Head transplant: 1928-2017

Professor Canavero's head

Sofya Kabanova, "Biomolecule"

The head, living separately from the body, is the subject of more than one fantastic story: "Professor Dowell's Head", "The Man without a Body", "Frankenstein", and finally, even the animated series "Futurama"! Science fiction and science are so closely intertwined that sometimes it is not possible to understand what is more real. In the arena of medical discoveries, under the gaze of millions of viewers, there is now an Italian neurosurgeon Sergio Canavero, who is confident that he can turn fiction into a genuine scientific breakthrough. He is going to help step medicine into the future by transplanting the head of a patient with muscular atrophy onto a donor body.

From the history course

Sergey Bryukhonenko

The roots of science fiction novels about head transplants grow straight from Soviet laboratories. In 1928, the scientific community was shocked by the living head of a dog resting on a saucer and reacting to external stimuli (Fig. 1a). Physiologist and Doctor of Medical Sciences Sergey Sergeevich Bryukhonenko at the Voronezh Institute of Experimental Physiology and Therapy created the world's first artificial blood circulation device – an autojector, which allowed the dog's head to live 1 hour 40 minutes apart from the body, while reacting to the effects of the surrounding world: she blinked, stuck out her tongue and swallowed pieces of cheese, which immediately slipped out of the esophageal tube [1].

Figure 1. The Bryukhonenko experiment. a is a dog's head resting on a saucer. b – The autojector supplies blood to the dog's head. Drawings from the website rumbur.ru and from the video youtube.com .

The autojector was an imitation of an animal's heart and carried out two circulatory cycles. The role of arteries and veins was performed by rubber tubes connected in a large circle with the dog's head, and in a small circle with amputated lungs (Fig. 1b). The autojector consisted of a reservoir that fed arterial blood through a system of tubes to an arterial pump supplying the brain. Venous blood outflow took place through venous deposition. The blood in the tank was constantly supplied with oxygen (video 1).

Video 1. The 1940 Soviet documentary "Experiments on the revival of the body" about the works of Sergei Bryukhonenko

Bryukhonenko wrote: "Especially active movements followed the irritation of the nasal mucosa with a probe inserted into the nostril. This irritation caused such an energetic and prolonged reaction in the head that even bleeding from the cut-off site opened and the tubes attached to its vessels were almost torn off. I had to hold my head on the plate with my hands. It seemed that the dog's head was trying to free itself from the probe embedded in the nostril. The head opened its mouth several times, and, according to Professor A. Kulyabko, who observed this experiment, it seemed as if it was trying to bark and howl."

Although the pupillary, corneal and some other reflexes of the dog's head were preserved, it certainly was not viable. But Bryukhonenko did not seek to ensure full viability of the head by separating it from the body; he wanted to maintain the life support of the body and its individual organs in conditions of large blood loss. Modern resuscitation and transplantology owes its existence to the autojector Bryukhonenko, for which he was posthumously awarded the Lenin Prize in 1965. His experience served as the starting point for Sergio Canavero's idea.

Vladimir Petrovich Demikhov

The first successful mammalian head transplant was performed in 1954 by Vladimir Petrovich Demikhov [2]. He transplanted the head of a donor puppy with front paws to an adult German Shepherd recipient on the neck. Two large vessels of the donor puppy (aorta and vena cava) were connected to the large vessels of the adult dog's neck. The creation of the anastomoses took place in such a way that the blood circulation in the hooked head did not stop for a minute. After stitching the vessels, a common blood flow circle was created, and the transplanted puppy's head began to live due to the breathing and blood circulation of an adult dog (Fig. 2).

Figure 2. Demikhov's experiment. a – Scheme of blood supply to the head of the donor puppy and the body of the recipient shepherd dog. b – A two-headed dog laps water from Demikhov's hands. v – Demikhov demonstrates an adult recipient dog and the head of a donor puppy attached to it. Drawings from the website nikakult.de , unbelievable.su and kp.ua .

