Synthetic Biology: Playing God
Artificial organisms
Ivan Yamshchikov, Habr
For links, see the original article.
Xenomorphs exist. Scientists create xenomorphs. Scientists create xenomorphs for security reasons. I'm shocked myself. Read more about this (and this, by the way, is officially called xenobiology) and about many other things that modern biologists do. Not all of you about COVID-19 to read!
We talked to Masha Shutova from the venture fund 4biocapital, Inna Sucher 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 for an amateur. I immediately remember glowing green mice or a startup that creates fluorescent indoor plants. Anyone who hears about glowing cacti, mice and pigs for the first time in their life immediately begins to torment the question: "Why are scientists doing this?"
One of the clearest examples of the benefits of this kind of research is a beautiful discovery that has shed light (in every sense of the word) on the detection and treatment of rectal cancer. Scientists placed a genetic construct in the intestinal cells, which consisted of four genes sequentially connected to each other, glowing in different colors. Then these genes were mixed in a random sequence and at the output we had an infinite number of cells glowing with different colors. Then they were allowed to grow up, and their "children" inherited the color corresponding to them. It turned out to be a very beautiful picture that shows where the "parents" are cells, and where the "children" are cells. With this method, it is possible to show from which cells cancer occurs with a high probability.
Speaking of green mice, there is one interesting fact. Now there are a lot of colors with which you can "highlight" proteins, but one of the first ones is green squirrels from jellyfish. The idea to use them for such "illumination" was patented in Russia, so they can be considered our national pride.
In 2006, glowing green piglets were bred at the National Taiwan University by inserting the gene of these proteins into the DNA chain of the embryo and implanting it into the uterus of a female pig. At that time, green pigs already existed, but they had only partial fluorescence. The animals obtained after an experiment led by Professor Wu Shin-ji became the only pigs in the world whose hearts and internal organs were green. As in the first case, these experiments are regarded by scientists as an opportunity to visually observe the development of tissues during stem cell transplantation.
Glowing pigs on the background of an ordinary piglet.
The ability to visually track what happens to cells of a certain type is still actively used by researchers who study regeneration. For example, a scientist saws off the fins of some unfortunate fish, and then watches how these fins grow back. Fluorescent proteins are very actively used for such studies. The genome of the fish is modified so that the glowing protein allows you to track how the distribution of cells of a certain type occurs along the restored fin.
It is also possible to make biosensors based on these luminous proteins: put 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 is research that is trying to make a biosensor for detecting the decay products of explosives. So, for example, you can detect mines that have not yet been cleared.
In the beginning there was a word, and the word was made of nucleotides
Let's move from artificial organisms that we can 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: it is possible not only to replace some cells that the body lacks, but also to 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 none of them is coming to its logical conclusion. However, ideas in the spirit of "let's make cells that will release insulin in response to glucose, and thus help people with type I diabetes" sound regularly.
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 institute, respectively, Craig Venter. For the last 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 does not have very many genes, about a thousand. For comparison: E. coli has almost five thousand. So they took one type of mycoplasma, removed DNA from it and placed there an artificially synthesized chromosome of another type of mycoplasma. Thus, they showed that one mycoplasma can be made into another. It was their number one synthetic organism.
Colonies of the number one organism.
This resulting number one synthetic organism still somehow had too many genes. So the researchers decided to remove all unnecessary. At first they decided that they would sit down now and just figure out what is "vital" and what can be thrown away. They tried to be in the role of a reasonable creator of life. They tried and 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 alive 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 brute force.
Scheme of experiments conducted at the Venter Institute.
Venter and his friends decided to get an organism with a minimal set of genes by brute force. They took these nine hundred genes of their organism number one, began to assemble them in small bundles, shove them into bacteria, and see without which genes the bacteria die. After some operations, after testing hundreds of combinations, they were able to create an organism that had about four hundred genes. It was indeed a living, dividing, colony-forming organism with fewer genes than in any natural organism. Although it should be understood here that this 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.
This resulting minimal organism was called organism number three for convenience, because organism number two was some kind of intermediate stage. In fact, the natural environment or "nature" is a brute force test, which boils down to the fact that the dying die, and the survivors divide and multiply. So the most reliable way of experimenting with synthetic organisms now boils down to the fact that a scientist feeds nature something, gives her 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 such adeno-associated viruses that are very actively used now to deliver genetic therapy. There are quite a lot of adenoassociated viruses in nature, but one of the properties that is important for therapy is where they get into the human body. There are viruses that "get stuck" in the liver, there are those that can pass the blood-brain barrier and get into 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.
The visible is temporary, and the invisible is eternal
On the one hand, the very realization that we can now easily synthesize the genome of almost any microorganism from scratch should be somewhat frightening. 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, we can not be in a hurry: the main thing is to freeze a sufficient amount of DNA.
On the other hand, synthetic biology opens up new possibilities in terms of restoring extinct species. For example, George Church and his group are trying to make a new mammoth out of an elephant by mutating the corresponding sections of DNA. A Korean scientist with an extremely controversial reputation, Hwang Woo-seok, worked together with scientists from Yakutia and tried to recreate a mammoth directly from the remains of DNA. There's even a documentary about it. There are projects all over the planet to restore 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 already at last"!
A frame from the Genesis 2.0 documentary.
Against the background of the development of the capabilities of modern biology, the struggle for the preservation of species is also being transformed. There is a whole direction (conservation biology) in which scientists are fighting to ensure that endangered species have a genetic backup. There are a number of genome sequencing projects for species that are on the verge of extinction and are about to leave our planet.
In his image and likeness
There is a standard set of ribonucleotides and deoxyribonucleotides that encodes all living things that exist in nature. However, it is absolutely not necessary to limit yourself to them. If scientists use an alternative set of nucleotides and create an artificial organism out of it, then this thing can't exactly turn out in any natural way. This area of research is called xenobiology.
"After four billion years, a new tree of xenobiology blooms in Eden."
It is important to understand that this is not just an idle interest. Xenobiology has several important and very understandable applications. 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 susceptible to natural viruses. On the other hand, there is no danger 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 underway in this direction, and there are no insurmountable restrictions here. 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 all are occupied, and each combination means something in a living cell. If we add a couple more letters to these four letters, then the genetic code expands in a remarkable way. We get a lot of new codons that can allow, for example, to add all sorts of unusual amino acids to proteins. However, to add these additional nucleotides, it is necessary not just to teach the bacterium to synthesize these nucleotides, and insert all this into DNA. We also need to add protein synthesis machinery that will recognize these codons, and make many other changes. While scientists are just 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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