On the afternoon of May 30, 2015, Du Hong, a 61 year old female writer from Chongqing, died peacefully in her hospital bed from pancreatic cancer. In the next room, two surgeons from the United States have been waiting for 8 hours. They have preliminarily frozen the head of her body, and then transported it to the United States for long-term storage in -196 ℃ liquid nitrogen. After 50 years of medical progress, they seek the possibility of resurrection.
This is the first case in China to participate in human cryopreservation for "Resurrection". Although "resurrection from the dead" sounds like a fantasy, scientists are working hard towards this goal.
Recently, the University of Utah and Scripps Institute in the United States published a paper in the journal Nature describing the process of "Reviving" retinal cells in the eyes of organ donors and restoring their "communication", which can even reach the level that retinal cells regulate human vision in the living eyes. "In the eyes obtained within five hours after the death of an organ donor, these cells respond to bright light, colored light, and even very weak flashes of light," the researchers said.
As the first recorded b wave in the retina after death, this study has aroused widespread concern. So how hard is it to revive a human eye? How do Chinese scholars view this research? Doctor newspaper specially invited Professor wangningli, director of Beijing Tongren Eye Center and member of the academic department of Chinese Academy of Medical Sciences, and postdoctoral Chengying of Beijing Tongren Hospital Affiliated to Capital Medical University to have an in-depth discussion.
Restore the most sensitive human vision
How difficult is macular sensitization?
In the study published in nature, researchers first removed the retina of dead mice and restored the light response of photoreceptors and bipolar cells. Subsequently, the researchers made several attempts to obtain the retina of the organ donor within 20 minutes after death, and finally recovered the specific electrical signal seen in the living eye - b wave in the macula, indicating that the researchers recovered the ability of the eye to sense light and transmit the light results to other cells.
Professor wangningli introduced the biggest challenge of this research to the doctor: restoring the sensitivity of the macula. Different from the rodents who like nocturnal activities, the human retina has a very complex structure, with a special macular structure. It can see more details and distinguish rich colors, which is mainly reflected in four aspects.
(1) Size: the diameter of human retina is about 40 mm, while that of mouse retina is only about 5 mm. The larger retina area indicates the complexity of human retina anatomical structure and the diversity of cell types.
(2) Difference of photoreceptor distribution: the density distribution of photoreceptors in primate retina is uneven. The density of cone cells in central retina is high, while the density of rod cells in peripheral retina is high. The density distribution of photoreceptor cells in the retina of rodents is basically uniform.
(3) Foveal structure: the macular fovea on the retina is an important feature of primate retina. There are only cone cells and no rod cells in this part. In rodents, the structure does not exist.
(4) other retinal cell differences: there are about 1million ganglion cells in the human retina, which are mainly concentrated in the central retinal region. In this region, the ganglion cell layer is composed of about 6-8 layers of cells, which gradually becomes thinner towards the peripheral ganglion cell layer, and the distribution of cell density varies greatly. In the rodent retina, the ganglion cell layer is a monolayer cell, and the cell density distribution has little difference. Due to the numerous cell types of human retina, the signal communication between cells is also more close. When the retina is damaged, it is more difficult for the human retina to recover the photosensitive and neural signal communication.
Cheng Ying added that the reason why this study focused on the macula is because of the particularity of this anatomical structure. First, the macula is located in the center of the retina, where a large number of cone cells are concentrated with the highest density. Therefore, it is the key part of vision formation and the most sensitive area of vision. Once macular disease occurs, visual acuity will be obviously abnormal. Therefore, in-depth understanding of macular structure and function is the research focus.
Retina is sensitive to ischemia and hypoxia
No "Resurrection" advantage
Generally speaking, death is irreversible. So, does the retina have some advantages of easy "Resurrection" and easier stimulation to generate electrical signals?
Professor wangningli said that the retina is the part that produces vision through photoelectric conversion. A large number of neuronal cell bodies and axons are distributed on the retina. Neurons are active. At the same time, they generate cell signal communication with surrounding glial cells and bipolar cells. They have a great demand for oxygen and energy. Therefore, they are sensitive to adverse stimuli such as ischemia and hypoxia and do not have the advantage of easy "revival".
