A patient without a head

Have surgeons learned how to repair a severed spinal cord

A group of researchers reported successful recovery of motor function in animals with severed spinal cord. Among the authors of the publication is Sergio Canavero, the same Italian neurosurgeon who has been promising to transplant a person's head onto a donor's body for many years. About the history of this project and how to treat the promises of Canavero, at the request of N+ 1, Peter Talantov, the author of the just published book "0.05. Evidence-based medicine from magic to the search for immortality."

Head transplantation is a favorite subject of science fiction films and scientific news sections. And it's not just the incredible technical complexity of the transplant. On the one hand, the thought of living with someone else's body stirs the imagination, touches the sense of identity and makes us think about what we are. On the other hand, it opens the door to immortality. If we ever learn to shed our bodies like worn-out clothes, we can no longer be afraid of old age and death.

All this condemns any news about a head transplant to a stormy discussion. For some time now, Sergio Canavero, the chief newsmaker of transplantology, has been promising for years to write his name into the history of surgery with this operation. If you take his word for it, all the necessary technologies have been created and it's just a matter of assembling a team of experienced surgeons and finding a lot of money. But the deadlines mentioned once passed, and even the first potential patient managed to change his mind. Maybe it's true, as the skeptics (and most of them) say, we are still too far from planning such an operation seriously?

Any organ transplant operation requires solving several problems at once, each of which, if not eliminated, will lead to failure. In the case of a head transplant, protecting the brain from ischemia (decreased blood circulation) is critical – even a few minutes of ischemia will lead to irreversible changes in the brain and the death of the recipient's personality. Apparently, that is why the first attempts to transplant a dog's head onto a donor body at the beginning of the XX century were unsuccessful.

Restore blood supply

Attempts to maintain life in a head separated from the body were made by our compatriot Sergey Bryukhonenko. In the 1930s, while working at the Institute of Experimental Physiology and Therapy, he created one of the first artificial blood circulation devices, called an autojector. The twenty-minute film "Experiments to Revive the Body" shows a dog's head separated from the body. She is attached to the device and remains alive – reacts to tickling with a feather, blinks and licks her lips. The voice-over tells that the head connected to the autojector remains in this state for many hours. However, later witnesses admitted that it was possible to maintain the dog's heads in this state for only a few minutes. And the famous scene from the film is now considered a fabrication.

Bryukhonenko's experiments inspired surgeon Vladimir Demikhov to even bolder experiments. He transplanted the upper part of the trunk – the head and front legs – of puppies onto the body of larger dogs. Demikhov's method allowed the operation to be performed without ischemia threatening brain death. The animals survived for up to twenty-nine days, while moving, responding to stimuli and drinking water. But Demikhov remained in history not so much because of this strange experiment, but because he was the first in the world to transplant a heart, lungs and liver from one animal to another. Thanks to his developments in 1967, a successful human-to-human heart transplant became possible. The surgeon who made it, Christian Barnard, repeatedly came to Demikhov's laboratory and subsequently called him his teacher.

The scheme of a dog's head transplant according to Vladimir Demikhov's technology...

...and its result.

Demikhov's dogs died from an immune process called the transplant rejection reaction. In the absence of effective immune suppression technologies, such an outcome was inevitable. During a head transplant, the rejection reaction can be directed both to the donor body and, more likely, to the recipient's head. Even now, despite the drugs suppressing immunity, acute rejection occurs after 10-30 percent of liver and kidney transplants. And if the rejection of the kidney leaves the patient a chance to wait for a new donor organ on an artificial kidney, then the rejection of the head certainly threatens death.

Suppress rejection

The methods of suppressing immunity that appeared in the middle of the XX century contributed to the relative success of the experiments of the American neurosurgeon Robert White. He took on an even more difficult task: transplanting the isolated brain of one dog into the skull of another. Six operations were relatively successful: the nervous systems of the donor brain and the recipient body were not connected, but the brain was effectively supplied with blood - this was confirmed by sufficient electrical and metabolic activity, after the operation the animals lived up to two days.

Subsequently, White transplanted monkey heads: a few hours after the operation, they could chew, swallow food, bite and follow moving objects with their eyes. However, they did not live long: the blood supply was still not efficient enough. And although the super-acute rejection reaction of the transplanted heads was prevented, White achieved this with such high doses of immune-suppressing substances that they themselves contributed to the death of the animals.

