Thursday, May 21, 2009

Genesis of Life

This was not an easy problem to solve and as it turns out, the research took years of trying every possible combination. Now we have a clear road forward to understanding how life may have fallen together to be formed in the first place.

Somehow in a primitive environment not unlike a test tube, a lot of necessary organic chemistry got done. A lot of it was low energy chemistry and the world filled up with a solution of stray organics.

I wonder if anyone has ever separated the fluid contents of ordinary cells and subjected that fluid to a variety of environments to see if further self assembly was plausible and what did occur. Of course, what is important may be also low yield.

This is an important breakthrough and clearly directs further research and is very welcome.

Last year we had a report of a twenty year frozen experiment that produced precursor chemicals. This is all food for thought and it finally looks as if the tools are falling into place.

Life began in a flash; Science takes four billion years to catch up
Brendan Borrell

This week's issue of Nature
features a welcome discovery for those of us enthralled, mystified and frustrated by the study of the origins of life. John Sutherland, a chemist at the University of Manchester, and his colleagues claim to have figured out how ribose, phosphate and the nitrogenous (nitrogen-bearing) molecules known as nucleobases first came together to form nucleotides—the building blocks of the RNA world from which life is thought to have emerged."My assumption is that we are here on this planet as a fundamental consequence of organic chemistry," Sutherland told The New York Times. His secret was running the experiment in stages, only adding phosphate in the final step. So far, the team has succeeded in building two of the four nucleotides; the molecule pictured [left] is cytosine, the nucleobase that, until now, scientists were unable to combine with sugars and phosphates to form the RNA nucleotide ribocytidine phosphate.*

Is the latest discovery a real breakthrough or just another high-profile paper to tease the navel-gazers of the science world? Jack Szostak of the Massachusetts General Hospital wrote in a commentary that the new discovery "will stand for years as one of the great advances in prebiotic chemistry."

The findings also serve as a reminder that the pace of scientific discovery does not always move as quickly as scientists would like. In 1871 Darwin first postulated that life began in a "warm little pond, with all sorts of ammonia and phosphoric salts."

Almost a century later, Stanley Miller conducted the great-grandaddy of origin-of-life studies at the University of Chicago with his colleague Harold Urey, experiments which left scientists with more
questions than they answered.

In 1994
Leslie Orgel wrote in the pages of Scientific American that growing evidence was supporting the theory that life emerged from RNA, but he despaired, "how that RNA came into being remains unknown." Last year, scientists got perhaps a little bit too giddy when some minor results were published in Science based on forgotten vials from the original Miller–Urey studies.

Chemist Robert Shapiro of New York University,
who wrote about his alternative theory on the origin of life for Scientific American in 2007, told Chemistry World that Sutherland's results "have nothing to do with the origin of life on Earth whatsoever."

*Correction (5/15/09): This sentence was changed after posting. It originally incorrectly identified cytosine as a nucleotide.


Nature 459, 239-242 (14 May 2009) doi:10.1038/nature08013; Received 11 December 2008; Accepted 24 March 2009

Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions
Matthew W. Powner
1, Béatrice Gerland1 & John D. Sutherland1
School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK
Correspondence to: John D. Sutherland
1 Correspondence and requests for materials should be addressed to J.D.S. (Email:

At some stage in the origin of life, an informational polymer must have arisen by purely chemical means. According to one version of the 'RNA world' hypothesis
1, 2, 3 this polymer was RNA, but attempts to provide experimental support for this have failed4, 5. In particular, although there has been some success demonstrating that 'activated' ribonucleotides can polymerize to form RNA6, 7, it is far from obvious how such ribonucleotides could have formed from their constituent parts (ribose and nucleobases). Ribose is difficult to form selectively8, 9, and the addition of nucleobases to ribose is inefficient in the case of purines10 and does not occur at all in the case of the canonical pyrimidines11. Here we show that activated pyrimidine ribonucleotides can be formed in a short sequence that bypasses free ribose and the nucleobases, and instead proceeds through arabinose amino-oxazoline and anhydronucleoside intermediates. The starting materials for the synthesis—cyanamide, cyanoacetylene, glycolaldehyde, glyceraldehyde and inorganic phosphate—are plausible prebiotic feedstock molecules12, 13, 14, 15, and the conditions of the synthesis are consistent with potential early-Earth geochemical models. Although inorganic phosphate is only incorporated into the nucleotides at a late stage of the sequence, its presence from the start is essential as it controls three reactions in the earlier stages by acting as a general acid/base catalyst, a nucleophilic catalyst, a pH buffer and a chemical buffer. For prebiotic reaction sequences, our results highlight the importance of working with mixed chemical systems in which reactants for a particular reaction step can also control other steps.
School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK
Correspondence to: John D. Sutherland
1 Correspondence and requests for materials should be addressed to J.D.S. (Email:

Chemist Shows How RNA Can Be the Starting Point for Life
Published: May 13, 2009

An English chemist has found the hidden gateway to the RNA world, the chemical milieu from which the first forms of life are thought to have emerged on earth some 3.8 billion years ago.

