Several Nobel prizes in Physiology or Medicine were awarded for helping us understand how our nerve cells evolved to make us aware of ourselves and our surroundings.

The fact that we are a cluster of cells in space, which takes on a very particular shape and assigns very specific functions to each cell, still does not necessitate that this multi-trillion-cellular cluster should be self-aware. Indeed, if we are not only a cluster of our own cells. Within our organism, we also host trillions of bacterial cells. So, we resemble a mixed bag of diverse cells — both our own and those foreign to us — that are held together by the complex mechanisms of our immune system. Why do we, then, think of ourselves as a single, unique being? Obviously, we possess an awareness of our own existence as individuals. Moreover, we were born with the ability to remember everything that happened to us over time. Both our consciousness and our memory are rooted somewhere in the network of cells of our nervous system. Our brain, the processing centre of that system, continuously absorbs the information that it receives from every part of the body, to which the nerves and their thin branches extend.

The importance of the brain for our self-awareness is illustrated by the following example. In various unfortunate circumstances, people can be left without limbs. Due to trauma or illness, they can have their spleen, kidney, lung, a large part of the intestine removed. They can also have their heart, liver, kidney or other organs replaced by a transplant. Clearly, we can be left without many parts of the body, which implies the absence of the billions of cells that built those parts. However, we still maintain self-awareness as a single being. The only part of our body that we really can’t remove if we still want to feel aware is the brain. We still don’t know how to repair its damage or any discontinuation in the spinal cord or nerves. Importantly, we understood the precise function of the other organs in our body from their cellular structure, in a rather mechanistic way. Everything that happens in our other organs resembles a very elegantly designed biological machine. But we can’t understand the functions of the brain in the same way. The nature of thoughts and consciousness and their material basis remains elusive to science, at least at this point.

In his 1968 masterpiece “2001: A Space Odyssey,” Stanley Kubrick pointed to a problem in a visionary way. If humanity continued to develop increasingly complex technologies, but without a firm understanding of what consciousness is and how it arises, it will be difficult to predict where this could lead. Kubrick and Arthur C. Clarke, the leading science fiction author of the time, wrote a script together. Fifty years ahead of their time, they foresaw a problem that preoccupies many scientists today: can we continue to develop computers and artificial intelligence in absence of sufficient understanding of the material basis of consciousness? In Kubrick’s cult film, the spaceship is managed by a computer named Hal 9000. Hal was supposed to be infallible, but during the voyage, it begins to show signs of own consciousness. Eventually, Hal stops agreeing to orders from the human crew. When outwitted by the crew member, while losing the battle, the computer began to show emotions — such as the fear of being turned off. This interesting story, which in 1968 seemed like utter science fiction, has become a genuine concern for many scientists today. The recently deceased physicist Stephen Hawking, innovator Elon Musk, Google research director Peter Norvig, as well as the founders of artificial intelligence-based companies — DeepMind and Vicarious — signed an open letter in January 2015 with about 150 other scientists. In doing so, among other things, they jointly warned society of the danger of developing something that is potentially so powerful and superior to humans and over which we might lose control.

The basis of the fear of artificial intelligence is that today’s science still does not understand what consciousness is, how it arises, and how we can properly study it at all. In nature, there are many so-called “emergent phenomena,” which occur spontaneously when something that underlies them becomes sufficiently complicated. Thus, in a large wheat field, thanks to the number of ears of corn, wind waves will begin to emerge. Similarly, large enough flocks of birds will create beautiful wavy figures in the air. The concern of some scientists today is that consciousness may also be an emergent phenomenon — a consequence of a large number of our neurons, their interconnections, and electrical impulses in the brain. If this is true, then the increasingly complex modern computers that support artificial intelligence could at some point also gain awareness and cancel their obedience to us, their creators. Artificial intelligence is already proving superior to human intelligence at many levels, so such a development could prove rather catastrophic for humanity. Therefore, it is of great interest for modern science to gain insights into the material basis of consciousness as soon as possible.

Credit: Pelle Asplund, Unsplash

Several interesting studies with this intent have been published in recent years. There were examples of patients with so-called brainstem injuries. The brainstem is the part of the nervous system that connects the brain to the spinal cord. It thought to possibly hide the secret of the organism’s state of wakefulness. Some patients with brainstem injuries are completely unconscious, in a deep coma, while others manage to maintain consciousness despite the injuries. With in-depth scans of their injuries, the scientists link the preservation of the function of parts of the brainstem with the retention of consciousness, and the injured parts with a comatose state. In this way, they are trying to discover “where” consciousness is physically rooted in the nervous system. But consciousness is not easy to define, although we all intuitively know what it means. Namely, it is not only a state of alertness and response to external stimuli but also includes the impression of one’s own unique existence. Where does that impression come from?

