The Rise of Human Singularity

Written by: José Hidasi Neto.

Biologist and PhD in Ecology and Evolution.

Hi there,?

This work aims, step by step, to demonstrate our knowledge about biology, focusing especially on the human brain and conscience. We start by talking about basic biological concepts. We study the main concepts present in the literature and arrive at human evolution. Next, we focus on the evolution of the human brain. Then, we see how the brain works, highlighting the mechanisms involved in our thoughts and feelings. Then, we come to the area of biomedical engineering, focusing on the presentation of neuroengineering, mainly in the area of 'Brain-Machine Interface'.

Summary

1. Cytological and Genetic Bases of Evolution
2. Evolution Itself
3. The History of Evolution Focusing on Humans
4. The Functioning of the Human Brain
5. Psychoactive Drugs
6. Neuroengineering
7. References

1.?Cytological and Genetic Bases of Evolution

First, let's look at basic concepts about cells and their genetic characteristics. The content presented here has as reference mainly Alberts et al. (2017) and Klug et al. (2010), two very important biology books.

1.1.?Domains of Life and Cell Organelles

Being very brief, life is divided into groups. There is that history of Kingdom, Phylum, Class, Order, Family, Gender and Species. But, there are several other divisions that are not normally taught in school. For example, above the Kingdom is the Domain. In this domain, life is normally divided into three major groups (image 1): Bacteria, Archeobacteria and Eukaryotes. As a curiosity, scientists are still trying to create more domains, for example including viruses (image 2), but this needs much more research.

We will now focus on animal eukaryotic cells (image 3). In these cells, we observe several cytoplasmic organelles, each with a function. The nucleus is where our genetic material is. More specifically, there is the nucleolus in the nucleus, where there is genetic material responsible for creating ribosomes and helping in cell division. Ribosomes translate a messenger RNA (transcribed in the nucleus) into a protein. The rough endoplasmic reticulum (rough because it has several associated ribosomes) normally helps to synthesize proteins that will be transported by the cell or out of the cell. The smooth endoplasmic reticulum produces lipids, normally used in the plasma membrane. The Golgi apparatus modifies, stores, and transports proteins that are formed in the rough endoplasmic reticulum. It also generates lysosomes, responsible for cell digestion (destroying and harnessing waste compounds within the cell). Peroxisomes counteract the toxic effects of certain substances (such as alcohol). Centrioles help with cell division. And mitochondria are responsible for most of the cellular respiration (energy generation), through the krebs cycle and the respiratory chain (oxidative phosphorylation).

1.2.?The Structure of DNA and RNA, and the Transcription

This structure is one of the most important in the history of science. DNA (deoxyribonucleic acid), present in the cells of most living beings, is composed of several nucleotides (image 4). Each nucleotide is formed by a phosphate group, a pentose (deoxyribose, in the case of DNA) and a nitrogenous base. In DNA, there are 4 possible nitrogenous bases for each nucleotide (images 5 and 6): Adenine, Thymine, Cytosine and Guanine. Remember that DNA is composed of two strands of the aforementioned nucleotides. When you have Adenine on one strand, the other strand has Thymine. When you have Cytosine, the other strand has Guanine. A note: our DNA is divided into several molecules called chromosomes (in the case of humans, 46).

RNA (ribonucleic acid) is slightly different from DNA (images 6). Its pentose is ribose (instead of deoxyribose). Also, instead of the nitrogenous base thymine, it has the Uracil base. For the formation of RNA from DNA, the RNA polymerase protein acts (image 7). The RNA is formed based on one of the DNA strands. When you have Adenine in your DNA, you have Uracil in your RNA. For Timine in the DNA, Adenine in the RNA. For Cytosine in DNA, Guanine in RNA. For Guanine in DNA, Cytosine in RNA. Now, why transcribe DNA into RNA. There are many functions, which we will see in another post. One is the creation (translation) of proteins for the cell to function.

1.3.?DNA functions

DNA has several functions. One of them is the capacity for self-replication (which occurs in a semi-conservative manner, with the help of various enzymes and RNAs; image 8). Another is the ability to transcribe into messenger RNA (mRNA; image 9). This messenger RNA can have, as well as DNA, complex three-dimensional shapes (image 10). When the mRNA leaves the nucleus of the cell, it is read by several ribosomes, where the action of transporting RNA will occur (RNAt; image 11). These tRNAs have an anticodon, each corresponding to three nucleotides of the RNA (for example AUG). The proteins formed in this translation process (mRNA in protein) can have 20 different types of amino acids, but there are 64 codons (cracked nucleotides) possible in the RNA. This means that some codons translate into the same amino acid for the protein. The proteins created in the translation process are very diverse and complex, presenting catalytic sites, where they do something important (image 12). For example, lysozyme cuts pieces of polysaccharides (carbohydrates or sugars; image 13). There is an important definition of a gene: a part of the DNA that encodes some specific function. But, it can often be said, more specifically, that genes are parts of DNA that produce one or more proteins, or that produce mRNA molecules that themselves act as catalysts, regulators or structurers. But, that part of the different RNAs is another story.

1.4.?Cell Division: Mitosis

The cell cycle (image 14) of a cell that does not make meiosis is normally divided into interphase (image 15) and mitosis. The interphase has some subdivisions: G1, S, and G2, in addition to a possible G0 (or rest). Especially in phases S and G2, the cell duplicates its interior for future mitosis (DNA duplication happens in S). When it reaches mitosis, the cell goes through certain stages, called: prophase, metaphase (including prometaphase), anaphase, and telophase. In the prophase (image 16), the chromatic (DNA in the nucleus) condenses, the nuclear envelope disappears and the centrioles begin to migrate to opposite poles. In the metaphase (image 17), the spindle fibers are formed (made of tubulin), connecting the centrioles to the chromosome centromeres, and the centromeres line up with the metaphasic plate (equatorial part of the cell). In anaphase (image 18), motor proteins act on the spindle fibers, causing them to pull each sister chromatid (which now becomes child chromosomes) to each pole of the cell. In telophase (image 19), there is an important cytokinesis, which is the division of the cytoplasm into two parts (two cells).

1.5.?Cell Division: Meiosis

This time we are going to talk about another type of cell division, which happens to the germ cells of diploid living beings (usually having a chromosome set from the father and another from the mother). This is meiosis (image 20), which, from a diploid cell, can generate four haploid cells (a set of chromosomes). In humans, meiosis occurs in spermatogonia (in men), producing sperm, or in ovogonia (in women), forming oocytes and, possibly, eggs (image 21). As in mitosis, before meiosis there is an interphase, when the genetic material is duplicated and the cell prepares for division. Meiosis itself is divided into two phases: meiosis 1 and meiosis 2. Each has its own phase of prophase, metaphase, anaphase and telophase.

In meiosis 1, the first phase is prophase 1. It is there that the chromatin (DNA) will condense, the homologous chromosomes (unlike mitosis) synapse (they are close to each other; gene permutation (or crossing over), with the exchange of genetic information between homologous chromosomes. More specifically, meiosis prophase 1 is divided into 5 phases (image 22): leptotene, zygote, pachytene, diplotene and diakinesis (to remember, repeat, "lezipadidi"). Leptotene: chromosomes become visible, due to chromatin condensation. Zygote: denser chromosomes, and there is a "rough match" of the counterparts. Pachytene: even more dense chromosomes, and there is a more intimate pairing (called synapse) of homologous chromosomes. It also becomes apparent that each homologous chromosome has two chromatids. It is in pachytene that crossing over occurs (exchange of information between non-sister chromatids. Diplotene: the pairs of sister chromatids begin to separate, but some parts between non-sister chromatids remain together. These parts are called chiasms. Diakinesis: the nucleolus and the nuclear envelope disintegrates, and the chromosome centromeres attach to the spindle fibers.

The remainder of meiosis 1 is similar (but not the same) to mitosis (image 23). In metaphase 1, the centromeres are aligned on the metaphasic plate (equatorial plate). In anaphase 1, each homologous chromosome (and not each chromatid) is pulled into each pole of the cell. In telophase 1, each cell resulting from meiosis 1 is left with a homologous chromosome (two chromatids). Since the resulting cells have half the number of chromosomes, meiosis 1 is called reductive division. The division of chromatids will occur in each of the cells formed in meiosis 1. This division of each cell is called equational division (does not decrease the number of chromosomes). Therefore, at the end of meiosis, there are 4 haploid cells.

Meiosis 2 is divided into 4 phases (image 24). In prophase 2, the spindle fibers are linked to the centromeres of the sister chromatids. In metaphase 2, the centromeres are aligned on the metaphase (equatorial) plate. In anaphase 2, the sister chromatids are pulled into each pole of the cell. In telophase 2, each resulting cell has one of its sister chromatids. As the process occurred in each cell at the end of meiosis 1, we have 4 haploid cells at the end of the process.

1.6.?Mitochondria and Chloroplasts

Realize that the eukaryotic mitochondria probably came from an engulfment between a primordial eukaryotic cell derived from an archeobacterial type (image 25). In addition, the chloroplasts came from the engulfment of an aerobic cyanobacterium (image 26). Eukaryotic cells in general have much larger DNAs than prokaryotes (image 27). Something that makes a lot of difference is the size of the part of the DNA that does not encode proteins. While 98.5% of the human genome is non-coding, only 11% of the genome of an Escherichia coli bacterium is non-coding.

1.7.?Cellular Communication

We will also have an idea of how cell signaling works, or inter and intracellular communication. Basically, communication between cells occurs by transmitting signaling molecules from one cell to another. When it arrives at the other cell, it activates some receptor, producing a response within the target cell (image 28). Not only that. Within the cell there will also be several processes for the signals to be understood by the cell (see image 29 for a notion). The processes are complex and differ between biological groups, but we can observe some patterns that are repeated.

After the signaling molecule binds to a receptor on the plasma membrane of some cell, intracellular signaling proteins will end up generating effector proteins, which will alter the cell's metabolism, change its gene expression or change its form of movement (image 30). There are 4 types of transmission of signaling molecules (image 31): through contact, in a paracrine way (sending through some medium), in a synaptic way (as occurs in neurons, there are axons and neurotransmitters associated with electrical signals), and in a way endocrine (transmitting with the help of the bloodstream). The signals can have different effects on the target cell, such as to survive, grow, divide and differentiate (image 32).

