How do scientists "see through" the "true identity" of the virus? Extreme Speed ​​Electronics gives humans "wisdom eyes"!

There are many diseases that are caused by viruses infecting the human body, such as influenza. In order to better defeat these diseases, we must understand the viruses that cause the diseases.

So the question is, the virus is too small to be seen or touched, and it may infect researchers, so how can we study the virus safely and conveniently? In this regard, researchers have come up with many good ideas, let's talk about them briefly below.

To see the true form of the virus, you need electricity

We hear sounds because of sound waves and see objects because of light waves. The only light that human vision can perceive is called visible light, and its wavelength is generally between 400 and 760 nanometers. Therefore, based on this data, it can be calculated that no matter how precise an optical microscope is, its resolution cannot exceed 200 nanometers. It can see the appearance of bacteria but cannot capture any trace of viruses.

The lens principle of the optical microscope is the wave-particle duality principle of light. In 1905, Einstein proposed that light has the dual nature of waves and particles. In 1924, de Broglie proposed the concept of "matter wave", believing that all matter has the dual nature of waves and particles, and electrons also have wave phenomena such as interference and diffraction, which was later confirmed by electron diffraction experiments.

In short, what light can do, electrons can also do. What light cannot do, can electrons do? Electrons are tiny particles with negative charges outside the nucleus. This "electric" halo allows people to use electromagnetic fields to accelerate electrons. The high-speed electrons greatly shorten their wavelengths, just like the principle of focusing light in an optical microscope, focusing high-speed electron beams to achieve the effect of improving resolution.

Electron microscope model diagram. Book "Influenza virus is an enemy that cannot be avoided"

In 1931, Erst Ruska and Max Knoll developed the first perspective electron microscope; in 1934, the resolution was improved to 50 nanometers; in 1939, the resolution of the high-resolution electron microscope reached 3 nanometers; in 1978, the resolution of the scanning tunneling microscope could reach 0.01 nanometers, and the minimum resolution distance between two points was 1/10 of the atomic diameter, and the electrons returned to the atoms.

The development of high-resolution microscopy technology has enabled humans to see not only viruses, but also viral proteins and nucleic acids, and to see everything from the outside to the inside. The extremely fast electrons have endowed humans with "wisdom eyes", solving the problem of "shape" at the microscopic scale of life.

How to obtain viral genetic information?

If humans want to conduct life science research, it is far from enough to just "see". To deeply understand the essence of life, using genetic information as a breakthrough is a good choice. A new problem has arisen. If we want to obtain the nucleic acid of cells or viruses, we still use the bandage-like extraction method, which requires the cultivation and consumption of a large amount of biological materials. Is there any way to directly copy and amplify the target DNA fragments we need and work directly at the molecular level?

It is easy to change from "big" to "small", but difficult to change from "few" to "many". If we synthesize and link them one by one according to the chemical properties of A, T, G, and C, it will be a costly, time-consuming and laborious project. Semiconservative replication of DNA is an important way for biological evolution and transmission. Double-stranded DNA can be denatured and unwound into single strands under the action of various enzymes. With the participation of DNA polymerase, it is replicated into two identical molecular copies according to the principle of base complementary pairing.

DNA "Codon" Book "The Influenza Virus is an Inescapable Enemy"

Based on this, the double helix structure of DNA is opened to form two complementary single-stranded DNAs. Under the action of a certain nucleic acid polymerase, the unwound single-stranded DNA is used as a template, following the principle of four types of base pairing, to synthesize new complementary DNA single strands, and this reaction is repeated in logarithmic growth, ultimately realizing an "assembly line" type automated assembly system. This basic principle is: polymerase chain reaction (PCR).

Just like discovering the guide and beacon of the code of life in the vast ocean of bases, PCR technology has opened up a channel for the acquisition and application of nucleic acid molecules.

Safety is essential when studying pathogens

Pathogenic microorganisms are microorganisms that can invade the human body and cause infection or even infectious diseases. They are also called pathogens. Among pathogens, bacteria and viruses are the most harmful. Pathogens grow and reproduce in the host, release toxic substances, etc., causing pathological changes in the body to varying degrees. This process is called infection, and in severe cases it can even lead to death.

