Nobel Prize History
The Nobel Prize is the most prestigious award in the scientific world. It was created according to Mr. Alfred Nobel’s will to give a prize “to those who, during the preceding year, have conferred the greatest benefit to humankind” in physics, chemistry, physiology or medicine, literature, and peace. A sixth prize would be later on created for economic sciences by the Swedish central bank.
The decision of who to attribute the prize to belongs to multiple Swedish academic institutions.
Legacy Concerns
The decision to create the Nobel Prize came to Alfred Nobel after he read his own obituary, following a mistake by a French newspaper that misunderstood the news of his brother’s death. Titled “The Merchant of Death Is Dead”, the French article hammered Nobel for his invention of smokeless explosives, of which dynamite was the most famous one.
His inventions were very influential in shaping modern warfare, and Nobel purchased a massive iron and steel mill to turn it into a major armaments manufacturer. As he was first a chemist, engineer, and inventor, Nobel realized that he did not want his legacy to be one of a man remembered to have made a fortune over war and the death of others.
Nobel Prize
These days, Nobel’s Fortune is stored in a fund invested to generate income to finance the Nobel Foundation and the gold-plated green gold medal, diploma, and monetary award of 11 million SEK (around $1M) attributed to the winners.
Source: Britannica
Often, the Nobel Prize money is divided between several winners, especially in scientific fields where it is common for 2 or 3 leading figures to contribute together or in parallel to a groundbreaking discovery.
Over the years, the Nobel Prize became THE scientific prize, trying to strike a balance between theoretical and very practical discoveries. It has rewarded achievements that built the foundations of the modern world, like radioactivity, antibiotics, X-rays, or PCR, as well as fundamental science like the power source of the sun, the electron charge, atomic structure, or superfluidity.
Understanding Our Brains
The nature of the human mind and animal intelligence have been matters of philosophical debate for millennia. For a long time, it was mostly a matter of opinions and preconceptions that decided which view would be dominant.
This has changed with the emergence of modern neuroscience. With the discovery of neurons and their ability to transmit electric signals, the idea of studying individual neurons to explain complex mental mechanisms has become realistic.
This would be combined with animal studies and experimental psychology to provide the first true insights into how our brains function.
The discovery of “signal transduction in the nervous system” was awarded a Nobel Prize for Medicine in 2000. Neurology is a field that has been rewarded by this prestigious prize, as well as the Nobel Prize for Medicine in 2021 “for their discoveries of receptors for temperature and touch”.
However, a potentially even more impressive discovery was the one that was rewarded with the 2014 Nobel Prize in Medicine, “for their discoveries of cells that constitute a positioning system in the brain”. In essence, it was discovered that our brain’s mental mapping of the environment is physically present in a similar neuronal map in a specific part of the brain.
Half of this prize was attributed to John O’Keefe and a quarter to both May-Britt Moser and her husband, Edvard I. Moser.
Source: Nobel Prize
Creating A Sense Of Place
The first idea of the brain being able to create a connection between places and events through semi-conscious thought was envisioned by experimental psychologist Edward Tolman.
Observing animals, Tolman hypothesized in 1948 that animals mentally connected places and events, creating a mental map allowing them to navigate a place and connect mentally unrelated locations.
This idea would turn out to be correct, but it requires more advanced techniques to start studying the brain activity itself to be proven.
John O’Keefe had training in physiological psychology, a field concerned with the impact of biological structure on mental phenomena. In the late 1960s, he started to study the activity of neurons in rats’ brains in relation to their movement and location, using implanted microwires.
Source: Research Gate
Thanks to this advanced measurement method, brain activity could be studied when the animal is moving freely, replicating a natural pattern of behavior.
This was where John O’Keefe’s research was unique, as previous researchers recording hippocampal activity had limited their investigation to restricted behavioral tasks or strict stimulus-response protocols.
Doing so, he discovered a class of neurons called “place cells,” located in the rat’s hippocampus, a place known for being the physical location of many memory-related mental mechanisms.
Source: Nobel Prize
Hippocampus & Place Cells
The hippocampus has been known since the 1950s to be the seat of memory-related function of the brain. For example, the loss of both hippocampi in human patients caused severe memory deficits.
