Category Archives: Biotechnology

The human brain and its augmentation

The augmentation of the human brain is probably the most radical method to vastly enhance our abilities and improve our life. We have several potential options to improve the brain. But in order to do this, first of all, we should very clearly understand how the brain works.

The structure of the brain

The brain is a part of the central nervous system. Different locations of the brain have specific functions.

The outer layer of the brain is the cerebral cortex. This layer is only 2 to 4 mm thick. In higher mammals, especially in humans, the cerebral cortex is intensely folded: the more convolutions, the greater the surface area, and therefore, the larger the number of nerve cells the brain contains.

Under the cerebral cortex, there are deeper brain’s regions, such as the brain stem, the thalamus, the basal ganglia, the hypothalamus, the cerebellum. These subcortical structures are also very important. The brain stem, for example, controls many absolutely necessary vital functions of the body, such as heart beating or breathing.

The cerebral cortex is the region of the brain that is most responsible for our cognitive capabilities.

The cerebral cortex structure

The cerebral cortex has a horizontal and vertical organization. The horizontal organization is characterized by six layers. Neurons within some layers send signals to other areas of the neural cortex or subcortical structures of the brain; whereas neurons of the other layers receive signals from different areas of the neural cortex or other brain regions.

The vertical organization of the cerebral cortex represents 3 million cortical columns. Within each cortical column, all the neurons are interconnected with each other. Every column is connected to approximately 1000 other columns. Within each cortical column, there are about 50-100 minicolumns. Each minicolumn comprises about 100 neurons and has a specific function. For example, a single cortical minicolumn in the visual area of the brain recognizes only a very specific visual stimulus, whereas, in the primary auditory cortex, each minicolumn recognizes only a very specific frequency of sound.

Different areas of the cerebral cortex perform different functions, but if certain areas have been damaged, other areas can, to some extent, replace the functions of the damaged areas. The principles of information processing in all regions of the cortex are identical.

The frontal lobe of the cerebral cortex is crucial for higher mental functions such as reasoning or planning, and it is most developed in humans compared to other mammals.

Neurons

The major cell type in the brain, as well as in the whole nervous system, is a neuron. Each typical neuron cell consists of a cell body, axon, and multiple dendrites. Usually, the axon has numerous branches which connect to dendrites of other neurons forming myriads of junctions called synapses. On average, the human brain has about 100 billion neurons interlinked to each other by approximately 100 trillion synapses, comprising a gigantic neuron network. The structure of synaptic connections between neurons is influenced by both genes and experience, and this structure largely determines a person’s mentality.

The number of neurons in the adult brain does not change very much during a lifespan until severe neurodegenerative processes start to take over under some circumstances. However, neurogenesis, the birth of new neurons, also continues throughout entire life, but it is a relatively small amount of neurons. It has been shown in some studies on animals that the process of neurogenesis in the brain is more vigorous if the animals are located in a new environment and they actively learn something new.

In most cases, signals in neurons are sent from an axon of one neuron to a dendrite of another, but there are many exceptions to this rule. For example, there are neurons that lack dendrites and others that lack axons.

The neuron is quite a long cell. The neural signal or the action potential, which is basically a flow of electrically-charged ions, moves along the axon to the synapses. When the impulse of ions arrives at the synapse, a pre-synaptic neuron can release special molecules called neurotransmitters. These signaling molecules travel across synaptic cleft and bind to the receptors of a post-synaptic neuron. This process is called neurotransmission. There are many types of neurotransmitters both excitatory and inhibitory. Some neurotransmitters can be either excitatory or inhibitory depending on the type of receptors they bind to. Different neurons release different neurotransmitters. The postsynaptic neuron may receive excitatory and inhibitory inputs from many neurons at the same time. These influences are summed up in some sense in the postsynaptic neuron. If the net effect is inhibitory, the neuron will be less likely to transcend the signal to the next neurons and if the net effect is excitatory, the neuron will be more likely to transcend the signal.

Naturally, the speed of signals between neurons is substantially slower than, for instances, the speed of electrons in metals. A neuron can be fired up about only 200 times a second, and yet a transistor in modern processors does it several billion times, which is several million times faster.

In addition to neurons, the nervous system contains other types of cells – glial cells. These cells also perform essential functions. For example, the major function of some glial cells is axon myelination – an electrical insulation of axons, without which electric impulses along axons would be propagating even slower.

Brain’s work

The brain consumes a considerable amount of energy of the body – around 20% – and constantly requires oxygen and glucose. If oxygen or glucose uptake to the brain is temporarily constrained, neurons very soon start to act incorrectly and disintegrate, so the person dies in a few minutes.

