Scientific significance of the discovery of DNA double helix structure
Why is the discovery of DNA double helix significant? The DNA double helix chosen by Watson and Crick has just grasped the most critical molecule in the material basis of life science, which has produced such great significance. From this perspective, how to grasp the most important issues is the key to scientific innovation.
Li Zaiping: Why is the discovery of DNA double helix significant? Although a lot of work in science is done at a certain point, the significance of choosing this point is different. The DNA double helix chosen by Watson and Crick has just grasped the most critical molecule in the material basis of life science, which has produced such great significance.
The development in the past 50 years has proved more and more clearly that to study life science, we must know the difference between the living world and the inanimate material world. This difference mainly lies in that the life system has two characteristics, one is heredity and the other is development. Both plants and animals can develop from very simple systems such as seeds or embryos into very complex adults. DNA molecules only "shoulder the heavy responsibility", which not only bears the genetic work, but also bears the developmental work. According to the book "Double Helix" written by Watson, he just wants to know how genes carry information. I think he just grasped the structure of the most important molecule in the field of life science research, so once this breakthrough is achieved, it is of great significance. Then some successive scientific research achievements derived from this, such as the central law, mRNA, genetic code and a lot of other achievements, all won the Nobel Prize (research in this field has produced dozens of Nobel Prize winners). Why? Because they caught the most crucial thing. In an interesting interview, Watson and Crick made DNA famous, not DNA made them famous. Therefore, how to grasp the most important problem is the key to scientific innovation.
Zhao: I agree with Mr. Li Zaiping's evaluation of Watson and Crick's work in discovering the double helix. From the perspective of genetics, in fact, genetics has solved three problems so far: the first thing to be solved is why it is inherited, and what is the similarity between the previous generation and the next generation? This was solved by Mendel and Morgan, and it was transmitted by what Mendel called "genetic factor" at that time, and it was designated as "gene" in 1908. Genes are arranged on chromosomes, and chromosomes can be passed on to the next generation twice. Because there are genes that transmit genetic information, there will be melons and beans. This is the main contribution of Mendel and Morgan, that is, to clarify that genetic information should be transmitted through genes.
Exploring what genes are leads to the second question. Morgan predicted that gene was a chemical entity, an organic molecule, but he didn't know it was DNA at that time. It is clear that the genetic material is DNA, and this second problem is solved. Watson and Crick solved the problem of how DNA transmits genetic information. A gene can transmit genetic information because it is a double chain, and the four bases on this double chain are complementary, so that a mother chain can be divided into two sub-chains, and each sub-chain has the same information as the mother chain. From a genetic point of view, it used to come from hybridization. If a character has changed, it means that the gene has changed, which is seen from the appearance; Knowing that DNA is genetic material, we can isolate DNA, clone genes, change genes in vitro (through expression), and see what changes in their functions (from inside to outside), so that we can directly study the functions of genes, which opens up a new road, not only improves our understanding of life phenomena, but also can be verified through experimental operations. This is a very remarkable thing.
Wu Jiarui: Let me first talk about the significance of the discovery of DNA double helix from a historical perspective. I quite agree with what Mr. Zhao and Mr. Li said just now. The discovery of DNA double helix is actually a pursuit of unity and simplicity, which implies a reductionist idea. That is to say, all systems, even complex systems like life, can be explained by the simplest physical laws, or conversely, even the most complex systems should abide by the simplest laws. It is precisely because of this reductionism that the development of biology follows, because it is basically a laboratory operation, which turns complex phenomena into simple phenomena to explain.
However, the reductionism has also encountered some new challenges today. Although we can simplify (complex life phenomena) to a simple DNA molecule, does understanding the DNA double helix molecule mean revealing life phenomena? To give the simplest example, cancer can't be overcome until now. What does this mean? It means that complex life phenomena cannot be simply explained by reductionism. The function of the genome is actually not the behavior of a single gene, but the result of the action of thousands of genes. In the human genome, only 2% to 2.5% are gene coding sequences, and 80% are other non-coding sequences. So what are these gene-related sequences? The double helix structure of optical DNA cannot be explained. Moreover, there are thousands of genes in these 2%. What is the relationship between these genes? It is difficult to give a complete explanation with the existing knowledge of life science.