Cheng Ying said that in this study in nature, Frans vinberg team restored the oxygenation and other nutrition supply of the retina of organ donors through a specially designed transport device, and detected the b wave of the neuroelectric signal in the isolated retina using ERG, which is only found in the living eyes. Therefore, this study has a good reference and promoting significance for the treatment of retinal transplantation.
(picture source: qianku.com)
It is very difficult to recover the whole eye
It is possible to maintain some physiological functions
In the eyeballs obtained up to 5 hours after the death of the organ donor, the research team enabled the photoreceptor cells on the retina to preserve certain functions and communicate with each other through special means of energy recovery and transportation. Can we think that not only the retina, but also the whole eye after death can be completely restored?
Professor wangningli said that the retina is an important part of photoelectric conversion and one of the most important structures for imaging. Preserving retinal function is an important progress in promoting retinal transplantation. By improving the treatment and preservation of eyeballs, we may obtain the technology that the eyes still maintain some physiological functions for a certain period of time after death in the future. But considering the whole operation of eye transplantation, including the recovery of blood vessels, optic nerve structure and function, it is very difficult.
It can provide reference for retinal transplantation
Professor wangningli said that this study can provide some reference significance for the development of retinal transplantation. Frans vinberg's research team has observed the communication between photoreceptor cells in the retina of these organ donors, but the amplitude, latency and cell communication between other layers of the retina are difficult to recover to the level of living retina. Future research directions can focus on improving preservation technology or adding protective cytokines. At the same time, through continuous technical improvement, we can gradually try to carry out retinal allograft experiments with certain functions in rodents and primates, and evaluate their therapeutic potential.
On the other hand, retinal transplantation is a delicate operation, which needs to seamlessly place the graft in the recipient's existing visual circuit, and needs to consider the problem of tissue rejection. Therefore, retinal transplantation is still a challenging work.
Cheng Ying further added that in this study, photoreceptor cells were recovered in the donor's retina, and ERG electrophysiological signal b wave was detected only in living people. ERG b wave may be considered as an index to evaluate the photosensitive function of retina in vitro in future research. Through further primate experiments, this technology is expected to be applied to the treatment of patients with retinopathy in the future, such as age-related macular degeneration. At present, this research has restored the communication between rod and cone cells. Due to the short connection path between photoreceptors, how to restore the communication between other cells in the retina is still a research direction that needs to be paid attention to in the future. In addition, the key techniques and results of this study can be analogically applied to the treatment of other types of central nervous system diseases.
Thoughts on the research of "resurrection from the dead":
Based on respect for life and human dignity
"We need to think about whether the photoreceptors in the retina really come back from the dead?" Professor wangningli raised a question, "the photoreceptor cells in this study are more similar to the 'shock' in which the photoreceptor cells are on the verge of death due to ischemia and hypoxia caused by changes in the internal environment after the death of the body, and the isolated retinal environment is restored through special external intervention, so that its function can be temporarily restored."
Professor wangningli believes that the ethical disputes caused by such "Resurrection" related research need to be paid attention to. At present, the definition of brain death is the irreversible death process of neurons in the whole brain. It is known that the retina is an extension of the central nervous system and has many similarities with the central nervous system. So, this study reinvigorated photoreceptors after the death of donors, which prompted us to think whether the neurons in brain death are really irreversible in the short term? Does the evaluation index of irreversible neuronal death need to be updated? How to define the boundary of death from the perspective of ethics? A study on recovering brain circulation and some brain cell functions of the pig brain four hours after death, which was also reported in the journal Nature in 2019, has triggered widespread ethical debate. In this study, although the researchers recovered some functions of the pig brain, they did not recover their consciousness, which poses a challenge to the previous definition of brain death.
Therefore, this kind of "resurrection from the dead" research suggests that the formulation of ethical norms still needs to be further improved. Be vigilant to open Pandora's box before you fully understand it, and take respect for life and human dignity as the benchmark.