Dr. Pauling’s Chiral Aliens

[A guest post expanding on Pauling’s idea for a science fiction novel. Post authored by the blog’s East Coast Bureau Chief, Dr. John Leavitt, Nerac, Inc., Tolland, CT.]

Pauling lecturing with the “fish model” (foreground) that he used to demonstrate chirality, ca. 1960s.

In basic chemistry we have something called “chirality” which refers to a molecule with two possible non-superimposable configurations. One way to picture this is to look at your hands and place one on top of the other (not palm to palm) – your left and right hands are essentially the same shape but their shape is reversed. At the molecular level we can use one of the main building blocks of all proteins and all life – the amino acid alanine, depicted in the image below – to examine handedness.

The diagram shows the arrangement of atoms of two alanine molecules, both of which exist in nature, arranged so that they are mirror images. They are the same molecules but if you turn the one on the right around so that it is facing in the same direction as the one on the left, the R (a single carbon atom in alanine with three bonded hydrogen atoms) on this alanine molecule faces toward the palm of the hand and the COOH moiety (a carboxyl group) and the NH2 moiety (an amino group) face outward away from the palm.

No matter how you rotate the alanine on the right, you can’t get the three moieties attached to the central carbon to line up in the same position as the alanine on the left. Likewise, you can’t get those hands to super-impose each other no matter how much you twist and turn them. So the alanine on the left is called L-alanine (levo- for the direction the molecule rotates photons) and the alanine on the right is called D-alanine (dextro- for the direction the molecule rotates photons). They are called “enantiomers,” or chiral forms, of alanine, and both exist in nature with identical chemical properties except for the way that they rotate polarized light.

There are twenty natural amino acids comprising the building blocks of all proteins. Of these twenty, only glycine is symmetrical around a central carbon atom and therefore glycine has no enantiomers. The other nineteen can exist in the L- and D-conformation.

Funny thing though, only the L-enantiomer is used to make proteins by the protein synthetic machinery of all life-forms, from single-cell organisms up to humans. It’s quite easy to understand why one enantiomer is used in life over random use of either enantiomer. In explaining this, note the pictures below, which show the three-dimensional globular structure of human beta-actin on the left and, on the right, the architectural arrangement of this actin in the cytoplasm of a cell.

The protein composed of 374 amino acids has an intricate folding pattern with coils which would not be possible if both amino acid enantiomers for the nineteen amino acids were randomly incorporated into the protein. This three-dimensional structure has to be preserved in order for actin to perform its dynamic architectural function inside living cells, as shown in the picture on the right. The coils are possible because the amino acids are all L-amino acids and glycine is neutral; otherwise the protein would behave like a wet noodle. The precise structure of the actin protein determines its function, which has been preserved and conserved since the beginning of all eukaryotic life-forms (that is, cells with a cytoplasm and a nucleus). Understanding the atomic forces that fold proteins in a unique shape is part of the reason why Linus Pauling received the Nobel Prize for Chemistry in 1954.

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Aside from those who closely follow this blog, it is not well known that Linus Pauling was an avid reader of science fiction. In a 1992 interview with biographer Thomas Hager, he described his motivation to write a science fiction novel. The story line was to be the discovery of a human-like race from another planet that had evolved to use only D-amino acids (D-humans) rather than the L-isoform (L-humans). He explained that he never got around to writing this novel because the real science he was doing took all of his time.

If our L-humans met up with those D-humans, what consequences would there be? Well, what we would see in D-humans are people virtually indistinguishable from ourselves – barring, of course, the possibility that these extraterrestrials evolved out of some unearthly environmental niche. However, no mating, blood, or tissue sharing would be possible between these two races.

To explain this, consider the experience you have had when you accidently put your hand in the wrong glove. As you know, this doesn’t work well. All protein interactions and reactions catalyzed by enzymes require a direct fit to work. Substrates of enzymes have to fit precisely into the catalytic active site of the enzyme, like your hand fitting into the correct glove. Since L-humans have a different chirality from D-humans, nothing would fit or be transferrable, because of asymmetric incompatibility between L- and D- macromolecules. Even the food on our planet would not likely be nutritious for D-humans because all living things on Earth are L-organisms. In D-lifeforms, the actin coils would coil in the opposite direction and the DNA double helix would have to spiral in the opposite direction as well; otherwise the analogous D-proteins would not bind or fit on the chromosomal DNA.

It seems reasonable that D-humans might be found on other planets if you consider how life got started. By a quirk of nature on Earth, L-amino acids got a head start and self-assembled into peptides (small proteins) when this essential process for life as we know it got started. The assembly of only one enantiomer isoform into a peptide may have been favored thermodynamically over co-random assembly of L- and D-isoforms. This essential process evolved into a well-organized, membrane-protected and energy-driven protein synthetic machinery in single cell organisms like bacteria. Today, humans have essentially the same protein synthetic machinery that evolved in primordial bacteria and all life-forms on Earth have the same genetic code.

