(Seoul = Yonhap News) Reporter Kim Young-shin = Scientists who pioneered 'optogenetics', which controls specific nerve cells by turning them on and off with light, won this year's Nobel Prize in Physiology or Medicine.
Optogenetics, which has become a key research tool to reveal how the brain works, is expanding its scope as a technology to treat actual diseases, with recent reports of treatment effects for patients with visual impairment.
The Nobel Committee at the Karolinska Institutet in Sweden announced on the 5th (local time) that it had selected three people, including Karl Ditheros, Peter Hegemann, and Georg Nagel, as joint winners of this year's Nobel Prize in Physiology or Medicine.
Optogenetics, which they pioneered, is a compound word of light (Opto) and genetics, and is a technology that expresses microbial proteins that respond to light in specific nerve cells and then shines light to activate or inhibit the activity of those cells.
It is evaluated that it has opened a new field of research in understanding life phenomena by allowing the function of specific cells to be selectively controlled using light.
In existing brain research, correlations were observed as to which cells were activated when a certain behavior or emotion was expressed, but it was difficult to confirm whether a specific cell caused or suppressed that behavior or emotion.
In addition, electricity or drugs were used to stimulate or inhibit nerve cells, but electricity and drugs had a widespread effect not only on specific cells but also on surrounding cells, making them less sophisticated.
Optogenetics is a technology that overcomes these limitations and selectively controls only specific cells of interest, opening the way to identifying how certain cells create behavior, memory, and emotions.
Simply put, a switch was created that turns cells on and off by shining light on them.
Professor Kim Ki-hyun of the Department of Ophthalmology at Seoul St. Mary's Hospital explained, "In addition to observing the correlation between nerve cell activity and behavior, optogenetics has made it possible to directly test the function of specific circuits," adding, "It has brought about a significant change in the way we study complex brain functions such as memory, emotion, reward, and movement."
Optogenetics began with basic research by Hegemann and Nagel published in 2002 that revealed the principles of how microorganisms respond to light.
Hegemann and Nagel discovered a protein called 'channelrhodopsin' that opens a channel when light of a specific wavelength is received in a single-celled green alga called 'Chlamydomonas' that moves towards light.
When channelrhodopsin receives blue light, a channel inside the protein opens, and charged ions move into the cell through this channel, creating an electrical signal.
In particular, Hegemann and Nagel confirmed that no matter what channelrhodopsin was added to any other cell, that cell responded to light.
Carl Ditheros is the founder of optogenetics, who developed optogenetics in earnest by applying these basic research results to nerve cells.
In 2005, Diceros announced the results of a successful study in generating nerve signals by inserting the channelrhodopsin gene into mouse nerve cells and shining blue light on them.
In 2007, he succeeded in controlling only specific circuits with light in the brain of a living mouse.
Optogenetics is developing rapidly and is widely used in the field of neuroscience.
In particular, it is being used to study the mechanisms of development of various neurological diseases such as Parkinson's disease, epilepsy, and sleep disorders, and to verify new treatment targets and new drug candidates.
Professor Kim Jun-ki of the Department of Convergence Medicine at Asan Medical Center in Seoul said, "Using innovative optogenetic technology, medical scientists can now not only understand the function of specific brain circuits in experimental animals at the cellular and molecular level, but also test hypotheses about the effects of new drugs under development on the brain."
Initially, channelrhodopsin responded to blue light, but there was a problem that blue light had difficulty reaching deep into tissues and strong light could damage cells.
In mouse experiments, this limitation was overcome by inserting an optical fiber, but it was difficult to use the same method in the human brain.
In addition, in order to deliver microbial-derived proteins into cells, they must be delivered using viral vectors (virus-shaped carriers), so challenges such as immune response, expression location, and safety remain.
Accordingly, researchers have recently focused on reducing side effects by redesigning proteins and light wavelengths to suit clinical conditions.
According to the medical community, a treatment study was conducted to insert a light-sensing protein into the remaining retinal nerve cells of patients with retinitis pigmentosa, a genetic disease in which retinal visual cells are damaged, and recovery of some visual functions was reported.
This is a strategy to recreate visual signals by giving light detection functions to the remaining cells in place of damaged visual cells in the retina where photoreceptors have disappeared.
Last month, U.S. biotech company Nanoscope Therapeutics submitted an application to the U.S. Food and Drug Administration (FDA) for biological product approval for โMogenlyโ, a treatment for retinitis pigmentosa with severe vision loss.
Mozenly is a treatment that inserts a light-sensing protein into the bipolar cells remaining after photoreceptors are lost, and if approved, is expected to be the first treatment option that can be used regardless of the causative gene.
Professor Hyeong Su-jin of Samsung Seoul Hospital said, "Optogenetics has become a standard method for uncovering how the brain works, and it is encouraging that its principles are beginning to provide clues to functional recovery in patients who had no existing options, such as those with terminal blindness. We expect that winning this Nobel Prize in Physiology or Medicine will speed up its application to organs other than the eyes."
Meanwhile, Professor Diceros visited Korea in March last year after receiving the Asan Medical Award in the basic medicine category selected by the Asan Social Welfare Foundation.
He said at the time, "Disease can be treated directly by stimulating specific cells with light, and the disease-affected cells can be identified through optogenetics, which can also have an impact on the development of new drugs. As research progresses on which cells should be delivered to which brain disease can be treated, the scope of application of optogenetics will expand."