The brain has a remarkable plasticity – as we learn, our brains change: certain synapses are getting strengthened, which at a molecular level means that more neurotransmitters bind to receptors in those synapses. Also, new synapses are being formed and some old synapses are being lost all the time, especially when we learn. In general, these mechanisms are called a synaptic plasticity. Reinforcement of synapses or formation of new ones between neurons is quite similar to learning in artificial neural networks. There are also profound distinctions, however.

The basic unit of logic in the brain is not a neuron cell. Molecules such as neurotransmitters, receptors, and maybe some others represent the smallest logic units in the brain.

Most likely, we can specify the complete number of basic logic units in the brain as a total number of receptors in all synapses of the brain. Different studies show the different numbers of receptors in different types of synapses. (http://www.jneurosci.org/content/jneuro/27/8/2135.full.pdf). If we assume that the average number of receptors in a single synapse equals 100, then the total number of these receptors in the brain must be around 100 × 100 hundred trillion, which is 1019. This is an astonishing figure. Does it mean that we should have a computer with about 1019 logic units to be able to simulate the brain effectively? It seems not necessary because the information processing in the brain is significantly slower than in electronic computers.

Strategies for human brain augmentations

There are several different possible strategies for dramatic improving mental capabilities of the brain: gene therapy, stem cells, pharmaceutical interventions, nanotechnology, using specific magnetic fields, brain-computer interfaces. Let’s briefly go through all of these possibilities.

Neurological drugs

Apparently, there are numerous neurological processes that can be influenced by pharmaceutical interventions. For example, it was shown that a mutation of a specific receptor in dendrites can decrease the ability to forget, thus increasing the ability to remember. Although this mutation is not beneficial (the ability to forget unnecessary or harmful to our psychology information is vital), in principle, we may use a specific chemical that temporally blocks this receptor, so we can increase our learning capabilities when we need it. This is a possible example of using drugs to enhance memorization and learning. Other examples can also be adduced.

The brain is protected by the blood-brain barrier from potentially dangerous substances and particles that may be circulating in the blood system in some situations. Only relatively small molecules can penetrate through this natural barrier, and in many cases, it impairs delivering drugs to the brain.

Nanotechnology

Medical nanotechnologies have amazing benefits. Combining drugs with neuro-nanotechnology is a very promising approach in augmentation of brain functions. (To read more about that: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064704/). For example, using nanoparticles enables crossing the blood-brain barrier, so drugs can be delivered to the brain. Furthermore, this method allows us precise delivering drugs in specific areas of the brain.

Direct Brain-machine interfaces

There is an idea shared by many futurologists that we can significantly extend our cortical cortex by connecting it with artificial neuron networks. For my humble point of view, this has several very significant technical challenges. First of all, as we’ve shown earlier, the cortical cortex has its very fine structure, where the neurons within the cortical cortex are interconnected with one another and neurons of other regions of the central nervous system. So, in order to truly enlarge a natural cortical cortex, we should extensively, probably each mini-column, interconnect it with an artificial analog of the cortical cortex.  Besides, creating the artificial cortical cortex is beyond our modern technical capabilities.

There is an opinion that if we directly connected the brain to digital computers, we would expand natural intelligence tremendously by harnessing the advantages of electronic computing devices – much higher speed of information processing, bigger memory capacity (both temporal and permanent), more accurate storage of data. However, under more careful examination, the situation looks different. Direct brain-computer interfaces often require neurosurgery.

Neurosurgery can be a very helpful tool for some disabled individuals, but, so far, using it for improving cognitive capabilities of healthy people remains impractical and produces many adverse side effects.

Magnetic fields

We know that synapses can be strengthened when the neurons that form them are fired. When a neuron is fired, some amount of electrical charge flows through it. If we apply a specific magnetic field to a very specific area of the brain, electrical charges may occur in the neurons of this are. So, in principle, we can provoke neural activity by applying a specific magnetic field to the brain. It can be used, for example, to pass information directly into the brain. For instance, by using transcranial magnetic stimulation (TMS), one can selectively silence or stimulate various regions of the brain. By doing so, people can temporally acquire miraculous mental skills like savant-like, for example. Also, downloading memories and therefore new skills and knowledge into the brain seems possible and to be only a matter of time.

The living brain is constantly broadcasting radio waves. These signals are extremely faint, and seemingly cannot be perceived and decoded by other brains. Computers, however, can decipher these impulses and convert them into meaningful machine instructions. Such brain-machine interfaces based on radio waves will be a big game changer in the near future and alter the way we communicate with machines and, supposedly, even with people. We will be able to communicate with computers and perhaps even with people mentally.

Stem cells

Using stem cells is another alternative that scientists can use to increase cognitive functions. Stem cells are such cells that can differentiate into any type of specialized cells in the body including neurons. All regenerative medicine is largely based on different applications of stem cells.

