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Our future, our universe, and other weighty topics


Tuesday, October 8, 2019

The Measly Results of Origin-of-Life Researchers

For many decades, scientists have been doing research trying to understand how life could have originated on this planet. They have never really got to first base in their efforts. But based on the hype you read in the press, you might think that these scientists are hitting doubles, triples and grand-slam home runs. For several decades I have read more outrageous exaggerations and misleading distortions on this topic than on perhaps any other scientific topic. It didn't seem very different when I visited a science news site on Saturday, and saw two new articles on this topic.

The first article was one on nature.com, an article announcing “Lab-made primordial soup yields RNA bases.” To put this into perspective, we need to first consider some of the requirements for the origin of life:

Large-scale requirements Chemical sub-requirements
100+ proteins, each consisting of 100 or more amino acids arranged in just the right way to achieve a functional end The twenty amino acids used by earthly life must all be available. Most of them are far more complex than the simplest ones (alanine and glycine). The amino acids must be exclusively left-handed, as we see in earthly life.
Genetic information in a molecule such as DNA, specifying the amino acid sequences of these 100+ proteins Ribose sugar molecules, phosphate group molecules, and four DNA nitrogen bases (adenine, guanine, cytosine and thymine)
RNA molecules Ribose sugar molecules and four RNA nitrogen bases (adenine, guanine, cytosine and uracil)
Genetic code Additional complex requirements.



Now, it should be rather clear from the list above that if someone merely makes in a lab the four RNA nitrogen bases, then such a thing is hardly anything in regard to explaining the origin of life. It's rather like merely showing someone a handful of nails after he asks, “Show me that you are all set to build a house.”

A long-standing problem in trying to explain the origin of RNA molecules is that such things require ribose sugar molecules. But in the “primordial soup” imagined by scientists (existing before life), ribose sugar molecules would not be stable. This was demonstrated by a scientific paper which stated the following:

The generally accepted prebiotic synthesis of ribose, the formose reaction, yields numerous sugars without any selectivity. Even if there were a selective synthesis of ribose, there is still the problem of stability. Sugars are known to be unstable in strong acid or base, but there are few data for neutral solutions. Therefore, we have measured the rate of decomposition of ribose between pH 4 and pH 8 from 40 degrees C to 120 degrees C. The ribose half-lives are very short (73 min at pH 7.0 and 100 degrees C and 44 years at pH 7.0 and 0 degrees C)... These results suggest that the backbone of the first genetic material could not have contained ribose or other sugars because of their instability.

What this paper told us is that at the very warm temperature needed for any kind of “origin of life from chemicals” scenario, ribose sugars are unstable, lasting about 73 minutes. So it is very hard to imagine any credible scenario in which a ribose sugar would combine with an RNA nitrogenous base such as adenine to make one of the building blocks of RNA. Having only the RNA nitrogenous bases would be like trying to build a big hotel with only lumber and no metal, nails or screws, or trying to build such a hotel with only nails or screws, and no lumber.


nucleoside

The Nature.com article quotes a scientist named Thomas Carell insinuating that his experiment tells us something hopeful about the probability of life naturally arising on other planets.  This is not at all correct.  In this article, the distinguished chemist James Tour analyzes a previous 2016 experiment by Carell on the same topic. He describes the experiment as follows (I have added boldface to one of the lines):

"Starting with 2,4,5,6-tetraaminopyrimidine-sulfate and suspending it in formic acid and sodium formiate, the mixture was heated to 101°C for two hours. The solvent was evaporated under reduced pressure and water was added to dissolve the product. Concentrated ammonium hydroxide was then used to raise the mixture to pH 8. The solution was cooled overnight at 4°C, yielding substantial amounts of formylated tetraminopyrimide as a crystalline solid. This was isolated from the other products. Then, they allowed the formylated product to interact with 15 equivalents of homochiral ribose by grinding the two together thoroughly in the solid state and heating the mixture in an oven at 100°C for eight hours. The team purchased its ribose...There is no reason to suppose that nature could have commanded these exquisite laboratory skills."

So the ribose sugar (a key part of a nucleoside, as shown in the diagram above) was purchased, not experimentally created; and some very contrived technique was used that we would not expect to find occurring naturally.  Yet the study was written up with a title claiming a "nucleoside formation pathway," as if some natural path to such a thing had been found. 

Was an equally cheesy method used in the latest experiment, described in Becker and Carell's October 2019 paper "Unified prebiotically plausible synthesis of pyrmidine and purine RNA ribonucleotides"? The article on Nature.com seems to suggest a similar shortcoming in Carell's latest experiment, for the article merely announces that 4 nitrogen bases were produced (without claiming that a full nucleoside was produced); and it also says, "The next major problem Carell wants to tackle is what reactions could have formed the sugar ribose, which needs to link to nucleobases before RNA can form.”  That sure makes it sound like the experiment did not actually produce a nucleoside (including a sugar ribose) from scratch, and that the experiment therefore did not at all produce one of the building blocks of RNA in conditions simulating the early Earth (but merely some building blocks of the building blocks of RNA). 

