This articleFrom WeChat official account:Gezhi Lundao Forum (ID: SELFtalks) author: (Doctor of Engineering, Institute of Genomics, Chinese Academy of cancer genome) Chen Ke, original title: “ This geeky face is composed of 1×10^14 cells | Chen Ke”,The title picture comes from: Visual China
“The book of life has been opened, and personalized cuts and personalized treatments are made for each person’s genetic background and protein background. This is precision medicine. To put it vividly, it is where it is broken.”
Chen Ke Chinese Academy of Sciences Doctor of Cancer Genomics, Institute of Genomics
Hello everyone, I’m Ke Chen, from the Beijing Institute of Genomics, Chinese Academy of Sciences. The topic I share with you today is the genome of life.
When I was young, people often said, “Chen Ke, you look so like your father”; some people also say, “Chen Ke, you look more like your mother”.
Why is this happening? Anyone who has studied biology knows that half of our DNA, or bases, comes from our father and half from our mother.
There is no doubt that our features are the combination of them.
In fact, not only in terms of appearance, but our height, fatness and thinness, and whether we are susceptible to certain diseases are all closely related to our genetic background.
This is a fascinating photo. Most people are familiar with him. Yes, he is Beckham.
In terms of genomics, it is composed of 1×10^14 cells. Each cell is composed of cell membrane, cytoplasm and nucleus from outside to inside.
The nucleus, as its name implies, is the core and the most important component of the cell. Cells are the basic unit that constitutes every organism in the world of life.
What is the state of the nucleus further down? It is the DNA double helix structure discovered by humans in 1953. Observe from big to small, from cell nucleus, chromosome, to DNA.
DNA is the most basic unit, we call it base, there are four types of A, T, G, and C. In other words, we are made up of these four structures of DNA.
3.2×10^9 base pairs, this is the number of our human genome.
The above is to observe from the macro to the micro, from Beckham to the base DNA. Look at the process in turn?
First is DNA. There are four basic components, namely A, T, G, and C. They form a certain sequence; further on, the functional sequence is called a gene. Protein and RNA are called the genome; the genome constitutes the nucleus, and the nucleus is the main component of the cell; the cells go up to form organs and form systems, such as the respiratory system, blood system, and digestive system; in the end, Beckham is assembled , This is a process from micro to macro.
Where is the magic of this process? You may ask what is gene and what is its role?
There is a so-called “central law” in biology textbooks. From DNA, to RNA, to protein, the ultimate goal of this process is to form protein.
Children’s smiles and flirtations between lovers, I’m here to talk, you’re listening below, all actions are protein performing functions.
DNA is so important that it is called the source code of our lives and supports all our activities. These activities can be traced back to the DNA, so we can find the cause of a certain problem in the DNA.
Human Genome Project
Because of the importance of the genome, human scientists began to unite for research
In the 1990s, to be precise, since 1990, scientists in the field of genetics, led by the United States and the United Kingdom, jointly launched the Human Genome Project. This project is called HGP for short and is composed of scientists from six countries.
At the time, it was planned to sequence a person’s genome in 15 years. Why did it take so long?
Because the size of our genome is 3.2×10^9 sequences, more than 75% of them are not completely different from others. In other words, there are a lot of repetitive sequences. The existence of such repetitive sequences makes it difficult for us to fully understand the process from 1 to 3.2×10^9.
The Human Genome Project started in 1990. In 2000, the President of the United States said that we had completed one of mankind’s greatest plans, and announced the sketches, and by 2003 the detailed drawings were released.
By 2016, this version has been updated to version 38, and the latest update time is December 2013. It is expected that its update will continue, and the update rate may become smaller and smaller, getting closer to the truth.
After the launch of the Human Genome Project, related sequencing industries have also flourished. The direct effect is that we can understand what the genomes of more species look like.
By 2016, the genome sequences of nearly 10,000 species have been determined.
People who don’t do the genome may not know how much similarity does Mr. President and chimpanzee have?
I just guessed that 60%, 70%, 80%, 90% of people have it. In fact, it is 99%.
From a genomics point of view, it is meaningless how different we think we are. The difference between us and the apes is actually only 1%.
Moreover, from a larger perspective, the human genome is not the largest, and the number of genes is not the largest; the largest genome and the largest number of genes come from a Japanese plant.
In this table, the usual humble corn has about 50,000 genes; the genetic difference between Chinese and Americans is only 0.1%; 99.99% of the genes for me and you are the same, there is little difference.
However, because the base is 3.2×10^9, after multiplying the base, the difference between 10^4 and 10^5 is obtained.
We often hear that gene mutations are related to certain diseases, such as tumors, diabetes, and cardiovascular and cerebrovascular diseases.
However, please be aware that in many cases, it is just an association, and the association is not causal.
