The Chemistry That Leads to Biology<\/p>\n
Sutherland is not a biologist by training. He\u2019s an organic chemist, educated at Oxford, who drifted toward one of science\u2019s hardest problems almost by accident. What drew him was the question of whether simple chemistry could plausibly generate the molecules biology depends on.<\/p>\n
That question led to a breakthrough in 2009<\/a>, when Sutherland and his colleagues showed that key building blocks of RNA could form without enzymes, under conditions that might have existed on early Earth. The result gave new credibility to the RNA World hypothesis<\/a>, which proposes that RNA came before DNA and proteins, acting both as genetic material and as a primitive catalyst.<\/p>\n But the work also drew criticism. The chemical precursors Sutherland used\u2014acetylene and formaldehyde\u2014were simpler than RNA, but still complex enough to raise an awkward question: Where did those come from? It\u2019s the same circular game all over again. <\/p>\n Rather than defending the chemistry as-is, Sutherland and his team went backwards.<\/p>\n In a series of papers culminating in work published in 2015 in Nature Chemistry<\/a>, Sutherland\u2019s group demonstrated that you can start with a remarkably small set of ingredients\u2014hydrogen cyanide (HCN), hydrogen sulfide (H\u2082S), ultraviolet light, and simple minerals\u2014and end up with precursors not just to RNA, but also to amino acids and lipids.<\/p>\n In other words, the same basic geochemical environment could generate all three major classes of biomolecules required for life.<\/p>\n Hydrogen cyanide may sound like an odd candidate for life\u2019s raw material. After all, it\u2019s infamous as a poison. But that toxicity is a modern problem (modern by geological standards). Cyanide interferes with oxygen-based metabolism, and oxygen didn\u2019t accumulate in Earth\u2019s atmosphere until roughly two billion years ago. On the early Earth, cyanide would have been chemically active but biologically harmless, because biology as we know it didn\u2019t yet exist.<\/p>\n More importantly, cyanide is chemically efficient. It contains carbon and nitrogen already bonded together, in just the right oxidation state to build complexity. Compared to carbon dioxide and nitrogen gas\u2014the molecules modern biology laboriously fixes using elaborate protein machinery\u2014cyanide is practically eager to react.<\/p>\n Sutherland\u2019s work doesn\u2019t claim that life sprang fully formed from a single pond or pool. In fact, he\u2019s careful to argue the opposite.<\/p>\n The reactions that produce nucleic acid precursors, amino acids, and lipid components don\u2019t require identical conditions. Some favor different metal catalysts; others need slightly different energy inputs. Early Earth, Sutherland suggests, was less like a single \u201cprimordial soup\u201d and more like a patchwork of chemically related environments.<\/p>\n Rainwater, tides, and erosion would have transported molecules between these sites, pooling them together over time. The point is that chemistry didn\u2019t have to get everything right in one place\u2014it just had to get enough things right somewhere.<\/p>\n This view aligns with a growing emphasis on systems chemistry: the idea that life emerged not from one lucky reaction, but from networks of reactions reinforcing one another. Instead of trying to isolate a single \u201cfirst molecule,\u201d systems chemistry looks at how collections of molecules behave together\u2014sometimes producing surprising order rather than chaos.<\/p>\n Ending Vitalism, One Experiment at a Time<\/p>\n In November, I caught up with Sutherland at the 2025 Falling Walls<\/a> conference in Berlin. He told me he believes the field is approaching a moment when laboratories will be able to start with chemical mixtures that are obviously not alive and end, sometime later, with simple systems that show key hallmarks of life: compartmentalization, metabolism, and replication with variation. And at some point, someone will be able to make life from scratch in the lab, although he joked it probably won\u2019t happen during my lifetime, so I won\u2019t be able to bash his prediction. <\/p>\n If that happens, it won\u2019t just be a technical achievement. It will mark the final collapse of vitalism\u2014the old belief that living systems are animated by something fundamentally beyond chemistry. That idea took a major hit in the 19th century, when chemists learned to synthesize \u201corganic\u201d molecules like urea<\/a>, Sutherland told me. But traces of it linger whenever life is treated as irreducible or exceptional.