Nerve cells cannot divide, so it had been thought for a long time that a total number of neurons in the brain can only decrease over time of a life span. However, it was shown that there are stem cells in the brain, and a certain number of new neurons do emerge during life. In the adult human brain, stem cells can naturally form only in two regions:  the subgranular zone (SGZ) in the dentate gyrus of the hippocampus, and the subventricular zone (SVZ) of the lateral ventricles (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106107/) These stem cells give rise to the formation of only two very specific types of neurons; in most natural cases, they cannot form nerve cells in the cerebral cortex, but we can use certain procedures to turn these natural stem cells into neurons of the cerebral cortex.

In addition to natural stem cells, external stem cells can be placed in the brain. It seems very promising to use stem cells to cure a damaged brain, especially when we deal with such neural disorders like Alzheimer’s disease. Furthermore, stem cells could be used to create new neurons in special regions of the brain. Perhaps, we can inject additional stem cells in certain locations of the brain in order to vastly increase our specific mental skills. However, it has shown that using external stem cells in the brain is not safe; it can provoke the formation of cancer in brain tissue. So, these techniques remain to be improved.

Gene therapy

It is known that intelligence is a heritable trait, determined by many genes. Moreover, it has been shown that additive effects between genes are greater than epistatic (combinatorial) ones in determining this trait. This means that significant increase of intelligence can be achieved by collecting more appropriate genetic elements in one genotype.

Although there are serious ethical considerations associated with changing genomes of human beings that have not even been born yet, it’s possible to pick out embryos with preferable combinations of genes. Pre-implanting genetic screening is already in practical use. However, selection has its limitations. By combining selection with genetic engineering, more prominent results can be achieved.

Gene editing or therapy is a very promising field, which continues to develop very steadily. Scientists have recently developed new promising methods in this area, for instance, CRISPR   gene editing. Obviously, the progress in this field will continue.

Genetic code can be changed before a birth, or during a life span of a person (somatic gene therapy). Using somatic gene therapy for the enhancement of cognitive capacities of an adult brain has its drawbacks. The main point is that the brain largely forms during very early phases of body development, and in later phases presumably cannot be substantially augmented by means of genetic therapy, at least in the near future.

On the other hand, if the genome is changed before the brain formation, it seems very realistic to increase intelligence (as well as other important traits). It’s possible that, for example, undesirable sequences of DNA be removed from the genome prior fecundation or right after the formation of a zygote (a cell formed as a result of fertilization that gives rise to the embryo), so the whole genome in every single cell of the body will be changed.

The desired transmission of a mitochondrial genome of a human zygote has been already obtained, and this technology is already in use in medical practice. However, the technologies that would enable precise controlling the formation of the whole nuclear genome will not likely emerge very soon. Moreover, the role of many elements in the nuclear genome is still not entirely clear, as well as epigenetic factors, some of which are apparently inherited and substantially contribute to the formation of various phenotypic traits including intelligence.

On the contrary, genetic manipulations with individual genes now seem more realistic than the whole genome interventions and are already in use.

As we said, intelligence is determined by many genes, but certain specific genes play more prominent roles in its regulation. There are many studies reviling many such genes influencing mental processes. For example, it has been shown that the gene HAR1 is at least partially responsible for the convolution of the cerebral cortex, and presumably, some modifications of this gene can yield more intensive folding of the cerebral cortex so that the number of neurons in the brain becomes larger. At the cellular level of neurons, there are also other prominent targets to increase intelligence by genetic modifications. For instance, overexpression of the NR2B subunit of the N-methyl-D-aspartate neuroreceptor has led to improving the formation of new memories in transgenic mice in several studies.

Also, researchers have already developed certain techniques for therapy of brain illnesses by methods of genetic therapy. Probably many of these techniques will soon be used in conventional medicine, first of all for the neural disorders that are caused by single genes like Huntington disease, for example.

Obviously, gene therapy seems a very powerful method to increase cognitive capabilities. On the other hand, we don’t know to what extent we can increase human intelligence with the help of genetic therapy. Potential augmentation of intelligence is limited by the capabilities of the human body. As we said, brain cells must constantly receive oxygen and glucose, which are supplied with blood, and we cannot vastly increase the supply of these resources to the brain. Probably, there are many other strong restrictions to increasing intelligence by genetic therapy.

Why do we age and How to prolong the maximum duration of human life

 

The average lifespan of humans had doubled since the prehistoric period to the 19th century and doubled again over last hundred years. But the maximum duration of human life hasn’t changed so much. In fact, it’s known that many centenarian lived in the ancient world.

