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Game of God: Artificial Organisms

Something like a teaser. Xenomorphs exist. Scientists create xenomorphs. Scientists create xenomorphs for security reasons. I'm shocked myself. Under the cut, more about this (and this, by the way, is officially officially called xenobiology) and much more than what modern biologists do. Not all you need to read about COVID-19!

This is the first part of a text based on a podcast episode about artificial organisms.



Posted by Malcolm Lightbody

This is one of the episodes of my podcast. An article based on the burnout episode can be found here .

We spoke with Masha Shutova from the 4biocapital venture capital fund , Inna Zucher from Oxford, and Sergey Nurk from the National Human Genome Research Institute.

Let there be bioluminescence


In the context of artificial organisms, luminous objects are the first thing that comes to mind to an amateur. I immediately recall the luminous green mice or the startup that creates luminescent indoor plants. Anyone who for the first time in their life hears about luminous cacti, mice and pigs, immediately begins to torment the question: “Why do scientists do this?”


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One of the brightest examples of the benefits of this kind of research is a beautiful discovery that shed light (in all senses of the word) on the detection and treatment of colorectal cancer. Scientists have postedin intestinal cells, a genetic construct that consisted of four genes sequentially connected to each other, glowing in different colors. Further, these genes were mixed in random order and at the exit we had a certain number of cells glowing in different colors. Then they gave them to grow up, and their "children" inherited the corresponding color. The result was a very beautiful picture that shows where the “parents” are cells and where the “children” are cells. Using this method, it is possible to show from which cells cancer occurs with high probability.

Speaking of green mice, there is one interesting fact. Now there are a lot of flowers with which you can "highlight" proteins, but one of the first is green squirrels from jellyfish. The idea to use them for such a "highlight" was patentedin Russia, so they can be considered our national pride.


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In 2006, luminous green piglets were bred at the National University of Taiwan, by introducing a gene of these proteins into the DNA chain of an embryo and implanting it in the uterus of a female pig. At that time, green pigs already existed, but only partial fluorescence was observed in them. Animals obtained after the experiment under the guidance of Professor Wu Shin-ji became the only pigs in the world whose green heart and internal organs were green. As in the first case, these experiments are regarded by scientists as the possibility of visual observation of tissue development during stem cell transplantation.


Glowing pigs on the background of an ordinary pig

The ability to visually monitor what is happening with cells of a certain type is still actively used by researchers who are studying regeneration. For example, a scientist saws off the fins of some unfortunate fish, and then watches how these fins grow back. For such studies, fluorescent proteins are very actively used. The fish’s genome is modified so that the luminous protein allows you to track how the propagation of cells of a certain type occurs on the restored fin.

You can also make biosensors based on these luminous proteins: insert them into the bacterium, and make it begin to express the protein in exchange for a certain external stimulus. A cool example of the application of this technology - researchwho are trying to make a biosensor for detecting decay products of explosives. So, for example, you can detect mines that have not yet cleared.

In the beginning there was a word, and the word was from nucleotides


Let's move from artificial organisms that we see with the naked eye to artificial organisms that cannot be noticed with the naked eye, but which are no less useful. For example, in cell biology and, in particular, in cell therapy of the future, there is a separate direction: you can not only replace some cells that the body lacks, but also make these cells produce something that is important and interesting to us For example, the same insulin. Now there are a lot of studies in this direction, but so far not one of them is reaching its logical conclusion. However, ideas like “let's make cells that release insulin in response to glucose and thus help people with type 1 diabetes” sound regular.

In general, now there is a whole separate line of research related to the creation of artificial microorganisms. There is such a person Craig Venter, he has an institution, respectively, Craig Venter. For the past twenty years, scientists at this institute have been trying to create a bacterium with a minimal set of genes. They took a bacterium called mycoplasma. This is a parasitic bacterium, which initially doesn’t have very many genes, about a thousand. For comparison: E. coli has almost five thousand. So they took one kind of mycoplasma, removed the DNA from it and put the artificially synthesized chromosome of another type of mycoplasma there. Thus, it was shown that one can make another from one mycoplasma. It was their number one synthetic organism . Colonies of that very organism number one



