boldly publish new theories, and recently two theoretical articles were published in Nature and Proceedings of the National Academy of Sciences. The former attempts to become a theoretical framework to unify biology and physics, but it has also caused great controversy; the latter announced the discovery of a "missing" natural law that can explain the evolutionary system, which seems to be more recognized by peers.

Assembly: The process of assembling from non-life to life

Lee Cronin, a chemist at the University of Glasgow in Scotland, has long pondered the question: Given the myriad ways that atoms can be combined, why did nature create some molecules and not others? Meanwhile, on the other side of the world, astrobiologist and theoretical physicist Sara Walker at Arizona State University in the United States was pondering the origins of life. This question parallels the creation of complex molecules, because the plethora of complex molecules that exist in living organisms is no accident, and she suspects that something must have been guiding biological processes before Darwin’s theory of natural selection took over. [1]

In 2012, the two scientists met at a NASA astrobiology seminar. During the meeting, they discussed various topics such as information theory, life, and the construction of autonomous replicators. The two people with similar interests then formed a research group and led the team to explore the mechanism of complex organisms, especially the emergence of complex life, and tried to establish a self-consistent theory that can be accurately described mathematically. This is a very classic thinking mode of theoretical physicists. [1]

In 2021, the team published a paper in the journal Nature Communications, formally proposing the assembly theory for the first time [2]. The authors hypothesize that the difference between living systems and non-living systems is that the former can generate complex molecules in quantities and abundances that the latter cannot match. Complex molecules, however, are assembled step by step from many simple molecules through biochemical reactions, just like building blocks. Therefore, the authors infer that there should be a minimum number of assembly steps to construct a given complex chemical molecule, which serves as a threshold for the emergence of life - the assembly index defined by the authors; conversely, any chemical molecule with a complexity exceeding this threshold has life or life-like processes at work behind it. It can be seen that the original intention of this theory is to provide a set of theoretical paradigms and measurement methods to set new biological characteristics from a biochemical perspective, helping humans to determine whether the traces found in the search for extraterrestrial life are life phenomena or at least similar to known life processes on Earth. [3]

Two years later, the researchers further expanded the assembly theory and published an article titled “Assembly theory explains and quantifies selection and evolution” in the journal Nature in October this year [4]. In the authors’ own words, the further developed assembly theory always puts chemistry at the center of the stage, “providing a unified framework across physics and biology to describe natural selection and understand evolution.” Based on this, the team constructed a new set of assembly universe views, including a nested hierarchical structure of four different “universe” concepts:

The author published a preprint of the paper on arxiv.org.

The first and largest universe is the Assembly Universe, in which all permutations of the basic building blocks are allowed. Next is the Assembly Possible Universe, in which the laws of physics impose constraints on these combinations, so that only some objects are possible. Then, the Assembly Contingent Universe whittles down the large number of physically allowed objects by picking out those that can actually be assembled along possible paths. The fourth universe is the Assembly Observed Universe, which includes only those assembly processes that produce the specific objects we actually see.

In order to understand how the assembly process works in the author's conceptual universe, the author introduces Darwinian evolution as a dividing line. Before Darwinian evolution can take effect, multiple copies of objects with high assembly indexes must be selected from the universe of possible assemblies. Ordinary chemical reactions "select" certain products from all possible arrangements because they have faster reaction rates. The specific conditions in the pre-biotic environment have screened the pool of molecular precursors that constitute life in the universe of possible assemblies, and these pre-biotic environmental preferences are remembered by today's biological molecules: molecules encode their own history. Later, once Darwinian evolution and natural selection begin to take over the operation of life, life will tend to select those objects that can replicate themselves better. In this process, this encoding of history becomes increasingly powerful, which is why scientists can reverse the evolutionary relationships of organisms through the structure of protein and DNA molecules. [3, 4]

Next, it is important to set up a set of mathematical equations that can be measured accurately. Building on the assembly index proposed in the 21st paper, the team also created another variable in the new paper: the abundance or copy number of a given object. Cronin said this variable is very critical: "Complex objects with similar copy numbers are absolutely the golden marker of selection." Because the more complex the object is, the less likely it is that similar copies will exist without the information-driven mechanism that selects to create it. This is why complex objects are not randomly generated, but rather mediated by selection and defined by their formation history [3]. The more steps an object has to be assembled, the more natural selection it needs to undergo to appear. Therefore, combining the assembly index and the copy number gives an equation that determines the amount of selection necessary to generate a collection of objects. In other words, the transition from no selection to selection, such as the critical moment of transition from inanimate matter to life, changes the path in the assembly in a mathematically definable way, which can be reflected by this equation. In essence, objects with both a high assembly index and a high copy number are evidence that "selection" has taken effect [5].