Humans can study viruses through genetic information or protein structure and function, but the ultimate goal is to study living viruses, which is a dangerous undertaking. In the 1940s, people around the world began to pay attention to the problem of laboratory infection. In the 1980s, the World Health Organization (WHO) divided the world's biosafety laboratories into four levels.

my country's classification criteria for the degree of harm caused by pathogenic microorganisms gradually decrease from level one to level four (while the classification criteria for the degree of harm caused by pathogenic microorganisms in the World Health Organization and other countries gradually increase from level one to level four):

Category I pathogenic microorganisms refer to microorganisms that can cause very serious diseases in humans or animals, as well as microorganisms that have not yet been discovered in my country or have been declared eradicated.

The second category of pathogenic microorganisms refers to microorganisms that can cause serious diseases in humans or animals and are more easily transmitted directly or indirectly between humans, animals, or animals.

Category III pathogenic microorganisms refer to microorganisms that can cause diseases in humans or animals but generally do not pose a serious threat to humans, animals or the environment, have limited transmission risks, rarely cause serious diseases after laboratory infection, and have effective treatment and prevention measures.

Category IV pathogenic microorganisms refer to microorganisms that do not normally cause diseases in humans or animals.

Schematic diagram of the P4 laboratory structure. Source: Book "Influenza Virus: An Inescapable Enemy"

A biosafety laboratory is a biological laboratory or animal laboratory that can avoid or control the hazards of harmful biological factors being operated through protective barriers and management measures to meet biosafety requirements. The laboratory biosafety protection level (Biosafety Level, BSL; or Protection, P) is divided into level 1, level 2, level 3 and level 4, with level 1 being the lowest and level 4 being the highest. This is consistent with the international classification of pathogenic microorganisms, but is exactly the opposite of my country's classification of pathogenic microorganisms.

Biosafety level 1 laboratory (P1): suitable for operating microorganisms that do not normally cause human or animal diseases, that is, microorganisms with level 1 hazard defined by the World Health Organization (four types of pathogenic microorganisms, such as measles virus, mumps virus, etc.).

Laboratories with a biosafety level of Level 2 (P2): are suitable for operating microorganisms that can cause human or animal diseases, but generally do not pose a serious hazard to humans, animals or the environment, have limited transmission risks, rarely cause serious diseases after laboratory infection, and have effective treatment and prevention measures. These are microorganisms classified by the World Health Organization as level 2 hazard (Class III pathogenic microorganisms, such as Staphylococcus aureus, hepatitis B virus, etc.).

Laboratories with a biosafety level of three (P3): are suitable for operating microorganisms that can cause serious diseases in humans or animals and are more easily transmitted directly or indirectly between humans, animals, or animals, that is, microorganisms with a hazard level of three as defined by the World Health Organization (Class II pathogenic microorganisms, such as Vibrio cholerae, rabies virus, etc.).

Laboratories with a biosafety level of four (P4): are suitable for operating microorganisms that can cause very serious diseases in humans or animals, as well as microorganisms that have not yet been discovered in my country or have been declared eradicated, that is, microorganisms classified by the World Health Organization as level four (Class I pathogenic microorganisms, such as Ebola virus, Nipah virus, etc.).

"If you want to do your work well, you must first sharpen your tools." Electron microscopes show the original form of viruses, and the photos record the shapes and sizes of almost all known viruses; PCR technology obtains sufficient biological background, and the data stores the nucleic acid sequences of various types of viruses that can be separated and detected; biosafety laboratories provide a platform for protecting against viral infection conditions. Humans have already possessed and upgraded facilities under all safety protection levels. "Today, with the long rope in hand, when will I tie up the blue dragon?"

author

Gao Fu, academician of the Chinese Academy of Sciences, vice president of the Chinese Medical Association, director of the Chinese Center for Disease Control and Prevention

Liu Huan, associate researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences, and member of the China Science Writers Association

Source: Book "Influenza Virus: An Inescapable Enemy"