Origins of Life Systems Chemistry, John Sutherland, Cambridge

John Sutherland

Programme Leader, Medical Research Council Laboratory of Molecular Biology, Cambridge

"Origins of Life Systems Chemistry"

By reconciling previously conflicting views about the origin of life – in which one or other cellular subsystem precedes, and then ‘invents’ the others – we suggested a new modus operandi for its study. Guided by this, we uncovered a cyanosulfidic protometabolism which uses UV light and the stoichiometric reducing power of hydrogen sulfide to convert hydrogen cyanide, and a couple of other prebiotic feedstock molecules which can be derived therefrom, into nucleic acid, peptide and lipid building blocks. We are now considering the transition of systems from the inanimate to the animate state through intermediate stages of partial ‘aliveness’, and recent progress in the elaboration of building blocks into larger (oligomeric) molecules and systems in this context will also be described.

The Origins of Life Speaker Series explores the conditions and circumstances that led to the diversity of life on Earth. The interdisciplinary series will connect the formation of planets, the evolution of early Earth, and the complex chemistry and delivery of the fundamental organic molecules that serve as the building blocks of early life, and how they can establish complex, self-replicating systems of cells and genetic material.

About the University of Chicago Physical Sciences Division
The Physical Sciences Division (PSD) at the University of Chicago has a rich history of advancing and defining new fields of discovery in the physical and mathematical sciences, and this tradition of innovation continues today. Our inquiry and impact spans from the edge of the observable universe to human-computer interaction, from biophysical materials science to the geologic record of seawater composition, from gravitational waves to geometric flows, and beyond.

The division includes the academic departments of Astronomy & Astrophysics, Chemistry, Computer Science, Geophysical Sciences, Mathematics, Physics, and Statistics. In addition, PSD is home to a number of interdisciplinary research institutes and centers, including the Enrico Fermi Institute, the James Franck Institute, and the Kavli Center for Cosmological Physics.

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[Ilovelimabeans]

That picture at 9:30 of the biochemical pathways and control and feedback mechanisms gives overwhelming sense that there is a higher mind behind it all.

[edthoreum]

@15:50 Hydrogen cyanide &meteors
19:25-plasma /impact
Henry's law
22:00 need of HEAT to create ferro- cyanide;compounds.
H20 & solar radiation =aminos
&
Hydrosulfate
30:00 carbonate rich lake
40:00 jezera crater, MARS
45:00 q&a, , ,

[blahblahsaurus]

Probably the best lecture on the subject that I've been able to find on YouTube. Regarding the question discussed around 1:08:00, I think a MUCH simpler polymer than RNA is necessary as a starting point for life. You need a polymer that is made of two or more different monomers. The polymer needs to "like" wrapping around or sticking to other strands of the polymer, and strands with similar sequences need to stick together better than ones that don't.

If a nanogram of such material forms, some sequences will have the property of catalyzing the formation of more polymer - at least a tiny bit. As a strand grows, its sequence needs to be influenced by the catalyzing sequence - at least somewhat. From this starting point, genetic evolution can set in and you're pretty much off to the races.

There is no need for this first polymer to be RNA or anything like it, and the trouble with RNA is that each building block is already too specific and complicated. A nucleotide is formed from a phosphate, a sugar, and a base, each of which have specific structures with many variants. I don't know enough chemistry to guess what polymer could fit the bill. Something similar to a polysaccharide seems promising to me. Or maybe a peptide. Or some other kind of molecule that has long since gone extinct. The most important property is that strands with similar sequences stick together better. I'd like to see research into every polymer with that property, regardless of whether it resembles any existing biotic molecule. I think trying to start with RNA and working backwards is completely the wrong notion.

The first genetic polymer doesn't have to be an ancestor of our modern genetic polymers! As long as life is thriving and evolving, it will create all sorts of byproducts. One of those could be the ancestor of RNA - if the ancestor is being produced for any purpose it could then become an autocatalyst just like the first polymer and independently of it.

