The 2020 Nobel Prize in Chemistry was awarded to Jennifer Dudner of the United States and Emmanuel Carpenter of France for their invention of genetic modification method CRISPR-Cas9. This award is related to biological evolution. From a broad perspective of life phenomena, CRISPR involves biological parasitism, symbiosis, and mutual restriction of life. In a narrow sense, CRISPR is closely related to immunity and disease, and can explain the immune mechanism of organisms.
Simply put, the appearance and essence of CRISPR can fully explain that even without vaccines and drugs, new coronary pneumonia and many other diseases can be overcome by human immune mechanisms. Of course, drugs and vaccines are better.
CRISPR is called regular clustered interval short palindrome repeats, which is a type of repetitive structure widely distributed in the genomes of bacteria and archaea. Cas is the abbreviation of Caspase, its full name is cysteine-containing aspartate proteolytic enzyme, which is a group of proteases, Cas9 is one of them. In addition, there are other enzymes that function together with CPISPR, such as the nuclease protein Cpf1, so it can also be called the CRISPR/Cas system.
CRISPR is present in nearly half of bacteria and all archaea, and is an immune method for bacteria to deal with phage and virus invasion. Like eukaryotes and humans, prokaryotes such as bacteria also have two major types of immune methods to deal with foreign invaders: the innate immune system (non-specific immunity, innate immunity) and the acquired immune system (specific immunity, acquired immunity or adaptation) Sexual immunity).
Bacterial natural immune system includes restricted modification (RM) system, DNA interference, toxin anti-toxin system, etc., which are non-specific defense measures; bacterial acquired immune system is a highly specific defense method, and the CRISPRCas system is a typical representative.
When bacteriophages infect bacteria, some bacteria will insert an inter-region sequence that is consistent with the bacteriophage sequence near the leading region of the CRISPR sequence. When the same bacteriophage infects the bacteria again, the CRISPR-Cas-related gene products of the bacteria will be cut off by a mechanism similar to RNA interference. Invading phages to protect themselves from being swallowed by phages. This acquired immunity of bacteria resides in nucleic acid, so this immunity can be inherited. The researchers also discovered that there are 10 other unknown immune defense systems in the bacteria, which give the bacteria a powerful ability to resist invasion by foreign organisms.
Compared with bacteria, human immune function is stronger. Human genes have accumulated many defense mechanisms against the new coronavirus and other pathogens in the long evolution of life, but it is still unclear.
Fortunately, researchers are discovering human immunity with great potential. The research team of the Karolinska Institute in Sweden and the Max Planck Institute for Evolutionary Anthropology in Germany recently published an article in the journal “Nature” and pointed out that modern people and Neanderthal who lived in Europe about 60,000 years ago After marriage, a gene that is vulnerable to disease is replaced by the latter. Therefore, most people will not develop severe illness even if the new coronary pneumonia is on the 7th today, thus avoiding the risk of death. This gene can also be called the core risk gene of the new crown severe disease.
This gene is located on chromosome 5, has about 50,000 base pairs, and is a haplotype. Due to the cross between Homo sapiens and Neanderthals, there are still 1% to 4% Neanderthal genes in the genome of modern humans today. The probability that patients with the core risk gene of COVID-19 need a ventilator (artificial ventilation) is about 5 times that of ordinary COVID-19 patients without this gene.
Among all living beings, only a few people carry the core risk genes for the severe disease of the new crown. They are more likely to develop respiratory failure, so the risk of death is higher. For most people, since the core risk genes of the new coronavirus are not retained in the body, even if they are infected with the new coronavirus, they will not worsen to respiratory failure and oxygen inhalation. Statistics show that 50% of South Asian populations carry the core risk gene for new coronary disease, about 8% of European populations carry this gene, and about 4% of American populations carry this gene. But in the African and East Asian populations, almost no one carries this gene.
Therefore, even if the average person suffers from new coronary pneumonia, they are unlikely to suffer from severe respiratory failure. Coupled with better medical conditions, there is a high probability that they will fully recover.
The evolution of phagocytosis and anti-phagocytosis, invasion and anti-invasion between different organisms has always been a bilateral or multilateral game, and eventually formed a result of evenness, balance or restriction. The same is true for the new coronavirus invading the human body. Infectious diseases and immunologists have proposed a hypothesis that the spread of the new coronavirus or other viruses from animals to humans (one host to another new host) mainly follows two principles. One is that the virus is not very adaptable to the new host (human), will reduce its toxicity, and will not cause great harm to humans, but it can live in the human body for a long time and maintain a longer life cycle. The second is that the virus adapts to a new host (human). It may also become more virulent and become more virulent, causing death to humans, and then all die.
The new coronavirus is the former, and the rabies virus is the latter. Now, although the global case fatality rate of the new crown pneumonia is about 2.5%, which is much higher than the 0.1% case fatality rate of influenza, compared with the plague and rabies, which have a case fatality rate of 60% to 100%, the pneumonia caused by the new crown virus has become annoying. But influenza viruses that do not pose a major threat are similar. The reason is that the new coronavirus, like the influenza virus that is not too threatening, has a limited and usually streamlined genetic code that can evolve to adopt strategies to evade, attack, or hijack the host’s immune system. This adaptation and compromise with the characteristics of the host environment will change the phenotype and characteristics of the pathogen, so that it can achieve sustainable development and coexist and die with humans.
The development of the epidemic shows that the new coronavirus is mutating and its toxicity is decreasing. As early as February 2020, European and American researchers discovered the D614G variant of the new coronavirus that is circulating in Europe and the Americas, but there is no evidence that this variant causes severe new coronary pneumonia. Later, many countries discovered that the new crown virus variant D614G is spreading widely, but the mortality rate of new crown pneumonia in these regions and countries is declining. This coincidence shows that this may be a variant of the new coronavirus with reduced toxicity.
On the other hand, the new research on the rabies virus, which is in sharp contrast with the new coronavirus, also indirectly proves that the other of the two strategies for the virus to invade the human body is to die with the host. British researchers published a meta-analysis article in the “Proceedings of the National Academy of Sciences” published on November 17, 2020, showing that rabies virus infection is a relatively distantly related transmission. It is more adaptable to humans and will increase virulence. Cause death. This means that when the rabies virus crosses species to humans, it will limit its further spread. The vast majority of infected people will die, which will stop the spread of rabies from person to person.
However, biological evolution does not only involve pathogens and people, but also pathogens and other organisms (animals and plants). Not long ago, Denmark planned to kill 17 million minks. The reason is that since June 2020, Denmark has found that more than 200 people have been infected with the new coronavirus related to mink farms, and more than 10 patients have been infected with a “unique” Mutated new coronavirus. This means that the new crown virus may mutate in the cultured mink and pass it back to humans. In addition, the mutant virus in the mink may pose a risk to the effectiveness of the new crown vaccine in the future.
If we only consider the evolution of people and the new coronavirus, as well as the improved medical standards and vaccines that will come out, we can be optimistic about the development of the new coronary pneumonia. However, if there are other intermediate hosts, such as mink as the virus’s evolution and adaptive transfer environment, it is necessary to comprehensively evaluate the harm of the new coronavirus.