A schematic diagram of the relationship between evolution, selection and copy number in assembly space depicted in the preprint of the paper. Source: arxiv.org

Of course, experimental verification of the validity of the theory is also an important part. The researchers said that through this theory, it is possible to quantify the selection and evolution in systems including diethyl phthalate, short peptides and cell structures. Although the theory has been developed at the observable molecular level, it also has the potential to be used in a wider range of models to simulate the evolution of various complexities, not only complex life, but also language and technology. [3]

Once this "ambitious work" that attempts to unify complex life and non-life was published in a top authoritative journal, it received quite mixed reactions. On the one hand, Nature also published a review article written by George Ellis, a complex systems scientist at the University of Cape Town in South Africa[5], which supported that assembly theory is a universal framework for unifying physics and biological selection, but how to apply it to complex environments, such as explaining the emergence of biological hierarchical structures, needs further exploration. The scientific media also praised assembly theory as a "bold and groundbreaking new theory of everything"[6].

On the other hand, academic experts seemed unable to accept this theory. Soon after the paper was published, scientists quickly engaged in a "war of words" in the paper's comment section and in the media. Some people felt that their profession was offended, while others were confused. They were all colleagues, but they couldn't understand what their colleagues' articles were trying to say. Evolutionary biologists were particularly angry. Bill Bateman, an associate professor at Curtin University, criticized the content of the paper based on his understanding of the paper's abstract, saying that "as a broad new paradigm aimed at unifying evolution and physics, assembly theory seems - to me and many others - to be solving a problem that does not exist." [7]

First of all, in the opinion of academic experts, this article is full of misunderstandings of existing biological concepts.

Professor Kasper P. Kepp of the Technical University of Denmark criticized the title, abstract and the beginning of the paper word by word in the paper comment area, and the wording was quite harsh. Taking the title as an example, Kepp immediately corrected it: "A theory that does not apply to evolutionary biological units (nucleic acids and amino acids) cannot quantify selection and evolution." Moreover, the title is exaggerated and can easily mislead readers. Regarding the selection theory, the author of the paper believes that "it (selection) reveals that objects are characterized by a forward dynamic process, taking into account their assembly." But Kepp immediately pointed out: "Selection is not a forward dynamic process, but the result of the degree of phenotypic adaptability in a population within a given fixed period of time." Next, the author goes on to say that if we want to understand how the physical world can emerge into endless forms without a pre-designed blueprint, we must have a new way to understand and quantify selection, and Kepp explains the real situation: "We have long understood selection and can quantify it without 'design' (genes, amino acids, etc.). The limitation is the complexity of the data. The paper also describes the selection pressure during the early emergence of the first batch of assemblies in an ambiguous way that has nothing to do with the biochemical forces that actually act on molecular assembly." In short, in Kepp's view, this paper has so many misunderstandings about evolution and biochemistry, and the language is obscure, but in the end it actually passed the review of editors and reviewers, which shows that even for journals like Nature, peer review is not perfect.

Two days after the comment was made, Dr. Walker also responded in detail paragraph by paragraph and refuted Professor Kepp's criticism. Taking the discussion on the title as an example, Dr. Walker said that in the era when the theory of evolution and selection were proposed, people did not know nucleic acids and amino acids. Although most of the evolutionary theories currently unfolding in the form of organisms eventually mention nucleic acids and amino acids, many existing theories in biology do not rely solely on these specific molecules. What the research team wants to challenge is that there is currently no theory (based on the theory of evolution or other ideas) that can solve the problem of the origin of life, so the assembly theory is the best solution the team can come up with.

Secondly, from a technical perspective, the measurement methods and mathematical equations used in the paper are not entirely the author's innovation.

Professor Hector Zenil, a researcher at the Department of Chemical Engineering and Biotechnology at the University of Cambridge, wrote a long article on his blog[8], pointing out that the assembly index can be replaced by a simple statistical coding scheme, because the assembly index is very similar to Huffman coding and other works. Huffman coding refers to a lossless data compression algorithm that encodes symbols based on the predicted frequency of repetition. The higher the frequency, the shorter the length of the encoded symbol. Zenil also pointed out through experiments that the correlation obtained by traditional one-dimensional Run Length Encoding (RLE), Huffman coding and other methods is higher than the assembly index. Therefore, in Zenil's view, the use of the assembly index as a criterion for judging life and non-life by the assembly theory is not only like reinventing the wheel, but also somewhat misleading[9].