There are three main types of receptors on plasma membranes. The first type is that of receptors associated with ion channels (image 33). In it, a signaling molecule binds to the receptor, allowing specific ions to enter the target cell. The second type is that of receptors coupled to the G protein (image 34), and that this protein is activated, also activating some enzyme within the cell by means of the G protein. The third type is that of receptors coupled to enzymes (image 35), in which signaling molecules directly or indirectly activate an enzyme.

Within the cell, there are two main types of signal-transmitting molecules (image 36). The first works through ATP, becoming ADP. The molecule (usually a protein) then becomes active. Then, the protein phosphatase causes it to become intact. The second works through GDP, becoming GTP. Then, the GTP is hydrolyzed, inactivating the molecule.

1.8.?Mendelian Genetics

Mendelian genetics officially started with the publication of Gregor Mendel's work (image 37) with peas in a monastery (image 38). With great planning and use of statistics, he demonstrated how the physical characteristics of organisms (phenotypes) are passed on from one generation to the next. To begin with, he studied seven characteristics of peas (image 39). For example, a line in which only round peas (purely round) was obtained was crossed with a line which only had rough peas (purely rough). In this example, the crossing always resulted in round peas (no roughness). When this new strain (called F1) self-fertilized, the offspring had 3/4 round peas and 1/4 rough peas. This pattern is repeated for the seven characteristics studied by him.

To explain his repeated patterns, Mendel first invoked 3 postulates. In current language, they are: (1) the characteristics of individuals are controlled by allele genes, (2) some genes are dominant over others, and (3) during the formation of gametes, the allele genes segregate (separate) randomly, and each gamete receives a gene allele of a trait (Mendel's first law). Thus, Mendel was able to explain his results (image 40), which were obtained by the self-fertilization of heterozygotes (individuals with different allele genes).

Not only that. Mendel saw that a gene for one trait was independent of a gene for another trait at the time of gamete formation (independent segregation; Mendel's second law). He observed this by first crossing different individuals with respect to two characteristics, then self-fertilizing the children (image 41). As a result, he obtained a proportion of 9/16, 3/16, 3/16, and 1/16 for the phenotypes observed in the individuals. A very important finding for science.

Note that Mendelian genetics is not perfect, but realize that it is possible to predict human diseases through genealogies (image 42). With this, we can also know if a disease comes from a dominant or recessive gene (image 43). What about patterns not predicted by classical Mendelian genetics? This is another story that we will see right now.

1.9.?Extensions of Mendelian Genetics

Now let's talk a little bit about what classical Mendelian genetics does not explain. These are very important cases to understand how the characteristics (phenotypes) of individuals are expressed.

Incomplete dominance or lack of dominance:

When this happens, there is a mixture of the phenotypes expected by each of the alleles observed in the individual (image 44). For example, in the dandelion plant, one allele gene is responsible for white flower, but another for red flower. When you have heterozygosis (the two genes present), the pink phenotype is observed.

Codominance:

When this happens, the two allele genes have their phenotypes expressed equally. For example, in human blood groups (ABO; Image 45), gene Ia generates antigen A, gene Ib generates antigen B, and the presence of both at the same time generates both antigens (A and B).

Inheritance linked to sex:

When this happens, some phenotype (for example, of a disease) is linked to one of the sex chromosomes (images 46 and 47). For example, color blindness is linked to the X chromosome. In a woman, it would always be recessive, but in a man it functions as if it were dominant.

Gene interaction:

When two or more genes are responsible for the same phenotype, we see a genetic interaction. For example, chicken crests are determined by two genes. As we saw in the post of Mendelian Genetics, two genes can present a 9: 3: 3: 1 phenotype. This is what happens to the chicken crest (image 48). There is a proportion of walnut crests of 9/16, of pea type of 3/16, of wheel type of 3/16 and of simple type of 1/16.

Epistasis:

When the presence of one or more alleles of one gene prevents the expression of another gene, we observe epistasis. For example, the color of the chicken is determined by two genes (C or c, and I or i; image 49). When there is the allele I (dominant), the chicken is always white. Otherwise, it is brown.

Quantitative inheritance:

When several genes are additively responsible for a phenotype, we observe the quantitative inheritance. For example, the color of human skin (image 50) is determined by several genes that, with the presence of specific alleles, add the amount of melanin to the skin.

Notice how all this extension of Mendelian genetics is important for us to understand how phenotypes (such as the presence of diseases; image 51) occur in the polulations of species, including ours.

1.10.?Sources of Genetic Innovation

Did you know that there are several ways to obtain genetic innovation in cells (image 52)? One way is through intragenic mutation. In this type of innovation, there is a change in one or more DNA nucleotides, causing a change in the protein that will be translated after the transcription of a messenger RNA. Another way is through gene duplication. That is, the duplication of a specific gene occurs. Another way is by shuffling DNA segments. As the name says, a mixture of the nucleotides of two genes occurs. Finally, horizontal transfer may occur, which is the passage of a gene from one cell to another.

1.11.?Chromosomal Mutations

Let's talk a little bit about types of mutations called chromosomal mutations. First, we should note that there are two more general types of chromosomal mutations: aneuploidy and polyploidy (image 53). In aneuploidy, an individual receives or loses a chromosome. This is the case of human syndromes related to trisomies (3 chromosomes). We have, for example, down syndrome (trisomy of chromosome 21; image 54), Patau syndrome (trisomy of chromosome 13; image 55), Edwards syndrome (trisomy 18; image 56), and the syndrome of Klinefelter (a Y added to two X chromosomes; image 57). Still, it can be noted, for example, Turner's syndrome, which is the non-existence of a chromosome other than the X (only an X; image 57). These syndromes can be acquired through the non-disjunction of chromosomes or sister chromatids during meiosis (image 58).

In addition to this type of mutation, we can also have some more specific mutations along the chromosomes (image 59). Thus, we can have the deletion of a part of a chromosome, the duplication of a part, the inversion of the nucleotides of a part, the movement (translocation) of a part of a chromosome to another, or the exchange of a part of a chromosome by another chromosome (and vice versa). As an example of these mutations, we have the Cri du Chat syndrome, which is the deletion of part of chromosome 5 in human individuals (Image 60).

Note that the duplication of parts of the chromosomes can be seen as a great source of new genetic information in the species. In this way, parts of DNA are accumulated so that they can be used in various functions. Also, note that polyploidy can also, in some cases, generate new species very quickly, including in plants. The mutation does not necessarily cause harm to the individual in which it occurs.

1.12.?RNA interference

RNA interference (image 61) is a process that takes place in cells, which aims to cleave (cut) a target RNA, interrupt the translation of an RNA (messenger - mRNA), destroy an RNA or create heterochromatin where the Target RNA is transcribed (that is, condensing the part of the DNA from which the RNA is transcribed so that it is no longer transcribed. This process can be carried out by three types of RNA: micro-RNAs (miRNAs), small interference RNAs (siRNAs), and RNAs that interact with piwi (piRNAs). The coolest thing is that these RNAs are all non-coding (they don’t translate into proteins), so you can imagine the importance of the non-coding part of our DNA (that part we used to call trash or garbage in high school).

Micro-RNAs act with the help of a protein called argonaut. When they are together, they form the RISC (RNA-induced silencing complex). This RISC joins the target RNAm, slicing it or getting stuck to it, preventing its translation and also allowing degradation (image 62). SiRNAs (image 63), also with the help of the argonaut protein, can either function as micro-RNAs, destroying the target mRNA (forming RISC) or creating another type of complex (also including the argonaut), called RITS ( RNA-induced transcriptional silencing). These RITS attract and modify histones, generating heterochromatin where the target mRNA is being transcribed. The piRNAs, on the other hand, also silence the part of the DNA and destroy target RNAs. These piRNAs are larger than micro-RNAs and siRNAs, and they join the piwi protein, instead of the argonaut.

In addition to the many possible applications that you can imagine for the RNA interference process, there is a very similar process that is the CRISPR defense system in archeobacteria and in some bacteria. In this defense process, a part of an invading virus can be added to the host's DNA. That part of the DNA will then produce what is called crRNAs (CRISPR RNAs, which destroy the DNA of the virus if it reappears in the target cell (or in any descendant of it).

1.13.?Genetic engineering

Do you know the basics about how genetic engineering works? Well, we have genes in our genetic material. They carry the information that will give us specific characteristics (or phenotypes) (like blue eye). It turns out that some of these genes can greatly modify the characteristics that we see in a living being. For example, you may have a gene pool that makes you not produce insulin. However, you can make bacteria produce insulin for you (and that is what they do to make so much insulin for diabetics). You basically take a human cell and use a molecule (an enzyme) of the "endonuclease" type. It will take a piece of DNA from the human cell. Imagine that this piece can synthesize insulin. You then take a bacterium, cut out its genetic material and glue the piece that you took out of the cell. You now have bacteria that produce insulin, and that have daughters that also produce!

Okay, and what is the danger in that? Imagine that the piece of DNA has other genes that have functions unknown to scientists. It can happen that these foreign genes produce proteins that cause allergic reactions in some people. This danger is one of the best known in Genetic Engineering. Anyway, with techniques like the one indicated above, genetic improvement arose, which through crosses between selected individuals (artificial selection) or through genetic engineering causes individuals in a population to have characteristics desired by "breeders". You may want to buy a giant tomato, or a more pest-resistant sugar cane. That is why the improvement is so desired.

Currently, a CRISPR ("Clustered Regularly Interspaced Short Palindromic Repeats") has emerged, which is a very important type of molecule (Image 64)! It basically makes it possible to edit genetic material, just like the aforementioned endonucleases, but its performance is very high. Using CRISPR, scientists are making several advances. Even doing genetic engineering on humans:

"Russian ‘CRISPR-baby’ scientist has started editing genes in human eggs with goal of altering deaf gene": https://www.nature.com/articles/d41586-019-03018-0?utm_source=Nature+Briefing&utm_campaign=a5b08495ab-briefing-dy-20191018&utm_medium=email&utm_term=0_c9dfd39373-a5b08495ab-43405753&fbclid=IwAR0UMQ4rMcGRcha8zh4VAN2B6e9P8YAZIo2CbxsT-fYSD6MUdqArECfNDu0

"CRISPR Babies Scientist Sentenced to 3 Years in Prison": https://www.scientificamerican.com/article/crispr-babies-scientist-sentenced-to-3-years-in-prison/

There is a very good film about how far genetic engineering could go. It is called GATTACA (trailer below); and note that the name is composed of nitrogenous bases: Guanine, Adenine, Thymine, Thymine, Adenine, Cytosine and Adenine). It is worth assisting him to think about whether it is worth creating a new ideal of being human.

