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Can the head really be transplanted?
From 2065438 to February 2005, Sergio Canavelo, a neurologist from Turin, Italy, declared that the main obstacles of head transplantation were spinal cord fusion and immune rejection, and the current medical technology could completely overcome them. He plans to conduct the world's first head transplantation in the next two years.

The head transplantation scheme is not limited.

As early as 20 13, the neurologist published his plan publicly. Compared with the technical abstract published in the International Journal of Surgical Neurology published in India a few days ago, his head transplant plan and steps have not made significant progress, mainly including:

Different from the usual organ transplantation, the recipient (a "frozen person" with a healthy brain and a serious physical disease like Hawking or a paraplegic patient) and the donor (a brain-dead but healthy person) must be alive from a physiological point of view.

They were put in the same operating room and beheaded from the neck under deep hypothermia (the core temperature of human body dropped to 12~ 15℃) and anesthesia. The blood vessels and muscles in the neck are carefully dissected, and the spinal cord needs to be cut off very neatly with an unusually sharp knife.

Then put the recipient's head and the neck of the donor's body together to fix the broken cervical vertebra and anastomose the blood vessels and muscles. Directly align the two neat parts of the key spinal cord, inject a membrane fusion agent called polyethylene glycol, and then inject this "biological adhesive" according to the situation. This method is called spinal cord fusion.

He believes that the key to success is that the time from the beheading of two people to the successful head change must be controlled within 1 hour, so as to minimize the time of ischemia and hypoxia in the recipient's brain and donor's body.

In the next 3-4 weeks, the "newcomer" whose head and body have been reconstructed will remain in a coma to prevent activities and wait for the neck to heal. The spinal cord will be implanted with electrodes for regular electrical stimulation, which is said to promote nerve regeneration and connection.

Canavero predicted that when this new life was awakened, his head and face would feel and move again, and his voice would be the same as before. After receiving physical therapy 1 year, newcomers can resume walking.

History of head transplantation

Head transplantation is not a new topic. As early as last century 1954, Vladimir Demikhov, a former Soviet scientist, transplanted a puppy's head, forelimbs and part of its chest into the back of a big dog, and "successfully" made a "two-headed dog". Both dog heads can see and exercise independently.

In the first experiment, the two-headed dogs lived for 4 days, and in 24 experiments, the two two-headed dogs lived for 2~6 days respectively.

In that era when there was only one big brother in the Soviet Union, China's medical community naturally didn't want to lag behind, and they followed suit to do experiments on two-headed dogs. Among them, Zhao Shijie of Harbin Medical University created the best domestic record of two-headed dogs' survival for 5 days and 4 hours in 1956, and published it in the second issue of Heilongjiang Medicine 1960 with the title of "aim high and climb the scientific peak bravely".

1965, American scientist Robert White transplanted the head of one dog into the neck of another dog and made a double-brained dog.

1970, White successfully performed the first "real" head transplantation in the world, transplanting the head of a monkey into another headless body. After the operation, the feeling and movement of the monkey's head recovered, and even almost bit the experimenter's hand, but the feeling and movement of the body completely disappeared. It only relied on the ventilator to maintain its life for 9 days, and eventually died of rejection.

In fact, none of these experiments can be regarded as real head transplantation, because only the recipient's body temporarily provides life support for the transplanted head, and none of them involve spinal nerve transplantation and functional reconstruction. Nerve connection cannot be established between the transplanted head and the body, let alone restore nerve function connection.

Why is the Canavero project unconstrained?

With the development of modern surgical technology, spinal fusion and fixation, blood vessels and muscles have long been conventional mature technologies, and the key problem of head transplantation lies in the nerve connection and functional reconstruction between the recipient and the donor.

Canavero's plan simply sidesteps this key issue. The so-called spinal cord fusion in his scheme only refers to cutting the spinal cord neatly with a sharp blade, simply putting the spinal cord slices of the recipient and the donor together, and trying to use the so-called polyethylene glycol as a membrane fusion agent for bonding. It is unrealistic to predict that walking can be resumed after 1 year.