<\/p>\n Recreating the transition from chemistry to biology wouldn\u2019t strip life of its wonder. It would deepen it\u2014showing how something astonishing can arise from ordinary matter, given time and the right conditions.<\/p>\n Life Elsewhere, Life Otherwise<\/p>\n The implications extend far beyond Earth. If the chemistry Sutherland studies is robust\u2014if it works whenever cyanide, sulfur, water, and energy coincide\u2014then life may not be rare in the universe. It may be constrained, but common.<\/p>\n That possibility is already shaping collaborations between chemists and astronomers, who are trying to identify atmospheric \u201cbiosignatures\u201d on distant exoplanets. Knowing which chemical pathways lead most naturally to life helps scientists decide what to look for\u2014and what combinations of gases might signal biology rather than geology.<\/p>\n If life is found elsewhere, even once, the statistics change dramatically. Two independent origins would suggest that life is not a cosmic fluke, but a frequent outcome of planetary chemistry. And if that life shares our basic molecular toolkit, it would imply that chemistry itself funnels biology toward a narrow set of solutions.<\/p>\n None of this proves how life began. The crucial transition from molecular building blocks to self-sustaining, evolving systems remains unresolved, and may always be partly speculative. <\/p>\n But science doesn\u2019t advance by eliminating mystery all at once. It advances by shrinking the gap between the known and the unknown.<\/p>\n What Sutherland and others have shown is that the origin of life no longer needs to hide behind paradox. The chicken-and-egg problems that once made biology seem impossible are giving way to something more interesting: a picture of early Earth as a chemically creative world. <\/p>\n Below you can read the transcript of my interview with Prof. Sutherland or watch the video version<\/a>. The transcript has been edited for brevity and clarity. <\/p>\n Interview Transcript<\/strong><\/p>\n Tibi Puiu:<\/strong> Prof. John Sutherland:<\/strong> And that success really arose from collaborating with people outside chemistry, because chemistry on the early Earth isn\u2019t isolated chemistry. It\u2019s chemistry taking place on the surface of the Earth, and it helps if you understand the geochemistry. That\u2019s essentially how we learned how to make nucleotides, and that\u2019s what people tend to remember or recognize our work for.<\/p>\n Tibi Puiu:<\/strong> Prof. John Sutherland:<\/strong> Of course, now there is much more collaboration, much more communication between people in those areas. The second thing I think was that people were limited by their ability to understand what had happened when they mixed things together, so their analysis was weak.<\/p>\n Modern chemistry has very advanced analytical tools, so we could probe more complex mixtures, and contrary to expectation when you make a mixture more complicated, it doesn\u2019t necessarily produce more complex results.<\/p>\n Sometimes there\u2019s a kind of simplicity that emerges in collections of molecules. We refer to this as systems chemistry. Studying isolated reactions isn\u2019t enough for life\u2014you need many reactions happening at the same time. People avoided that because they couldn\u2019t analyze it and because they expected it would just make a mess. We\u2019ve shown that if multiple reactions occur simultaneously, the outcome can actually be simpler than you might imagine.<\/p>\n Of course, that\u2019s not enough on its own. You need to make the biological building blocks, then link them together into macromolecules. At some point, small and large molecules have to start using energy in an ordered way to replicate, with mutation, so errors are generated and the system can improve. <\/p>\n So I don\u2019t think we\u2019ve got to that point now but at least by understanding what the building blocks are, I think we\u2019re better positioned than ever before to start dealing with that next phase.