The result of the integration and complementarity of biology and physics
In the future, if molecular biology wants to create more glory and truly solve the mystery of the origin of life, it not only depends on the new transformation of biology itself, but also needs the further progress of mathematics, physics and chemistry based on biology, thus promoting the great revolution of biology in the new century.
Shen? I study physics and teach physics, so I can't help but admire and praise from time to time: beautiful, physics! In fact, perhaps the most beautiful is life science, because it reveals the essence and meaning of life. Just like the double helix structure of DNA, it has obvious symmetry and is quite simple, and it becomes very regular through the complementary pairing of bases. No wonder Watson and others realized that "such an elegant and beautiful structure must exist" as soon as they made this model. From the aesthetic point of view, all disciplines are also interlinked; Beautiful things are often not distorted.
In the 1940s and 1950s, many people were exploring the structure of DNA. Why did Watson and Crick get ahead of them? These two people can be regarded as a wonderful complementary match: Watson is a biologist who is keen on studying the molecular structure of life by physical methods, and Crick is a physicist who is keen on exploring the genetic mechanism of life. Fortunately, many scientists have done a lot of effective preliminary work, and they can learn from the experience of others and make full use of existing achievements. Their strength may be that they attach great importance to X-ray technology and its test results, especially Crick, who is quite skilled in this technology; Based on the correct analysis of X-ray diffraction pattern, the spatial structure of DNA can be set flexibly and decisively. The insight into the detection results, coupled with rich imagination, naturally leads others. The most important thing, I think, is "the times make heroes". At that time, the development of biology from experiment to discipline itself had reached the stage of trying to reveal the essence of life at the molecular level. The progress of physics and chemistry, from concepts and principles to methods and experimental means, has prepared enough conditions for in-depth study of living matter. The combination of biology, physics and chemistry is imperative, and molecular biology is about to break ground. Crick and Watson stepped onto the historical stage as two trend leaders.
In recent days, I reread Schrodinger's masterpiece What is Life, and I feel that some of Schrodinger's views have profound meanings. Don't say a specific point of view, just say a general conclusion. He said, "We must discover new physical laws governing living matter", which is just a repetition of the principles of quantum theory. The 50-year development history of molecular biology just proves that the movement and change of biological substances do not violate some basic laws of physics, and when describing the interaction between molecules and intramolecular particles of biological substances, we need to rely on the principle of quantum mechanics and its nonlinear expansion form. In the long run, the in-depth study of life science will inevitably bring new breakthroughs in physics.
In the future, if molecular biology wants to create more brilliant achievements and truly solve the mystery of the origin of life, it not only depends on the new revolution of biology itself, but also needs the further progress of mathematics, physics, chemistry and other disciplines on which biology depends, as well as taking high and new technologies such as computing technology and information technology as research tools, so as to promote the great revolution of biology in the new century. From this grand goal, it should be said that some universities attach importance to the construction of biology departments and it is extremely necessary to strengthen the teaching of basic knowledge of life science for non-biology majors.
Zhao: I think interdisciplinary is very important. The discovery of the double helix is a typical combination of life science and physics. 193 1 year, niels bohr, the originator of quantum science, wrote an article "Light and Life". He pointed out that according to the concept of Newtonian physics, everything in the world obeys the same laws under the same conditions, so life science can also be studied from the perspective of physics, and once it is studied by physical methods, life science will definitely rise to a higher stage.
His student Delbruck began to study phage. He determined that phage was the simplest living substance. It is not as complicated as other organisms' genetic system, but it can also be replicated. However, in the study of phage replication law, whether we can find physical laws that have not been found before, so he focused on phage.