As a result of the experiment, complete preservation of all vital functions of the head was observed: she reacted to her surroundings, looked into the eyes of people who approached her, licked her lips at the sight of food, could bite the ears of the recipient dog if she caused inconvenience to the head, stuck out her tongue at elevated temperature in the room and made rapid breathing movements. Sleep at the transplanted head occurred regardless of the wakefulness or sleep of the recipient dog.

A few days after the operation, swelling of the tissues of the transplanted head began, blood circulation was disrupted. The transplanted head took the shape of a ball, the eyes were completely swollen, the tongue did not fit in the oral cavity. If they pressed on the skin with a finger, then a hole remained. "Someone else's head had to be removed in order to save a dog that had taken in a part of another organism," Demikhov wrote. Out of many dozens of experiments, only one transplanted head remained viable for 32 days, due to the close relationship of dog tissues and the coincidence of blood groups.

Vladimir Demikhov, the father of world transplantology and the teacher of Christian Barnard, who performed the world's first human heart transplant, trampled the path laid by Bryukhonenko into the dense unknown of head transplantation [3].

Robert White

Demikhov's follower, Robert White, successfully transplanted the head of a donor monkey onto the body of a recipient monkey in 1970 (Fig. 3).

Figure 3. Schematic representation of Robert White's experience with monkeys. Drawing from the website cbsnews.com

The head transplant was successful, but White was unable to connect the spinal cord stem to the brain, so although vital functions were preserved, the trunk was paralyzed. In addition, the monkey died nine days later due to the body's immune response (video 2).

White wrote: "What has been achieved on the animal model is fully feasible in the human sphere. What has always belonged to science fiction will become a clinical reality at the beginning of the 21st century. Head transplantation, together with significant improvements in surgical technologies and the management of the postoperative period, can already be considered for the adaptation of head transplant methods to humans" [4-6].

Video 2. A film about successful head transplant operations. An amazing documentary tells about an unusual competition between Russian and American scientists for a head transplant.

Gemini Protocol

Sergio Canavero hopes for a more favorable outcome of the experimental operation than his predecessors: he is striving for full restoration of viability. There are a great many problems facing him: from ethical to practical medical.

I. Is it ethical to cut off a head?

How will representatives of different religions perceive head transplantation? According to some confessions, it is the head that is the receptacle of the soul. Therefore, it is unacceptable to separate it from the body and move it to another. However, a heart transplant met with a storm of negative emotions at one time, and later became an ordinary operation that saves hundreds of lives every day.

What about a person's personality? Will the patient feel like himself? Transplantation of limbs, kidneys, liver or heart separately already carries a psychological trauma for a person. What will the recipient feel if someone else's torso is transplanted to him? Will it be perceived by the brain as its own? An endless stream of questions is addressed to the Italian neurosurgeon. Psychological problems that the patient will undoubtedly have, he intends to stop with a course of psychotherapy.

Normally, information from proprioreceptors, which are responsible for muscle tension, as well as tactile receptors responsible for touch, enters the cortex of the cerebral hemispheres, where, together with information from the organs of vision, it forms a human body image. With any change in data from these receptors, the image changes. Usually this happens gradually and almost imperceptibly – for example, when a person grows up. A radical change in the composition of the body can lead to disastrous consequences. Perhaps the patient will not be able to accept a new body, the cerebral cortex will remember the shape and strength of the limbs of the previous body, and since their sensation has not gone anywhere, these no longer existing limbs will be perceived as phantom [7].

II. From words to the body. To cut or not to cut?

Ethics is only one side of the coin. The other is the practical problems of the functioning of someone else's torso.

Reinnervation

One of the main problems facing the surgeon is reinnervation – the restoration of conductive nerve pathways from the brain to the spinal cord. Otherwise, the brain will not be able to control its new body, and the patient will suffer the fate of White's monkeys, who, although they received new bodies, remained paralyzed.