When I examined Becker and Carell's paper "Unified prebiotically plausible synthesis of pyrmidine and purine RNA ribonucleotides" published in the October 4, 2019 Science, I found that there was no generation of a nucleoside through an experimental procedure simulating the early Earth.  The experimenters took something supposedly "acheived in a plausible prebiotic setting," and then manually mixed that with ribose (probably off-the-shelf or purchased ribose) "in the presence of boric acid."  So there was no production of a nucleoside (a molecule consisting of both ribose and ribonucleotides) produced under conditions simulating the early Earth.  A nucleoside "building block of RNA" was not produced under conditions simulating the early Earth.

In a 2018 paper Thomas Carell and his colleagues claimed that "wet-dry cycles" can "enable the origin of nucleosides."  But the paper described a very artificial-sounding technique. First, some salts were obtained with a variety of methods like this:

"1-methylguanidine (2a) hydrochloride salt (10.95 g, 100 mmol, 1 eq.) and malononitrile (1) (6.65 g, 100 mmol, 1 eq.) was dissolved in H2O (230 mL, containing 6 mL of AcOH) in a 500 mL beaker. A solution of NaNO2 (7.00 g, 101 mmol, 1.01 eq., in 20 mL of H2O) was slowly added at room temperature. After stirring at room temperature for 2 h the reaction mixture was kept at 45 °C in an oil bath for 3–4 days open to the air until the mixture was concentrated to about 100 mL. The reaction mixture was placed in a fridge overnight at 8–10 °C. The formed yellow crystals were filtered off to give the desired product (6.70 g, 40 mmol, 40%)."

Then (according to the supplementary materials) ribose sugar was added to this strange mixture:

"Ribose (56.5 mg, 0.375 mmol, 15 eq.) was thoroughly ground up with the corresponding FaPy compound 5a-h (0.025 mmol, 1 eq.) and heated to 100 °C for 8 h in an oven. The remaining reaction mixture was taken up in basic solution (3 mL, 0.5 M Et3N) and heated in a sealed tube (ACE 15 mL pressure tube) at 100 °C for several days (see below)."

These are artificial chemist procedures that can be hardly compared to anything that might have occurred naturally, and the ribose is not arising naturally, but is being added.  The chemist is simply dumping in off-the-shelf ribose or purchased ribose, not producing ribose in a simulation of early Earth conditions.   So in no sense can an honest claim be made that the building blocks of RNA (nucleosides that include ribose) have been produced in a simulation of early Earth conditions. 

On the same day that www.realclearscience.com referred us to this www.nature.com article, it linked to a cockeyed Universe Today article about origin-of-life research. The story starts out by stating that the Cassini-Huygen space probe “delivered the most compelling evidence to date of extra-terrestrial life.” This is entirely false. The probe did nothing of the sort.

The article then tries to back up its imaginary claim by stating this:

For instance, a team of German scientists recently examined data gathered by the Cassini orbiter around Enceladus’ southern polar region, where plume activity regularly sends jets of icy particles into space. What they found was evidence of organic signatures that could be the building blocks for amino acids, the very thing that life is made of!”

Once again, meager and measly results are being hyped to sound like something big. First, the article does not say that amino acids were actually found, but merely talks about the “building blocks for amino acids.” Second, the article does not actually say that “building blocks for amino acids” were found, but that something was found that “could be” the building blocks for amino acids.

The simpler amino acids are fairly simple molecules. For example, glycine and alanine (two of the simpler amino acids) are about half as complex as the nucleoside depicted in the diagram above. So finding “building blocks for amino acids” is an unimpressive result, involving finding molecules of only a few atoms. The building blocks of life are proteins. So the tiny molecules in question (possible building blocks of amino acids that are the building blocks of proteins that are the building blocks of life) merely qualify as possible building blocks of the building blocks (amino acids) of the building blocks (proteins) of life. Of course, finding a mere building block of a building block of a building block of something is unimpressive, and gives you no reason whatsoever to suspect that such a thing could naturally appear. Similarly, finding by chance a mere pixel-sized dot that is the building block of a letter or character that is the building block of a book gives you no reason at all to think that books can form by chance.

Origin-of-life researchers have failed to produce a single nucleic acid in any experiment accurately simulating conditions of the early Earth, and have not even produced from scratch a single building block of a nucleic acid (a nucleoside) in such an experiment. Such researchers have also failed to produce a single functional protein through any such experiment. In experiments accurately simulating conditions of the early Earth, origin-of-life researchers have failed to produce more than a few of the 20 types of amino acids used by living things. 