Delbruck later held a seminar on phage at Harvard University, and Watson was one of the members of the seminar. At the university, his first favorite was ornithology, and later, after listening to Delbrouck's workshop, he turned to the field of biochemistry. At this time, the Cavendish Laboratory of Cambridge University in the United Kingdom used X-ray diffraction to study protein and phage. So Watson went to Cambridge and began to cooperate with Crick to study nucleic acids by X-ray diffraction. The cooperation between these two people can be regarded as a biologist and an X-ray crystallographer coming together. At that time, both of them accepted the speech "What is life?" Schrodinger delivered on 1943. (later published in 1944), in which Schrodinger explained many basic phenomena in life science with physical concepts, such as the concept of genetic code, the aperiodic structure of chromosomes and so on. It can be said that the discovery of double helix structure is the result of physicists' long-term intervention and real participation in research with biologists. Now the Bio-X promoted by Stanford University is actually a continuation of this good atmosphere.
I read a report that the focus of Bio-X at Stanford University has shifted to undergraduate and postgraduate courses. In addition to discussing learning with scientists who have made great achievements in the field of biology, it is more important to let the ideas of Bio-X really penetrate into students' courses. Only by laying a solid foundation between biology and other disciplines can we achieve and develop in the future.
Wu Jiarui: Actually, now is a new round of interdisciplinary era. Since the double helix of DNA opened such an era of molecular biology experimental science, we found that the existing tools were not enough, so we considered whether we could find what we needed from new methods of mathematics or physics and combine it with life science again. For example, the Bio-X Salon in Fudan University and the Bio-X Center in Jiaotong University all embody this concept.
Zhao: The involvement of physics is very important for life science. At that time, physicists wanted to enter the field of life science to study biology for two purposes: one was to see whether the existing physical laws could explain the life phenomena in the process of life activities, and the other was to know whether some new physical laws that were not known so far could be found in life science. So they take biology as the research object and return to physics itself. But so far, my opinion is that no new physical laws have been found. Life phenomenon is basically the movement of life, and the basic components of life are the same as physical inorganic substances. So the basic law is to follow the existing physical and chemical laws.
Li Zaiping: But on the other hand, physicists' way of thinking and pursuit have achieved great success in biology. Why? Because physicists strive for the most basic and simple (object), is there such a basic and simple (object) in biology? In the past, biologists' research was devoted to finding different things. When they find a bacterium, they first look at the difference between it and other bacteria. Biologists think too much in this way, but few people pursue the same point from another angle. The pursuit of "simplicity" and "identity" happens to be a way of thinking that physicists are good at, so I think the intervention of physicists in this respect is very successful. If it was before, who would have thought that there were so many complex creatures in the world, and their genetic material was DNA. For example, the genetic codes of human and phage are almost the same. When Darwin put forward the theory of evolution, someone asked him why trees have something to do with people, but Darwin couldn't answer. But now from the genetic point of view, the genetic code of trees is the same as that of people, so people can express their genes in plants and insulin can also be expressed in bacteria, which means that there is a universal genetic code in the biological world. Such a simple law has turned the whole biological world into a "great unity", so I think this simple thinking mode has achieved great success.
Enlightenment from DNA double helix
Watson and Crick are really smart, but their success lies more in an original thinking, which is very important. This kind of original thinking is exactly what we should pay attention to in education.
From the perspective of genetics, the double helix model solves the problem of how to transmit genetic information. Its significance has gone far beyond the scope of genes and occupies an important position in the whole life science.
Chen: Watson and Crick did get a lot of criticism after winning the prize. For example, Chagaff said that their work was very difficult, but they were lucky. It should be said that Chagaff's base pairing theory is very enlightening to the work of double helix. It is conceivable that Chagav spent many days and nights in the laboratory for this purpose, but from Watson's description of the discovery of the double helix in the book, it seems that he did not spend too much time on scientific research. No wonder many people will put forward some opinions about them later. In this regard, I think that on the one hand, Watson and Crick are really smart, but perhaps more importantly, their success lies in an original thinking, which is very important. This doesn't mean that you have to work out a complicated subject in the laboratory every day. This kind of original thinking is exactly what we should pay attention to in education. I remember reading the book "Double Helix", and I was deeply impressed by a plot: once, Chagav asked Crick what the molecular formula of the base he studied was, and Crick always said that he couldn't write it. Later, Chagaff said contemptuously, you can't even write this thing, and you want to study the double helix. Crick is unconvinced, and thinks that this formula can be found in every textbook as long as you go back and look it up. There is no need to recite it. Seeing this, I am very emotional. In our education, students have too many things to recite.
