Everyone's logic of life is the same.
--Wei Wensheng
Research Fellow, School of Life Sciences, Peking University
Doctoral supervisor
There is a cartoon in which the hen says to the duck, "I promise to lay a duck egg." "We certainly know that no matter how strong its own will, this is impossible to achieve. Why? This brings us to the secret of the fertilized egg.
There are 3 fertilized eggs in the image below, what kind of individuals will they grow into? As can be seen from the pictures, they eventually develop into sea urchins, mice and seaweed. When they are single cells, it is difficult to distinguish them from each other in terms of size and shape, or in any other way, but the genetic code that exists inside them determines the life forms they eventually develop.
01
Our code of life
With the completion of the Human Genome Project and the development of high-throughput sequencing technology, people's ability to read large amounts of sequence information has been rapidly improved. The improvement of the ability to "read" has further stimulated the need to rewrite the genetic sequence information in organisms, and the rapid development of gene editing technology in recent years has greatly improved the ability to "write".
Gene editing is a special kind of biotechnology that allows researchers to artificially edit genome sequences or gene transcriptions to alter the gene of interest and regulate the sequence, expression, or function of elements.
This revolutionary technology has shocked various research fields in the life sciences as soon as it is introduced, and it will have a broad and far-reaching impact on human health, disease treatment, new drug research and development, species improvement, and basic research in life sciences for a long time to come, and gene editing technology is also the next generation of core biotechnology with the most fierce competition in the world.
The factors that determine the variety of life forms after the development of a fertilized egg are complex, but the logic behind going back to the single-cell level is very similar.
The reason is actually very simple, the composition of human life code is based on a set of completely consistent logic, that is, everyone's life logic is the same - for example, we all know that there are 46 chromosomes in human cells, and the specific code is A-T, C-G, and then combined by their 4 permutations. Although as genes, RNA proteins are the carriers of the most important functions, so that the forms of life present a colorful appearance, the underlying logic behind them is the permutation and combination of A-T and C-G.
This is why mutations in any gene, even very small mutations, can lead to various genetic diseases, and even affect people's external manifestations such as height, fat and thinness.
We usually think that the combination of A-T and C-G can be changed in several ways, such as substitution, insertion, and deletion. Mutations in any gene, even very small mutations, can lead to various genetic diseases, and even affect people's external manifestations such as height, fat and thinness.
Here is a simple example, but in fact, whether it is Alzheimer's disease or premature brain failure, the logic behind all diseases can be very simple at the molecular level. This is also the reason why human beings are obsessed with the interpretation of genome sequences, and it is also fundamental to our study of the code of life.
To make an analogy with these sequences, the life code is quaternary, A-T, C-G, very simple. In the IT field, behind all the information expressed by the code, its logical basis is binary, whether it is the views of the Internet giants, or people's daily chat records, behind it is the sequence of 0101, and the high-level language used by humans, although it is detached from 01, is essentially just a combination of simple elements.
So on the surface, 01 is very simple, but the complexity and richness of the information that can be carried through its permutation and combination are often beyond our imagination. Although A-T and C-G are only quaternary, they carry a lot of information, and it is for this reason that life is very rich.
02
The three actions of gene editing
Life is so complex that in some ways we even feel that it can never be surpassed, and the reason why it is so is because human beings have new ideas about life.
We have three actions for sequences.
The first action is "read"
We need to know how the sequences of genes are arranged and what they look like. To know this, the idea is very simple, that is, sequencing. From the initial sequencing, in nearly 20 years, we've measured the entire human genome, and only a little bit remains. If you print it all out and publish it in Nature and Science at the same time, you will inevitably bind a thick book.
If we spend a few hundred million dollars and measure the rest, will we be able to know all the information and secrets of life? not necessarily. But sequencing can pave the way for us to understand the function of genes. Relatively speaking, "reading" is the simplest.
The second action is compositing, also called "writing."
Now that we know what the sequence looks like, what the arrangement of a gene sequence looks like, and what mutations will form and cause what kind of problems, is it possible to intervene, synthesize, or assemble artificially?
In fact, synthesis has always existed in our bodies. A cell divides into two cells, it is already "reading", it is already "writing", and it is "writing" very precisely. Even, from one generation to the next, genes are "writing" the action — your genes come from your parents, and your parents each provide half of the genetic information, and together they form your genes.