<\/p>\n Tibi Puiu:<\/strong> Prof. John Sutherland:<\/strong> One reason is that it took time to work out what the key molecules on the early Earth might have been\u2014what the feedstock molecules were. Biology today fixes carbon from carbon dioxide and nitrogen from nitrogen in the atmosphere. Either of those fixation events is extremely tricky and represents a masterpiece of biology.<\/p>\n Imagining that both of those were fixed early on in biology is incomprehensible. You can\u2019t imagine that. But if you start with hydrogen cyanide, you have carbon and nitrogen in the same molecule, already in roughly the right oxidation state. Cyanide turns out to be very well set up to start making the molecules you need. If you instead use modern biology\u2014starting from CO\u2082 and N\u2082\u2014as your guide, you go badly wrong.<\/p>\n Tibi Puiu:<\/strong> Prof. John Sutherland:<\/strong> Oxygen only appeared in Earth\u2019s atmosphere about two billion years ago, during the Great Oxidation Event. Before that, there were no enzymes passing electrons to oxygen, so cyanide wouldn\u2019t have been toxic. So we shouldn\u2019t look at cyanide now and assume it was always toxic.<\/p>\n Tibi Puiu:<\/strong> Prof. John Sutherland:<\/strong> We know much better what the building blocks are. We have a clearer idea of what we\u2019re aiming for: a protocell with replicating RNA, possibly with simple peptides synthesized at the same time. We\u2019re also getting a better sense of what energy sources might have driven the process.<\/p>\n I would say we\u2019re getting remarkably close to the point where someone will do an experiment where you start in a laboratory with a mixture of chemicals that is obviously not alive, and within a couple of weeks you end up with simple cells showing all the hallmarks of life.<\/p>\n That will be an extraordinary experiment. It will finally remove the last vestiges of vitalism\u2014the idea that there\u2019s something special about biology that means it can\u2019t be recreated from chemistry. W\u00f6hler\u2019s synthesis of urea destroyed most of vitalism, but some elements still persist.<\/p>\n If we can demonstrate by experiment that we can kick-start biology just by mixing the appropriate chemicals in the right sequence in a way that simulates what happened on early Earth, that will dispel vitalism completely. Then we\u2019ll have a rational explanation for how it all started and why we\u2019re here.<\/p>\n Tibi Puiu:<\/strong> Prof. John Sutherland:<\/strong> What he\u2019s doing is simplifying biology from the top down. Those of us working on the origin of life are approaching it from chemistry up. At some point, we hope those two approaches will intersect.<\/p>\n If you keep simplifying biology, you eventually reach systems with far fewer than 20 amino acids. We think we know what the first amino acids were, because they\u2019re the ones we can make from our chemistry. It\u2019s like tunneling under the English Channel from both sides\u2014eventually the tunnels meet. It\u2019s a very long tunnel, about 3.7 billion years of biological history, but humans are good at solving puzzles.<\/p>\n We\u2019re not doing this just for fun. We\u2019re doing it because we really believe it can be achieved. More and more people are working on this now because they can see that the end is in sight.<\/p>\n Tibi Puiu:<\/strong> Prof. John Sutherland:<\/strong> Chemists can suggest what astronomers might look for, and astronomers can tell chemists what they actually have a chance of seeing. We talk about biosignatures\u2014gases, or combinations of gases, that might indicate life.<\/p>\n If life exists elsewhere, it might resemble Earth biology, which would suggest there\u2019s only one solution. Or it might be different, which would suggest multiple solutions. Humans will create artificial life at some point, possibly superior in some respects to natural biology, which is constrained by the fact that it had to start on a rocky planet with a limited set of chemicals.<\/p>\n If life is found elsewhere, even once, it changes everything. If n equals two, then n almost certainly equals many more than two. And if that second form of life turns out to use the same chemistry as ours, with no possibility of panspermia, that would be a very strong indication that there may be only one way for life to start.<\/p>\n So I\u2019m hugely in favor of these explorations. I think observations elsewhere may end up telling us more about our own chemistry than our chemistry tells us about them.<\/p>\n![\"\"](\"https:\/\/www.europesays.com\/us\/wp-content\/uploads\/2025\/12\/nt_project-1024x532.jpg\")
