Setting constraints on origins of life’ hypotheses. Example 1: thioester world and metabolism first in hydrothermal vents

When it comes to origins of life (Ool) hypotheses, we are often served with beautiful stories on how one event follows another and then you get life. But, the devil is always in the details and we want it to be out, to be known and to be addressed.

“Only when negative results are permitted and theories can be abandoned will science  progress in this area (OoL)”

-Robert Shapiro (1935 – 2011)

Here is a summary of my recent paper addressing a weakness in the metabolism first hypotheses in hydrothermal vents.

Thioesters, the prebiotic analogues of Acetyl coenzyme A is a linchpin organic compound in respiration processes in life. Its occurrences have been transposed into geochemical settings such as hydrothermal vents to form many metabolism first schemes for origins of life in the last 40 years or so. One glaring problem, despite the usual poised narration, is that, this hypothesis have survived so long without through investigations for that many years. Now, researchers at Earth-Life Science Institute (ELSI), an institute incepted to exclusively study the origins problem is doing just that, to set constrains on current OoL models and to produce more experimentally driven principles to understand the origins of life.

The open-source paper available in, has demonstrated that the accumulated concentration of thioesters in HT vents are too insignificant to launch any meaningful progression in metabolism first schemes. Additionally, thioester (like Acetyl-Co-A) has a very limited shelf life; the researchers measured the decay rate and concluded that, depending on thioesters speciation and physical conditions, they are unlikely to persist in hydrothermal vent conditions for long, thus constraining the metabolism first hypotheses.

p.s: We are extremely delighted to get this piece out in an open source journal.


Figure is showing the possible formation of thioacetic acids, in blue and thioesters (methyl thioacetic acid) , in pink in hydrothermal vent systems.


Authors: Kuhan Chandru, Alexis Gilbert, Christopher Butch, Masashi Aono and Henderson James Cleaves II

Title: The Abiotic Chemistry of Thiolated Acetate Derivatives and the Origins of Life

Journal: Scientific Reports, 2016

DOI: 10.1038/srep29883


Scribbles on the Gordon Research Conference (2016) for the Origins of Life

January is often a horrendous month for ELSI researchers; first we have our own in-house annual international symposium and then this is followed by our intense internal evaluation seminar, a two-day affair where all ELSI members present their work for the past twelve months. This year I decided to one up that schedule by attending the Gordon Research Conference on the Origins of Life in Galveston, Texas in between these two important events.


This was my first trip to the UNITED STATES OF AMERICA, and I was very excited about it before boarding the flight. After 15 hours of journey, I started to develop mixed feelings about this trip until I was shown to my room at the famously haunted Hotel Galvez (be sure to watch the video in youtube), where I slept for the next 15 hours. That is a personal record.

Here are some of my random observations during the GRC’s intense science program.

  1. You are forbidden to record electronically any of the talks or posters given by the presenters. Because of that very fact, we are ALLOWED to argue aggressively. Rumor has it that there was a legendary argument that took place in the past. When I say argument, I don’t mean light ones. But to my surprise nothing like that happened this time. This was probably because they wasn’t anyone trying to sell/convince you their version of OoL scenario (which usually happens in Origins kind of conferences). This GRC, in my opinion, was amazing since the focus was only in what we know, what we don’t know, and what the current evidence is showing. That was such a relieve for me after witnessing many sales pitches in the field in the past.
  2.  GRC likes placing their conferences in, sorry Galveston, remote areas to create an intimate group setting. This is something that didn’t go well with the enthusiastic foreigner like me who wants to spend some time off as well. But in any case, science always comes first, and I was immensely satisfied with what I have gained (talks and meeting people) and not to mention having the time-off to visit Johnson Space Center with some of my favorite people on board.
  3. The scientific talks were exclusively made for an interdisciplinary crowd, meaning that one never saw a physicist showing only equations and expecting the biologists and chemist to understand, as if it were “matter of fact” knowledge. I don’t mean this in an offensive way but it is really hard to be able to give a talk to an interdisciplinary crowd, something we do almost everyday at ELSI. The GRC Origins was good demonstration of this with few minor exceptions.
  4. The GRC starts from 9 to 12 pm, we then have a huge break until dinner, and talk resumes again from 7.30 to 9.30. This was thoughtful and pleasing as it helps the jet-lagged foreigner to sleep and feel refreshed for the sessions.