Note that genetic engineering is a major advance, but that it presents several dangers. It is always good to find out if the food we buy is genetically modified.

2.?Evolution Itself

Biological evolution means changes in the characteristics of individuals in a population over the generations. But, do you know what are the different theories of evolution of species? It’s not just Darwin’s. In "The Growth of Biological Thought" (Mayr, 1982), Ernst Mayr lists six distinct theories:

1. Intrinsic capacity for growing perfection

This is not considered a scientific theory, it is more mystical.

2. Use and disuse plus inheritance of acquired characters

This theory is attributed to Lamarck. In it, for example, if you become very strong during your life, you will have a strong child.

3. Direct induction by the environment

Very similar to the previous one. The living being would "learn" and store in its DNA directly through the environment, passing this information on to its descendants.

4. Saltationism

It has to do with macromutations. As if from one generation to the next a living being (for example, a fox-like being) had an extremely different descendant (whale). It goes against gradualism.

5. Random evolution

It also uses the concept of mutation. In it, only the randomness of mutations would be able to produce biodiversity. However, she is not able to answer about the order (direction) existing in the formation of adaptations.

6. Direction imposed by natural selection on random variation

This is Darwinism, and it is the most widely accepted theory. It is as if there were filters allowing only individuals (of a certain species) to pass that have more descendants. The characteristics present in those who pass, tend to be present also in their descendants.

Note: mutations, genetic drift and epigenetics are important for evolution, but what rules the most is natural selection. These theories are also mentioned in "Science in the Soul" (Dawkins, 2017). Following the section, we will see a little more about Evolution, based mainly on Ridley (2006).

2.1.?The Synthetic Theory of Evolution or Neodarwinism

Let's talk a little about Neodarwinism, or synthetic theory of evolution (image 64). We will see by the end of the post that the second name should be used more from now on. Well, we know that there is a theory of evolution through the mechanism of natural selection. In this Darwin theory, two populations of a species have little or no interbreeding (for example due to geographic isolation) and have different selective pressures. For example, the Galapagos finches (image 65) had a relatively recent common ancestor. In each division of the population, they had different pressures in terms of obtaining food. Therefore, we see that different species of finches have different shapes of beaks.

However, Darwin, even more so in 1859, did not know how traits were passed down from generation to generation. That is, he did not know how a trait (such as blue eye in humans) was passed on to the offspring. Until then, he thought that there were things called pangenes, which would be like forces that would carry biological characteristics from the body to the sexual organs. But if he knew so little and wrong about the subject that he did not even venture to say it in his most famous book. That's where the figure of Gregor Mendel came in. His work with peas, in 1866, shed light on the possible existence of genes, which would be segregated for the formation of gametes (first law of Mendel), and which would independently form the characteristics of living beings (second law of Mendel). This work was little known during the rest of the 19th century.

In the 1880s, researchers were able to observe condensed chromosomes, duplicated (hence the X) and close to the cell division under the microscope (image 66). Then they were able to see that the cells had two types of division (mitosis and meiosis). It was not until 1900 that Mendel's work was rescued by Carl Correns, and in 1902 Sutton and Boveri independently put the genes on chromosomes (chromosomal theory of heredity).

As time went on, in 1944 Avery, Macleod and McCarty, showed that chromosomes are formed from DNA, and that this is the substance that carries our genetic information. For example, viruses, when attacking cells, leave their protein capsule and inject their viral DNA into the cell (image 67). Finally, in 1953, Watson and Crick described the structure of DNA. All of these discoveries helped us to understand the bases of heredity, and formed the basis of the Neodarwinian theory, in which species evolve by the mechanism of natural selection, but function according to the way our genes are passed on. It can be said that the first half of the twentieth century was when Neodarwinism developed.

Recently, much more has been discovered about heredity. For example, the way in which mitochondria appeared in eukaryotic cells was a type of inheritance of an acquired character, as is the case with the conformation of DNA (which comes from the parents, through the inheritance of histones), or with mutations in the mitochondrial DNA, that are inherited by the children. These Neolamarckist characteristics of evolution are also important. So, understand that "synthetic theory of evolution" is a much fairer name than Neodarwinism.

2.2.?Epigenetics or Neolamarckism

The inheritance of acquired characters had become almost a legend after the spread of Neodarwinism. But, some new studies are showing that epigenetics puts our notion of evolution in a place between Neolamarckism and Neodarwinism. First, we must note that the mechanisms by which epigenetic regulation works so that we can understand it better. The first form, which is the most studied, is DNA methylation, determined as the addition of methyl groups to DNA. This process silences regions of the DNA. Another form of epigenetic regulation is through the modification of the proteins that wrap the DNA: histones. The third way is through non-protein coding RNAs. Yes, what we've already seen about RNA interference is an example of epigenetics.

Note that epigenetic patterns (such as the shape of DNA) determine the regulation of DNA, indicating how much the genes may or may not be expressed. These patterns can be passed through mitosis and meiosis. What is most fantastic is that organisms can "learn" something in life, and pass it on to their offspring. This may seem wrong, but it is what epigenetics is contributing to the resurgence of neolamarckist arguments in the scientific community. For example, in a recent study (Stanford et al., 2018), researchers note that rats that exercise exercise offspring with better glucose metabolism. If this were also corroborated for humans, it would be better for people close to being parents to do several exercises regularly. Another example of the role of epigenetics is also in determining divergent sexual characteristics between the sexes (sexual dimorphism). Not only are sex chromosomes different, but also how much genes are, in general, expressed (Rice et al., 2016). The right thing to do is not to become a conservative neo-Darwinist or neolamarckist, but to learn from what both views can teach.

2.3.?Natural Selection and Genetic Drift

Natural selection is one of the greatest forces that cause changes in species. Notably, there are three types of selection in relation to a characteristic of a population of a species. For example, imagine a population of mice with different intensities of fur colors (image 68). Imagine that, for some reason, rats with stronger colors begin to survive (that is, they are selected), leaving more of their genes. The young, dark-skinned population would be the product of a directional selection. Now, imagine that only the rats of intermediate colors died (were not selected). The new population with light and dark mice would be the product of a disruptive selection. Finally, if only rats with very intermediate colors were selected, the new population would be the product of a stabilizing selection. Knowing these types of selection is important, as we can also artificially select individuals with certain characteristics in a population of a species. In this case, it would be an artificial (rather than natural) selection.

And what is genetic drift? It is a process in which phenotypes of a species are influenced (as if selected) at random (image 69). For example, a volcanic eruption occurs on an island. Some individuals of a species can survive more just by luck. If these individuals have specific characteristics that are not very common before, that characteristic may become more common in the future.

2.4.?How a species arises: speciation

We've already seen a little bit about natural selection and genetic drift. They are processes that occur at the individual level (selection or not). When we talk about speciation, we are talking about populations of species changing over time. This change can occur, for example, in all individuals of a species, changing the frequency of genes over time (for example, increasing mass, or changing color). That would be anagenesis. That is, the production of a species from an old one. If the population somehow divides into two, then we will observe cladogenesis (image 70). Still on cladogenesis, we can think that the species are in constant and gradual change in their characteristics. This would be what is called gradualism. If the changes occur only in periods of greater environmental or coevolutionary pressure, this would be called punctuated equilibrium (image 71).

There are three main forms of cladogenic speciation (image 72). The first is allopatric speciation, which is the origin of two species from one through a geographical separation of two populations. These two populations would undergo anagenesis until, both by selection and by genetic drift, they became so different that they were unable to interbreed. Even if the populations got together again, they would be different species. Paraparatric speciation is when a population (usually large and very dispersed) begins to have points in which species intersect more than in others. This would generate sites with the appearance of hybrids. If this discontinued form of intercrossing continued (for example, for behavioral reasons), we would have the production of two legitimate species. A third form of speciation, called sympatric, could happen if within a population of one species a new species arises (without a geographical barrier). This could occur in bacteria through horizontal gene transfer, or in plants, through mutational polyploidy events. Realize the importance of cell biology and genetics for studies on evolution. See also that we already have enough knowledge to generate a phylogeny (image 73). This phylogeny of ours has a root, nodes and branches.

2.5.?How to analyze and build a phylogeny

Let's consider a phylogeny (image 73). It has a node (a species or biological group), a branch (the time the group has been in existence), and the root (the common ancestry of phylogeny groups). In a phylogeny, we can consider different types of characteristics (image 74). One type is apomorphy, which is a feature derived from a pre-existing feature. Another type is synapomorphy, which is an apomorphic characteristic shared by two or more species or biological groups. Another type is plesiomorphy, which is a primitive characteristic shared by one or more species. An apomorphic characteristic present in only one species or biological group (taxon) is called autapomorphy.

When it comes to building a phylogeny, the biologist must make a table of what species he is studying and what characteristics he is analyzing in them (image 75). Then, he must build a phylogeny (image 76) that considers synapomorphies between species in order to gradually join them in groups that have more derived characteristics. Sometimes, a feature may have appeared more than once in the evolutionary history of species. Thus, the biologist must assemble the phylogeny that makes not only more sense, but also follows the parsimony method. That is, it has the least number of evolutionary steps (simplest phylogeny) to explain the evolution of species.

Still on phylogenies, we can see that some groups have a common ancestor (image 77). These groups are called monophyletics. When a chosen group considers only part of the species derived from the same common ancestor, this group is called paraphyletic (images 77 and 78). This is the case with reptiles that, for example, disregard birds as their descendants. When a group has species or biological groups from several different monophyletic groups, we can call it polyphyletic.

3.?The History of Evolution Focusing on Humans

In this section, I will focus on telling about the history of mankind going back in time to the origin of life. I will start with an ordinary human and we will step by step understand who our ancestors or close or distant relatives are. It is as if we take a time machine and return to the steps of evolution. To write this section, I referred mainly to Neves (2015) and Dawkins (2009a, 2009b, 2012).

3.1.?Human evolution

The history of human evolution is a recent topic in scientific literature. It started basically in the late 19th or early 20th century, when Darwinian biological evolution started to become more popular. Since then, we have learned a lot and developed teaching techniques that help to disseminate your information. During the text, I will make use of information from books such as “Thus walked humanity” (but it can be translated as "This is How Humanity Walked") or "Assim caminhou a humanidade" (Neves, 2015), in addition to using a phylogenetic tree as a basis for locating our relatives and ourselves (Image 78). Note that I am going to use a tactic of teaching evolution from front to back going from us Homo sapiens to our common ancestor with the chimpanzee. This technique is also used in books such as "The great history of evolution", as called in Brazil, and in English as "The Ancestor's Tale: A Pilgrimage to the Dawn of Evolution"?(Dawkins, 2009a) and "The greatest show on Earth" (Dawkins, 2009b).