Zhao: It is worth pointing out that the significance of these major discoveries was not as clear as it is now. Take the work of Watson and Crick for example. Their article is only two pages, and it was published in Nature. They were all very short and small articles, and there was no special sensation in academic circles at that time. Why? Let me give you an example: the double helix model was put forward by 1953, and the Nobel Prize was won by 1962. Every year from 1953 to 1962, they won the Nobel Prize only after 9 years. Chen Drew and Perut, who are engaged in the research of hemoglobin and myoglobin, won the chemistry prize of that year. Their article was published in 1960 and won the Nobel Prize in 1962. Why? Because at that time, the understanding of protein's role was still relatively traditional. At first, many people thought that the gene was protein, including Morgan, but it turned out to be DNA. Scientific discoveries or great achievements of great significance like this did not attract so much attention and sensation in the academic circles at that time; This incident has given us a revelation that we should mainly leave time to evaluate the academic achievements of a basic research, and let history make an evaluation instead of relying on the hype at that time. Many so-called major achievements were sensational at that time, but they disappeared after a year or two. So my opinion is that from the perspective of genetics, the double helix model solves the problem of how to transmit genetic information. Now, its significance has gone far beyond the scope of genes and occupies an important position in the whole life science.
Combining Watson and Crick's discovery of the double helix structure with China's situation, I think we should pay attention to at least two points: First, the achievements of major basic theoretical research need to be summarized and evaluated by history and time, which is the most objective and fair. As long as it is a truly valuable work, even if it is buried for a long time, its light will eventually emerge, and it will not be buried for 35 years like Mendel's theory. So did Watson and Crick; Second, the major decision-making of basic research direction should not be mixed with non-academic vision, but should listen to the opinions of scientists extensively and make correct decisions.
Pay attention to genetic ethics
There is a difference between "person" and "person". People have dignity, and people living in society also have personality and privacy, but as "people", it does not involve the so-called "dignity" problem. The classical theory of evolution shows that human beings evolved from lower animals. People and mice and monkeys are very similar in DNA. Is there any shame in that? When discussing ethics, we should pay attention to some problems.
Chen: I won't elaborate on all the positive effects of the discovery of the double helix structure, but I have recently seen a phenomenon. Many popular science books emphasize that all our behaviors, including emotions, are determined by genes. We have always respected science, and we think what scientists say is reasonable. Will this lead to "genetic determinism" and have some negative effects? From the western point of view, they always have two kinds of tension. One emphasizes that everything should seek a final cause (source). The representative view that extends to the category of biology is that everything we have is determined by genes. Many biologists are advocates of this idea, including Wilson, the pioneer of social biology. Their view is that "this is an era in which genes decide everything." Whether genes can determine everything has crossed biology.
Wu Jiarui: Life is unique and has its unique value. If it is explained by physics or chemistry, it is inappropriate. Therefore, behind the ethical debate lies the concept, not whether it can be explained, but whether we are willing to use it to explain it. The general view in the west is that people are regarded as machines. In this case, people are not devalued. Therefore, when we use DNA double helix to explain it, we have to consider this problem. When the genetic information is leaked, is it worthless to people? On the other hand, from a commercial point of view, is it necessary to keep the genetic information confidential after it is leaked? For example, we all know that genes determine genetic diseases. If a person has a genetic disease, but his genes are not kept secret, then the insurance company will collect this information and only find those who are not sick or only have minor illnesses to join the insurance, then they will definitely only make money. Therefore, foreign countries have specifically discussed whether insurance companies have the right to collect genetic information. Of course, we can also look at it from an ethical point of view. As Teacher Zhao said just now, is the human genome as a blow to people as the mouse genome? These problems will become an ethical issue.