[sergeyslomchinsky]

Immense gratitude and best wishes for your great work, and many thanks for making public that wonderful talk. Just an idle though from a stranger to the field - May it be that our life started in a rich environment of small compounds, where some undergone repeated cycles of selective assembly and polymerization caused by cracks on mineral chips that presented intricate patterns of positive, negative, and hydrophobic regions. One pathway could be that monomers were assembled on cracks and polymerized with solvent evaporation and then formed polymers were displaced with a gain of solvent. The other possibility could be that assembled compounds served themselves as an assembly pattern for complimentary monomers. If a polymer was not entirely displaced then repeating copies could accumulate in some amount in a single strand given the rise for even more complicated structures. Simply stated - there could be a unique combination of events and conditions that produces the very base for the life to form on our planet. Speculating further, one could assume that the life machinery had started the moment an entity facilitating polymerization had been synthesized. That would lead to the consumption of nearly all surrounding substrate of more stable forms of polymers giving them more time for interaction limited by natural degradation. The appearance of entity facilitating polymer degradation either would stop the process or trigger polymer diversity and thus the appearance of a polymer-based systems of synthesis and degradation. That would lay the base for selecting more stable forms of polymers and promote metabolic pathways of its monomer synthesis. It could be that RNA and peptides were developing in parallel and their monomers at the very earlier stage formed symbiotic associations. Compartmentalization and further functional specification seems to be products of already formed and stable evolutionary machinery with very developed metabolic processes. As we know of life, it consumes less productive and less efficient of its forms given food for more advanced. Origins of life could be as many and diverse as one could imagine, but the race for food had begun, and the process is untwisting. No trace would be left of yesterday winners succumbed for the newly emerged creatures.

[TonyTigerTonyTiger]

Trying to figure out what he says beginning at 42:50. Can anyone figure it out?

"Although I'm a [...] chemist, as Andre points out at the beginning, I've learned over the course of my career that being a single-minded, or narrow-minded, chemist on your own doesn't get you very far in origin of life research. You absolutely have to collaborate and learn from colleagues in other disciplines."

[petercoderch]

The theory that compounds got stuck inside oil bubbles in the ocean, and that these chemicals interacted inside the bubble to form the first cell, is interesting. But that RNA can replicate itself by placing nucleotides insequence and then bending on itself to create two identical copies, and that these copies grew inside the ooil bubble, which eventually splitted into two when the amount of RNA inside become too big, does not solve the two major problems: first, is a self-replicating molecule that does not perform any activity other than produce copies of itself really "alive"? Snowflakes will often form quartz-like strcutures next to each other that are exact replicas of the ones in snowflakes next to it. Are snowflakes alive? And most importantly, . even if RNA can duplicate itself spontaneously, how exactly it got to manipulate amino acids into forming proteins? I mean, if we are talking RNA with no machinery of the ribosome, then RNA must *absolutely* have the ability to auto-catalyse amino acid reactions. Has this been demonstated? Because if it can't auto-catalyse protein reactions, . then how it created the machinery for creating even more complex proteins? Can an pure RNA create a riubosome from nothing? I mean, the oily bubbles, the precursors to cell walls, only make sense if RNA would need a contained space to create a machinery that is capable of performing it's own function(self-replicating) but with proteins that are too complex for it to form on it's own.

The whole debate of which came first, replication or metabolism, seems like a semantic debate. Because both replication and metabolism to arise, something is essential: a molecule that has an innate abilitty to manipulate the matter around it to rearrange matter intelligently. "Intelligently" here, means according to instructions. Both self-replicating and creating a metabolism requires that ability to fold other matter into designed structures. So the whole debate of which came first, metabolism or replication, does not really matter since both of them require the same feature of a simple moilecule that can arise naturally through the laws of chemistry, that has *itself* the ability to catalyse matter into patterns according to instructions. This is the key to understanding the origin of life. We know that RNA can catalyse some fractions of itself, but not entirely. RNA also, outside a cell, cannot catalyse the formation of proteins. So where does this leave us? Well, we need to find a molecule that that can auto-catalyse amino acids into protein chains. What are the candidates?

[rocketpsyence]

This is great I cant believe i can just get on the internet and watch this for free. Gonna go follow up on what the 2020 mars mission found. 👀

[jerubaal]

You have shown interesting picture of Darwin's pond with streams! Nice and interesting. What temperature was there? I am asking because, RNA would dissolved in temperature above -80*C. But what kind of reactions would you get below zero? From the other hand, If there was so much UV light, lighting, nuclear radiation, how could you possibly assume that there was no trace of electrolysis of water???

[alexwelts]

You know when an orchid is about to die, so it'll flower quickly or put a kiki out as it's last effort?

[mellertid]

Interesting, if also beyond my grasp. So this is but a random reflection.
Some pathways or optional possibilities were considered "cumbersome", "inefficient" and "messy". I wonder if chemists by and large are implicitly biased towards chemistry that makes sense in a laboratory or industry setting? To some extent, biology appears to be a fair bit cumbersome and messy.

