“People who wait for the Nobel Prize become neurotic.” This sentence stuck with me from a conversation with Peter Hegemann just a year ago. Since yesterday this worry, if it was his own, has been put to rest once and for all. The busy, multi-award-winning Berlin biophysicist Peter Hegemann from Humboldt University was awarded the Nobel Prize for Medicine or Physiology in Stockholm yesterday, along with another German discoverer of canal rhodopsins, Georg Nagel from Würzburg, and the American co-founder of optogenetics, Karl Deisseroth.
In the early years of this century, the three researchers took brain research in a completely new direction - brain research and, as can now be seen in view of the worldwide activity in the field, also medical research. In fact, the idea of using light to control genes and thus targeted body functions, to operate optically, so to speak, has awakened the hope of new therapies among scientists around the world. Blind and deaf people, people with heart disease and people with severe stomach problems, as well as patients with the most severe degenerative brain diseases or addictions, could ultimately be helped by manipulating the molecules of life in a targeted manner with light - if, yes, if it can be implemented, which is currently being tested primarily in so-called preclinical experiments on animals.
But how should that be possible? To explain this, the representatives of the Nobel Committee at the Karolinska Institute had to go back a bit in history yesterday. Peter Hegemann and Georg Nagel, they reported, laid the foundations for the discovery of channelrhodopsins: Hegemann, then at the Planck Institute for Biochemistry in Munich, and Nagel, who worked at the Max Planck Institute for Biophysics in Frankfurt am Main. Both wanted to know one thing above all: how light could cause the membrane proteins originally found in bacteria to literally open these cells to charged atoms and how these ions then created a current, literally activating the cell. Every time light falls on such a channelrhodopsin, the channel in the cell membrane opens, the ions flow and change the cell. And best of all: These membrane proteins can also do this in other cells if you manage to firmly anchor them there, for example through genetic engineering.
Hegemann and Nagel experimented with channelrhodopsins in various places, sometimes also with different membrane proteins, but they were by no means the first and nor were they alone. In fact, their findings are based on discoveries that date back to the middle of the twentieth century and in which numerous German scientists played a key role: first of all, the famous Berlin geneticist Max Delbrück, who fled the Nazis to the USA 90 years ago and switched to so-called photobiology there. The biochemist Dieter Oesterhelt, who died four years ago and in whose Munich research group Hegemann worked and who succeeded in actually detecting the rhodopsin-like protein bacteriorhodopsin in the cell membrane of Halobacteria, must also be mentioned as one of the early pioneers of optogenetics.
In the 1990s, Nagel was able to show through experiments on frogs that the channelrhodopsins from bacteria also functioned in amphibian cells. They harvested light and triggered a current of ions in the cells that could be used in molecular biology. A light switch for biotechnology was born – but initially only theoretically. Only when the channelrhodopsins were genetically decoded by Peter Hegemann in the first years of this century and later genetically modified in such a way that the effect of light could be directed in a physiologically desired direction, was optogenetics born as a tool for molecular biology and biomedicine. It was the key moment in optogenetics, which the US researcher Karl Deisseroth from Stanford University used from then on in various large experiments in different target tissues.
Nerve tissue was particularly suitable for this because the electrical currents in the nerve cells, which are triggered by ion pumps in the cell membrane, had long been known and widely researched as an elementary process. But it hasn't stopped with brain tissue. The possibilities were discovered everywhere, but not in Germany for a long time, Hegemann regrets. “The Germans examined everyone else’s work, but didn’t do anything themselves.” The first applications that were published in the most influential journals after the German basic work almost all came from the USA and China: Zhuo-Hua Pan, then working in Detroit, Michigan, was the first in 2006 to use optogenetics to correct the pathologically altered sensory cells in the retina of laboratory mice and to present it at a scientific conference. Then came the US brain researcher Karl Deisseroth, who fired the imagination of biomedical scientists.
Despite long-standing reservations about genetic engineering, there are now numerous approaches in Germany to use optogenetics therapeutically. At the University Hospital of Göttingen, for example, and especially at the Else Kröner-Fresenius Center for Optogenetic Therapies, the first patient trials to make “optical hearing” possible with a completely new, light-controlled cochlear implant may be scheduled for next year or the year after. The Göttingen laboratories are also already working on animal experiments to develop the opportunity to treat blind people and help seriously ill people with a gastric pacemaker.
With such projects, the first question that naturally comes to mind is how the light should get into the body to control the corresponding genes. In fact, this is the sore spot of optogenetics. Visible light, to which the conventional channelrhodopsins react, only penetrates a few millimeters into the skin. That's why intensive work is now being done on processes and molecules that are intended to optimize this light harvesting with the membrane proteins, even at greater depths. And to take the whole thing to the biomedical extreme, scientists around the world are now working on activating the light sensors anchored in the cells in other targeted ways - for example using radio waves or focused ultrasound. Not only do they have the advantage that they can penetrate deep into the body, but they have also long been used in medicine as therapeutic instruments.
Such ideas continue to trigger storms of enthusiasm in America's top scientific journals. There, however, the optogenetics pioneer Deisseroth became a scientific star at a young age. Hegemann and Nagel, on the other hand, collected their numerous top-class research awards, which they received even before the Nobel Prize in Medicine, virtually behind closed doors.
