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How far is human being from "resurrecting from the dead"

   The "resurrection" experiment of pigs only proves that multiple organs are "active" at the cellular level, but it also brings about the redefinition of death. To explore the resurrection of human beings, multiple factors such as ethics and science must be considered.

  This is a dead sow. It had been dead for an hour, and a special perfusate was being slowly injected into its body, circulating through its veins and arteries, along with fresh oxygen.

  In the next six hours, the researchers quickly discovered that some cells in the pig's heart, liver, kidney and brain began to restore function and activity, and the pig's circulatory system gradually recovered. Although the pig's heart did not fully resume beating, electrophysiological activity could be scanned, indicating that it had the ability to contract. In every vital organ, cells responded more strongly to glucose, suggesting they were restarting parts of their metabolism.

  During the whole process, people were also surprised to observe that its head and neck began to show involuntary muscle movements. Also, as a medically dead animal, it did not show rigor, edema, or plaques.

  It seems that this pig is slowly "resurrecting".

  On August 3, 2022, the team of Nenad Sestan, a neurobiologist at Yale University School of Medicine in the United States, published this "resurrection" experiment and its results in the journal "Nature", which aroused widespread attention and discussion. The last time a similar discussion took place three years ago, in April 2019, when Sestan's team "resurrected" a pig's brain four hours after its death, which overturned the established concept for many years: brain death is irreversible.

  From the brain to the organs of the whole body, at this moment, a natural question is: Is it possible for human beings to achieve true resurrection from the dead in the future along this technological path?

  "Opening the door to the future of organ transplantation"

  This is the first time someone has been able to "resurrect" various organs in a mammal's body at the same time. Some experts pointed out that this achievement is "subversive". Generally speaking, the organs of mammals are deprived of oxygen for about 15 minutes, and they will die completely.

  In this experiment, Sestan's team injected pigs with "resurrection medicine" after one hour of ischemia and hypoxia, mainly composed of pig blood, artificial hemoglobin, nutrients needed by cells, antioxidant drugs and drugs to prevent cell death mixed with various compounds.

  Zhang Shupei, a co-author of the study and a doctoral candidate at Yale University School of Medicine, pointed out that this is an optimization and improvement of the perfusion fluid in the pig brain experiment in 2019. The oxygen-carrying capacity of artificial hemoglobin is very strong. This time, a system called OrganEx was used for the experiment. In the OrganEx perfusate, the ratio of hemoglobin to blood is 1:1, "so that the cells can receive oxygen at the highest efficiency." In addition, drugs such as antioxidants in the perfusate can be used to inhibit and alleviate cell damage, "compared to targeting a single organ brain Compared with the improved version, it is more compatible with various organs in the whole body." She said.

  A key system to "resurrect" pigs The

  experiment also set up a control group using extracorporeal membrane oxygenation equipment (ECMO). ECMO is often used as an important tool for rescuing patients with heart and lung failure in clinical practice. It can partially or completely replace the patient's heart and lung function, which is equivalent to an artificial heart-lung machine. However, ECMO generally uses venous blood perfusion. In recent years, the function of ECMO as a transplant organ preservation facility has been gradually developed, because ECMO can provide stable oxygenated blood perfusion immediately after cardiac death, so as to better maintain the quality of transplanted organs and improve transplantation efficiency.

  A problem that has existed in organ transplantation for many years is "reperfusion injury", that is, cells are reinfused with oxygen after hypoxia and ischemia, which will cause cell damage such as blood vessel collapse. The study found that compared with the ECMO group, the cells in the OrganEx group were less damaged after perfusion, and the bleeding and tissue swelling were less, which can maximize the perfusion efficiency. Cellular function was better restored in all major organs of OrganEx pigs. In pig kidney cells, cell proliferation also appeared.

  Zhang Shupei pointed out that in clinical practice, the perfusion efficiency of ECMO is "actually very low", and the requirements for the use time are very strict, and the effect becomes worse as the time goes by. "That's why we chose to perform the perfusion an hour after the pig died, because the average time for an ambulance to transport a critical patient in the United States is about an hour," she explained.

  In her view, the key to "reviving" the pig is the perfusion system OrganEx, a computer-controlled extracorporeal perfusion system through which perfusate is injected into different organs throughout the pig's body. During this process, real-time sensors monitor important circulatory indicators, metabolites, and signaling pathways "related to cell repair," allowing researchers to intervene at any time. The system also includes an oxygenator and a hemodialysis unit to maintain a steady level of electrolytes and other essential molecules in the perfusate.

  "This is the most difficult part of the experiment," Zhang Shupei said. OrganEx needs to better simulate the functions of the organs of the whole body. Taking the kidney as an example, the most important function of OrganEx is to "do exchange" to expel toxic substances and leave hemoglobin behind. , and the system needs to achieve "more efficient exchange" by "well controlling" the corresponding hemodynamics.

  Zhu Tongyu, deputy dean of Shanghai Medical College of Fudan University, is one of the well-known organ transplantation experts in China. He pointed out that the next step, the difficulty of perfusion technology in organ transplantation is to increase the adaptability to different organs, because the size of each organ, the The shape is different. For example, the blood vessels of the kidney are "thinner than chopsticks". Among the blood vessels of the liver, there are differences between the hepatic artery and vein, and the heart has very large blood vessels. Therefore, for these different organs, more targeted perfusion fluids and perfusion systems should be equipped.

  "Resurrection from the dead" is a very distant

  plan . As far as brain research is concerned, the pig brain "resurrection" experiment of Sestan's team uses the system BrainEx, which is a "new beginning".

  While dedicated research on the human brain has been difficult for many years for ethical reasons, experiments with pig brains have allowed the brain to "live" intact outside the body. Zhang Shupei pointed out that previous studies were limited to brain slices of dead animals, so humans lacked understanding of the fine structure of the brain. Now, for the first time, humans can study the brain in three dimensions.

  A deeper understanding of these complex neural networks will help scientists further study the principles and test drugs of brain diseases such as Alzheimer's disease and autism. "We are equivalent to providing a platform on which some drug screening can be done." Zhang Shupei said.

  More importantly, the BrainEx experiment may help scientists break through the most sensitive issue in brain research: "consciousness." So far, no one has created consciousness in the laboratory, and some experts believe that the BrainEx experiment "is the most likely one". However, Sestan's team is very cautious about this, repeatedly emphasizing in public that "recovery of consciousness was never the goal of this research."

  Zhang Shupei explained that due to ethical considerations, the BrainEx experiment isolated the "generation of consciousness" from the root, because the researchers injected neuron activity blockers into the pigs, which can prevent any neural interactions that may lead to consciousness, and cooperate with the pigs. There is an EEG to monitor brain activity at all times. If any conscious activity was detected, that is, if the EEG showed that it was not a straight line, the experiment was immediately terminated.

  Under this premise, in order to test the activity of brain cells, the researchers cut the brain into thin slices of about 300 microns after perfusion, and observed whether there were signal fluctuations by stimulating the neurons in the slices, and finally proved that "a single Neuron cells are alive." But Zhang Shupei pointed out that consciousness must be born from "the overall linkage between neurons and cells in the whole brain."

  Therefore, the paradox is that if human beings want to further understand the nature of the brain, the field that must be touched is: how do millions of brain nerve cells and the trillions of connections between them work together? One day in the future, human beings will not stop at "resurrecting" brain cells, but thinking and character. Are we ready for this? What kind of world would it be if humans could "create consciousness"?

  Zhang Shupei pointed out that, from cells to tissues, organs, and the functions of the whole body, "this is a very, very long-term plan" in order to achieve "resurrection from the dead".



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