Liu Yu, a distinguished associate researcher at the International Center for Complex Systems at Beijing Normal University Zhuhai Campus, also added that [6], assembly theory and Kirschner complexity face the same problem, that is, the most random and irregular sequences have the highest "complexity". Therefore, assembly theory defines the assembly index as the minimum number of steps to generate a molecule, but the article uses a split-branch algorithm to calculate the index, which essentially iteratively counts the number of repeated submolecular structures and cannot give the "minimum number of steps to generate a molecule". [10]

Finally, in the main text of the paper, John Timmer, a senior science editor of the science news website Ars Technica and a graduate student in biology, pointed out several problems after reading the full text [11]: First, the author's own proposal of "unifying selection with physics" is just a distraction that interferes with the reader's understanding of assembly theory, and the author did not give a good explanation of assembly theory in the main text. In contrast, Carl Bergstrom, an evolutionary biologist at the University of Washington, pointed out that if the discussion is only from a chemical perspective, the unification effect of assembly theory is indeed very good. However, in the main text, the author did not actually unify it with physics. The author even admitted: "Combinatorial space does not play a prominent role in current physics because its objects are modeled as point particles and combined objects." Moreover, "In a sense, this definition is completely opposite to standard physics, which regards the objects of interest as the most basic and unbreakable." However, none of this prevented the author from writing a completely opposite statement in the abstract.

Despite the controversy, Palli Thordarson, a professor at the School of Chemistry at the University of New South Wales in Sydney, posted 19 tweets on his personal Twitter account[12]. His views were relatively neutral and his attitude was more open. He said: “In my opinion, the assembly theory obviously has its advantages and has advanced our thinking about complex chemical systems, especially the study of the origin of life and astrobiology. But I feel that we still need to better confirm the chemical background before the origin of life under experimental conditions before we can accept the assembly theory and let it play a more profound role in the intersection of the three major disciplines of chemistry, biology and physics.”

Discovering the "missing" laws of natural evolution: from life to the universe

Assembly theory refers to Darwin’s theory of evolution. As we all know, this theory is used to explain the phenomenon of life on Earth, but it does not apply to more complex systems such as planets, stars, atoms, etc. A paper published in the Proceedings of the National Academy of Sciences in September this year [13] described a "missing law of nature, recognizing for the first time an important principle of the operation of the natural world, which clarifies the evolution of complex natural systems into more patterned, diverse and complex states."

This paper is written by a team of American astronomers, planetary scientists, mineralogists and philosophers, and focuses on exploring the parallel relationship between evolutionary selection and other complex system construction processes. Various system evolutions are common in nature, and the phenomena cited in the article include the mixed construction of elements in stars and the occurrence of mineral complexity in planets, which are exactly what astronomers and planetary scientists are interested in.

The authors treat parallel relationships between evolving systems as conceptually equivalent because they all exhibit three distinct features: first, they are composed of a large number of components that can be combined to form a large number of configurations with different properties; second, there are processes that form a large number of different configurations; and third, configurations are preferentially selected based on function.

Taking biology as an example, Darwin equated biological functions with survival, that is, the ability to live long enough to produce offspring. This study further expanded Darwin's view, pointing out that there are at least three functions in nature: the most basic function is stability, that is, the selection of stable arrangements of atoms or molecules to survive, and at the same time, there is change in stillness, that is, the continued existence of dynamic systems with a continuous energy supply. The third function is also the most interesting, which is the "innovation function" in the author's words. Evolved systems tend to explore new configurations, and sometimes unexpected new behaviors or characteristics will appear, such as photosynthesis.

The same evolution occurred in the mineral kingdom, where the earliest minerals were particularly representative of stable arrangements of atoms, and these primitive minerals laid the foundation for the evolution of the next generation of minerals, which participated in the origin of life. The evolution of life and minerals is intertwined, and the shells, teeth, and bones of animals are all innovative results of life's use of minerals.