When an interviewer questioned this, Canavelo turned to say that if the polyethylene glycol spinal cord fusion scheme is not feasible, then local injection of neural stem cells or olfactory ensheathing stem cells can be tried to promote the regeneration and functional reconstruction of nerve axons.

Therefore, Canavero himself admitted the unreliability of his "thoughtful" plan.

Head transplantation, body transplantation or brain reconstruction?

In fact, it is different from the general organ transplantation. Assuming that the operation is really successful and the new person's self-awareness belongs to the donor of the brain, then the donor of the brain is the receptor, and the body can only be the donor of life support. Therefore, it is incorrect to call the operation a head transplant. More strictly speaking, it should be called a body transplant or a brain reconstruction.

Why is head transplantation not feasible at present?

No matter what the name is, according to the current standards of organ transplantation, the so-called success should include two aspects, survival and functional reconstruction or recovery. For example, last year, Norway announced that the world's first uterus transplant operation was successful, because the transplanted uterus successfully gave birth to the first transplanted uterus baby.

The key of head transplantation is to reconstruct the structure and function of spinal nerve, restore the function of brain itself, and control and adjust the new body. It is difficult to achieve in the foreseeable long term.

Brain function

The nervous system is divided into central nervous system (brain and spinal cord) and peripheral nervous system.

Brain function can include 1) advanced functions of neocortex, including self-awareness, cognition, memory, personality embodiment, etc. These functional brain tissues can be realized separately. 2) Perception function, which receives various sensory signals of the body through afferent nerves, such as vision, hearing, skin tactile pain and temperature sensation, joint and muscle proprioception and position sensation, visceral traction pain, etc. It depends on the connection between the peripheral afferent nerve and the brain. 3) Dominating motor function requires brain signals to be transmitted to the executive tissues and organs of the body through efferent nerves. 4) The function of internal organs, including endocrine organs, is mainly regulated by autonomic nerve fibers and neuroendocrine mechanisms of afferent and efferent nerves.

That is to say, in addition to the advanced functions of the brain, several other functions must be completed through the connection between the brain and the peripheral nervous system, and the parts involving the body must be used as a "bridge" through the spinal cord.

spinal cord

The spinal cord is that nerve tissue connecte the brain and the peripheral nervous system of the body, in which the part called gray matt is some relay neurons, while the white matter part is nerve fibers compose of neuron axons, and the functions corresponding to perception, movement and visceral regulation are ascending afferent nerve and descending efferent nerve respectively.

Nerve function is usually highly differentiated and precise. For example, if you stimulate the skin side by side with two needles, you will feel different parts of the skin. If the stimulus intensity reaches a harmful level, you will feel pain. These are all sensed by different receptors, encoded into electrical signals along different nerve afferent fibers, and finally transmitted to the brain. Through brain analysis and synthesis, sensory judgments such as position, nature and intensity are produced.

Therefore, nerve fibers, like optical cables for wired communication, are huge in number, transmitted accurately respectively, and usually do not interfere with each other, while the spinal cord, especially the cervical spinal cord, like all communication optical cables in the country, are concentrated in a narrow channel.

Canavelo's scheme, the so-called spinal cord fusion scheme, is tantamount to cutting the optical cable and then sticking the broken ends together with a chemical glue. It is absolutely impossible to establish communication, let alone expect correct and accurate signal transmission.

nerve regeneration

The difference between nerve fiber and optical fiber is that even if the optical fiber is cut off, although the connection between the two broken ends is interrupted, the structure will not be destroyed.

Nerve fiber is an active cell part composed of axons of neurons. Once cut off, the distal axon will disintegrate. Although the proximal axon has certain regeneration ability, it is weak and grows slowly compared with other tissues.

More importantly, the axon regenerated from the proximal end must be correctly docked with the distal end, and it can be fully repaired before it can return to normal function.

Unfortunately, the regeneration of nerve axons lacks navigation mechanism, so it is almost impossible to completely regenerate and dock correctly. What's more, it can also form local scars and prevent nerve regeneration that is already difficult.