We will go from us to our common ancestors with other species. Let's start with you. You have ancestors, starting with your parents, your grandparents, then great-grandparents. Note that, at the same time, you also have first cousins, second cousins, and so on. You are not like your grandparents or your cousins. In fact, the more distant you are, the more they are different from you. This explains a lot about evolution.

There are differences that are very noticeable between certain human populations. When did these human populations with different biological characteristics diverge? Some 30-50 thousand years ago, when Homo sapiens migrated out of Africa. Homo sapiens was not the only human species in that recent past. There were several human species coexisting in the world, including Neanderthals. It turns out that not only did Homo sapiens leave Africa during this period, but they crossed with other races and species of humans. Yes, you greatgreatgreat ... greatgrandfathers that did that. Thus, with these crossings and the pressure of the environment, the human "races" that we see today have emerged. We all have a common ancestor, and we are even cousins (near or far). Approximately 40-50 thousand years ago, something that could be called a "creative explosion of the Upper Paleolithic" occurred. It was here that our species really defined itself as we know it today, because there was an increase in our ability to create symbols. With that, the first cave paintings, necklaces, and even religions appeared. Animist and shamanistic religions expanded, and religious sculptures appeared, such as that of Venus of Willendorf, 30,000 years ago and the lion-man, 35,000 years ago. Going back a little more in time, we can see something that may have served as a selective pressure for humans, because some 70000 years ago there was a human population bottleneck. In other words, something happened that almost led human species to extinction. It may have been the eruption of the Toba supervolcano in Indonesia. Let's go even further back in time, when you had a grandfather a little different from you, 200,000 years ago. Finally, we come to our greatgreat... greatgrandfathers, common ancestors of the people of Earth, Homo heidelbergensis.

3.2. The?Homo?genus

There is a debate as to whether our closest common ancestor would be Homo heidelbergensis or Homo erectus (which we will learn about later). However, some factors indicate that they are Homo heldebergensis. For example, there is no evidence that H. erectus went to Europe, unlike H. heidelbergensis, which colonized it. In addition, Homo heidelbergensis has a much larger brain volume and is closer to ours. Its name is very strange, isn't it. This is because it was found and registered in Germany from 1908, when a worker found a jaw in an excellent state of conservation of this species. Males were around 1.7m and weighed 62kg, while females were 1.6m and weighed 51kg. Like other human species, they used very sophisticated tools.

It is important to note that these grandparents of ours also had their own grandparents (Image 78). Going back in time we find another common ancestor of ours, Homo erectus, which was present on the planet from approximately 2 million to 143 thousand years ago. This species was not only our ancestor, but also most likely generated a cousin of ours that was soon extinct, called Homo floresiensis. The story of our ancestor, Homo erectus, began when, in the late 19th and early 20th centuries, fossils of it began to be found in Java and China. He could be quite large compared to his ancestors (such as Homo habilis).

A very important characteristic of H. erectus is already in the name. He was more terrestrial (or less arboreal) than his ancestors. Therefore, he had short arms and long legs, featuring a good strictly terrestrial bipedalism. He also used tools, as well as other humans, showing that he had a certain manual skill. H. erectus also characterized a large cerebral increase in relation to its ancestor. More interesting than the use of tools was his ability to handle fire. This is perhaps the most interesting evidence of our ancestor. Archaeological sites in southern Africa and Israel point to the use of fire, such as making fires, 1 million years ago by our ancestors. Also, H. erectus was the first ancestor of ours to leave Africa, colonizing the Caucasus and the eastern part of Asia. All of this evidence shows how important this human species was. We already know that one of our common tarpaulins (of all individuals of Homo sapiens) was of the species H. erectus. But what was the common grandfather of all H. erectus individuals like? He was Homo habilis (Image 78), a species that lived between 2.4 million to 1.4 million years ago. He is considered the debutant of the Homo genre, for some reasons. One of them was the great increase in his brain capacity in relation to his ancestor, Australopithecus (which we will talk about in the next episode). While Australopithecus had 450cm3 of brain, Homo habilis had 650cm3. Another factor is that he is a very ancient ancestor of ours who used chipped stone tools. However, it is now known that even Australopithecus ancestors achieved this feat (3.3 million years ago).

3.3. Before?Homo?genus

However, it is now known that even Australopithecus ancestors achieved this feat (3.3 million years ago). Homo habilis is certainly very interesting, but let's leave it now to get to know his ancestors, who are also our ancestors. Let's get to know Australopithecus afarensis (Image 78), which lived from 3.85 to 2.95 million years ago. In the 1970s, A. afarensis fossils were found in Africa (places like Tanzania and Ethiopia). Among these fossils is the famous "Lucy", named after the song "Lucy in the Sky With Diamonds" (Beatles). These fossils were very important, as they made it evident that human evolution had taken much longer than previously thought. Australopithecus were low compared to us. Males were around 1.5m, weighing 42kg, while females were 1m, weighing 29kg. They also had a bipedalism very similar to ours, even if it was optional. In addition, A. afarensis had more brain (450cm3) than its ancestor Ardipithecus ramidus (350cm3). This would make Australopithecus, at the time of its existence, have the same brain volume as that of a current chimpanzee.

It is quite remarkable that in 1976, in Tanzania, footprints were found, most likely Australopithecus afarensis, in volcanic ash before they hardened. These footprints date back to around 3.7 million years ago. They help to define the species as an optional biped, having a curvature in the back, as there are phalanx marks on the feet and hands. The great ... grandfathers of Australopithecus were of a species called Ardipithecus ramidus, which in turn was possibly a descendant of the species Ardipithecus kadabba, which lived approximately 4.4 million years ago and 5.2 to 5.8 million years ago back. Researchers inferred through the dentition of Ardipithecus ramidus that, unlike chimpanzees, he did not fight much with his companions (between males and between populations of the species). Through cranial analyzes, it was seen that Ardipithecus could have considerable vocal capacity. Evidence was also found that, although he was bipedal, he also had characteristics of arboreal animals.

Ardipithecus ramidus was very important for showing that strictly terrestrial bipedia did not come out of nowhere, but with gradual steps. Still, looking at his skull next to that of a more distant individual (a cousin of varying degrees), called Sahelanthropus tchadensis, we see that the skull is not much bigger than his. But Ardipithecus probably had an ancestor who, like him, also inhabited forests or savannas. It is called Ardipithecus kadabba.

We realize that these species are very important for us to know the most distant past of our ancestry. Then comes the figure of Sahelanthropus tchadensis (Image 78). This species was most likely not a direct ancestor of mankind, but it may be as close a cousin as possible to what we call the missing link. This missing link is the closest common ancestor between both man and the chimpanzee. S. tchadensis lived around 7 million years ago. The discovery of S. tchadensis was made in the early 2000s. Its discovery was very important for a number of reasons. For example, he showed that our very old relative species were able to walk upright (even if optional). In addition, as Sahelanthropus was found far from East Africa, it was realized that the distribution of these ancient species could be greater or more variable than previously thought. At the beginning of the species' findings, the author of the species thought that it could be a common ancestor between us and the chimpanzee. In other words, it would be a tat ... tarot, both ours and the chimpanzee's. If it were, it would be considered the "missing link" between species. However, researchers later refuted this theory, and even today we do not know who our missing link with chimpanzees would be. Today, we know that this missing link could have existed approximately 7.5 million years ago.?

We realized that Sahelanthropus is extremely important to have an idea of what our missing link with chimpanzees, who are our closest living relatives, would be like. Well, this is where we arrive at the missing link, the closest common ancestor between humans and chimpanzees. We still don't know what our grandfather was like, but he would certainly reveal a lot about our bipedalism, our habitats, our ways of life. Anyway, it would reveal a lot about the evolutionary history of humanity. The theme that will be the target of many studies during this century and that needs more and more good researchers. Archeology and paleontology are now making good use of recent statistical methods, in addition to modern dating techniques. As a result, studies are becoming more complete, revealing information that was much debated before such methods of analysis existed. Nevertheless, computer programs and simulations are paving the way for a more detailed methodology, identifying historical, genetic, or spatial patterns of hominin forms of life.

3.4. Before humans

On our journey, we stopped when we joined the chimpanzees with the so-called missing link. This occurred approximately 6-7 million years ago. This missing link is expected to have primitive characteristics for both humans and chimpanzees. Another common ancestor that we can notice is the ancestral that we have with gorillas, which would have lived more than 7 million years ago. Then, a little further away, is the orangutan, with whom we have an ancestor 14 million years ago. An important junction we have is with the monkeys of the old world (like baboons and big-nosed monkeys). Our common ancestor would have lived 25 million years ago. Still, our common ancestor with the monkeys of the new world would have lived 40 million years ago, and that with the lemurs 63 million years ago.

It should also be noted that our common ancestor with Afrotheria (such as elephants and manatees) lived 105 million years ago. 140 million years ago, we also had our common ancestor with marsupials. These marsupials often have evolutionary convergences (similar forms) with placentals, looking like we are much closer than we really are. Next, we have the common ancestor, 180 million years ago, with the mammals that lay eggs: the monotremes. Finally, we come to our common ancestor with reptiles, who lived about 310 million years ago. We also had our common grandfather with amphibians, 340 million years ago.

Continuing, we also had a common ancestor with lungfish, 417 million years ago, and with Echinodermata, like starfish, more than 500 million years ago. Interestingly, we have had a common ancestral plant with 1.6 billion years ago (Meyerowitz, 2002). Finally, we have a common ancestor with all other living beings on Earth, approximately 3.8 billion years ago. This primordial being, most likely composed of molecules that somehow reproduced, is called LUCA ("Last Universal Common Ancestor") by biologists. This is where the life story of Earth ends. Or rather, start! Realize how much biology only makes sense in the light of evolution.