Canavero claims that it is possible to provide the recipient with a full life activity. In addition, he strives for the least damage to the nerve pathways. The neurosurgeon suggests using a silicon nitride nanoknife (Fig. 4) to simultaneously separate the heads of the donor and recipient. (The structure of the silicon nitride molecule – from the site wikipedia.org .)

This compound of silicon and nitrogen has a high impact strength, and the greater the force applied to the spinal cord during its intersection, the less the nerve pathways that make up it are damaged.

Dr. Canavero intends to connect the recipient's brain and the donor's spinal cord by means of polyethylene glycol (PEG), a synthetic polymer used for decades in industry, pharmaceuticals, mechanical engineering, cosmetics. In medicine, the first mention of PEG occurs in 1990, in the article "Accelerated fusion of separated axons using polyethylene glycol" [8]. Professor of neuroscience George Bittner described the effect of PEG as a "bioclay" on the mechanically crossed nervous system of an earthworm: the fusion of nerve cells reached 80-100%. Bittner demonstrated the result of the action of "biological cement" on data from electron microscopes (Fig. 5) [9, 10].

Figure 5. Electron microscopy data – functions of the musculoskeletal system after spinal cord injury under the influence of PEG and without it. Figure from [9].

In the control sample without the use of PEG, cell integrity was not observed under identical conditions. PEG is non-toxic, protects the membranes of disconnected axons from decay, prevents the formation of a scar at the site of the spinal cord incision, which under normal conditions completely blocks the conduction of nerve impulses (Fig. 6). In 2001, PEG was used in experiments on guinea pigs. Richard Borgens and Deborah Boner in the article "Rapid recovery after spinal cord injuries with the use of polyethylene glycol" claim that when injected through the vascular system, the polymer concentrates at the site of rupture, skipping untouched areas, and causes spontaneous growth and connection of up to 20-30% of animal spinal cord cells [11].

Figure 6. Positive effect of PEG on disconnected nerve fibers. a – The body tries to heal nerve damage by forming bubbles that seal both ends.
b – A standard surgical operation reconnects nerves, but seals at the site of the rupture prevent the passage of some signals.
b – The new method allows you to stop the sealing of the rupture site with a solution that prevents the formation of bubbles, freeing the damage site from calcium.
d – The use of polyethylene glycol to bind the ends.
d – Adding a calcium-rich solution to stimulate the production of bubbles and "sealing" the compound.
Drawing from the website newscientist.com .

Korean scientists collaborating with Canavero conducted such experiments on mice. After 4 weeks, five of the eight animals treated with PEG had their motor ability restored (video. 3).

Video 3. A mouse, which by processing PEG severed spinal cord and brain, returned full motor activity

In addition to PEG, the neurosurgeon plans to use epidural stimulation, through which the spinal cord will receive electrical signals that encourage it to work (Fig. 7).

Figure 7. Schematic representation of epidural stimulation of the spinal cord. Drawing from the website nibib.nih.gov . Click on the drawing to view it in full size.

Oxygen starvation

To ensure the safety of the Canavero brain is collected by storing it in hypothermia (at 10-15 ° C) – this will give the cells the opportunity to remain viable for a long time without oxygen. Hypothermia is used during operations on deep areas of the brain [12].

A Chinese colleague of the Italian surgeon Zhen Xiaoping, who performed the world's first hand transplant in 1999, repeated White's experience with head transplantation to a monkey, only under hypothermia, and the monkey underwent the procedure without neurological damage (Fig. 8, 9) [13].

Figure 8. A monkey who underwent a head transplant. Drawing from the website newscientist.com .

Figure 9. Sections of the monkey's spinal cord. a is a schematic representation of the slice. b – Nanoscale slice: visualization of the cut cortical-spinal pathway and its axons. Figure from [14].

