Can a brain grown in a laboratory be conscious?

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(ORDO NEWS) — According to some neuroscientists, human-made organelles are capable of experiencing “endless horror” at the realization that they exist separately from the body. And this needs to be stopped urgently.

Some experiments have prompted scientists to ask the following questions: can groups of cells be intelligent? What about the brain separated from the body? And if yes, how will scientists know about it?

In the laboratory of Alysson Muotri, hundreds of miniature human brains, like sesame fruits, float in Petri dishes, sparking, showing electrical activity.

These tiny structures, called brain organelles, are grown from human stem cells; seeing them in laboratories studying the properties of the brain is a common thing. The neuroscientist Alisson Muotri of the University of California, San Diego (UCSD) has found some unusual ways to investigate this problem. He connected organelles to walking robots, modified their genomes with Neanderthal genes, launched them into space aboard the International Space Station, and began using them as models to develop more human-like artificial intelligence systems. Like many other scientists, Muotri has now temporarily switched to studying COVID-19 using brain organelles; he would like to test exactly how drugs are fighting the SARS-CoV-2 coronavirus.

But one experiment attracted more attention than others. In August 2019, a research team led by Muotri published an article in Cell Stem Cell, reporting on the creation of organelles in the human brain that are the source of coordinated waves of activity similar to those seen in premature babies. These waves appeared for several months before the team of scientists stopped their experiment.

This type of coordinated electrical activity in the brain is one of the properties that indicate the presence of consciousness. This discovery prompted ethicists, along with other scientists, to ask many moral and fundamental questions about whether we even have the right to grow organelles that have reached such a high stage of development? Are organelles “conscious” subject to some special regime of legal regulation and some special rights that do not apply to other cellular structures? Is it possible at all, so to speak, to construct consciousness?

The idea of ​​an autonomously existing and self-aware brain has been addressed more than once by many neuroscientists and bioethics. For example, just a few months ago, scientists at Yale University in New Haven, Connecticut announced that they had succeeded, at least in part, in reviving the brains of pigs that had been killed several hours before the experiment. By removing the brain from the pig’s skull and treating it with a special chemical composition, the scientists restored the cellular functions of neurons and their ability to transmit electrical signals.

Other experiments have also been conducted, such as attempting to implant human neurons into the brains of mice. However, such experiments continue to raise questions for us, with some scientists, along with ethicists, argue that such experiments should not be allowed.

These studies have paved the way for a debate between those who oppose all attempts to construct consciousness and those who believe that complex organelles are a means of studying serious human diseases. Alisson Muotri and many other neuroscientists believe that with the help of human brain organelles, scientists will be able to better understand the mechanism of pathological changes in the human body (for example, autism and schizophrenia) that cannot be studied in detail in mouse models. Muotri argues that in order to achieve this goal, he and other scientists may need to specifically create intelligent structures.

Scientists are now calling for a set of guidelines, similar to those used in animal research, for the humane use of brain organelles and other experiments that could lead to the construction of consciousness. In June, the US National Academies of Sciences, Engineering, and Medicine (NASEM) launched scientific research to identify potential legal and ethical problems associated with brain organoids and chimeras in humans and animals. … transl.].

Concerns about growing the brain in the laboratory have also highlighted the following “blind spot”: there is no consensus among neuroscientists about how the concept of “consciousness” should be understood and how it should be measured. And since there is no working definition, ethicists fear that the experiment cannot be stopped before the no-go line is crossed.

The abundance of behavioral experiments may pose a difficult question for us: “If scientists suddenly notice that an organoid suddenly regained consciousness, then they may have to hurry up and come up with a hypothesis that would explain how this all could have happened,” says cognitive neuroscientist Anil Seth from the University of Sussex, near Brighton, UK. But if, according to some hypothesis created by scientists, Anil Set continues, one of the organelles will be considered endowed with consciousness, and the other will not, then in the case of such a dual interpretation of “consciousness” we no longer have the right to assert that we have really created a certain an entity with consciousness. “All our confidence largely depends on which hypothesis we believe in. As they say, the circle is complete,” adds Seth.

States of sapience

It can be much easier to create a system of organelles with intelligence than to define it precisely. Scientists and doctors give different definitions of the concept of “consciousness” – that is, depending on specific goals; however, these definitions are difficult to combine into a single clear and workable definition that can be applied to a brain grown in a laboratory.

Usually, doctors talk about the presence of some degree of consciousness in patients who are in a vegetative state, based on the following signs: whether he blinks, whether there is a reaction in response to local pain or other stimuli. For example, using electroencephalogram (EEG) readings, scientists have also learned how to detect the brain’s response to an electrical impulse. If the brain is conscious, then it exhibits much more complex and unpredictable electrical activity, which cannot be said about the unconscious brain – its EEG is characterized by simplicity and regularity.

But such tests for the presence of consciousness may not give us an adequate answer to the question of whether a person has consciousness or not. In the course of studying the brains of people in a coma or a vegetative state, scientists have shown that the brain of a person who does not respond to external stimuli is able to exhibit some activity that somewhat resembles consciousness (for example, if a person is asked to think about walking, then in the motor zone activity is recorded in the cerebral cortex).