Zhao: As for genetic determinism, I agree that genes are the center, which is true. Why? There is little difference between human and monkey genomes, but human genes develop into adults, monkey genomes develop into monkeys instead of adults, and so do humans and mice. When I was in class with my students, the first class was about "genotype+environment = phenotype", which is the most basic law of genetics. Genotype only determines what kind of phenotype is produced after interaction with the environment. For a basic example, farmers plant apples and paste the word "hi" on immature red apples. When they are ripe, they tear them off. The side that shines in the sun is red, and the place that doesn't shine in the sun is blue. Of course, the genotypes of the blue part and the red part are the same, but the environment is different. It can be seen that although genes play a decisive role, only after interacting with the environment can genes determine the final phenotype and appear specific traits.
On ethical issues, some people say that the study of genome has affected human dignity. It should be pointed out here that human beings are different from others. People have dignity. People who live in society have individuality and privacy. But as a "person", what is "dignity"? The classical theory of evolution shows that human beings evolved from lower animals. People and mice and monkeys are very similar in DNA. Is there any shame in that? When discussing ethical issues, we should pay attention to some issues, such as when people were defined as "people". Now there are three opinions. One view is that the moment a fertilized egg is formed is the beginning of a person's life, but somatic cells can be cloned without sperm-egg combination or fertilization, so this view is lacking; The second view is that a baby can only be considered a person after the mother is born, so the fetus is not considered a person when it is in the mother's belly. Some people retort that in this case, abortion is not equal to killing people. The third argument is that the British Parliament generally adopts embryos after 14 days of pregnancy, but strictly speaking, embryos develop into three layers of germ layers after implantation, which has the "biological independence" of developing into individuals of specific species, and it is impossible for them to develop into another individual, so it is not illegal to experiment with embryos before 14 days of pregnancy, and it is illegal to do it later. However, what standards should be adopted in China's ethics is a very thorny issue. If we adopt the first or third statement, it will go against family planning. If the second statement is adopted, all restrictions on embryo experiments should be lifted (because it was not human at that time and it was not illegal), but our ethicists here have no clear position, so they are not convincing.
Breakthroughs in future life sciences
After the completion of human genome sequencing, there are still more important discoveries and greater challenges waiting for life scientists.
Today, the 50th anniversary of the discovery of DNA double helix and the completion of human genome decoding, we can also think that all this does not mean the end of a science. On the other hand, we are now facing a new turning point.
Wu Jiarui: Regarding the future development of life science, in fact, today, the double helix of DNA has led to the current human genome project and the so-called post-genome era. The post-genome era involves a big problem. As Mr. Li said just now, whether we can achieve the so-called "decoding the genetic information of life" after sequencing the human genome is actually a great challenge. This does not mean that there is only some repair work after sequencing the human genome. I think there should be. In fact, as far as our current understanding of the genome is concerned, there are already many phenomena that are difficult to explain with existing knowledge. For example, the difference between human and mouse genomes is only 1%. Why such a small difference shows such a huge difference between species? I once put forward a point that this situation is not caused by the difference of their genomes, but by the difference of interaction between different protein in the process of gene expression in protein. Perhaps the interaction between simple creatures and protein is simple, while complex creatures are relatively complex. For example, the same 10 protein may have only 5 interactions in simple organisms and 20 interactions in higher organisms. So for us, these are all new challenges.
On the road of life science development in the future, there must be many fundamental and important things waiting for us to discover, just like physics in the early 20th century. At the beginning of this century, physics was originally thought to be fragmentary, but suddenly a great change gave birth to quantum physics and relativity, which completely changed people's views on the whole physics and the whole world. Today's life science may also face such a barrier, and the results derived from the double helix may jump to another brand-new realm that we can't imagine now. Today, the 50th anniversary of the discovery of DNA double helix and the completion of human genome decoding, we can also think that all this does not mean the end of a science. On the other hand, we seem to have found a platform now. If the discovery of DNA double helix provides us with a broad field and a favorable tool, then we have basically used this tool now, and the field has developed almost. We must enter a new field. I think this is us.