As researchers studying the human brain in isolation from the body

The journal Nature publishedThe ethics of experimenting with human brain tissue robin 17 leading neuroscientists, where scientists discussed the progress in the development of the human brain models. Fears of experts are as follows: likely in the near future the model will be so advanced that they would play not only the structure but also the human brain functions.

Is it possible to create an "in vitro" a piece of nervous tissue, has consciousness? Scientists know the brain structure of animals in great detail, but not found until now, what kind of structure "Encode" the mind and how to measure its presence when it comes to the isolated brain or the like.

The brain in the aquarium

"Imagine that you woke up in an isolated isolation tank - around there is no light, no sound, no external stimuli. Only your consciousness, hanging in the void. "

This picture represent themselves experts on ethics, commenting on a statement from Yale University neuroscientist Nenad Sestao (Nenad Sestan) that his team managed within 36 hours to maintain the isolated pig brain in the "live" condition.

MessageResearchers are keeping pig brains alive outside the body successful experiment was made at a meeting of the Ethics Committee of the National Institutes of Health at the end of March this year. According to the scientist, using a pump system with heated titled BrainEx and synthetic substitute for blood, researchers supported fluid circulation and oxygen supply to hundreds of animals isolated brain, put to death in a slaughterhouse in a couple of hours before the experiment.

Judging by the conservation activity of billions of individual neurons, the bodies remained alive. However, scientists can not say whether the preserved pork brains, placed in the "aquarium", signs of consciousness. The absence of electrical activity, a proven standard method using an electroencephalogram, Sestao convinced that "the brain is either not worried about anything." It is possible that an isolated animal brain in a state of coma, which, in particular, could contribute to washing the components of its solution.

Details of the authors do not disclose the experiment - they are preparing a publication in a scientific journal. Nevertheless, even in the poor parts Sestao report it aroused great interest and a lot of speculation about the further development of technology. Apparently, the preservation of the brain is not technically much more difficult than any other organ preservation for transplantation, such as heart or kidney.

This means that, theoretically, can be stored in a more or less natural state and the human brain.

Isolated brains could be a good model, for example, for the study of drugs: because the existing regulatory restrictions apply to human beings, and not on the individual organs. However, from an ethical point of view, this raises a lot of questions. Even the issue of brain death remains a "gray zone" for researchers - despite the existence of formal medical criteria, there are a number of similar states from which a return to normal life more available. What can we say about the situation, when we say that the brain is still alive. What if isolated from the body the brain continues to be kept in itself all or some of the signs of identity? Then it is possible to imagine the situation described earlier in this article.

Where consciousness lies

Despite the fact that up to 80-ies of XX century existed among scientists advocates of the theory of dualism that separates the soul from the body, in our time, even philosophers, devoted to the study of the psyche, we agree that all that we call consciousness is generated by the material brain (history of the issue can be read in more detail, for example, in this chapterWhere is consciousness: the background and research perspectives from the book by Nobel laureate Eric Kandel "In Search of Memory").

Moreover, with today's techniques, such as functional magnetic resonance imaging, scientists can see to what kind of areas of the brain are activated during the execution of specific mental exercises. Nevertheless, the concept of consciousness as a whole is too ephemeral, and scientists still have not agreed whether it is a set of processes occurring in the brain, or it is encoded meet certain neural correlates.

It tells in his book, Kandel, in patients with surgically separated hemispheres of the brain consciousness, as it were split into two, each of which receives an independent view of the world.

These and similar cases of neurosurgical practice indicate at least the fact that the existence of consciousness of brain integrity as a symmetrical structure is not required. Some scholars, including the discoverer of the structure of DNA, Francis Crick, who at the end of life became interested in neuroscience, it is believed that the presence of consciousness is determined by the specific structures in the brain.

Maybe it's certain neural chain, and can be the case in support of brain cells - astrocytesThat a person has, compared with other animals, it is quite specialized. Anyway, before the modeling of individual human brain structures in vitro ( "In vitro"), or even in vivo (As part of animal brain) scientists have already reached.

Wake up in the bioreactor

It is not known how soon it comes to experiments on whole brains extracted from the human body - first specialists in neuroscience and ethics must agree on the rules of the game. Nevertheless, in laboratories in Petri dishes and bioreactors are already being grownThe rise of three-dimensional human brain cultures "Mini-brain" that mimic the structure of "big" the human brain or a specific department.

During embryonic development of its organs are formed according to certain stages of certain genes embedded in the program according to the principle of self-organization. Is no exception and the nervous system. The researchers found that if a culture of stem cells using certain substances to induce differentiation into nerve cells tissue, this leads to spontaneous rearrangements in cell culture, similar to those that occur during neural tube morphogenesis embryo.

"Default" induced in this way stem cells differentiate to end up in the cortex neurons brain, but by adding external signaling molecules in a petri dish can be prepared, for example, cells midbrain, striatum or spinal cord. It turned out that in the cup can be grownAn intrinsic mechanism of corticogenesis from embryonic stem cells this bark, as well as in the brain, consisting of several layers of neurons and astrocytes containing auxiliaries.

It is clear that the two-dimensional cultures are highly simplified model. The principle of self-organization of the nervous tissue has helped scientists to quickly jump to three-dimensional structures called organelles spheroids and cerebral. On the process of organization of the tissue can be affected by changes in the initial conditions, such as the initial density of the culture and the heterogeneity of the cells, and exogenous factors. Modulating the activity of certain signaling pathways, you can even achieve formation of organelle advanced structures such as the optic cup with retinal epithelium, responsiveCell diversity and network dynamics in photosensitive human brain organoids to light.