[platzhirsch]

The assembly of complex molecules involves a series of enzymes that must react in a proper sequence, very often producing intermediates that are useless to the cell until the final product is formed. Evolutionists imagine that these enzymes evolve randomly, often from a duplicate gene, and that the succession of steps in the synthesis, at least often, represents the succession of steps in the historical evolution of the process (the Granick hypothesis). But forces of natural selection could not operate to favour an organism which had ‘evolved’ a series of enzymes which merely produced useless intermediates until it somehow got around to making the end product. The Calvin cycle requires eleven different enzymes, all of which are coded by nuclear DNA and targeted precisely to the chloroplast, where the coding sequence is clipped off at just the right place by a nuclear-encoded protease. In reality, as described in the preceding paragraph, none of the enzymes can be missing if the Calvin cycle is to function. It is true that many of these enzymes are ubiquitous in living systems because every living cell needs to generate ribulose phosphates for the production of RNA, but evolutionists cannot solve the problem by merely pushing it back in time.

The assembly of chlorophyll takes seventeen enzymes.21 Natural selection could not operate to favour a system with anything less than all seventeen being present and functioning. What evolutionary process could possibly produce complex sophisticated enzymes that generate nothing useful until the whole process is complete? Some evolutionists argue that the assumed primeval organic soup had many of the simpler chemicals, and that only as they were used up did it become necessary to generate the earlier enzymes in the pathway. In The Mystery of Life’s Origin: Reassessing Current Theories, the authors set forth the good basic chemistry that demonstrates that there could never have been an organic soup, and present some of the evidence out there in the world indicating that there never was.22 Denton23 and Overman24 also cite a number of experts who suggest that there is no evidence for such a primitive soup but rather considerable evidence against it.

Chlorophyll itself, and many of the intermediates along its pathway of synthesis can form triplet states, which would destroy surrounding lipids by a free radical cascade apart from the context of the enzymes that manufacture them and the apoproteins into which they are inserted at the conclusion of their synthesis.25 According to Asada26 ‘triplet excited pigments are physiologically equivalent to the active oxygens’, and according to Sandmann and Scheer, chlorophyll triplets ‘are already highly toxic by themselves . . . .’27 The entire process of chlorophyll synthesis from δ-aminolevulinic acid to protoporphyrin IX is apparently tightly coupled to avoid leakage of intermediates.28 Almost all of the enzymes of chlorophyll biosynthesis are involved in handling phototoxic material.29 For many of these enzymes, if they are not there when their substrate is manufactured, the cell will be destroyed by their substrate on the loose in the wrong place at the wrong time. Apel30 has cited four of the enzymes of chlorophyll biosynthesis for which this has been proven to be the case. This is a significant problem for evolutionists, who need time for these enzymes to evolve successively. Each time a new enzyme evolved it would have produced a new phototoxin until the next enzyme evolved.

[hainetkorea]

The Origin of Life is Chemical Synthesis.Marine algae(green seaweed):Cellulose is a cell

[jimdandy]

I find this whole thing ridiculous. Put your end product on paper then figure out a completely impossible path to get there then take that impossible chemistry to create more impossible reactions. I may be completely wrong but it seems most of the reactions require an alkaline environment. That seems to make this whole video worthless because in that environment there is no way to produce stable proteins so what’s the point then?

[jerubaal]

I would like to see debate between you and dr James Tour. He is real opponent.
How would you answer his questions? What would you ask him about to falsified his believes?

[jimdandy]

He lost me when he said the chemistry will “learn” as if non life can evolve and understand where it failed and fixed the problem as if it knew it’s end goal.

[phillipjoy]

So many caveats. assumptions and circularities. Life needs these constituents, so we can posit the existence of these early environmently constituents, which thus brought forth life. Please.

[louise]

Came here for the talk: left the talk by busting Professor Leroy Cronin (Glasgow), who is pretending to be Tony Maurice (see comments), and 'Tony Tony' on Twitter. So, so weird.

[jerubaal]

How could you assume that there was a panty of Hydrogen (which escapes from the atmosphere even today!) and no trace of free oxygen?The Earth is made of oxygen in 46% ! So are amino-acids and the whole of organism! How it came into those products without being freed from water? Water consists of 80% of it too! And you assumed that there was no free oxygen? HOW?

[johnathanmiller]

In short ... how did life form on earth ? answer ... We have no idea !

[stevedoetsch]

Forget the circular reasoning of atheistic evolutionists; the reason that understanding RNA is important right now is because the current shot for a certain worldwide disease is mRNA and people should understand before getting it how RNA could be the precursor to new genetics inside their own body. Is that kind of therapy experimental? It's never been done en masse before so you tell me.