3.5. The Cambrian explosion

The Cambrian explosion was an event that occurred ~ 540 million years ago, in the Cambrian period (image 79), and lasted ~ 25 million years. In it, the extinction of the "Ediacaran fauna" mysteriously occurred (image 80). The origin of a huge variety of animals, including the curious predator Anomalocaris and the trilobites, which looked like giant aquatic cockroaches. It was also during this period that spiders, crustaceans and insects appeared (image 81), in addition to many other groups! There are several chances to explain the Cambrian explosion. One of them was an oxygenation event on Earth, in which the oxygen levels in the air were similar to the current ones. Another hypothesis is the evolution of the eyes, which enabled several different types of animals. Another hypothesis is the appearance of hox genes, which are genes related to the body structure of animals. Of course, it may have been a mixture of all that evidence.

Currently, a great place to study the Cambrian explosion is Canada. More species from that era are being discovered: https://www.newstatesman.com/future-proof/2014/02/massive-trove-canadian-fossils-gives-near-unprecedented-glimpse-cambrian-explos

3.6.?The Origin of the Nervous System

It is already known that choanoflagellates (a biological precursor group of animals) have a communication system similar to the nervous system. In fact, they even have neurotransmitters (Burkhardt, 2011), and they are single-celled! This group (not the species studied by Burkhardt, but a common ancestor of all animals) originated the animals about 850 million years ago, so giving a form of intercellular communication to all their descendants in the animal kingdom. However, it was approximately in the Cambrian explosion, about 550 million years ago, that the nervous system, which is a cluster of neurons, or cells specialized in communication between parts of the body, originated, even in invertebrate animals! Thereafter, we see the brain in the animal groups best known to us (image 82).

The nervous system can be more than 500 million years old: https://theconversation.com/our-500-million-year-old-nervous-system-fossil-shines-a-light-on-animal-evolution-55460

Brain chemistry existed before animals themselves: https://www.newscientist.com/article/mg21128283-800-your-brain-chemistry-existed-before-animals-did/

A brief history of the brain: https://www.newscientist.com/article/mg21128311-800-a-brief-history-of-the-brain/

360 million years ago, animals colonized the land, and gave birth to mammals 200 million years ago. These ancestral mammals already had a considerably large neocortex to allow for the high diversity of mammalian behaviors. When there was the extinction event of the dinosaurs, the ancestral mammals that gave rise to the primates started to live in trees, being selected to have a good view for, for example, the capture of insects. This increased the visual part of the neocortex. We are, in fact, very visual animals. That's why we always need images and videos to better understand things.

Our story reaches humans again, but this time with a focus on perhaps the most important organ in our bodies: the brain. But, what makes our human brain so special? Well, what is postulated is that our great intelligence comes from the size of our cortex, part of the brain that makes us capable of discovering patterns, having logic in thinking, making predictions and preparing for them, in addition to creating and transmitting technologies and other forms of culture (Herculano-Houzel, 2017). Notably, the size ratio of the part of the frontal cortex to the entire brain is quite large in humans (Images 83 and 84; Passingham, 2002).

It is notable that the human brain is not the one with the most neurons (image 85). Elephants, for example, have larger brains and more neurons. Scientists postulate that the great advantage of the human brain, associated with the large amount of neurons in the cortex, exists only because of the ability that man has to cook his food. This capacity, which came from the manipulation of fire more than 1 million years ago (at least by Homo erectus), made the energy expenditure of the stomach to become smaller, allocating this energy to the cortex (Herculano-Houzel, 2017). Still, according to Haller's rule, formulated in 1762, larger animals have larger brains, but the ratio of brain size to body size is smaller in larger animals. Following this rule, humans still have larger-than-expected brains.

For genetic bases the size of the human brain:

4.?The Functioning of the Human Brain

In this section I will discuss how the human brain works. First, I will address basic characteristics of our brain, then I will move on to the functioning of neurons, indicating how information passes through the brain through the action potential. Next, we'll look at the synapses. Finally, we'll look at the anatomy of the brain and what parts matter most to each human sense. To write this section, I referred mainly to Herculano-Houzel (2017), Tieppo (2019) and Harvard University (2018).

4.1.?The Human Brain

As mentioned earlier, the human brain is in particular the size of its cortex. We can see in the following video by Herculano-Houzel that we have, on average, 86 billion neurons (and a similar number of glial cells), with 16 billion of them being allocated in the cortex. This makes us extremely intelligent, because, as already said, the cortex is the part of the brain that most relates to human intelligence. So many neurons in the brain need up to a third of all the energy consumed during the day.

For comparisons of neuron numbers between species:?https://www.verywellmind.com/how-many-neurons-are-in-the-brain-2794889

4.2. History of the Brain

Until the 5th century BC, it was thought that the mind came from the action of different parts of the body. However, after this century, Greek thinkers divided into two currents: cardiocentrist and encephalocentrist. Cardiocentrists thought that the mind was produced in the heart, and that the brain was only an organ for cooling the blood. Aristotle, from whom we inherited much of current science, was, interestingly, a cardiocentrist. For example, when we are afraid, our heart beats faster, in addition to other responses from the same organ. His passion for experimentation led him astray on this point. On the other hand, encephalocentrists thought that the mind was produced in the brain. Platonists and Pythagoreans had this view. Another famous encephalocentrist was Hippocrates, the father of medicine. Research on the human brain would have been more advanced at the time if the dissection of corpses had not been banned before and, mainly, after the Christianization of Europe.

A physician who had his work admired by Christians was Galen (129-217). For him, the body had three souls: a vegetative of the liver (linked to pleasure and desires), a vital one of the heart (linked to passions and courage), and a rational one of the head (linked to intelligence). This theory was supported because it was linked to the most holy trinity by Christians. This view of Galen would remain strong in medicine throughout the Middle Ages. It was only in 1537 that André Vesálio would dissect and analyze a human, updating everything that was wrong or missing in Galen's studies, which were used even then until shortly after the 17th century. The resumption of classical scientific values was becoming clearer from the 16th century onwards. The painting "The Creation of Adam" (image 86), by Michelangelo would have a brain behind the divine figure. This would represent that the "holes" of the brain would house the human spirit, as previously thought in Ancient Greece.

In the 17th century, René Descartes did two things that impacted the world. He not only created modern scientific thinking out of "The Method", but he also hypothesized that the body and the mind were two different substances. This dualism helped scientists to be able to study the body and its concepts, such as reflexes (which were previously considered normal human thoughts by the church). Of course, the materialists were against Descartes' dualism, saying that the body and the mind were the same substance. In the 17th and 18th centuries, scientists began to observe that the brain was made up of white matter (which has continuity with nerves) and gray matter. Luigi Galvani and Bois-Reymond also show that muscles move when nerves are electrically stimulated. In addition, they show that the brain (upper part of the central nervous system) is capable of generating electricity. This electricity was what controlled the human body. In the eighteenth century, much is already known about the brain structure, and then begins the scientific discussion about the possible functions of each part of the brain. Until the end of the 19th century, the study of the brain was based on two things: phrenology (which considered emotions and feelings as products of the superficial parts of the brain and therefore analyzed by the shape of the person's skull) and inferences about the functions of each part of the brain by analyzing human brain injuries. Notably, phrenology was used by charlatans to make money or make racist hypotheses.

At the end of the 19th century, Willian James, Wilhelm Wundt and, later, Sigmund Freud began with studies on psychology. In addition, brain cell staining techniques are developed by Camilo Golgi (1843-1926) and Santiago Ramón y Cajal (1852-1934), who won the Nobel Prize in Physiology or Medicine in 1906. The neuron was finally visible (image 87), and it was from him that the brain was made. Still in the 20th century, Scott Sherrington (1857-1952) discovers communication between neurons: the synapse! He also saw that there are both excitatory and inhibitory signals in the nervous system. For his contributions to neurology, he received the Nobel Prize in Physiology or Medicine in 1932. In addition, Ivan Pavlov (1849-1936) studied reflexes, supporting the learning area, and James Papez (1883-1958) studied smell, ending up discovering the limbic system, responsible for emotions.

In 1909, Harvey Cushing assembled an electroencephalograph, a device with electrodes that identified where intense brain activity began when a patient had an epileptic seizure. Then, the site was removed from the patient's brain. There was enough success to end epileptic seizures, but some characteristics of the patient were compromised (such as the movement of a compromised body part). The brain mapping had thus begun. Doctors also began to anesthetize patients and stimulate brain areas with shocks, in order to verify what each part did. It can be noted that this was a major breakthrough for neuroengineering (technologies related to the brain). In addition, people with epilepsy, psychosis or schizophrenia began to experience lobotomies. This normally occurred until the 1950s and 1960s, when antipsychotic remedies and began to be invented based on antihistamines. For example, from the molecule of promethazine (an antihistamine), they created chlorpromazine, an anti-psychotic. But recently, we have great drugs that can treat a high diversity of psychiatric illnesses.

In the 1970s, Paul MacLean (1913-2007) created the concept of a brain divided into three parts. One part would be the reptilian brain, more instinctive, for example related to hunger and thirst. The second part is the limbic brain, related to emotions, and which was found in mammals. The third part is the neocortex, more recent and responsible for rational thoughts. MacLean went so far as to say that the only difference between a man and another animal is the brain (controversial discussion). In the 1980s, neuroimaging (another advance in neuroengineering) began. These neuroimages became much more developed in the 1990s (image 88). Also, in 1987, fluoxetine, an antidepressant medication, was invented. With such a remedy, it is shown that diseases previously thought of as diseases of the mind, and not of the physical body, can be physically treated by medicines. Well, this is a brief story of how we stop being people who treat mental illness with trepanning (opening a hole in the head) to let the demons out (image 89) and become people who use neuroimages and overdeveloped remedies to solve mental problems.

To have an idea of how the brain develops into adulthood:

4.3.?Neurons and Glial Cells

Basically, the brain is made up of neurons and glial cells. Neurons (image 90) are the main cells of the nervous system, where nerve impulses pass. They are composed of its cell body, its nucleus, its dendrites (where the nerve impulses arrive) and its axons (where the nerve impulse passes to the next cell, through the axon terminals), in turn presenting myelin sheaths and , among them, Ranvier's nodules. Glial cells (image 91) are cells that provide support and protection to neurons. There are several types of glial cells. Some types are: astrocytes (connect neurons to their blood sources and remove excess potassium), oligodendrocytes (form the myelin sheaths in neurons), ependymal cells (create and secrete cerebrospinal fluid), microglia (are macrophages specialized in protection neurons), and Schwann cells (also help myelination of neurons).

