When I was a child, my father told me a story "Ji Chang Learns Archery". The general story is that there was a young man named Ji Chang in the State of Zhao. He dreamed of becoming an archery master, so he sincerely worshiped Fei Wei, a sharpshooter, as his teacher. Fei Wei said: "You must first learn to see without blinking, and then you can talk about archery." Ji Chang returned home, lay on his back under his wife's loom, and watched the shuttle on the loom with his eyes to practice without blinking. Two years later, even if the awl was stuck in his eye socket, he would not blink an eye. Ji Chang told Fei Wei about his practice, and Fei Wei said: "Young man, this is not enough. You must practice until you can see small objects as clearly as big things, and then tell me." Ji Chang returned home, Tie a louse with a string and hang it on the window, facing south and watching it from a distance. Watch it every day and month by month. Gradually, the louse becomes bigger. Three years later, the louse has a wheel in Ji Chang's eyes. So big. Ji Chang took a bow and shot an arrow, and one arrow penetrated the louse's heart. Ji Chang told Fei Wei about his practice again. Fei Wei clapped his hands and said, "You are already a marksman!"
That’s the end of the story, which seems to have little relevance to today’s topic. Nowadays, we are all eager to follow the big names, apply for projects, publish papers, apply for patents, and engage in cooperation. However, most scientific researchers seem to have neglected the basic skills that should be exercised. In the troupe profession, whether it is Wusheng, Wudan, Wuchou, Qingyi, Laosheng, or Hualian, doing somersaults with a loud voice is almost a compulsory course every day.
Biochemistry or molecular biology, as the most basic disciplines in the field of life sciences, how many scientific researchers can persist in practicing them? In fact, taking virology as an example, workers with a few years of scientific research experience know that if virology research is a little more in-depth, it will be biochemistry or molecular biology.
Because the essence of a virus is a nucleic acid & protein complex, the essence of its mainstream research direction is countless biochemical/molecular biological reactions. Virus invades → binds to the receptor → enters the cell → removes the capsid → nucleic acid replication → mRNA transcription → protein translation → processing and modification → virus assembly → budding and reproduction → stimulation of immunity → immune response → antibody secretion... This whole process is a circle. They are all closely related and are basic biochemical reactions.
Nowadays, it is said that poverty limits imagination. In fact, poor knowledge in biochemistry or molecular biology limits the imagination of scientific researchers. The result is: if the experiment succeeds, it is attributed to good luck; if it fails, no one knows where to find the reason. A few days ago, someone suddenly called me very excitedly and said that he had come up with an unprecedented idea through reverse thinking. By modifying the African swine fever virus, it can be reproduced industrially on traditional cell lines. He wants to use African swine fever virus to express an exogenous ligand, and then infect common cell lines (such as Vero), thus solving the embarrassment of the availability of cell lines for African swine fever virus.
This seemingly “unprecedented” idea is actually very difficult to implement. There are three reasons: first, this ligand expression must be display expression on the surface of the virus envelope, rather than traditional intracellular expression; second, since it is display expression on the virus envelope, it must be an exogenous ligand. Fusion expression with the virus's own protein, and the expression level must be acceptable; the function of the virus's own protein must not be affected; the most important thing is to ensure that the spatial structure of the ligand cannot be affected by the fusion protein, and must be perfectly displayed on the surface of the viral envelope. In fact, at this point, experimental design has become extremely difficult, which requires the serious participation of structural biologists. Third, even if the exogenous ligand can be perfectly displayed on the outer surface of the virus, how can we ensure that the recombinant virus can successfully enter the cell? Will the virus definitely be able to enter the cell when its exogenous ligand binds to the cell receptor? Why can't antibodies enter cells when they bind to cell receptors? In essence, if the virus wants to successfully enter cells, this is controlled by a series of signal transduction pathways, which is a complete set of cascade reactions.
When I told him the above three doubts, he still insisted that his idea was unique and unprecedented. He said that scientific research sometimes requires a sudden inspiration. However, he overlooked one point. The prerequisite for a sudden flash of inspiration is to have extremely solid basic skills in biochemistry or molecular biology. The purpose of giving this example is to illustrate that sometimes some seemingly "unprecedented" ideas are actually caused by the basic skills of biochemistry or molecular biology being too rough.
2020-03-18
F. Liu