This is why it is usually difficult to reconstruct the nerve function once the nerve is injured, at least it is impossible to completely reconstruct it, even if microsurgery is used for nerve anastomosis.

What's more, except neurons and their processes, 90% of cells in nerve tissue are glial cells that support nutrition. Glial cells in peripheral nerve and central nerve tissue are different. The former is a cell called Schwann's cell, whose only function is to produce myelin sheath, the raw material for nerve formation, without producing substances that inhibit axon regeneration.

On the contrary, there are two kinds of glial cells in the central nervous system, oligodendrocytes and astrocytes, which both produce chemical factors that inhibit axonal regeneration. In addition, other factors make axons in the central nervous system basically lack the ability to regenerate (although not completely).

The inhibition of axonal regeneration in the central nervous system is in line with the logic of life. If it can be actively regenerated, once the central nervous system is damaged and regenerated like a weed, it will inevitably lead to "chaos in the world" within the human headquarters.

The spinal cord belongs to the central nervous system, and the nerve reconstruction at the severed end of the spinal cord after head transplantation is precisely the transplantation and regeneration of nerve fibers, namely axons.

In Canaveral scheme, it is not feasible to achieve spinal cord fusion and functional reconstruction only by local use of polyethylene glycol.

Stem cell technology

After Canavero's spinal fusion was questioned, he turned to stem cell technology to solve his embarrassment. So can stem cell technology help rebuild the structure and function of the spinal cord?

So far, only a few animal experimental data are available for reference. In the experiment reported in the journal Neuron 20 14 by the Medical College of the University of California, USA, neural stem cells induced by skin cells of an 86-year-old man were injected into rats with spinal cord cut for 3 months, and it was found that a large number of mature neurons were regenerated at the injured transplantation site, and their axons grew far away and even extended to the brain. Axons pass through the injured tissue and connect with rat neurons. Similarly, the axons of rat neurons penetrated into the graft and formed a large number of connections with cells, but no functional recovery was found.

That is to say, although it is a potential technology that can help spinal nerve regeneration, it is only the preliminary result of animal experiments, and no signs of functional reconstruction have been found.

Therefore, although it is not a mature and feasible technology that can be used in human body, it is difficult to achieve complete neural function reconstruction like head transplantation with completely severed spinal cord because stem cell regeneration neurons need to establish correct bridging connections with proximal and distal nerve fibers at the same time.

However, after all, this method has realized nerve regeneration and brought a glimmer of light for spinal cord function reconstruction.

Other difficult problems

Ethical issues: Head transplantation is bound to encounter unprecedented ethical challenges, in which both the donor and the recipient are physically alive. The first step in the operation process is actually to behead two living people at the same time. This operation alone is difficult to be recognized and accepted. Once the operation fails, the operator will also face criminal charges of intentional homicide.

Rejection: It is impossible for recipients and donors of head transplantation to receive pretreatment such as lavage to prevent rejection, and they can only rely on rejection inhibitors, which makes it difficult to achieve ideal results.

Deep hypothermia resuscitation: At present, there is no successful precedent of "thawing" and resuscitation of frozen head and brain tissue. Although the lowest core temperature record of successful cold injury resuscitation has reached 65438 05.7℃, the power of old human hypothermia resuscitation is very low. There is little hope to recover from the lower cryogenic temperature of 12~ 15℃.

To sum up, it is not feasible to splice the broken ends together and establish a complete neural structure and functional connection after the spinal cord is completely cut off in the foreseeable future.

prospect

The infeasibility of Canavero's head transplantation scheme does not mean that human allogeneic head reconstruction is completely desperate. Dr. Ren Xiaoping, the First Affiliated Hospital of Harbin Medical University in China, together with foreign tutors, has made some beneficial ideas, such as keeping the head of the brain stem to maintain the basic life functions of human beings, which may at least greatly improve the possibility of physical survival. Of course, the operation itself has evolved into a brain transplant operation, and the problem of neural mechanism and functional reconstruction between the cerebral cortex and the lower brain is still insurmountable.