This included losing the ability to encode new memories while still being able to retrieve old memories. However, there is also more curious evidence, like how London taxi drivers, who undergo extensive training to learn how to navigate thousands of streets, grow significantly larger hippocampal volumes than control subjects during their training.
O’Keefe found that place cells would activate when the animal was in a particular location. Through systematic testing, he also demonstrated that it was not a response to specific stimuli, like, for example, the place being a certain color or containing food. Instead, the place neurons activated when the animal was in that particular spot and stopped when he left.
Each place cell was not specialized in a specific location; however, each location and environment would instead fire up a specific combination of place cells, similar to a complex coordinate system.
Further Discovery About Place Cells
Digging deeper, O’Keefe discovered that the activity of the place cells would rearrange itself when the rat was exposed to a new environment. And once acquired, the learned pattern would be persistent. This provides a solid base to theorize that place cells form a cellular substrate for memory.
The idea of a “cellular mapping” created quite a controversy before being more widely admitted. It then opened the way to further explorations of the physiological basis of memory. This time, the idea of finding new types of neurons and paying close attention to their exact location would provide the missing piece to the puzzle of how spatial memory works.
A Brain Grid For Mapping The World
The discovery of place cells focuses spatial memory research on the hippocampus. However, most of the hippocampus’ stimuli come from a structure on the dorsal edge of the rat’s brain called the entorhinal cortex. So, this area became the focus of research for May-Britt & Edvard Moser.
Source: Bright Focus
Some previous research has shown that the entorhinal cortex contains cells with similar characteristics to the place cells of the hippocampus. However, it would be the Mosers who found an entirely new type of cell, called grid cells, in this area of the brain.
Grid Cells’ Hexagonal Pattern
The grid cells are located in specific nodes that are all located together in a very regular hexagonal pattern. Such a grid pattern had never been observed in the brain before. It also became obvious quickly that its apparition was not just an accident but a tightly regulated process by complex network activity.
Source: Nobel Prize
Even more interestingly, the grid cells were found to be embedded in a network formed of head direction cells and border cells, and cells with both head and border functions cells at once.
Head cells are known to act as a compass and activate only when the animal’s head points in a certain direction. Meanwhile, border cells activate when the rat meets a wall or an obstacle.
The Moser spouses also discovered that the grid, head, and border cells all projected neural connections toward the hippocampal place cells.
Together, further research by the Moser spouses and O’Keefe would prove that the place cell “coordinate system” is activated and regulated by the grid cells and border cells, in a complex 2-layer system mapping on neurons the actual physical environment.
Source: Nobel Prize
A Conserved Mechanism Across All Mammals
While mostly conducted on rats (for practical, cost, and ethical reasons), the research conducted on place and grid cells is likely to be valid for other mammals as well, including humans.
Place-like cells were found in humans in 2003, and grid-like cells were found in 2010, providing further indications that such a system had been preserved throughout evolution. This does not really come as a surprise, as overall, the hippocampal-entorhinal structure is well preserved across all mammals. Even among non-mammal vertebrates, similar hippocampal-like structures can be found, suggesting such a mechanism is very ancient and well-conserved across very different species.
The location memory encoded in place cells is also being “replayed” during sleep, most likely leading to the consolidation of the pattern and the subsequent conservation of the memory in the long term.
Altogether, these discoveries provide a solid basis for explaining the neuron-level location memory and brain activity.
Applications
Unraveling Brain’s Complexity
This research work is about the fundamental functions of the brain. It nevertheless has plenty of potential applications, like most of the other neurology-focused Nobel Prizes. This is because the brain is a notably tricky organ to treat. It is locked away by the blood-brain barrier, blocking many chemical or biotechnological treatments from being effective. It is also an extremely complex organ. Studying it can be tricky, as most of the activity is transient and electrical, with chemical signals limited to neurons’ synapse interface.
Some scientists, like the Nobel Prize-winning Penrose (for unrelated research on black hole formation), even suspect that consciousness might emerge from quantum phenomena. An idea now vindicated by the discovery of quantum effects from neurons’ microtubules.
So overall, therapies targeting the brain are most likely to require a very deep understanding of how memory, consciousness, and perceptions are created & processed by the brain.