4.4. The nerve impulse

Our neurons communicate through nerve impulses. These impulses arrive through the dendrites (in structures called synapses, which we will study later), pass through the axon, and go from the axon terminals to the dendrites of a next neuron (again through synapses). First, let's focus our study on a neuron. More specifically at a point in the neuron that is about to receive a nerve impulse. First, that part of the neuron is in its resting potential. What is that? Well, there are two forces that move ions within cells: the diffusion force and the electrostatic force. The diffusion force indicates that an ion in a more concentrated medium of its own will tend to go to a less concentrated medium. The electrostatic force has to do with the charge of the ion. Cations are positively charged, while anions are negatively charged. Remember that opposite charges attract and equal charges repel each other.

For now, let's focus mainly on two ions: K + (potassium) and Na + (sodium). The concentration of potassium inside the cell is higher than the concentration outside the cell, while the sodium concentration inside the cell is less inside the cell than outside the cell. There are some proteins that serve as channels for the entry and exit of potassium and sodium (K + ion channels and Na + ion channels). But, there is an active mechanism that consumes energy (by means of ATP molecules) called the sodium and potassium pump, which is taking out 3 sodium ions and placing 2 potassium ions inside the cell continuously. The cell still has many different anions in it. This causes the neuron to have a difference in charge inside and outside the cell. The resting potential of the cell is created by this voltage and is approximately -70mV. In other words, for those who know electronics, the neuron is a type of capacitor (image 92).

For more on the sodium and potassium pump:

Well, how does the electric current pass through the cell? When a part of the cell begins to receive a considerable amount of sodium, the cell's membrane potential begins to increase (become more positive). This is the same as saying that the neuron has depolarized in a certain location (image 93). This depolarization causes the opening of some proteins that are channels of passage of sodium into the cell. Yes, like a sodium feedback system (the incoming sodium ends up depolarizing the cell and causing more sodium to enter via voltage-dependent protein channels). When the membrane at that point reaches a sufficient positive voltage (image 94), the voltage-gated sodium channels are inactivated, and potassium-dependent potassium channels are opened. The potassium starts to come out, hyperpolarizing (ie, making the membrane potential more negative) the neuron site again. When the action potential process is over, the cell needs to return to the correct concentrations of sodium and potassium. For this, the sodium and potassium pump does the necessary work (image 95). For you to be aware of the importance of this pump, up to a third of our daily energy is used for the functioning of it in our nervous system.

There is one more thing about the action potential that you should notice. The axon is not just a continuous part of the neuron. It has several myelinated parts. That is, it has a layer of lipids around some parts of the axon (image 96). In the middle of the myelinated parts (called myelin sheaths), there are the non-myelinated parts (called Ranvier's nodules). When the nerve impulse passes through the neuron, it jumps from node to node of Ranvier quickly (image 97). In other words, it is in these nodules that sodium will begin to enter most prominently after an initial depolarization. This type of electrical conduction in the neuron is called saltatory conduction.

To understand more about the action potential (nervous impulse):

4.5.?Synapses

Okay, we already know how the nerve impulse passes through the neuron, but how it passes from one neuron to the next. It is through neuronal connections called synapses! First, it is good to know that there are two general types of synapses: electrical and chemical. Electric ones are like sequences of a neuron connecting to other neurons (like one cell sticking to the other). But, most synapses are chemical synapses. At the end of the axons, there are several axon endings. When the nerve impulse arrives at them, naturally, depolarization occurs, but at the moment of repolarizing the axon termination, the activation of calcium channels occurs. The calcium then enters the neuron. Before we continue, it is good to note that at the end of the axon termination there are several vesicles that carry molecules called neurotransmitters. The vesicle has a membrane that has a protein called v-SNARE attached to it, while the neuron membrane has a protein called t-SNARE. The calcium that enters after the repolarization of the neuron causes these proteins to meet, causing the membrane of the vesicle to merge with the membrane of the neuron. As a consequence, the vesicle neurotransmitters, which in the future can be restored for use again, are thrown into a region called the synaptic cleft.

In the synaptic cleft, neurotransmitters will take very little time (much less than a second!) To cross the cleft and get to where the next neuron's dendrite is. That's where the neurotransmitter receptors (on the cell membrane) are going to be. There are two general types of neurotransmitter receptors: ionotropic and metabotropic. Ionotropics are receptors that, when activated by a neurotransmitter, will let ions pass from the external environment to the interior of the postsynaptic cell. Metabotropic receptors are molecules that have a connection with a protein called G, within the postsynaptic cell. This protein, when activated, can make several changes in the neuron. Continuing with the synapse process, after activation of the receptor, neurotransmitters may be degraded by enzymes or may even return to the presynaptic cell to form new vesicles of the neurotransmitters.

And what do neurotransmitters end up doing? Two general types of synapse action can occur: excitatory synapse and inhibitory synapse. For example, the synapse can directly cause calcium or sodium to enter the postsynaptic cell, depolarizing the cell and continuing the action potential. These would be excitatory synapses. On the other hand, it may happen that the receptor enters chlorine (Cl-), decreasing the capacity of the postsynaptic cell to make a nervous impulse. Two excitatory neurotransmitters are acetylcholine and glutamate, while two inhibitors are GABA and glycine. In fact, the same acetylcholine receptor is also a nicotine receptor. Acetylcholine and nicotine end up causing muscle contraction. Therefore, it is dangerous to unbalance this neuronal function through the use of nicotine. Two very important neurotransmitters in the nervous system, including the brain itself, are AMPA and NMDA. They are active in the learning and memory processes.

To review concepts about synapses:

Synapses are often, or perhaps even normally, not just two neurons. There may be a third neuron (image 98) secreting molecules called neuromodulators that can increase or decrease the efficiency of presynaptic cell neurotransmitters at postsynaptic cell receptors. Some important neuromodulators are well known, such as serotonin and dopamine. Serotonin helps to bring calmness to the body, while dopamine is very present in the body's reward system. Dopamine ends up being the target of several known drugs. For example, cocaine prevents dopamine from being destroyed quickly in the nervous system, acting longer and feeling good.

Neurons are not arranged in a straight line. They form extremely complex circuits with billions of neurons being excited or inhibited. In addition, three types of general neuron actions can be described: convergent, divergent and recurrent. The convergence occurs when several different sensations (for example, seeing a predator's tail and smelling it at the same time) go to the same neuron subcircuit. The divergent action is when a population of neurons ends up exciting neurons from several different parts of the body (for example, the convergent action of having seen and smelled the predator making both the heart beat faster and the breath increase). Recurrent action, on the other hand, is when two populations of neurons alternate in their actions in a rhythmic manner, such as the swimming of a fish, or the running of a person.

The neuronal circuit has an additional property, which makes it possible for us not only to act, but to have short and long term memories. It is the property of neuroplasticity. Neurons can increase (potentiate) or decrease (depression) their connectivity with other neurons. In the long run, these potentiations and depressions can form potentiations or depressions of long duration, forming, for example, a long-term memory. There is a rule called the Hebb rule, which says that cells that act mutually make more links to each other, while cells that act in a disorganized way lose their links. This rule helps to understand how Pavlov found the result that dogs increased salivation just by hearing the sound that indicated that the food would arrive. Looking at it from the perspective of neuroscience, neurons related to the hearing of the specific sound had more connections with neurons related to the taste of food.

4.6.?Neuroanatomy and the Origin of Nervous Impulse

Now, let's see a little bit of neuroanatomy as we talk about human sensory systems (the senses), where nerve impulses are usually generated. Realize that before we had only talked about the nervous impulse and its passage from one neuron to another. This time we will see a little of your generation.

Before we begin, it might be good to see this short video:

VISION

The human vision system is very complex and serves to detect, process and interpret light. But, what is light? First, the light can be seen as a wave. And all waves have a wavelength. You can get a sense of the lengths of different waves across the electromagnetic spectrum (images 99 and 100). Note that the visible light spectrum has relatively short waves (image 99), larger than radio, television, microwave and radar waves, but smaller than X-ray and gamma rays. Waves can be measured in length (in cm) or in frequency (in hertz). All of this information will be important for further discussions. The light still has the characteristic of wave-particle duality. That is, it can also be seen as particles. These particles of light are called photons.

In short, the light first meets the retina, in the eye (image 101). The light-charged image then becomes a nerve impulse, which is carried by the optic nerve after first processing the image. First, this nervous impulse goes to the thalamus (image 102), where it will be processed once again. Then, it goes to the visual cortex, where there will be a great processing of colors, objects and movements in the received images. Let's see in more detail how the image, made of light, is transformed into a nervous impulse.

First, let's focus on the eye (image 103). The light, when it passes through the eye, is focused by the cornea and the lens, by the activity of the ciliary muscles. After the light is focused, it reaches the retina, where photoreceptor cells are. In these cells, magic happens. There are two types of photoreceptor cells: rods and cones. Rods allow more vision in low light, while cones allow more vision with more light and color. In these cells, there is a protein (retinal, which is vitamin A - that is why eating carrots is good for your eyesight) which has its shape changed when exposed to photons with the frequency and length of visible light. We can imagine each rod or cone as a pixel of the images that we visualize. After the electromagnetic energy becomes chemical, it then becomes electric, through the nervous impulse (membrane potentials). As a note, the classic action potential (as we have studied) will only be formed when the chemical interactions of the retinal cells reach the retinal ganglion cells.

It is important to note that the retinal protein is linked with another protein, called opsin. Together, they form rhodopsin (which is a metabotropic receptor, linked to the G protein inside the cell). In cones, opsine is a little different than it is in rods. This helps in the production of colors. In fact, there are three types of cones (image 104): short wavelength cones, medium wavelength cones, and long wavelength cones. Each is responsible for one of the three basic colors (blue, green and red).

After following the optic nerve, at the end of the retina, the nerve impulses related to the image go through a path called retinofugal projection (images 105 and 106). In it, the impulses go to the optical chiasm, where the images of the two eyes come together. Then they go to the thalamus; more specifically for the lateral geniculate nucleus, where there is a little processing of the image, including its color. Then the impulses go to the visual cortex, where much of the remaining image processing takes place. During the study of this retinofugal projection, it was very important to develop, for example, a tungsten microelectrode (image 107). Note that technologies are developed along with the knowledge acquired by scientists.

HEARING

We have already seen a little about the vision, which has to do with light waves. Now, let's focus on hearing, which has to do with sound waves. To summarize hearing (image 108), the sound we hear first is converted into mechanical movements in an organ called the cochlea. This organ converts the mechanical energy of the incoming waves into chemical and electrical signals, which then travel to the brain. It is worth noting that there is a threshold of human hearing (image 109), including a threshold that, if passed, causes pain to the individual.