One glaring shift I noticed among some of the leading OoL workers in the field is that they are moving away from trying to only understand origins based on modern bio-molecules. This is good news, as we in ELSI are also having similar views and are working to explore new chemical domains within prebiotic chemistries and origins of life. I also noticed that the integration of theory and experiments are also coming into play more than before to understand this complex problem. In my opinion, interdisciplinarity between sciences cannot be forced upon but needs to grow organically. This puts ELSI in an amazing position with all the disciplines combining (sometimes clashing) to solve some of the pieces of the origins puzzle. In my world of complaints and criticisms (I’m an experimentalist), this is one of the best conference I have attended in this field, absolutely worth the jet-lag and crazy ELSI schedule of January.

kuhan2016-01-21 15.58.jpg

originally post on February 4, 2016 (ELSI blog)

38億年の時を 超え、 生体分子生成の瞬間に迫る

Researcher’s Eye 〜地球最大の謎に挑む研究者たち

Kuhan Chandru


kuhan01.jpg「日本での研究はスピードが速くて刺激的。その上、ELSIには第一線の研究者が集まっているから、知りたいことがあればすぐに聞きに行ける。この環境はとても貴重です」と話すのは、ELSI若手研究員 のクーハン・チャンドゥルー。「原始地球で、どのようにして生命誕生につながる生体分子ができたのか」に迫ろうと、自らが中心となって新たな実験を準備中だ。













Original interview appeared on February 2015 ELSI (Japanese) 

Kensei Kobayashi’s flow-reactor, the SCWFR, part 2

The SCWFR at Kensei Kobayashi's lab at Yokohama National University
The SCWFR at Kensei Kobayashi’s lab at Yokohama National University

Kensei Kobayashi’s group with the help of Takeo Kanaeko (a brilliant man) came up with another design where they named it Super Critical Water Flow Reactor (SCWFR) utilizing an infrared (IR) gold image furnace (Figure above). This enables the fluid in this system to heat up to 400 °C (or any desired temperature) within seconds (without pre-heating). This one specification is important as most autoclave and other flow reactors utilized an electrical heater which takes time to heat up to the desired temperature. This is undesirable as this “pre-heating” is also making the initial chemicals to react (or altered) to lower and rising temperature, which is not very realistic to a real vent. In other case, this is one of the slightly more realistic simulators i have worked to date.

Kobayashi’s ex-student, Nazrul Islam performed the survivability experiment using several amino acids (aspartic acid, threonine, serine, sarcosine, glutamic acid, α-aminobutyric acid, β- alanine, γ-aminobutyric acid, 5-aminovaleric acid and 6- aminohexanoic acid), 10 mM each) by heating them up at four different temperatures (250, 300, 350 and 400°C ) at 25 MPa for 2 min (that’s pretty fast). They showed that amino acids tend to show better recovery when it is hydrolyzed, suggesting some kind of aggregation and/or condensation is happening within the system. Additionally they also showed oligomerization of glycine (100mM) with the same temperature. At 400°C, no oligomerization was found. However, at 200-350°C, diketopiperazine, diglycine, triglycine and tetraglycine were formed. It was suggested that the glycine reactions in a supercritical fluid (300°C to 400°C) are quite different from those in the liquid phase (at 200–350°C). There were many other peaks of unknown compounds in all of the chromatograms of the unhydrolyzed products. Most of those peaks disappeared after acid hydrolysis. This particular findings however remains a mystery.

Another of Kensei’s sudent, Hironari Kurihara, used the SCWFR to test the stability of complex compounds produced from simulated primitive atmosphere (similar to Miller and Urey’s work). He then tested these compounds to assess the stability of some known amino acids. The complex-combined amino acids (from the primitive atmosphere simulation) preserved more amino acids (including amino acid precursors that give amino acids after acid hydrolysis) than free amino acids after heating in simulated SHS environments. In other words, these complex chemicals which could come from atmosphere (or space) could be better preserved if they are come into contact with the hot hydrothermal system which could have existed during the prebiotic-earth setting. This also hints that “clean or perfect” chemicals like amino acids used in many kinds of experiments are not necessarily showing the right picture when comes to chemical evolution on early earth. More on this in the future.