Clinical Needs
Memory loss is one of the first and most problematic symptoms of many neurodegenerative diseases, like age-related dementia and Alzheimer’s disease. O’Keefe and his team have proven that in animal models for Alzheimer’s, the degradation of place cells is correlated to the degradation of spatial memory.
As the hippocampal formation is one of the first structures to be affected in Alzheimer’s disease, a deeper understanding of the brain mechanisms might yield new therapeutic options.
Investing In Neurology
Neurology is one of the most advanced fields of biology and medicine today. Its importance is growing due to the aging of the population, with age-related psychological and brain diseases a growing issue.
We explored in further detail how this could be the “next big thing” for the pharmaceutical sector in “The Next Blockbuster Therapies: Curing Neurological Disorders.”
It is also the focus of the most advanced technologies, like, for example, Elon Musk-related Neuralink “brain chips”.
Source: Neuralink
You can invest in neurology-related companies through many brokers, and you can find here, on securities.io, our recommendations for the best brokers in the USA, Canada, Australia, the UK, as well as many other countries.
If you are not interested in picking specific companies, you can also look into biotech ETFs like the iShares Neuroscience and Healthcare ETF (IBRN), or the Tema Neuroscience and Mental Health ETF (MNTL), which will provide a more diversified exposure to capitalize on neurology-related stocks.
Neurology Companies
1. BrainStorm Cell Therapeutics
Not all neurology biotech companies are counting on new drugs. Others are literally trying to repair the brain directly, including by adding fresh new cells to the patient’s nervous system through stem cell therapy.
This is the strategy pursued by Brainstorm Cell Therapeutics, working with stem cells to heal or reduce the damage of neurological diseases.
Brainstorm Cell uses its autologous cellular technology platform (NurOwn®): the company takes the patient’s bone marrow cells and turns them into neurons and other nerve cells. This is a rather short process, taking only 7 days.
This process creates nerve cells that have the patient’s genetic code, removing risks of incompatibility or rejection of the transplanted cells.
Source: Brainstorm Cell
Brainstorm is focused on neurological diseases like Multiple Sclerosis, Alzheimer’s, Parkinson’s, Huntington’s Disease, or Autism Spectrum Disorder.
The ALS treatment is the only one in phase 3, with hopes to get it approved quickly, and preliminary results seemingly indicate it could help if used early enough to slow the disease progression.
Source: Brainstorm Cell
In the distant future, we can imagine such therapy as developed by Brainstorm to be able to “regrow” damaged cells, potentially with a focus on ultra-specialized neurons like place, grid, and border cells.
2. BICO Group AB (BICO.ST)
One way to study the brain and nerves is to use cerebral organoids. These artificially created mini-brains can be used to replicate in a lab the reaction of neurons to potential therapies, helping researchers find treatment for the full real brain.
We discussed in more detail how it works and the latest developments in that field in “Meaningful Steps Toward Organoid Intelligence Being Taken.”
Recently, much more complex cerebral organoids have been 3D printed by researchers at the University of Wisconsin–Madison. They did so with a Cellink bioprinter, opening new potential for this machine in neuroscience research.
Source: Cellink
In 2021, Cellink was renamed as the BICO Group, following its acquisition of Cytena in 2019 and Scienion in 2020.
Cellink is still the brand name for the bioprinting part of the business. It is the idea to re-use 3D printing methods to create on-demand 3D tissues or organs. (You can read a discussion on this topic in “3D Printing Human Organs – How Realistic Is It?”).
Bioprinting represents around 1/5th of the business, with the bioscience automation segment making more than 3/5th of revenues.
Source: BICO Group AB
While not alone in the field, Cellink is clearly a very advanced bioprinting equipment manufacturer. The achievement of Pr Zhang using these machines shows their potential in neurology research, a field that is not really using bioprinting at this time.
In the long run, bioprinting companies are likely to evolve from providing tools to researchers to becoming suppliers of pharmaceutical companies’ bioprinting therapies for patients. This will, in turn, completely change the number of bioprinters in use and, more importantly, the volume of consumables sold every month.
This is the same process that occurred for other biolab equipment manufacturers, including genome sequencing machines from PacBio (PACB) and Illumina (ILMN), which end up making 80% of their revenues from recurring sales of consumables.