Understanding the sound is extremely important. Sound can often be used as a weapon. For example, the military action of American ships looking for submarines using sonar has already caused several strandings of aquatic mammals (Parsons, 2017). Dolphins and whales often die from the action of these dangerous sound weapons (images 110 and 111).

Let's see, in more detail, how the hearing system works (image 112). The sound is the variation in air pressure. The sound first passes through the ear canal until it reaches the tympanic membrane. Then, the sound passes to bones inside the middle ear. These bones are: hammer, anvil and stirrup. When it reaches the end of the stirrup, the vibration passes through the oval window, which is a membrane covering a space, for the liquid inside the inner ear, where the cochlea exists.

Within the cochlea, there are some membranes, including the basilar membrane and the tectorial membrane (image 113). When these membranes move, hair cells mechanically open their ion channels, depolarizing them. To understand the different wave frequencies, the cochlea has a piano-like anatomy (image 114). Different parts are more influenced by different frequencies. The membrane potential then travels through the auditory nerve, reaching the auditory thalamus and then into the auditory cortex.

First, when it leaves the cochlea, the nervous impulse linked to hearing goes to the cochlear nucleus (image 115). Then it goes to the upper ear, where the sounds of the two ears are compared and processed a little. Then he goes to the lower coliculus, where he will help with human guidance through the sounds received. The next stop is the medial geniculate nucleus, which is in the thalamus. After it, the sound's nerve impulses go to the auditory cortex, where much of the processing (such as identifying sounds) is performed.

TASTE

Taste is a combination of several characteristics of a particular food or substance. They are: chemical perception, smell, texture, temperature, and even pain. There are some tastes: sweet (related to the presence of sugars), salty (related to the presence of sodium and potassium), sour (related to the presence of acids) and bitter (related to the presence of bases and toxins). More recently, a new taste has been discovered, umami, related to the presence of glutamate and other amino acids.

More about umami taste:

The feeling of taste begins in the taste buds, and is carried up to the brain. In these papillae, ion channels (sour and salty) or channels linked to G protein (remaining tastes) are activated by the presence of specific ions or molecules.

SMELL

Our nose serves to prepare the air for you to breathe, but it also has the function of smelling. When the odor passes through the nose, it passes through the olfactory cleft (image 116), where the olfactory epithelium exists. This olfactory epithelium is formed by several important cells, such as olfactory receptor neurons (image 117). On the surface of these cells in the olfactory epithelium there are cilia in the olfactory cells, which have receptor proteins that will initiate the nervous impulse related to what was felt. The impulses will pass through the olfactory nerve, then through the olfactory bulbs, and then into the olfactory cortex. An important observation is that olfactory information also passes through the amygdala and the hippocampus, which are parts of the limbic system, linked to emotion, memory, behavior and motivation. So, it is no coincidence that you have some smells that bring you good or bad memories.

TOUCH

Touch, or somatosensory sense, is what gives the sensation of touch, temperature, the position of body parts or pain. The receptors of this system are found throughout the body and serve to detect physical and chemical stimuli. The types of receptors are: thermoreceptors, photoreceptors and chemoreceptors. Heat, cold and pain are identified by the channels of transient potential receptors. They are ionotropic receptors. The sensation of touch is related to several types of mechanoreceptors. The somatosensory sensations are processed more prominently in the somatosensory cortex (image 118).

5.?Psychoactive Drugs

We now need to talk about psychoactive drugs. The main reference in this section is Emory University (2015). First, what is a drug? It would be any substance that, if consumed, will cause physical or psychic changes in the individual. This is a more general concept, involving medicines from pharmacies and also products like sugar. Sugar is one of the most dangerous drugs (image 119) today, and its control has already been suggested by the World Health Organization (WHO).

However, I want to focus here on psychoactive drugs (image 120), which are those that generate major changes in brain functions, causing changes in perception, mood, awareness, cognition and / or behavior. It is in this section that are well-known drugs, such as alcohol, nicotine, marijuana, cocaine, and coffee. Yes, coffee is a psychoactive drug, and its overuse can be quite dangerous.

Brief history of coffee:

Natural psychoactive drugs exist in the environment. For example, leaves of the coca plant are chewed in Macchu Picchu so that people can withstand the effects of high altitude. In addition, African animals drugged by Marula fruit have already been recorded (video below). Notably, the presence of psychoactive substances may even be part of the evolutionary strategies of plants, or they could be substances that formed in them, and that ended up having other uses by other species (image 121; perhaps a type of exaptation). The article below talks more about the subject in a biological and social way, within a phylogenetic perspective (relationship between species of psychoactive plants; image 121).

Marula effects on African animals (they begin at 0:50):

Article about psychoactive plants:?https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068365/

As there are several psychoactive drugs, we can look for a way to see which ones are the most dangerous (image 122; Fish, 2006) or which are harmful to the user or the people in the surroundings (image 123; Nutt et al., 2010). Looking at both, we note that heroin is the most dangerous drug, and that it creates the most dependency. Note that alcohol, nicotine and cocaine are all more dangerous and are more addictive than marijuana. Still, in the second image we can see that alcohol causes more damage to the user and the people around him than heroin itself. Note that the legality of a drug does not in any way mean that it is safe for society. Now, I will focus on four drugs that are still much discussed in our current socio-political context: alcohol, nicotine, marijuana and cocaine.

Realize that the concern with drugs is very old. For example, in the New Testament there is a passage that says, "And don't get drunk with wine" (Ephesians 5:18). This already shows a social concern with alcoholism since millennia ago.

5.1.?ALCOHOL

First, note that I am currently considering it as a natural drug, as it often exists naturally in the environment, or its process does not involve so many complex steps. When we say "alcohol", we are generally referring to drinks that contain ethyl alcohol as an active ingredient (ethanol; image 124). This alcohol is metabolized in the liver with the help of the "alcohol dehydrogenase" enzyme. However, if you overload your liver with alcohol, the cells will not be able to clean up all the alcohol in the organ. This can end up making you feel pain or even losing part of your liver. It is noted that alcohol generates a lot of dependence and causes a change in behavior, which increases the chance that its users cause traffic accidents or become involved in violent events. When alcohol is consumed, euphoria and disinhibition can occur in the first moment, but in the second moment, there is lack of control, lack of motor coordination and sleep. When users try to stop consuming it, they may have withdrawal syndrome, characterized by mental confusion, visions, anxiety, tremors and convulsions.

Effects of alcohol:

5.2.?NICOTINE

This is, without a doubt, one of the most perverse drugs that exist. When you smoke nicotine (image 125), you release dopamine as quickly as cocaine, heroin and crack. It has a big impact on how you become addicted to the drug. Unfortunately, people start smoking at a very young age (15 to 22 years), taking the addiction into adulthood. Several countries still have many smokers, such as France and Brazil itself (even with the great effort of the media against cigarettes in recent years). Cigarettes affect the entire cardiorespiratory system (image 126), causing problems for life.

Efeitos da nicotina:

Nicotine works in the body by activating nicotine-acetylcholine receptors, which causes, among other things, muscle contraction. Nicotine causes an activation of the reward system through dopamine, causing a good feeling in the smoker. It is noted that the body is able to destroy acetylcholine molecules, but not nicotine, so they act on the body for a long time. It is also important to note that nicotine is very addictive.

5.3.?MARIJUANA

Regarding marijuana, there is already a problem inherent to it: illegal trafficking. But I'm not going to focus on that right now. Just take into account the social problem associated with trafficking. Well, the main active ingredient in recreational marijuana is THC (image 127). It gives a feeling of lightness and disinhibition. By itself, it is not a very dangerous drug, but its chronic use can be associated with psychosis, memory and learning problems, anxiety and depression. In addition, it can serve as a gateway to other drugs (such as LSD, MDMA and cocaine). On the other hand, scientists can use another active ingredient in marijuana, cannabidiol (CBD) to treat serious illnesses. Therefore, there is a tendency to become more and more common to extract substances from marijuana for medical use. In Brazil, since 2015, some doctors can make special prescriptions indicating the use of CBD to the patient.

About THC:

It is also important to note that THC can lead the individual to a state of psychosis (Gage, 2019), which can be extremely bad for the user, and which is also part of symptoms of psychiatric diseases, such as schizophrenia. THC normally acts on the endocannabinoid system that exists naturally in our body, activating (being agonists) receptors many times, which normally would not be so activated.

5.4.?COCAINE

THE PLANT

The coca plant is common in the Andean region (more specifically in Bolivia and Peru) and has the scientific name Erythroxylum coca. Erythroxylum is a genus of plants that are common in Central and South America. These plants have alkaloids with several positive and negative effects. For you to have an idea, another species of the same genus is the famous catuaba (Erythroxylum vacciniifolium), common in our flora, and which is said to have an aphrodisiac effect.

COCA IN THE ANDES

Coca has been consumed by natives of the Andean regions for over 8000 years, helping them to reduce the negative effects of altitude and fatigue. The Incas called coca kuka, and also used it as a pain reliever. Even today, it is very common to see people in Peru, for example in Machu Picchu, chewing the leaf of the plant to improve their physical conditions at high altitude, and also because it is part of the culture of the region. The concentration of alkaloids in the leaf is very low, so there is no danger in this natural form. It was Europe that increased this concentration.

SYNTHESIS OF COCAINE

Europeans have known coca since the 16th century, but cocaine (a synthetic drug) was only synthesized in the 19th century in Germany. As the leaf has a very low amount of alkaloids, 1 kg of leaves are used to produce 1 g of cocaine. From its synthesis, cocaine started to have several applications in science and in the general market. For example, it came to be used as a potent pain reliever (Image 128; see the advertisement), and doctors prescribed it for various purposes (Freud was one of those who did this). Coca-Cola initially used plant alkaloids in its composition. Nowadays, she uses coca leaves, but removing these compounds (who does it for her is the Stepan Company, which is the only American company authorized to use coca leaves).

PROHIBITION

In a short time, cocaine started to be consumed in excess, becoming a public health problem. For this reason, it was banned in the USA in 1914, and in Brazil in 1921. Even so, the richest still had very easy access to the drug, which was more seriously banned by the UN in 1961. This ban had two effects: increased use of marijuana and the emergence of large drug cartels. The United States was, and still is, the biggest consumer of cocaine, so it represented a large consumer market. It was in this context that traffickers like Pablo Escobar appeared (but everyone already knows that part, so I'm going to jump to Brazil).