Reconstructing the Chemistry of Early Life
May 14, 2009)
He has solved a problem that for 20 years has thwarted researchers trying to understand the origin of life — how the building blocks of RNA, called nucleotides, could have spontaneously assembled themselves in the conditions of the primitive earth. The discovery, if correct, should set researchers on the right track to solving many other mysteries about the origin of life. It will also mean that for the first time a plausible explanation exists for how an information-carrying biological molecule could have emerged through natural processes from chemicals on the primitive earth.
The author, John D. Sutherland, a chemist at the University of Manchester, likened his work to a crossword puzzle in which doing the first clues makes the others easier. “Whether we’ve done one across is an open question,” he said. “Our worry is that it may not be right.”
Other researchers say they believe he has made a major advance in prebiotic chemistry, the study of the natural chemical reactions that preceded the first living cells. “It is precisely because this work opens up so many new directions for research that it will stand for years as one of the great advances in prebiotic chemistry,” Jack Szostak of the
Massachusetts General Hospital wrote in a commentary in Nature, where the work is being published on Thursday.
Scientists have long suspected that the first forms of life carried their biological information not in DNA but in RNA, its close chemical cousin. Though DNA is better known because of its storage of genetic information, RNA performs many of the trickiest operations in living cells. RNA seems to have delegated the chore of data storage to the chemically more stable DNA eons ago. If the first forms of life were based on RNA, then the issue is to explain how the first RNA molecules were formed.
For more than 20 years researchers have been working on this problem. The building blocks of RNA, known as nucleotides, each consist of a chemical base, a sugar molecule called ribose and a phosphate group. Chemists quickly found plausible natural ways for each of these constituents to form from natural chemicals. But there was no natural way for them all to join together.
The spontaneous appearance of such nucleotides on the primitive earth “would have been a near miracle,” two leading researchers, Gerald Joyce and Leslie Orgel, wrote in 1999. Others were so despairing that they believed some other molecule must have preceded RNA and started looking for a pre-RNA world.
The miracle seems now to have been explained. In the article in Nature, Dr. Sutherland and his colleagues Matthew W. Powner and Béatrice Gerland report that they have taken the same starting chemicals used by others but have caused them to react in a different order and in different combinations than in previous experiments. they discovered their recipe, which is far from intuitive, after 10 years of working through every possible combination of starting chemicals.
Instead of making the starting chemicals form a sugar and a base, they mixed them in a different order, in which the chemicals naturally formed a compound that is half-sugar and half-base. When another half-sugar and half-base are added, the RNA nucleotide called ribocytidine phosphate emerges.
A second nucleotide is created if ultraviolet light is shined on the mixture. Dr. Sutherland said he had not yet found natural ways to generate the other two types of nucleotides found in RNA molecules, but synthesis of the first two was thought to be harder to achieve.
If all four nucleotides formed naturally, they would zip together easily to form an RNA molecule with a backbone of alternating sugar and phosphate groups. The bases attached to the sugar constitute a four-letter alphabet in which biological information can be represented.
“My assumption is that we are here on this planet as a fundamental consequence of organic chemistry,” Dr. Sutherland said. “So it must be chemistry that wants to work.”
The reactions he has described look convincing to most other chemists. “The chemistry is very robust — all the yields are good and the chemistry is simple,” said Dr. Joyce, an expert on the chemical origin of life at the Scripps Research Institute in La Jolla, Calif
Dr. Sutherland’s proposal has not convinced everyone. Dr. Robert Shapiro, a chemist at
New York University, said the recipe “definitely does not meet my criteria for a plausible pathway to the RNA world.” He said that cyano-acetylene, one of Dr. Sutherland’s assumed starting materials, is quickly destroyed by other chemicals and its appearance in pure form on the early earth “could be considered a fantasy.”
Dr. Sutherland replied that the chemical is consumed fastest in the reaction he proposes, and that since it has been detected on Titan there is no reason it should not have been present on the early earth.
If Dr. Sutherland’s proposal is correct it will set conditions that should help solve the many other problems in reconstructing the origin of life. Darwin, in a famous letter of 1871 to the botanist Joseph Hooker, surmised that life began “in some warm little pond, with all sorts of ammonia and phosphoric salts.” But the warm little pond has given way in recent years to the belief that life began in some exotic environment like the fissures of a volcano or in the deep sea vents that line the ocean floor.
Dr. Sutherland’s report supports Darwin. His proposed chemical reaction take place at moderate temperatures, though one goes best at 60 degrees Celsius. “It’s consistent with a warm pond evaporating as the sun comes out,” he said. His scenario would rule out deep sea vents as the place where life originated because it requires ultraviolet light.
A serious puzzle about the nature of life is that most of its molecules are right-handed or left-handed, whereas in nature mixtures of both forms exist. Dr. Joyce said he had hoped an explanation for the one-handedness of biological molecules would emerge from prebiotic chemistry, but Dr. Sutherland’s reactions do not supply any such explanation. One is certainly required because of what is known to chemists as “original syn,” referring to a chemical operation that can affect a molecule’s handedness.
Dr. Sutherland said he was working on this problem and on others, including how to enclose the primitive RNA molecules in some kind of membrane as the precursor to the first living cell.

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