There are two essential enzymes that work together to catalyze protein synthesis in all living cells. One enzyme, called aminocacyl-tRNA synthetase, binds the amino acid to a transfer RNA molecule (there is one of these enzymes and a specific tRNA for each of the twenty amino acids). The second enzyme, peptidyl transferase, catalyzes the formation of a peptide bond linking two amino acids at the start of a chain and does this over and over again until the full length protein is synthesized and folded into its functional conformation. These two essential enzymes do not recognize the D-isoforms of the nineteen asymmetric amino acids. Thus, our chiral L-specificity has been preserved since the beginning of life.

I can’t think of any reason why the D-amino acids would not support life, but it has to be one isoform or the other, not both. Apparently Pauling felt the same way. Should it ever come to pass, D-humans will be interesting to meet and they will be equally interested to meet us, hopefully without mutual disappointment.

The Sci-Fi Author that Might Have Been…

…and featuring a debut story by Linus Pauling?

Along with detective stories, crossword puzzles and the occasional walk, reading science fiction was Linus Pauling’s primary form of leisure.  The hundreds of dog eared sci-fi monthlies spanning multiple decades in his personal library (used to good effect by a past Resident Scholar of ours) are testament to a keen interest in the genre.  It was not until recently, however, that we learned of Pauling’s one-time interest in dabbling as a fiction writer himself.

From an October 1992 interview with Thomas Hager, conducted in support of his 1995 biography, Force of Nature:

Thomas Hager: Do you continue to have an interest in science fiction now?

Linus Pauling: Yes, I subscribe to two of the science fiction journals. Argosy and Science Fiction and Science Fact, the two principle science fiction journals I subscribe to, and I usually read them. The serials sometimes are just too long, I don’t bother to read them. And of course the problem is first the characters have been changing recently. Instead of being adventure science fiction stories, they are sort of sexual relations science fiction stories – the way with novels, too. I don’t read novels anymore either except for old ones that I re-read. And then the science fiction stories, the plots all seem to me to be old ones that I have read before. Sometimes it seems to me that the stories aren’t so interesting as they were in the old days.

TH: Well, that’s probably true. You’ve been reading them long enough, they repeat.

LP: Yes, for years I thought I would write a science fiction story based upon the idea that one can have life essentially identical with life on earth which is based on DNA and proteins and amino acids, but with other handedness. In my General Chemistry or College Chemistry freshman chemistry text, I have a footnote about Alice in Wonderland, or I have a page or two about right-handed and left-handed molecules. And I quote Alice in Wonderland saying, ‘But would looking glass milk be good for me?’ And I said of course it wouldn’t be. It would be made of D-amino acids. And someone who had been converted to the dextral form would not be able to eat anything unless he could get food made of D-amino acids… And couldn’t get married and have children unless he could find a wife who had also been. Well I was going to have a catastrophe in the ship going through space. Some sort of catastrophe that changed everything from left-handed to right-handed.

Extracted from “College Chemistry,” 3rd edition, 1964.

TH: Now do you remember what sort of catastrophe it would’ve been?

LP: No. Well, it’s pretty hard for a scientist to invent a catastrophe that would do that. It had to be a catastrophe somehow involving multiple worlds, not just a shockwave. Because you would have to have angular momentum, chirality, and it’s very hard even to convert L-alanine to D-alanine, for example.

TH: If you lifted an L-being out of the third dimension into the fourth dimension and turned them over and put them back, would that…?

LP: Oh yes. Surely that’s exactly what people who have written about multi-dimensional space had said or the man who wrote Flatland. You could do that in three dimensions and go back to two dimensions.

TH: I wonder, but I’m trying to think, would that result in that sort of inversion in that…?

LP: Oh yes, well, if you had a scalene triangle, three edges unequal to one another, three edges all different, and turn it over, it goes from being a right-handed to a left-handed.

TH: So in any case, that’s an interesting idea. It is too bad you never finished that.

LP: Yes, well of course, one complaint about some science fiction writers is that their handling of interpersonal relationships is poor. This is a complaint I had of E. T. Bell‘s science fiction books. He wrote two or three science fiction books under the pseudonym John Taine. And they were mildly interesting from the science, sort of. Not more interesting than books or stories by many science fiction writers. Mildly interesting, but the handling of personal, interpersonal relationships was very poor. Of course, good science fiction stories depend to a considerable extent on the personal relationships, just as good novels do.

TH: Do you feel that would have been a weakness if you had tried writing one?

LP: Well, I thought I recognized the need for including a good story of this sort inside of the story, but I’m not sure that I could do it. But the main thing is I never have had time. There are always scientific problems that I am trying to solve and that interest me more.

Pauling’s personal collection of science fiction periodicals, as housed in the OSU Libraries Special Collections & Archives Research Center.