<\/a>A schematic representation of different stages of molecular evolution during the transition from chemistry to biology. Credit: adapted from Sutherland (2017).<\/p>\n![\"\"](\"https:\/\/www.europesays.com\/us\/wp-content\/uploads\/2025\/12\/sutherland-1024x546.png\")
<\/a>Prof. John Sutherland. Credit: ZME Science.<\/p>\n![\"\"](\"https:\/\/www.europesays.com\/us\/wp-content\/uploads\/2025\/12\/67777f8c4e4e14409d8e5e9518cfb20907de8770.webp.webp\")
<\/a>An artist\u2019s conception of a Hycean exoplanet like K2-18b orbiting a red dwarf star 120 light-years from Earth<\/a>. A repeated analysis of the exoplanet\u2019s atmosphere suggests an abundance of a molecule that on Earth has only one known source: living organisms such as marine algae. Credit: A. Smith, N. Madhusudhan\/University of Cambridge<\/p>\n
John, thank you so much for being here. For those who don\u2019t know you or don\u2019t follow your work closely, could you briefly introduce yourself and describe what you\u2019re most known for?<\/p>\n
I\u2019m a chemist\u2014an organic chemist. I trained in Oxford as a chemist, and over the years I became interested in the origin of life. I think we became known\u2014although I don\u2019t really like the word \u201csuccessful\u201d\u2014because we managed to make nucleotides in a way which people hadn\u2019t really thought of doing before, in a geochemical context relevant to the early Earth.<\/p>\n
The origin of life may be the biggest question in science. What do you think are the most likely explanations for how life first appeared? And what are the most important things people should keep in mind when thinking about this problem? How does this relate to your research?<\/p>\n
One reason people were less successful in the past is that science education is often based in silos. There\u2019s a silo of chemistry, a silo of geochemistry, planetary science, biology, and historically there was much less communication between them. <\/p>\n
And did everything go as planned when you embarked on this sort of quest? Were you surprised by your findings? You mentioned in today\u2019s talk hydrogen cyanide. Can you expand a bit about that?<\/p>\n
When I started, as a young man, I confidently expected that we\u2019d understand how the building blocks were made within a couple of years. I\u2019m now approaching the last quarter of my life, and we\u2019ve almost finished making the building blocks. It\u2019s taken much longer than we expected.<\/p>\n
I think some people watching us are scratching their heads right now. Isn\u2019t cyanide poison?<\/p>\n
Yes, cyanide is a poison. It inhibits an enzyme called cytochrome c oxidase, which is the terminal enzyme in the respiratory chain\u2014it\u2019s responsible for passing electrons to oxygen.<\/p>\n
What do you reckon is the main barrier now in this line of research?<\/p>\n
There\u2019s the perennial barrier of funding\u2014there are many pressures on governments and individuals to spend money on other pressing needs. But conceptually, the field is in a much better position now.<\/p>\n
So other research groups I\u2019ve read about showed some semi-synthetic RNA, semi-synthetic DNA, even. I think recently someone reduced the number of codons in an E. coli bacterium. There are interesting developments in sort of synthetic life, if you can call it this way, but I think you raise a super interesting point: we can imagine some point in time in the future when some research group actually makes life from scratch. And I\u2019m trying to imagine the implications of this. I mean, how will people cope with this?<\/p>\n
You mentioned reducing the number of codons. Jason Chin, for example, has reduced the number of codons<\/a> in E. coli down to 57 in the latest version, and that number will likely get lower.<\/p>\n
Finally, does your work inform the search for life on exoplanets? Should astronomers be looking for particular molecular signatures?<\/p>\n
That\u2019s a very thoughtful question, and it does connect directly to what we\u2019re doing. There\u2019s ongoing discussion between the chemistry community and the exoplanet community. In Cambridge, for example, I collaborate with people who study exoplanets and their atmospheres.<\/p>\n
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