All mammals, including humans, age in a very similar manner and unfortunately die of old age.  Why does this happen, and what are the fundamental biological principles responsible for this?

View from Evolutionary Perspective

It may sound rather sad, but we are evolutionarily predetermined to die of old age. Dying of old age is required to make possible alternation of generations. If humans or any other organisms didn’t perish, their populations would soon grow to its maximum, and there would be no place for new organisms with new traits.

Efficient adaptation of a biological species to changing environments requires the appearance of new organisms with new traits. Probably, if organisms were able to adapt to new environments much better during their lives, there would be no need for the appearance of new generations.

The species reproducing predominantly by asexual reproduction don’t actually die of aging. For instance, bacteria split but don’t die of aging.  In the case of asexual reproduction, the adaptation to environmental change mainly occurs due to a very large number of organisms, for example, like microorganisms. Because as a result of asexual reproduction, offspring don’t differ too much from parents, asexual reproduction might be more valuable in stable environments.

The emergence of sexual reproduction caused interchange of generations much more valuable. Bigger organisms like humans tend to reproduce sexually and therefore change generations. You can read more about evolutionary aging theories here.

Mechanisms of aging

There are many different mechanisms of aging, and much still remains unclear in this process.

There is a notion of the existence of the so-called genetic and epigenetic aging clock in multicellular organisms like humans. As we get older, our genes tend to express in a different manner – some genes turn off and some turn on (more genes turn on as we age). If we fully understand these processes, we can in principle slow down and even reverse the aging clock. You can read more about this here.

Some single genes play a bigger role in aging. These genes are conditionally divided into lifespan regulators, lifespan mediators, and lifespan effectors. For example, some lifespan regulators are responsible for rapid growth when we are young, but these genes can cause cancer in later stages of life. Sometimes mutations in a single gene may lead to very adverse effects.

It’s known that aging is associated with telomere (structures at the end of chromosomes) shortening. Presumably, if we kept our telomeres stable, we wouldn’t age.

External, environmental factors can influence internal mechanisms taken place in the body and alter the rate of aging in the organism. For instance, caloric restriction is a well-known factor that slows down aging presumably by retarding metabolism.  Also, some chemicals can alter the rate of aging. In some organisms, the alteration of aging has been shown by such chemicals as resveratrol, STACs (Sirtuin Activating Compounds), sirtuins, and some other compounds.  Notably, that using any drugs has never beat a simple calorie restriction in the effect on prolongation of lifespan.  (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004650/).

Damage to large macromolecules such as proteins, lipids, and nucleic acids by different external and internal factors such as radiation or free radicals can result in aging and death. There are different mechanisms in the body for repairing such molecules, but these mechanisms function worse as the organism gets older.

As we get older, the different functional deteriorations of our tissues increase due to different reasons. In most cases, these deteriorations occur as a result of impairment of cell reproduction in an older body, which in turn are caused by different factors mentioned above.

As we see, there are many different factors of aging. All of them matter and interact with each other, determining the average biological age.

However, we can trick our biology, at least to some extent. In fact, we do it already. For example, we get vaccinated for many various severe diseases, from which millions of people would die in the recent past. Many leading experts in the field of life expectancy prolongation think that aging is a curable decease.

Major potential strategies to significantly prolong the maximum duration of life or even achieve immortality of the human body

Medical nanodevices

For example, artificial nanorobotic white blood cells have been already created. These nanodevices can travel throughout the blood system, detect and destroy harmless bacteria or cancer cells. Other similar devices will presumably remove atherosclerosis plaques. But many nanotechnologists aren’t so optimistic about this.

Gene therapy

We can cure many devastating diseases by means of gene therapy, but these diseases are mostly monogenic (caused by one gene). Effective treatment of polygenic disorders by gene editing is still quite challenging.

Transplantation of biological or non-biological organs and entire body parts

Stem cells are the cells that can transform into any type of cells in the body.  Artificial organs have been already obtained by using stem cells. These artificial organs are not still flawless, but this is a very promising area.

At the same time, there is another option – creation of artificial organs from non-biological materials. An artificial heart, for example, has been already in use for a long time. Also, various prosthetic devices for different body parts like limbs or even teeth are very common. Such devices are getting better and becoming far more sophisticated. For instance, because of neural interfaces, people can manipulate such devices like an artificial hand in an almost natural way.

There is even an opinion that in the future people’s entire bodies will be almost totally artificial. Some believe that, in principle, we can even replace natural neurons in the brain to artificial ones.

But today we still have only one reliable method for significant lifespan prolongation and this is a caloric restriction. The restriction of the intake of calories can extend the duration of a lifespan to 40%, but all amount of necessary biologically active substances like vitamins and minerals should be provided.