COCAINE IN BRAZIL

Drug trafficking in Brazil was not as strong as in the USA. It only started to organize itself from the 70's mainly through two groups: Comando Vermelho and PCC. Currently, it is estimated that more than 3.5 million Brazilian users. As the country is close to cocaine producers, it also ends up being used as an export route to Europe.

As stated earlier, cocaine acts on the body causing dopamine (important in the reward system) to activate dopamine receptors several times, leading to a good feeling. Note that the use of cocaine can cause several problems. For example, drug abuse can cause drug dependence, causing the normal amount of dopamine to decrease without using the drug. In addition, the more the drug is used, the more it is needed to achieve the same sensation.

6.?Neuroengineering

In this section, we will talk about neuroengineering and its positive and negative points. Much of the technical part presented here is referenced in The University of California (2017). It is good to note that neuroengineering is increasingly in development. It is it that will determine how we care for people and how we fight. Neuroengineering is part of the field of biomedical engineering. In this type of engineering, technology is combined with medicine, creating robots. prostheses. X-ray cameras, electroencephalograms. All of it! It is an extremely large area and tends to grow along with cutting-edge scientific discoveries.

6.1.?Neuroengineering itself

Neuroengineering was born with the experiments of Luigi Galvani, who discovered, in 1780, that electricity could be used to stimulate muscles. However, the area of neuroengineering only gained its name in the 1990s. Many important technologies emerged from this area. Among them, the electroencephalogram (EEG), which is the measurement of the electrical activity of the brain, and magnetic resonance imaging (MRI), which uses electromagnetic waves to make images of organs, such as the brain. Not only that, since the 1970s, more than 300 thousand deaf individuals have been able to hear again thanks to the invention of the cochlear implant. Also implants in the retina and several other technologies. One of the most invested areas nowadays is the brain-machine interface, in which it is studied how hardware (such as computers in implants) and software (computer programs) can be made so that an activity on a machine can generate a result in the brain.

A little about electroencephalography (reading brain activity):

Galvani's experiment on a cockroach leg:

Recentemente, engenheiros constroem até jogos de computador que usam o literalmente o controle da mente como controle (Los Angeles Times, 2013), por exemplo para reabilitar pessoas com problemas neurológicos. Veja o vídeo abaixo para um exemplo:

This is a more recent game. See this for yourself and imagine what richer people can already do:

In Brazil, there is a very good postgraduate degree in neuroengineering in the Postgraduate Program in Neuroengineering at the International Neuroscience Institute Edmond and Lily Safra (IIN-ELS). In the video below, a professor from this program talks about the future of neuroengineering and the brain-machine interface:

6.2.?Artificial intelligence and its use outside and inside neuroengineering

Artificial intelligence has fascinated our minds since the first computers were developed. Books, like Isaac Asimov's, films, like "I.A." and "Me, Robot", and games, like "Detroit: Become Human", fill us with questions. The first Artificial Intelligence course in Brazil starts in 2020, and the surprise: at UFG (Universidade Federal de Goiás)! UFPB will also get a course on that. The theme is vast and presents several areas of study. One of them is the "Machine Learning" area. Professionals in this area develop computer programs that perform a certain job according to standards and inferences in the data.

For example, you can automatically generate texts to form artificial articles from news sites: https://articlegenerator.org

Or create a program that uses photos of plant species to automatically identify them: https://www.researchgate.net/…/263931628_Automatic_plant_id…

There are several applications. Governments even use it in areas of public security (such as through facial recognition or license plates), and the military uses it for various purposes in wars. Police can take advantage of these new AI professionals to protect us more effectively, or to transform our society into a dystopia. In fact, people can even use these technologies to interfere in elections. Just out of curiosity, if you want to learn more about this area, study two programming languages: R and Python.

?Now see this video about deepfakes, which are images, sounds and videos generated by artificial intelligence that are fake and usually feature celebrities saying or doing things they wouldn't do:

Course at UFG of Artificial Intelligence:?https://www.google.com/…/universidade-vai-oferecer-o-1…/amp/

Online courses on the subject:

https://www.udemy.com/course/machinelearning/

https://academy.zenva.com/product/deep-learning-mini-degree/

First, we can talk a little about two methods used in the Machine Learning area: simple linear regression and Convolutional Neural Network (CNN). As the name suggests, the first method is one of the simplest that can be considered in AI studies. The second, on the other hand, is much more complex and can still be much more developed in several areas of science.

Linear regression is very intuitive, and can be used for simple predictions. You basically assume that your data is distributed linearly, and you can predict where new data would fit. For example, the larger the area of a land, the greater its value (image 129). After generating the regression model, it would be possible to know what the value of an imaginary terrain would be based on that model, using the intercept and slope of the line. In an old post on this blog, I teach how to do a linear regression using an example using Star Wars (link below; image 130). It was pretty cool. In another, using a simple regression model, I calculate the game time of Final Fantasy XV through the known times (at the time I wrote the post) of the other Final Fantasy's (image 131). Realize that I didn't make a lot of mistakes. Note that engineers can use the idea of linear regression to automatically calculate possible data.

Time to finish Final Fantasy XV:??https://rfunctions.blogspot.com/2014/09/final-fantasy-xv-how-long-will-it-be.html

The convolutional neural network is much more complex. Its operation is based on biological neural processes, which explains its efficient processing (tends to minimize the effort of the processor). The method is mainly used for image recognition (static or video). For example, through it, it is possible to insert a photo on the computer and find out if it is an image of a cat or a dog. To see how to do this, follow the tutorial at the link below (in R language). However, the method can be applied in different areas: language study, discovery of new drugs (medicines), and in video games. In fact, one person managed to apply Neural Networks in order to make Mario (from Super Mario World; video below) pass a phase automatically. This area is very open to new research and promises to bring several advances. Imagine the reward system for future digital applications!

Tutorial - cat or dog:?https://www.r-bloggers.com/convolutional-neural-networks-i…/

Neural networks applied to games (Super Mario World):

Now, let's go to the more specific applications of Artificial Intelligence:

A recent application is the possibility to automatically create captions for certain photos (article below). The computer identifies each element of the image (image 132). Then he uses what he has learned about the image to generate a caption that makes sense (Image 133). For example, a photo with a man playing the guitar would have a caption similar to this description: "man in a black shirt playing the guitar". Such technology would be able to describe photos for easier search (for example on research sites). I also imagine this technology being used to remove censorship and remove pornographic photos.

Another application is even more impressive (article below). From one or more images of some artistic style, it is possible to generate a new image that has a similar artistic style (image 134). For example, if you insert Van Gogh paintings, the computer will draw a new image that looks like the painter's style. Also, it is possible to provide two (or more) photos and ask to combine your artistic styles in one photo. With this technology it is possible to dream of new images by authors that were important in our history.

The third is frightening, as it brings together a little of the previous ideas (article below). From a text provided by the user, the computer creates a realistic image on it (image 135). If you write something like "the black bird has a short beak and long legs", this is what will appear on the screen, with impressive details. This technology literally makes dreams come true.

Article about generating captions for photos: https://www.cv-foundation.org/…/Karpathy_Deep_Visual-Semant…

Article on automated artistic styles: https://arxiv.org/pdf/1508.06576.pdf

More about automated artistic styles: https://towardsdatascience.com/a-neural-algorithm-of-artist…

Article about image based on a text: https://arxiv.org/pdf/1612.03242.pdf

Did you know that our ability to read the mind is already relatively well developed in the scientific world? In an article (referenced below) published in 2011 (it's been a long time already), scientists were able to reconstruct not only images, but movie videos that were watched by volunteers from the study. Watch the video and see how impressive the reconstruction of images is.

Article:?https://doi.org/10.1016/j.cub.2011.08.031

An even more interesting and scary study is about capturing images that people view in real time. In the article below, the researchers talk about the video technology presented below. Note that the videos are very similar to reality. Imagine that in a few years!

On news: https://techxplore.com/news/2019-10-neural-network-reconstructs-human-thoughts.html

Article: https://www.biorxiv.org/content/10.1101/787101v2.full

Here is an article on using Artificial Intelligence to make people hear different voices from the computer. You can even create voices never heard before by people:

https://arxiv.org/abs/1806.04558

Another impressive application is the possibility of making quadriplegic people write only with thought. That's right you read. Below is a short note from Science about this feat:

https://www.sciencemag.org/news/2019/10/ai-allows-paralyzed-person-handwrite-his-mind

One more application is the creation of a human face that you would think is real. The "This Person Does Not Exist" website generates a new virtual face every time you access the website. See how impressive the technology is. I put a photo created automatically to exemplify. That person doesn't really exist.

https://www.thispersondoesnotexist.com/

Watch this interesting video about the possibility of recording dreams, perhaps with the help of Artificial Intelligence:

6.3. Estimula??o Cerebral

There are several ways to stimulate the brain. The types of stimulation are: invasive, semi-invasive and non-invasive. In the invasive type, electrodes are inserted into a patient's brain and shocks are made to stimulate some areas. In the semi-invasive type, there is ECT (electroconvulsive therapy; image 138), in which powerful electrical currents are used in unconscious and anesthetized individuals. In addition, there is the non-invasive type. In this type, there are two main methods: Transcranial Magnetic Stimulation (TMS) and Transcranial direct current stimulation (tDCS). The first uses an electromagnetic field to make a non-painful intervention in the awake or unconscious individual. If the stimulus is too strong, it can cause seizures. TDCS is the use of weak electrical currents in the scalp of awake individuals. This tDCS stimulation has several applications, as we will see below.

It is notable that brain stimulation devices can be used to improve the performances of musicians, scientists or even snipers (Davis & Smith, 2019; Kamali et al., 2019; images 139 and 140). Recently, scientists started using two techniques that we saw here at the same time (Schestatsky et al., 2013): electroencephalography and brain stimulation. Articles with this theme help to understand several concepts of the brain (Ragazzoni et al. 2019). However, there is also a growing concern that all this neuroengineering will become common in people's lives. An example of the potential use of these methods would be the creation of super soldiers, who know how to shoot well and who have great reflexes. Still, bioethics can go a long way in deciding whether brain stimulation would be a type of dopping.

Famous headset with brain stimulation capability:

That is it for now. We took a long journey to learn about human singularity and its applications. Please be concerned about what people can do with Biology and AI. Take a look at the references and...

Till' next time!

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