February 5, 2023

How to tell biological from non-biological molecules

How to tell biological from non-biological molecules
How to tell biological from non-biological moleculesHow to tell biological from non-biological molecules

WOULD YOU like the vanilla in your custard to come from a field of lovely orchids or a barrel of wood pulp? The second option may not seem as appetising, but synthetic vanillin, as vanilla’s flavour-inducing compound (C8H8O3) is called, has a hundredth of the cost. Which warrants suspicion. When you pay your money, are you getting the real stuff?

A way to find out is to take a sharp look at those eight carbon atoms, because carbon itself comes in flavours, too. On Earth, the vast majority is 12C, with atoms containing six protons and six neutrons. A mere 1.1% is its heavier sibling 13C, which has a neutron more. It turns out that when producing vanillin, orchids incorporate a little more 13C into the molecules they are making than synthesis by humans does.

Checking for the ratio of 12C to 13C in vanilla extract would thus seem to be the answer. But canny producers of cheap vanillin can evade that check by rigging their raw material to contain a bit more 13C than usual, to make their product conform to analysts’ expectations.

The counter-ploy is to look at where exactly in a vanillin molecule the heavy carbon atoms tend to be. The chemical steps the orchid’s bean-producing cells perform to create vanillin steers them preferentially to certain positions. Copying those steps in a test-tube is hard.

Probing molecules to see where different varieties of an atom camp out is called position-specific isotope analysis, or PSIA. And this technology has advanced rapidly in the past few years, as Katherine Freeman, a professor at Pennsylvania State University and director of the NASA Astrobiology Centre for Isotopologue Research there, told a conference of the Geological Society of America in Portland, Oregon, on October 10th. PSIA now stands ready not only to check the origin of foodstuffs, but also to prise information from molecules about Earth’s atmosphere millions of years ago, and perhaps help determine whether living organisms contributed to samples brought back from Mars.

The first step in any position-specific analysis is to cut up the compound under investigation. Vanillin molecules, for instance, have a protruding cluster of one carbon and three hydrogen atoms called a methyl group that is easily separated from the rest. This can then be tested in isolation by converting the carbon to CO2 and weighing the resulting gas.

More sophisticated approaches are also available. One is to break molecules up into several pieces and record the average masses of each, using mass spectrometry. Another is to employ NMR spectroscopy, which measures how radio waves interact with atoms held in a strong magnetic field (12C atoms behave differently from 13C).

David Hoffman and Cornelia Rasmussen of the University of Texas in Austin are investigating a number of amino acids, the building blocks of proteins, using a twist on this technique—looking not at the atoms themselves but rather at the bonds within molecules between carbon and hydrogen atoms. These react differently to radio waves, depending on the type of carbon involved. The two researchers hope to find differences between amino acids of biological origin and those made in a laboratory—knowledge that may be crucial for the investigation of samples from a planet where life possibly arose, such as Mars.

There are so many compounds worth checking for their inner isotopic life, that researchers are, Dr Freeman says, “like kids in a candy store”. Moreover, in addition to carbon, probing can be done for isotopes of nitrogen, sulphur, oxygen and hydrogen. But work on carbon has come furthest.

One of her own favourite molecules is glucose. In this, the isotopes’ positional preferences are strong. Since glucose is the “ur-molecule” from which most other biochemicals ultimately derive, that difference gets propagated far and wide into an organism’s molecular make-up. Indeed, it is preserved in molecules from the distant past, potentially enabling palaeontologists to track when life began on Earth in the absence of clearly distinguishable fossils.

Even farther out, literally, is what the method could reveal about compounds from meteorites. According to Dr Freeman, most of their molecules will have formed on the planet or asteroid the meteorite was once part of. But some could be much older. Weighing their isotopes may offer a taste of the interstellar medium as it was before the solar system started assembling itself. The opposite, then, of mere plain-vanilla research.