Causality is that the existence of my wife and I led to the birth of my daughter; and the association is not a causal relationship, but an accompanying relationship.
For example, my daughter happened to go to this kindergarten. Her going to this kindergarten is a connection, not cause and effect.
Gene mutations are often an association, not terrible. And just nowMentioned that even if we are 99.99% similar, there is only one out of ten thousand different, but the base is large enough.
The number of genetic mutations we inherited from our parents is about 72 in each generation. This is well-documented, and most of these 72 genetic mutations come from the contributions of fathers.
Some geneticists believe that the power of evolution comes from the father, because it shows more mutations, which is more likely to bring genetic diversity to the offspring, and is more likely to make the offspring unique.
Because genomics is so important, after the Human Genome Project, scientists all over the world did not give up chasing it.
The Human Genome Project at that time had only one research object, but one was too few, and everyone was different.
Therefore, the Thousand Human Genome Project came into being to test the yellow race, black race, and white race. Every race, whether it is Chinese or Japanese, although the difference can be reduced to 100,000 points One, but the number is still very large.
After the introduction of the Thousand Human Genome Project, in future sequence comparisons, HG38 in the Human Genome Project may no longer be compared with (the 38th of the Human Genome Project) Version), but compared to our own, compared to the Chinese population, compared to the genome of a certain sub-species population in the southern Chinese population.
In this way, it is more likely to find what I have mutated. Which disease is more likely to break out? This is the original intention of the Thousand Genome Project.
Later, in order to clearly explain the cancer problem that has been plagued humans, two major organizations around the world, namely the International Cancer Genome Alliance led by Canada and the Cancer Genome Atlas led by the United States, used genomics to sequence a certain category. Tumor.
For example, kidney cancer, they chose more than 500The same type of kidney cancer patients come to sequence their genomes, analyze which genomes have mutations, which mutations are associated with healing, and which drugs target which mutations, which can be used to guide the patient’s subsequent treatment.
The U.S.-led program (TCGA) has ended, and the Canadian-led program (ICGC) is not over yet. But there is no doubt that whether it is white people, black people, or us yellow people, the most important human tumors have basically been sequenced, and a lot of data has been generated.
A U disk is about 10G, 1024 times is 10T, and 1024 times is 10P. The data stored in our research is much higher than this, because the data is generated all the time, which means that we need a larger container to hold it, otherwise we can’t compare and use it well.
This has led to the emergence of biological big data, reaching T and P levels.
Precision medicine application
In terms of application, precision medicine is undoubtedly the best feedback on big data. After spending so much money, scientists from more than a dozen countries have invested in research, and over a dozen years, tens of billions of dollars of investment have produced so much data for us humans. If you don’t use it, wouldn’t it be garbage?
Precision medicine is not only mentioned by the President of the United States in his State of the Union address in 2015 and 2016. Before, in the Chinese Academy of Sciences, there were people who proposed precision medicine very early.
Personalized reduction and personalized treatment are needed for each person’s genetic background and protein background. This is precision medicine. From the point of view, it is the best idea to repair where it is broken.
The application of precision medicine in the field of cancer. The flow chart shown is based on the entire precision medical process of liver cancer.
Preoperative imaging showed a lump. After the imaging results came out, most patients would choose to undergo surgery.
After the operation, a pathological judgment will be made, which level and stage of liver cancer are diagnosed, and the genomics database of the surgical samples will be built; then genomics sequencing will be performed, followed by analysis after sequencing, and then the board of directors(Advisory Committee) Discuss what the patient’s genetic background is, which mutations may be pathogenic, and which are not the main mutations.
There are at least four categories of people on the board of directors: bioinformaticians, geneticists, clinical doctors, and pathologists. After the discussion, we verify the available mutation spectrum and report it to the patient after verification.
For example, for liver cancer, which level of pathology has been analyzed, the state of genomic analysis, and which drugs are available for patients? Such reports are the most direct manifestation of precision medicine.
Precision medicine has been applied in top foreign hospitals for about 5 years, but it has not been fully rolled out, and China has just started. But Chinese people have always been diligent, and it takes one month to complete the process abroad, and we can do it in 10 days in China.
Tell a story. The protagonist is an assistant professor at the University of Washington, doing leukemia research.
Unfortunately, in 2003, he himself got leukemia. Chemotherapy was performed according to the previous method, but his condition relapsed 5 years later. He had his brother’s bone marrow transplanted. The good times did not last long. He relapsed again three years later.
At this time, the progress of cancer genomics was at its peak, and it was found that he had an abnormally high expression of a gene, and targeted drugs could treat this abnormally high expression gene.
It is particularly emphasized here that this targeted drug is actually for the treatment of advanced kidney cancer. In other words, he treated leukemia with drugs for kidney cancer.