Immune blow to the head

Another global problem facing Canavero is the body's immune response to someone else's head. The monkey from White's experience died precisely because the body's immune system rejected the artificial acquisition of the organism. The graft-versus-host reaction is not uncommon. The probability that the body will rebel against the stranger is very high. The brain has a special position in the immune system: it belongs to the immunopriveligated organs (together with the testes, eyes, thyroid gland). The immune system "does not know" about the existence of these organs. However, in the case of injuries, when the antigens of barrier organs enter the systemic circulation and are "captured" by immunocompetent cells, a rejection reaction of their own tissues begins. The operation will be exactly the same injury. In addition, the brain has its own immune system, represented by microglia. Consequently, there is an immunological conflict between the microglia of the brain and spinal cord.

The neurosurgeon is going to suppress the reaction by using immunosuppressants.

Plan – K

Only an hour will be given to Professor Canavero's surgical team to perform cephalosomatic anastomosis.

To speed up recovery, he is going to put patients in an artificial coma for several weeks after surgery to eliminate possible movements and ensure better fusion of tissues and neurons. During this period, by means of epidural stimulation, the damaged parts of neurons will be stimulated to grow. In case of successful completion of the operation, Canavero recommends prescribing a course of psychotherapy and physiotherapy to the patient.

High hopes

The Gemini protocol developed by Sergio Canavero for head transplantation opened Pandora's box [14]. Skepticism about the real possibility of a head transplant on a donor body is gaining momentum every day. The scientific community is divided into supporters and opponents of the Italian neurosurgeon. Patients, doomed by their diagnoses to the torments of life, are holding their breath, waiting with hope for the results of the upcoming operation (Fig. 10). The surgeon himself believes that tetraplegia (paralysis of four limbs) can be cured only by transplantation: "In the long run, the organs of the body are weakening, so patients need a new body – otherwise, even if you restore the spinal cord, you won't get far."

2017 will open the veil of mystery: is such a fantastic operation as a head transplant really possible?

Figure 10. Sergio Canavero with his patient Valery Spiridonov, a patient with muscular atrophy [15]. Drawing from the website utro.ru .

Literature

1. Bryukhonenko S.S. (1937). The use of artificial blood circulation to revitalize the body. Sat. Tr. In-ta exp. physiology and therapy. 1, 32–34;
2. Likhacheva G.V. (2002). At the origins of transplantology. Biology. 43;
3. Demikhov V.P. Transplantation of vital organs in an experiment. Moscow: Medgiz, 1960. – 260 p.;
4. Segall G. (2010). Dr. Robert J. White, famous neurosurgeon and ethicist, dies at 84. Cleveland.com;
5. White R.J., Wolin L.R., Massopust L.C. Jr., Taslitz N., Verdura J. (1971). Cephalic exchange transplantation in the monkey. Surgery. 70, 135–139;
6. Brain transplants. (2014). BBC reports archive;
7. Kovanov V. Experiment in surgery. M.: Molodaya gvardiya, 1989. – 240 p.;
8. Krause T.L. and Bittner G.D. (1990). Rapid morphological fusion of severed myelinated axons by polyethylene glycol. Proc. Natl. Acad. Sci. USA. 87, 1471–1475;
9. Bittner G.D., Rokkappanavar K.K., Peduzzi J.D. (2015). Application and implications of polyethylene glycol-fusion as a novel technology to repair injured spinal cords. Neural. Regen. Res. 10, 1406–1408;
10. Bittner G.D. and Fishman H.M. Axonal sealing following injury. In: Nerve regeneration / ed. by Ingoglia N. and Murray M. NY: Marcel Dekker, 2000. P. 337–369;
11. Borgens R.B., Shi R., Bohnert D. (2001). Behavioral recovery from spinal cord injury following delayed application of polyethylene glycol. J. Exp Biol. 205, 1–12;
12. Canavero S. (2013). HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI). Surg. Neurol. Int. 4, S335–S342;
13. Wong S. (2016). Head transplant carried out on monkey, claims maverick surgeon. New Scientist;
14. Canavero S. (2015). The “Gemini” spinal cord fusion protocol: reloaded. Surg. Neurol. Int. 6, 18;
15. Granina N. (2015). “For me, this is freedom.” <url>.

Portal "Eternal youth" http://vechnayamolodost.ru   14.10.2016