In any case, standard medical tests designed to determine whether humans are conscious are difficult to apply to brain cells grown in a laboratory or to animal brains that are detached from the body. When Allison Moori hypothesized that the activity of organelles grown in a test tube was as complex as that of premature babies, scientists did not know how to react to it all.

According to some experts, the brain activity of a premature baby is not complex enough to be classified as conscious. If we talk about organelles, then they can neither blink, nor react in any other way in response to a painful stimulus; that’s why they won’t pass the clinical test for consciousness.

On the contrary, it is much more likely that the intact brain of a slaughtered pig has all the necessary structures that indicate the presence of consciousness in it, as well as neural connections formed as a result of the memories and experiences that animals experienced during life. “Just imagine a brain filled with all these structures! The brain is hardly empty. I don’t know what they’ve learned about thinking, but it certainly cannot be reduced to zero, ”says philosopher and neuroethics scholar Jeantine Lunshof of Harvard University in Cambridge, Massachusetts. When we try to look for some semblance of life in a dead brain, as the above-mentioned team of scientists from Yale University did, then here we may be later we will also encounter attempts to regain consciousness at least in some form; however, scientists – with the help of special chemicals that block brain activity – have made great efforts to prevent these attempts to prevent.

Scientists agree that they need to take seriously the promise of this research. In October 2019, UCSD hosted a conference attended by about a dozen neuroscientists and philosophers, as well as students and members of the public. The aim of the conference is to develop and publish ethical principles on the basis of which such experiments on organelles should be carried out in the future. But publication of the article was delayed for several months, in part due to the fact that some authors could not agree on the main issues related to the concept of “consciousness”.

Extremely difficult

Almost all scientists and specialists studying ethics agree that so far no one has succeeded, so to speak, to construct consciousness in the laboratory. But they ask themselves where to pay close attention and which theories of consciousness might be most relevant. For example, according to the so-called theory of integrated information, consciousness appears as a result of an increase in the number of interactions between neural networks in the brain. The more neurons interact with each other, the higher the degree of consciousness (it is denoted by the Greek letter “F”). If “F” is greater than zero, then it is considered that this organism has consciousness.

According to this theory, most animals reach this level. Christof Koch, president of the Allen Institute for Brain Research in Seattle, Washington, doubts that any existing organelle can reach this threshold, however, Koch admits that a more advanced organelle may well do.

Other competing theories of consciousness suggest sensory input or some feature of coordinated electrical activity in many areas of the brain. For example, an approach known as global workspace theory argues that the prefrontal cortex functions like a computer, processing sensory signals and interpreting them in order to shape a sense of life. Since organelles do not have a prefrontal cortex and cannot receive information from the outside, therefore, they are not able to have consciousness. “Neurons can communicate with each other in the absence of input and output signals, but this does not necessarily mean that we have received something that resembles human thinking,”

However, connecting organelles to the organs of living organisms can be quite a simple task. In 2019, Madeline Lancaster’s team connected a human brain organoid to the spine and back muscles of a mouse. After the nerves of a human organelle connected to the spine, the dorsal muscles began to contract spontaneously.

Most organelles grown in a laboratory reproduce only one part of the brain – the cerebral cortex. But if they are allowed to grow for a sufficiently long time in a special nutrient medium, then human stem cells begin to spontaneously recreate many other parts of the brain, which then begin to coordinate their electrical activity. A 2017 article reports that molecular biologist Paola Arlotta at Harvard University has succeeded in transforming stem cells into brain organoids, made up of many different cell types, including light-sensitive cells similar to those found in the retina. … Under the influence of light, the neurons of the organelles began to be activated. But, according to Arlotta, the fact that the cells in the experiment were activated, does not mean at all that organelles have acquired the ability to see the world around them and process visual information. Here we can only say that organelles are capable of forming the necessary chains.

Arlotta and Lancaster believe that the organelles they have grown are too primitive to be conscious, because they lack the anatomical structures necessary to obtain complex EEG shapes. However, Lancaster admits that when it comes to more advanced organelles, it all depends on the definition. “If you believe that a fly is conscious, then it is likely that this can be attributed to an organoid,” says Madeline Lancaster.

However, according to Lancaster and most other scientists, an object resembling a pig’s brain that has been revived in a laboratory is much more likely to be conscious than an organoid. A pig brain research team led by neuroscientist Nenad Sestan has tried to find new ways to animate organs, not construct consciousness. Scientists have succeeded in making individual neurons or groups of neurons activated, while the researchers tried to avoid the situation in which the waves produced by the brain would propagate in a wide front. However, as soon as Nenad Sestan team noticed something resembling coordinated EEG activity in one of the laboratory brain samples, the scientists immediately stopped the experiment. Even after the neurologist confirmed

Nenad Sestan also contacted the US National Institutes of Health (NIH) to advise on further steps. The institution’s neuroethics team, which included Lunshof and bioethics specialist Insoo Hyun of Case Western Reserve University in Cleveland, Ohio, reviewed the progress of the experiments and agreed that Sestan should continue with brain anesthesia. … But the commission did not engage in the development of some kind of universal regulatory rules and regulations; in addition, the commission usually does not analyze projects involving the use of organelles at all from the point of view of bioethics, since the members of the commission believe that consciousness is not amenable to construction. In addition, the NIH did not define the concept of “consciousness”. “It’s so subtle that everyone insists on their own definition, says Hyun. “And the lack of clear definitions is becoming a big obstacle to scientific discussion.”