This resulting number one synthetic organism still had somehow too many genes. So the researchers decided to remove all unnecessary. At first they decided that they would sit down and just figure out what was “vital” and what could be thrown away. We tried to be in the role of a rational creator of life. Tried, tried, but they didn’t succeed. Craig Venter was terribly surprised, but admitted that the state of modern science is not progressive enough to just sit down and create something living from scratch. After that, they abandoned the idea of ​​such a “reasonable” creation of life, and went the other way. We decided to get an organism with a minimal set of genes by enumeration. Design of experiments at the Venter Institute



Venter and his comrades decided to get an organism with a minimal set of genes by brute force. They took these nine hundred genes of their body number one, began to assemble them in small bundles, shove them into bacteria, and see what genes bacteria die without. After some operations, having tested hundreds of combinations, they were able to create an organism in which there were about four hundred genes. It was indeed a living, dividing, colonizing organism, in which there are fewer genes than in any natural organism. Although it must be understood here that it is a very simple parasitic bacterium, it does not live freely. An artificial organism with a minimal set of genes, capable of division, aka organism number three



For convenience, this resulting minimal organism was called organism number three, because organism number two was some kind of intermediate stage. In fact, the natural environment or “nature” is a brute force mechanism, which boils down to the fact that the dying - die, and the surviving - divide and multiply. So the most reliable way to experiment with synthetic organisms now comes down to the fact that a scientist feeds nature something, gives it variety, and then she selects what works.

In a similar way they experiment not only with bacteria, but also, for example, with viruses. There are adeno-associated viruses that are very actively used to deliver genetic therapy. There are a lot of adeno-associated viruses in nature, but one of the properties that is important for therapy is where they enter the human body. There are viruses that “get stuck” in the liver, there are those that can pass the blood-brain barrier and enter the brain, and there are those that settle in the lungs. This is an important parameter, because it allows scientists and doctors to make therapy more targeted.

Visible temporarily, and invisible forever


On the one hand, the very realization that we can now easily synthesize the genome of almost any microorganism from scratch should be somewhat scary. For example, the genome of the causative agent of anthrax, in principle, is in the public domain. At the same time, given that we are able to preserve DNA well in its original form for a long time, in principle, restoring the sequence, you can not be in a hurry: the main thing is to freeze enough DNA.

On the other hand, synthetic biology opens up new possibilities for the restoration of extinct species. For example, George Church and his group are trying to make a new mammothfrom an elephant, mutating the corresponding sections of DNA. Hwang Woo Suk, a Korean scientist with an extremely controversial reputation, worked with scientists from Yakutia and tried to recreate a mammoth directly from DNA residues. There’s even a documentary about it . Across the planet, there are projects to restore the Pleistocene megafauna . There is such a Pleistocene park in Russia. Such parks are waiting for the mammoth with open arms, they say: “Give the mammoth at last!” Frame from the documentary Genesis 2.0



Against the backdrop of the development of the capabilities of modern biology, the struggle for the conservation of species is also transforming. A whole direction (conservation biology) has appeared, in which scientists are struggling for a genetic backup to appear in endangered species. There are a number of projects for sequencing the genome sequence for species that are on the verge of extinction and are about to leave our planet.

In his own image


There is a standard set of ribonucleotides and deoxyribonucleotides that encodes all living things in nature. However, it is not necessary to limit yourself to them . If scientists use an alternative set of nucleotides and create an artificial organism from it, then this thing cannot be obtained in any natural way for sure. This line of research is called xenobiology. Source. “In four billion years, a new xenobiology tree is blooming in Eden.”



It is important to understand that this is not just idle interest. Xenobiology has several important and very understandable uses. For example, if we create such a strange organism that uses a different set of nucleotides in its DNA, then this organism, for example, is not exposed to natural viruses. On the other hand, the danger disappears that parts of these artificial organisms can somehow get into other cells living around us. That is, such "xenomorphs" will not be able to negatively affect the environment.

So far, it has not been possible to create such artificial organisms, but experiments are ongoing in this direction, and there are no insurmountable restrictions. There are twenty amino acids in nature, and each amino acid is encoded by a set of three letters. There are only sixty-four combinations, but everyone is busy, and each combination means something in a living cell. If we add a couple more letters to these four letters, then the genetic code is remarkably expanding. We get many new codons that can allow, for example, to add all sorts of unusual amino acids to proteins. True, in order to add these additional nucleotides, one must not only teach the bacterium to synthesize these nucleotides, and insert all this into DNA. It is also necessary to add the machinery of protein synthesis, which will recognize these codons, and make quite a few other changes.So far, scientists are only beginning to work in this direction, but the prospects here seem to be limited only by the imagination of the researcher.

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