Using a special processing vessel and growth factors allowed scientists receive directionallyModeling human cortical development in vitro using induced pluripotent stem cells human cerebral organoid corresponding forebrain (hemispheres) bark, the development of which, according to the expression of genes and markers corresponds to the first trimester fetal development.

A scientists from Stanford led Serghiou Pask (Sergiu Pasca) developedFunctional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture way to grow lumps that simulate the forebrain directly in the Petri dish. The size of such "brains" of about 4 millimeters, but after 9-10 months of ripening cortical neurons and astrocytes correspond in this structureHuman Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells postnatal development level, ie the level of development of the baby immediately after birth.

Importantly, the stem cells to grow these structures can be taken at specific individuals, such as patients with genetically determined diseases of the nervous system. A genetic engineering success suggest that scientists will soon be able to observe in vitro the development of the Neanderthal brain or denisovtsa.

In 2013, researchers from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences published a paperCerebral organoids model human brain development and microcephalyDescribing the cultivation in a bioreactor of the two types of stem cells, "the brain in miniature", imitating the structure of the human brain as a whole.

Organelle different zones correspond to different parts of the brain: the back, middle and front and "forebrain" even showed a further differentiation into shares ( "Hemisphere"). What is important, in this mini-brain, the amount of which is also no more than a few millimeters, the researchers observed signs of activity, particularly fluctuations in calcium concentration within neurons, which are indicative of their excitation (for details of this experiment read can here).

The goal of scientists has been not only to reproduce the evolution of the brain in vitroBut also to study the molecular processes that lead to microcephaly - developmental abnormalities, which occur in particular during the infection of embryo Zika virus. For this work the authors raised the same mini-brain of the patient's cells.

Despite the impressive results, the researchers were confident that such organelles are unable to realize anything. Firstly, in this brain contains about 80 billion neurons, and their organelles grown by orders of magnitude smaller. Thus, the mini-brain simply not physically able to fully perform the functions of the brain.

Secondly, due to the nature of "in vitro" some of its structures were located pretty chaotic and irregular shaped, non-physiological connections with each other. If the mini-brain something and thought it was clearly something unusual to us.

In order to solve the problem of interaction between departments, neuroscientists have proposed to model brain on a new level, which was named "assembloidy". For their formation first grown separately organelles corresponding to separate portions of the brain, and then they are fused.

This approach, scientists have usedAssembly of functionally integrated human forebrain spheroids to study how the crust built the so-called interneurons, which appear after the formation of the bulk of neurons by migration from neighboring forebrain. Assembloidy derived from two types of nerve tissue, allowed to examine violations of interneuron migration in patients with epilepsy and autism.

Wake up in someone else's body

Even with all the improvements possible "brain in vitro" severely limited by three fundamental conditions. Firstly, they do not have a vascular system that allows delivery of oxygen and nutrients to the internal structures. For this reason, the size of the mini-brains are limited to the diffusion of molecules through the tissue. Secondly, they have no immune system, provided by microglial cells: normal, these cells migrate into the central nervous system from the outside. Third, in structure, increasing in the solution, there is no specific microenvironment provided by the body, which limits the number of signaling molecules entering it. The solution to these problems would be to create a chimeric animal model the brain.

In recent workAn in vivo model of functional and vascularized human brain organoids American scientists from the Salk Institute led by Fred Gage (Fred Gage) it describes the integration of the human cerebral organelle (ie mini-brain) in the mouse brain. In order to do this, the researchers first built into the DNA of the stem cell gene green fluorescent protein to the fate of the developing nervous tissue could be observed with a microscope. From these cells were grown for 40 days organelles that after implanted into the cavity in the retrosplenial cortex immunodeficient mouse. After three months, 80 percent of the animals caught on the implant.

Chimeric mice brains were analyzed for eight months. It was found that organelles, which can be easily distinguished by the glow of a fluorescent protein, successfully integrated, formed an extensive vasculature, the axons grew and formed synapses with nerve processes master's brain. In addition, from the host into the implant moved microglial cells. Finally, the researchers confirmed the functional activity of neurons - they showed electrical activity and calcium fluctuations. Thus, the human "mini-brain" fully became part of the mouse brain.

Surprisingly, the behavior of the experimental mice integration of the human nervous tissue piece is not affected. In the test for spatial learning chimeric mouse brain showed the same results as that of normal mice, and differed even worse memory - the researchers explained this by the fact that they have done for the implantation of a hole in the bark hemispheres.

Nevertheless, the aim of this work was not getting clever mouse with human consciousness and the creation of in vivo model of cerebral organelles person is equipped with a network of vessels and microenvironment for various biomedical applications.

The experiment was a completely different kind of putForebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice Scientists from the Center for Translational neyromeditsiny the University of Rochester in 2013. As previously mentioned, auxiliary marrow cells (astrocytes) Human differ from other animal cells, in particular mice. For this reason, the researchers suggest that astrocytes play an important role in the development and maintenance of the human brain functions. To test how to develop a chimeric mouse with human brain astrocytes, scientists have placed predecessors accessory cells in the brain of mouse embryos.

It turned out that in the chimeric human brain astrocytes work three times faster than the mouse. Moreover, chimeric mice with brain were much smarter than the average in many respects. They think fast, better trained and focused in the maze. Probably chimeric mice did not think like people, but might have been able to feel the next stage of evolution.

Nevertheless, for the study of the human brain rodents far from the ideal model. The fact that the human nervous tissue matures according to some internal molecular clock, and transfer it into another organism does not speed up the process. Given that the mice lived for only two years, and the total formation of the human brain takes a couple of decades, any long-term processes in the format of chimeric brain study impossible. Perhaps the future of neuroscience still beyond human brains in aquariums - to find out how it is unethical, scientists just need to learn to read minds, and modern technology, it seems, will soon allow it do.

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