Fuzzy definitions

Some people think that it is useless even to try to fix some glimpses of consciousness in the brain studied in the laboratory. “It is impossible to say anything definite about such brain cells – whether they are able to think or perceive the world around them or not. And all due to the fact that we do not understand the nature of consciousness, – believes the neurologist Stephen Lauris from the University of Liege (Belgium), who was the first to use some visualization methods based on measuring consciousness in patients who are in a vegetative state. “We shouldn’t be overconfident.” Further research should be done with great caution, Stephen said.

According to Lauris and other scientists, the perception of the surrounding world by an organoid will probably be very different from the perception of the world by a premature baby, adult or even a pig, they cannot be compared in the full sense of the word. Moreover, the internal structures of an organoid may be too small to be accurately measured at all, and the similarity between the EEG of organelles and the brain of premature babies may be accidental. Other scientists studying brain organelles agree with Lauris that the question of the presence of consciousness in a particular organ may remain open. Many scientists don’t take this topic seriously at all. “I don’t know why we ask this question at all, because organelles are not the human brain,” says neuroscientist Sergiu Pasça of Stanford University in California.

Alisson Muotri wants the organoid systems he has grown to be comparable to the human brain – at least in a way. This is necessary in order to be able to study human diseases and find ways of treatment. Alisson is personally interested in this, since his 14-year-old son suffers from epilepsy and autism. “He’s having a hard time,” Muotri notes sympathetically. Organoids of the brain are a promising area, since they can be used to reproduce the process of forming connections in the brain at the earliest stages of development, because it is clear that it is simply impossible to study these processes in the human embryo. But, according to Alisson Muotri, studying disorders of the human brain without using a fully functioning brain is like, say, studying the pancreas. which does not produce insulin. “To understand all this, I need a model of a brain organoid that would really resemble a human. I may need an organoid that is conscious.”

Alisson Muotri says he doesn’t know how to detect consciousness in an organoid. According to Alisson, with the help of organelles, scientists could even understand the mechanism of the generation of consciousness in the brain. For example, mathematician Gabriel Silva of the University of California, USA is studying the neural activity of organelles obtained by Muotri in order to develop an algorithm that describes the mechanism of consciousness generation. The goal of his research project, which is partially funded by Microsoft, is to create an artificial system that works in the same way as the human mind.

At the moment, there are no rules and regulations in the United States or Europe that would prevent scientists from constructing consciousness. A group of national academies plans to release a report early next year that will review recent research work and decide whether to specifically regulate research in this area. The members of the group plan to consider, for example, questions such as obtaining a person’s consent to grow brain organelles from his body cells, as well as questions about humane research and utilization of organelles. The International Society for the Study of Stem Cells (ISSCR) is also developing guidelines for organelles, but it does not deal with questions of consciousness in living things, because it does not believe that science has come close to this issue.

According to Insoo Hyun, no proposals have yet been submitted to the NIH Commission on Neuroethics regarding the creation of complex, conscious organoids that would require new guidelines to work with. According to Alisson Muotri, Henu does not know anything about anyone trying to intentionally create such organelles, although some rather complicated organoid could, in terms of some definitions, accidentally turn into a conscious organoid.

Nevertheless, Alisson Muotri and other experts argue that they would accept some recommendations with approval, for example: the requirement for scientists to substantiate a certain number of organelles of the human brain taken to study; in addition, scientists should use them only in laboratory research, which cannot be done in any other way, as well as limit the painful effects on the organoid and dispose of them in a humane way.

The presence of such recommendations will help scientists to weigh in advance all the disadvantages and advantages associated with the creation of entities with consciousness. Many scientists emphasize that such experiments have great potential from a scientific point of view. “We do have patients with neurological disorders who are not getting treatment,” says Madeline Lancaster. “If we stopped all this research because of our philosophizing, it would be extremely detrimental to ordinary patients, for whose treatment it is really necessary to use new therapy methods.”

However, new therapies can still be tested in brain organoids derived from mouse stem cells or in conventional animal models. In addition, such experiments will initiate a discussion about the ethics of using human organelles. For example, Insu Hyun would like scientists to tackle the problem of comparing the EEG of mouse brain organoids with the corresponding EEG of the brain of living mice; thanks to this, specialists will finally have the opportunity to judge how adequately human organelles reproduce the human brain.

For his part, Alisson Muotri does not see much difference in the study of human organelles and laboratory mice. “We work with animal models that have consciousness, and there are no difficulties here,” says Alisson. – We need to move forward. And if it turns out that they suddenly have consciousness, then, frankly, I don’t see a big problem in that.”


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