There is a problem with some of the famous experiments attempting to produce amino acids by sending energy through gases simulating the early Earth's atmosphere. The gaseous mixtures used in such experiments often do not match the early Earth's atmosphere as it is now understood. A press release on a NASA web site states the following:

"For decades, scientists believed that the atmosphere of early Earth was highly reduced, meaning that oxygen was greatly limited. Such oxygen-poor conditions would have resulted in an atmosphere filled with noxious methane, carbon monoxide, hydrogen sulfide, and ammonia....Now, scientists at Rensselaer are turning these atmospheric assumptions on their heads with findings that prove the conditions on early Earth were simply not conducive to the formation of this type of atmosphere, but rather to an atmosphere dominated by the more oxygen-rich compounds found within our current atmosphere — including water, carbon dioxide, and sulfur dioxide. 'We can now say with some certainty that many scientists studying the origins of life on Earth simply picked the wrong atmosphere,' said Bruce Watson, Institute Professor of Science at Rensselaer."

An article in Scientific American discusses the famous Miller-Urey experiment that produced some amino acids in a brown broth:

But the Miller-Urey results were later questioned: It turns out that the gases he used (a reactive mixture of methane and ammonia) did not exist in large amounts on early Earth. Scientists now believe the primeval atmosphere contained an inert mix of carbon dioxide and nitrogen—a change that made a world of difference. When Miller repeated the experiment using the correct combo in 1983, the brown broth failed to materialize. Instead, the mix created a colorless brew, containing few amino acids.”

A 2017 experiment attempted a Miller-Urey experiment with a more realistic mixture of gases. It produced only a single type of amino acid: glycine, the simplest type.  As shown in Table 1, the glycine appeared in only tiny trace amounts of 40 parts per million. The other 19 amino acids used by living things were not produced. For well over 50 years following the 1950's Miller-Urey experiment, humanity was told the fairy tale that scientists showed that it was relatively easy for the early Earth to have made amino acids. It now seems that 19 out of 20 such amino acids cannot be produced in experiments realistically simulating the Earth's atmosphere. Mainstream media sources continue to spread  misinformation on this matter.  For example, the current wikipedia.org article on abiogenesis says near its beginning, "The classic 1952 Miller–Urey experiment and similar research demonstrated that most amino acids, the chemical constituents of the proteins used in all living organisms, can be synthesized from inorganic compounds under conditions intended to replicate those of the early Earth." We only hear much later in the article about how the experiment was not using the right mixture of gases to correctly simulate the early earth's atmosphere. 

At least 8 of 20 amino acids used by living things (arginine, asparagine, cysteine, glutamine, histidine, lysine, tryptophan and tyrosine) have never been produced by any experiment simulating early Earth conditions, including those that used inappropriate gaseous mixtures. Whenever amino acids are produced in experiments trying to simulate the early Earth's atmosphere, the amino acids are 50% left-handed and 50% right-handed. In contrast, the amino acids used by Earthly organisms are all left-handed. Accordingly, attempts to experimentally produce amino acids like those in living things can be called 100% unsuccessful. In experiments simulating the early Earth, no one has ever produced a liquid mixture that had even one type of amino acid existing in exclusively left-handed form.

When something is produced in origin-of-life experiments, it is often in negligible amounts such as an invisible millionth of a gram. But you won't learn that by reading the abstract of a paper, which will typically just brag about having produced something, without mentioning the just-barely-measurable quantity. 

The simplest living thing would consist of very many thousands of amino acids arranged in just the right way to achieve about a hundred functional proteins.  If it were ever shown that all twenty amino acids in living things can be naturally produced in a place like that of the early Earth, this would do nothing to show the mathematical possibility of a life form arising from random combinations of amino acids, which would be comparable to the likelihood of sea shells and driftwood brought up by the tide forming randomly into long, complex, functional instructions (like a long set of instructions on how to build a jet fighter). Showing that all of those twenty amino acids could naturally form would be rather like merely showing that a monkey placed at a keyboard or typewriter can strike each of twenty different keys, and would do nothing to show that natural events can randomly produce the vast amount of functional information required for life to originate.  

No hint of such a difficulty has been communicated in 99% of the science articles that have been written about the origin of life. The majority of these articles rather speak as if the origin of life could occur if some building blocks pile up, without ever communicating the mountainous organization requirements for life to originate, similar to discarded scattered auto parts in a junkyard forming into a long row of functioning cars after a tornado passes by.  

There is only one question we should be asking origin-of-life researchers who have produced such meager and measly results that come nowhere close to substantiating the possibility of the primordial soup hypothesis, that life can naturally form from chemicals. That question is: is that all you got?

Postscript: Another representative example of recent origin-of-life studies and their announcements is a study by Japanese scientists, which was touted with a press release entitled, "Life's building blocks may have formed in interstellar space."  The experiment (trying to simulate "giant gas clouds") merely produced nucleobases (nitrogenous bases such as adenine) that are not at all "building blocks of life" but at best "building blocks of building blocks of life." Getting this required very complicated manipulations with various high-tech instruments (and low-tech items such as quartz wool and glass vials) that presumably would not be floating about in interstellar space. The press release makes no mention of how much of these nucleobases were produced.  A table in the scientific paper tells us that none of the four nucleobases produced were produced in a quantity greater than 4 parts per million, with the average yield being about 1 part per million. In the press release a scientist shamelessly hypes this very meager result produced so artificially, saying, “This result could be key to unraveling fundamental questions for humankind."

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