So we've been doing "writing" unconsciously for a long time, and we're doing it every day. But we are now talking more about artificial "writing", and the length that chemical synthesis can "write" is obviously much smaller than the length that our own natural mechanism can achieve—in the case of the "writing" operation of one cell dividing into another cell, no company can do it even if it costs more money.
Therefore, in the action of "writing", the difficulty of research has increased.
The third action is editing
It is not to simply "read" or simply "write", but to "change". "Writing" is relatively simple, you can follow people's knowledge, arrange the sequence according to people's wishes, and then synthesize.
And "editing" requires real modification, which is extremely challenging - this shows that we can change some cells or some codes of a certain cell at the individual cellular level, so why it is the most difficult is because in this process, not all actions can be called "editing". And in terms of compliance, the recognition of this technology is also a difficult issue.
Usually when we talk about gene editing, we will talk about two keywords: the first is localization, because A-T and C-G look exactly the same, but the arrangement and combination are different, so how to accurately locate the place where you want to "write" and "edit" is the biggest problem.
In contrast, the second keyword, "editing," is not a challenge because it's your action itself. There are many ways to "edit", which is done by enzymes or other substances that perform the action. Accomplishing such a thing in the entire genome is what we call "gene editing."
Why the emphasis on gene editing? Because the gene pool is large, in the ocean of genes, it is a very big challenge to find exactly where to edit.
The entire scientific community has a long-standing vision of gene editing, but this article discusses more complex and advanced content, that is, in the so-called higher intelligence body, how to do precise fixed-point knocking or modification according to their own wishes.
You may have heard of the gene therapy method CRISPR, in fact, it is just a latest research result, and earlier there are various gene therapy methods such as humming endomclease, but it is CRISPR that has really entered thousands of households.
Whether it's using proteins to identify DNA sequences, or CRISPR gene therapy using RNA to identify DNA, it all comes down to the recognition, but the angles used are different.
Why do we want to be accurately positioned? It's because we want to do editing. Without targeting, you can't edit and you can't determine what you should edit. The reason why we want to do the job of editing is that we want to make some precise changes to the world according to our own wishes.
Among life sciences researchers, each person does a very different amount of research every day, but most of the experiments work on the same principle and expand on several problem levels:
What is the use of genes? What problems did the study find? What is the molecular logic behind genes?
In fact, all researchers have always wanted to establish a causal relationship - only by knowing the antecedents and consequences of genes can we improve the treatment of diseases, increase food production, and make livestock lean. Therefore, the study of life sciences is, to some extent, the most "utilitarian".
Genetic science studies include C. elegans, Fruit flies, and more advanced organisms such as mice, zebrafish, monkeys, etc., so why study these organisms? The reason is that scientists can use them to conduct genetic studies — existing technology has been able to support us to cleanly edit some of their genes and then build better causal models. The study of these creatures and models is ultimately also aimed at studying humans themselves.
If we want to achieve gene editing, then we not only need the technology itself, but also need to master the relevant knowledge of bioinformatics. If we can establish causal relationships between genes, we can quickly find answers to many key questions, such as: What can gene editing do in addition to high throughput?
In a sense, gene editing technology can drive many key breakthroughs. For example, in agricultural production, gene-editing technology can make mushrooms turn yellow. For example, we all know that after an apple is bitten, the rest of the apple will oxidize, and we can intervene through gene editing to prevent it from turning yellow, brown, or black. Gene editing technology can also help breed lean livestock.
We may even "resurrect" an extinct mammoth one day in the future.
(Note: The above content is excerpted from.)
"Good Questions That Matter More Than the Answer")
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Those good questions that are more important than the answer: 14 understandings about the future ¥19.9 Purchase
Every future requires a real tipping point. The tipping point of the future is such a "question of thought".
"Those Good Questions That Are More Important Than the Answers" will take you to start a journey of exploration for thinkers with 14 big questions, and 14 top domestic scientists, thinkers, and trend experts such as Wang Xiaofan, Zhou Tao, Song Jiqiang, and Hong Bo will walk into the fields of artificial intelligence, gene editing, brain-computer excuses, cognitive science, etc., to jointly explore the boundaries of thought and visit the 14 possibilities of the future. As for the future, although we cannot predict the answer, we can see the beginning of its emergence.