Now let us look at the universe. Soon after the Big Bang, the two main elements, hydrogen and helium, formed the first stars. The earliest stars went on to use hydrogen and helium to create 20 heavier chemical elements. Based on this diversity, the next generation of stars continued to produce more than 100 elements. [14]

The details of evolution may vary from system to system, but the authors argue that, whether the system is animate or inanimate, evolution is occurring when new configurations work well and functionality is enhanced. In addition, although never explicitly defined, the authors acknowledge that organisms possess what is called "functional information." In other words, when something "functions," the organism has the ability to keep producing that thing, as well as variants of it. While this is somewhat similar to stable atomic nuclei or minerals, the latter lack the external information storage provided by DNA. As a conclusion, the authors propose a "law of increasing functional information": if many different configurations of a system face selection for one or more functions, then the functional information of the system will increase (i.e., the system will evolve).

Of course, many things are not parallel. Evolution is constantly exploring new configurations, while the formation of elements and minerals is limited by physics and chemistry, respectively. Although these systems can withstand different pressure and temperature ranges, they are extremely restricted compared to biology. The researchers also acknowledged: "Recent studies have estimated that the combinatorial phase space of the Earth's current biosphere has already far exceeded the combinatorial phase space of the abiotic universe."

Nevertheless, the main purpose of this paper is to provide a theoretical framework for the search for extraterrestrial life in the universe. Jonathan I. Lunine, a member of the Carl Sagan Institute and from the Department of Astronomy at Cornell University, one of the co-authors of the paper, explained: "If the functionality of evolving physical or chemical systems is increasing due to natural laws, then we can expect life to be a common outcome of planetary evolution." [14]

As a new theory that spans non-life and life, Timmer believes that the paper in the Proceedings of the National Academy of Sciences is better written than the Nature paper. After all, the logic of the arguments in the article is clearer and easier to understand, but the scope is more limited than the assembly theory. At the same time, it is not clear whether these arguments can really prove the parallel relationship in the above examples, because they have deeper content than conceptual similarities that is worth exploring.

In addition, whether any theory is ultimately useful or not must be confirmed through experimental testing. Whether it is the hotly debated assembly theory or the new natural law that is more easily accepted in the circle of astronomers, there may be no way to use these theories to drive the development of experimental projects for the time being, but this does not mean that no one can do it in the end. As to whether the new theory is a new paradigm or a false proposition, there is no conclusion yet, but it is also a very common phenomenon in the scientific community that new theories are controversial. This can urge researchers to further reflect on the rationality and effectiveness of the theory, discover their own "blind spots", and thus establish more reliable theories that can withstand the most rigorous criticism and practical tests of their peers. Regardless of the final result, this is a testament to every step of human effort to uncover the deepest mysteries of all things.

References

[1] https://www.quantamagazine.org/a-new-theory-for-the-assembly-of-life-in-the-universe-20230504/

[2] https://www.nature.com/articles/s41467-021-23258-x

[3] https://www.chemistryworld.com/news/assembly-theory-puts-chemistry-centre-stage-to-explain-molecular-complexity-and-lifes-origins/4018228.article

[4] https://www.nature.com/articles/s41586-023-06600-9

[5] https://www.nature.com/articles/d41586-023-03061-y

[6] https://www.sciencealert.com/assembly-theory-bold-new-theory-of-everything-could-unite-physics-and-evolution

[7] https://mp.weixin.qq.com/s/oq6P1mqQFZB_UioBq23wrg

[8] https://hectorzenil.medium.com/the-8-fallacies-of-assembly-theory-ba54428b0b45

[9] https://arxiv.org/abs/2210.00901

[10] https://www.linkresearcher.com/theses/ebe4100d-563e-4da4-84f7-4157cc1e7b39

[11] https://arstechnica.com/science/2023/10/can-selection-tie-evolution-more-closely-to-physics/

[12] https://twitter.com/PalliThordarson/status/1711669007798165633?ref_src=twsrc%5Etfw%7Ctwcamp %5Etweetembed%7Ctwterm%5E1711669007798165633%7Ctwgr%5Edb06f9153e71643e6d528d973c44f0fbed0db ebf%7Ctwcon%5Es1_&ref_url=https%3A%2F%2Fwww.chemistryworld.com%2Fnews%2Fassembly-theory-puts-chemistry-centre-stage-to-explain-molecular-complexity-and-lifes-origins%2F4018228.article

[13] https://www.pnas.org/doi/10.1073/pnas.2310223120

[14] https://sciencesprings.wordpress.com/2023/10/23/from-the-college-of-arts-and-sciences-at-cornell-university-natures-missing-evolutionary-law-identified/

This article is supported by the Science Popularization China Starry Sky Project

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.

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