Two students of the senses win the Nobel prize for medicine

THE IDEA that there are five senses goes back at least as far as Aristotle. But it is not quite true. Four of the senses are obvious, not least because each is associated with a particular organ: sight with the eyes, hearing with the ears, taste with the tongue and smell with the nose. But the fifth classical sense, touch, is distributed over the whole surface of the body, albeit that it is particularly concentrated in the fingertips.

Touch, moreover, is only one of such distributed senses. Others, perceived consciously, include pain, heat and cold. And modern science has shown there are yet further, unconsciously perceived senses, known collectively as proprioception. These keep track of the position and movement of the body and its parts. This year, the Nobel Assembly of the Karolinska Institute, in Stockholm, which awards the Nobel prize for physiology or medicine, chose to honour the discoverers of the molecular mechanisms of two of these distributed senses—temperature and mechanical stimulation.

The winners were David Julius of the University of California, San Francisco and Ardem Patapoutian of Scripps Research, a biomedical institute in San Diego. Dr Julius did the pioneering work on temperature. He and Dr Patapoutian, acting independently, then advanced this work. After that, Dr Patapoutian moved on to look at mechanical stimulation.

Dr Julius’s chosen tool for his investigation, which he began in the late 1990s, was capsaicin. This is the active ingredient of chilli peppers. By a chemical coincidence (as was then assumed and is now known) capsaicin reacts with, and thus stimulates, one of the body’s heat-receptor proteins. Dr Julius set out to discover what this protein was. To do so he made millions of fragments of genetic material for proteins known to be active in heat-receptor cells. He then introduced these fragments into other cells, to encourage them to manufacture the relevant protein fragments. That done, he tested the modified cells for sensitivity to capsaicin.

The fragments which induced capsaicin sensitivity turned out to be parts of a protein now called TRPV1. This belongs to a class of proteins called ion channels, which do many jobs in the body. As predicted, TRPV1 turned out to be heat sensitive. When the temperature rises above 43°C, the channel through it opens, permitting ions of calcium and sodium to pass. That chemical signal stimulates a nerve impulse which tells the brain about the temperature change.

TRPV1 turned out to be one of several temperature-sensitive ion channels, some of which register heat, and some cold. It was one of the cold-sensitive varieties, TRPM8, which was discovered simultaneously by Dr Julius and Dr Patapoutian.

Dr Patapoutian then went on to look at the sensation of touch. Molecular biology having advanced in the interim, he was able to work with whole proteins—or, rather, the genes for whole proteins. He identified 72 such proteins expressed in a mechanically sensitive cell line that looked like potential touch-sensitive sensitive ion channels. He tested them one at a time, by silencing the genes that encode them and poking the resulting cells. The first 71 silencings had no effect. But the 72nd proved to be of the protein he was looking for. He called that protein PIEZO1.

In nature, PIEZO1 is found not in sensory neurons, but rather in organs like the bladder where local sensitivity to pressure is important. But Dr Patapoutian soon discovered a second, similar channel, PIEZO2, which is, indeed, found in nerve endings. It is this that is responsible for touch and proprioception.

Fascinating work, then. And important. It is through the senses, and the senses alone, that human beings are able to perceive the world. But to some people the award has come as a surprise. In a year of covid, many had been expecting the honours to go elsewhere—perhaps to the inventors of mRNA-vaccine technology. Like God, however, the various Nobel-prize committees work in mysterious ways their wonders to perform.