Another question also remains — how and why consciousness “turns on” and “turns off” when we are waking up and sleeping, and how is it possible to get the whole brain into a function from full sleep in a fraction of the time, given all its structural complexity? One possible answer is in the recent discovery of giant neurons that arise from the so-called “claustrum”, the area of the brain where the concentration of different pathways and connections is greatest and is considered perhaps the most important signal integrator in the brain. These giant neurons are wrapped around the entire brain like a “crown of thorns”. They interact with all the outer surfaces of the brain, i.e., wherever grey matter is found. Therefore, these neurons could — in some way — “turn on” and “turn off” the whole brain. But why consciousness needs to be turned on and off at all, and what is its material, i.e., biological, physical and chemical basis? Those are the questions that we still know very little about. We can only hope that our understanding of this issue will increase significantly in the coming years. That should help us to prevent, or at least learn to control, the development of consciousness in the increasingly complex computers we are developing.

Until then, we can at least try to recall some of the most significant insights and breakthroughs made so far in the field of research of the nervous system. Despite continuous progress, it would still be inappropriate to claim that we understand quite well how the nervous system works and gives us our sense of existence and of the uniqueness of our whole organism, which is built of so many tiny parts.

Let’s start by recalling two true giants — Italian pathologist Camillo Golgi and Spanish pathologist Santiago Ramón y Cajal — who received the Nobel Prize for Physiology or Medicine in 1906. During the previous, 19th century, scientists were learning how to stain tissues so that they could be better seen and examined under a microscope. Golgi discovered that nerve tissue cells, neurons, can be stained with silver nitrate. This led to the first significant insights into the structure and function of the nervous system. Golgi believed that all nerve cells in the body form a continuous network and that they are all physically interconnected in that network. Ramón y Cajal did not agree, although he also used Golgi’s method of colouring neurons. He proved that each nerve cell is completely independent of the others. He understood that individual neurons do not belong to a single, large physical network. Instead, the impulses transmitted by the nerves travel through the so-called synapses, i.e., the sites of communication of mutually separated nerve cells.

Then, it took more than a quarter of a century for the next Nobel Prize in this field. It was awarded in 1932 to English neurophysiologists Sir Charles Scott Sherrington and Baron Edgar Douglas Adrian. They already understood quite well, at the time, that the functions of our body are controlled by the nervous system, which consists of many nerve cells, i.e. neurons and their extensions. They also knew that neurons were forming a system of connections between them and that they connected the brain, spinal cord and the rest of the body. Stimulation of nerve cells can, in certain cases, lead to muscle movement without any influence of our will. This is unusual because those same muscles are normally under our voluntary control. This is why we call such uncontrolled muscle movements “reflexes”. Sherrington showed how muscle contraction is followed by relaxation, and how muscle reflexes are only part of a much more complicated system. In this system, the spinal cord and brain process the impulses that arrive at them. They can then convert them into new impulses without the role of the voluntary component and send those impulses to the muscles and organs.

Adrian’s credit is based on insights into signals within the nervous system, which are transmitted by very weak electrical currents. Adrian was able to develop methods for measuring electrical signals within the nervous system. He realized that the electric current within the neural connections, as well as the signals that travel through them, are always of the same strength. Therefore, perhaps surprisingly, the way in which we perceive a stimulus from the environment as stronger or weaker does not depend on the strength of that current. It will depend on the frequency of sending these electrical signals and the number of nerve endings through which the signals are sent.

In 1936, English physiologist Sir Henry Hallett Dale and German pharmacologist Otto Loewi were awarded the Nobel Prize for Physiology or Medicine for their discoveries related to the chemical transmission of nerve impulses. Thanks to their predecessors, they knew that nerve signals were propagated by electrical impulses. However, it was unclear whether chemical processes were also important in the transmission of signals by the nervous system. Dale discovered that acetylcholine stimulates a part of the nervous system called parasympathetic, which calms heart activity and other processes. Loewi demonstrated that acetylcholine is the important mediator between nerves and organs, at their points of physical contact. He proved this by stimulating the frog’s heart with electrical and chemical stimuli. These significant breakthroughs were followed by another discovery, thanks to which the American neurophysiologists Joseph Erlanger and Herbert Spencer Gasser also received the Nobel Prize in 1944. They studied the characteristics and distribution of nerve branches throughout the body very thoroughly. Based on this, they divided the nerve fibres into two different types, which are of different thickness, and showed that thicker nerves conduct impulses significantly faster than very thin ones.