Many critics of hydrothermal vent simulators often argues that, simulators mentioned on this post and previous ones have a rather short flow-rate and short flow-length (showing low residence time, meaning how long the sample stays in the system). Critics usually cite studies that refer to residence time of fluids in axial hydrothermal environments range from years to decades, while those in lower temperature off-axis diffuse flow systems may be on the order of thousands of years. The problem with these studies about residential axial time of fluids is that, they’re are based on models and calculation only, no work has been done so far in regards to real time sampling or measuring the length of vent system (although, there are work in measuring the velocity of fluid emitting from a vent which looks promising for future measuring). Despite this limitation, i believe the future of simulators will be done using computer simulators, where experimental data from physical simulators (like the ones mentioned in this blog) could be used as parameters. The biggest advantage in this, is that, we do experiments on a larger scale which is could make the origin of life more complicated, interesting and not so straightforward, which I believe is a good problem to have in the future.

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The flow-reactor, a better hydrothermal vent simulator, part 1

flow-reactor (HCFR) build by Ei-ichi Imai at Nagaoka Institute of Technology.
flow-reactor (HCFR) build by Ei-ichi Imai at Nagaoka Institute of Technology.

In the previous post, i wrote about a conventional kind of submarine hydrothermal simulator (SHS) called the autoclave. In today’s post i will talk about the flow kind of reactor which is more realistic compared to the autoclave. Jack Corliss, the man who discovered a real SHS, came up with the notion that a flow-type reactor is essential for new origin of life experiments, as he argued that the quenching effect of the cold seawater is important to hold the short-lived intermediates (hydrogen cyanide, sugars and etc) or as he calls it “quasi-species” in prebiotic synthesis of bio-molecules. This essentially means that a flow kind of simulators are required to better represent a real SHS to  produce more reliable results than the autoclave.

Initial Schematics of Jack Corliss in his paper
Initial Schematics of Jack Corliss in his paper

Co-incidentally, Koichiro Matsuno, designed a principle idea of a flow reactor which could reflow the fluids repeatedly in heat and cold (i will name here-forth as hydrothermal circulation flow-reactor (HCFR) for convenience). Ei-Ichi Imai, Koichiro Matsuno and co-workers went on to build  (image above, schematics diagram below) the reactor and experimented using many bio-molecules.

Their first paper which made it to Nature (big thing for scientist), reported that oligomerization of glycine could occur at 200-250°C, where a monomer glycine solution was circulating for 2 hours or so. Oligomers up to Hexaglycine was reported when metal (Cu2+) and controlled pH was introduced. Without them, only oligomers up to triglycine could be obtained. They also tried the same experiment using  glycine and alanine. They observed oligomerzation products such as

Schematic diagram of the HCFR system from Nagaoka Institute of Technology
Schematic diagram of the HCFR system from Nagaoka Institute of Technology

diketopiperaxine, gly-ala, ala-gly, gly-ala-ala, ala-ala, ala-ala-ala and ala-ala-ala- ala was created when the solution was heated with similar conditions. What i described abover is a big thing in origin of life studies. This land-mark discovery, was the first to show that oligomerization (a shorter version of polymerization) could occur using basic amino acid (gly), without the help of DNA and RNA molecules which are crucial in making proteins in life.

In their other works, oligomerization of nucleotide up to trimers (basic monomer of DNA) was also observed when 20mM of adenosine monophosphate was used with 1mM ZnCl2 were reflowed at 110°C.

Despite the findings made by HCFR, the system is rather hypothetical, since we know that real live vents don’t really circulate in that manner (shown below) however, this kind of reactor is useful when it comes to monitor chemical changes in the system. In my next post, i will review another kind of flow-reactor in Japan which i have also worked on in the past.

HCFR mimicking a circulatory system in a real life vent.
HCFR mimicking a hypothetical circulatory system in a real life vent.

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