What is his current situation? Recent information shows that he is still alive. This is a lucky person. Twelve or three years have passed since the start of treatment to 2016. For leukemia patients, this is a miracle, and it is also very exciting news for the application of tumor genomics.
Another example is related to predicting diabetes. This elder is a professor at Stanford University, doing genetics research. His story was published in Cell in 2012-this is the place where biology researchers dream of publishing articles and can be roughly understood as a top journal.
His story tells that in more than 600 days, he collected his own blood for genomic analysis in 20 time intervals, and found that he was at risk of developing type 2 diabetes. The risk value was about 0.5. At this time, he was a little worried. Up.
We have seen on the Internet that Angelina Jolie had all her breasts removed because her family was at too high a risk of breast and ovarian cancer.
After the professor knew that his blood sugar had risen, he started behavioral intervention, and the blood sugar dropped after that.
For him, precision medicine is a successful case, because it has successfully delayed the progress of diabetes, and it is very likely that his diabetes will be delayed or even not occur.
These are two classic examples: one is cancer and the other is diabetes.
Such a good example, can most of us pay? The answer is yes.
In 2000, the cost of genome sequencing for each person was 2.7 billion U.S. dollars. Today, (2015) has become 10,000 yuan. Time cost and labor cost have plummeted. From 13 years to 13 days, the labor cost can be settled from 3,000 people to three to five people.
Now (2016) 10,000 yuan can be used to test a person’s genome. This cost will drop. The industry’s ultimate goal is one Thousand dollars to test a person’s genome.
Because biological data is so complex and diverse, there are more levels besides DNA, RNA, and protein. With so much data, it is impossible for a doctor to fully remember.
For most people, there is no need to remember, because someone will do it for us.
Commercial organizations represented by IBM have launched a computer doctor platform-Doctor Watson. The biggest feature is to search millions of documents within 15 seconds of access time and provide relatively reasonable treatment plans. Among them, the diagnosis stage, the treatment stage, each plan has references, not in a vacuum.
Some people may worry that when we go to the hospital to see a doctor, the doctor may disappear and be replaced by a computer.
In fact, no matter how you change, a doctor is indispensable, because although the computer does so powerful, the answer is still based on the existing database and has no ability to infer.
Of course, based on the fact that AlphaGO defeated Li Shishi, it can be considered that artificial intelligence has infinite possibilities, but at least for now, computer doctors are only a database for people to search and retrieve, and they do not have the ability to push, calculate, deduct and think logically. Capable real people.
So everyone imagined that I went to the hospital and talked to a machine, and he told me where to go to check, take blood, do massage, and perform surgery. It will take a long time, but it cannot be said that it is absolutely impossible.
Precision medical promotion barriers
Since precision medicine is such a good thing, why is it not widely promoted?
In addition to the cost reasons mentioned earlier, as far as our domestic situation is concerned, there are several barriers that need to be broken down further.
The first aspect is that precision medicine is a new thing, so there are still many things that have not been straightened out at the regulatory level, and there are no real regulations to tell us what to do.
The second aspect is that for patients or their families, they really want to get involved, but they don’t know how to get relevant information.
I bought the sequencer, and the hospital will not analyze it after the sequencing results come out. If you rely on a third-party agency, the problem will come again. Third-party agencies are mixed and difficult to win.
Even we often see peddling behaviors in the streets and alleys, testing children’s genes to see if they are suitable for scientists, artists, or teachers in the future.
So far, because our database is not strong enough, these are all false advertisements.
There is another aspect. At present, no third-party organization canThe four types of certification experts are gathered together, because the industry is still in its infancy and there are still many areas that need to be improved, but the dawn has already appeared, and the future is very likely.
The main cause of death has been changing since human history.
More than 100 years ago, most of our ancestors died because of hunger and war;
In the first half of the last century, infectious diseases, Spanish flu, black death… left huge traumas to human beings. Today, we still have lingering fears when we read textbooks;
In the second half of the last century, cardiovascular and cerebrovascular diseases and cancer became the main causes of death.
Some scientists predict that when we solve these problems, in the coming future, neurological diseases will become the main cause of our human demise.
Can genomics solve all problems? the answer is negative.
Each person has only one set of genes, but the molecules that are modified, attached to, and attached to the genes are diverse, and there can be hundreds of sets of apparent modifications on genes. This number is still increasing. For example, our hair, face, bones, liver, etc., have the same set of DNA, but have different phenotypes.
To this day, the book of life has been opened, IWe expect it to bring us different applications, and ultimately benefit our human health and seek greater well-being for us humans. Thank you, thank you.
This article is from WeChat official account:Gezhi Lundao Forum (ID: SELFtalks), of: (Dr. Institute of genomics, Chinese Academy of cancer genomics) Chen Ke