After this important progress, there was again a bit of a lull in this area of science which lasted for another quarter of a century. This was then followed by the phase of rewarding the discoveries of the so-called “neurotransmitters”. They were chemical substances important for the transmission of information in the nervous system and its proper function. In 1970, German-Australian physician Sir Bernard Katz, Swedish physiologist Ulf von Euler, and American biochemist Julius Axelrod were awarded for discovering several key neurotransmitters in the nervous system, and the mechanisms of their storage, release, and silencing. Numerous neurons have their own extensions — nerve fibres. Signals travel through these fibres thanks to very weak electrical impulses, but also the so-called signalling substances — neurotransmitters. The transmission of impulses from one neuron to another occurs at synapses.

Katz investigated how impulses from neurons willingly activate muscles by measuring differences in electrical voltages. This led him to demonstrate how the neurotransmitter acetylcholine is released from synapses. von Euler discovered the neurotransmitter norepinephrine, which is very important in signalling impulses to choose a fight or a flee. He showed how norepinephrine is created and stored inside the bubble and how it also sends a signal from one neuron to another via synapses. Their colleague Axelrod, on the other hand, studied noradrenaline, a signalling substance that encourages increased activity in the event of aggression or danger. He showed that excess norepinephrine is released into the blood in response to signals from nerves. Then, it is returned to its storage again.

At the turn of the millennium, in 2000, Swedish neuropharmacologist Arvid Carlsson, American neuroscientist Paul Greengard and American-Austrian neuroscientist Eric R. Kandel were awarded for further discoveries of neurotransmitters in the nervous system. Carlsson discovered dopamine in the brain and its role in the human ability to move. This explained the symptoms of Parkinson’s disease and enabled new treatment strategies. Greengard clarified how signalling substances in the nervous system function, showing how they first affect a specific receptor on the cell surface. The protein molecules are then altered, by the addition or subtraction of phosphate groups. This is a mechanism of regulation of many functions within the cell. Kandel researched how memory is stored. Exploring sea snails, which have a very simple nervous system, he realized that snails can still learn. This happens because chemical signals alter the structure of connections between nerve cells, i.e. synapses. Based on this important insight, he went on to demonstrate how short-term and long-term memories can be formed by different signals. This mechanism is common to all learning creatures, from the sea snail to man.

All of these insights helped us to better understand some of the most fundamental principles and mechanisms of the nervous system’s functioning within the body, as well as its interaction with organs. However, how the brain itself functions remains quite a mystery. Swiss physiologist Walter Rudolf Hess was awarded the Nobel Prize in 1949 for his discovery of the functional organization of the midbrain, the so-called “diencephalon”, as a coordinator of internal organ activity. In his experiments, he introduced a very thin metal wire into different parts of the anaesthetized cat’s midbrain. When the cat woke up, he could prompt it to various behaviours through very weak electrical impulses. In doing so, he observed not only simple reactions, but also rather complex behaviours — among other things, defensive or aggressive behaviour, and squatting and sleeping.

American neurophysiologist Roger W. Sperry, who was awarded the Nobel Prize in 1981, was also responsible for a significant discovery related to brain function. He knew that the brains of humans and animals have two hemispheres with somewhat different roles. Sperry sought to understand the role of each hemisphere by investigating patients in whom the nerves, which connected the two hemispheres of the brain, were intentionally damaged. At the time, damaging those nerves was one form of treatment for severe epileptic seizures. Through his observations, Sperry realized that the left hemisphere was more engaged in abstract and analytical thinking, arithmetic, linguistic expression and language learning. The right hemisphere is more important in navigating space, as well as understanding complex sounds and messages, such as music.

In the 21st century, we gain more insight into how the brain works with every passing year. Perhaps the most ambitious project of the European Commission, worth a billion Euros, was awarded to create a computer model of part of the cerebral cortex. It was expected to simulate how so many connections between all those neurons work, and what they actually do. At the same time, new theories of consciousness are emerging, for which a method of experimental verification has yet to be devised. Still, unlike very significant advances in understanding the function of all of our other organs and organ systems, we are still quite far from properly understanding how the human brain works. This is why it is reasonable to expect that at least some of the 21st century Nobel Prizes will continue to be awarded for significant breakthroughs in this area.

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Declaration: Professor Igor Rudan, FRSE, is the President of the International Society of Global Health; co-Editor-in-Chief of the “Journal of Global Health”; Joint Director of the Centre for Global Health and the WHO Collaborating Centre at the University of Edinburgh, UK.

TWITTER: @ProfIgorRudan

FACEBOOK: Professor Igor Rudan

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Translation to English credit: Lauren Simmonds

Image credit: Pelle Asplund, Unsplash.com.