Over time, White planned to move on to human operations, trained on corpses in the morgue and dreamed of transplanting Stephen Hawking's head onto a donor body. Fortunately for the latter, he was not interested in this opportunity and outlived White by eight years.

The Chinese surgeon Ren Xiaoping was able to achieve a longer life span of animals. He changed the operating protocol, achieving the maintenance of sufficient blood pressure in the vessels of the recipient's head throughout the operation. In 2015, he reported hundreds of transplanted mouse heads, half of the animals lived more than 24 hours after surgery with a maximum survival rate of up to six months.

A-B – four mice of different colors before the head transplant operation according to the technology of surgeon Ren Xiaoping; C-D: a white mouse with a black head and vice versa; E – a black mouse with a gray head.

A – blood transfusion vessels; B – mice before surgery (from left to right: blood source, donor, recipient); C – mouse – blood source and donor mouse; D-E - mice after transplantation Dr. Xiaoping Ren et al.
/ CNS Neuroscience & Therapeutics

Ren also suggested changing the level at which the head was separated from the body. He suggested making an incision high enough so that the brain stem with the centers of regulation of respiration and blood circulation would remain on the donor body, which as a result would be able to breathe independently and be supplied with blood without the help of life support devices.

Human surgery

Around the same time, Sergio Canavero appears on the scene. A previously little–known Italian neurosurgeon said that he could solve the main problem of a head transplant - to restore the integrity of the spinal cord. So far, all attempts to fuse the spinal cord after the incision have been unsuccessful. There are several areas in which research is underway, but they are all at an early stage.

Attempts are being made to stimulate the regeneration of neurons with the help of electrical impulses, to use stem cells. Experiments with computer interfaces are interesting: one device reads brain signals and transmits it to another located below the site of spinal cord injury, which decrypts them and transmits them to motor neurons. Although all these technologies sound promising, in no case has it been possible to achieve complete success even in animal experiments. Moreover, we are not talking about results suitable for people: there are thousands of patients with damaged spinal cord in the world, and if there is an effective technique, there will definitely be someone to study it on long before head transplant operations.

Canavero named his technology GEMINI. It consists in a very precise and thin section of the spinal cord and the use of polyethylene glycol as a substance that "glues" the ruptures of neuronal membranes. Canavero said that all the technologies necessary for a successful head transplant have already been created and he will perform an operation on a person in the very near future. According to his estimates, it was supposed to cost about 15 million euros, last more than 36 hours and take place with the participation of 150 doctors.

Soon the first patient appeared. Kanavero announced that no later than 2017, he will transplant the head of 33-year–old Russian IT specialist Valery Spiridonov, suffering from spinal muscular atrophy, a rare hereditary disease accompanied by loss of motor neurons and a sharp decrease in muscle mass, onto a donor body.

Although Canavero claimed that the probability of success of the operation was at least 90 percent, he did not have the minimum necessary confirmations obtained in previous animal experiments. The only proof at that time that GEMINI could work in principle was the publication of his Korean colleague Si Yun Kim. He reported that polyethylene glycol led to partial restoration of motor function in mice with severed spinal cord. At the same time, an attentive reader will find that, although the experimental mice recovered slightly better, the difference with the control group was not statistically significant, that is, it could well be explained by chance.

Arguments against

Despite Spiridonov's willingness and Kanavero's enthusiasm, the possible operation raised many questions and sharp criticism from most professionals. The risk of death of the patient during the operation or shortly after it was exceptionally high: most of the animals died in the first days after transplantation. The risk of transplant rejection was also high – only powerful lifelong immunosuppressive therapy could reduce it, itself a source of deadly risk. The chances of gaining mobility were ephemeral and not confirmed by anything. But the risk of difficult-to-treat neuropathic pain was quite real. Canavero also intended to deal with this problem surgically – by destroying the part of the brain responsible for transmitting the emotional component of pain, which causes the suffering associated with it.

There would probably be other problems that we don't know about yet. But even the above is enough to understand that the balance of potential benefit and harm is unlikely in favor of the operation. The conclusion will remain the same, even if we consider patients who are facing imminent death.

Some skeptics recalled the story of another transplant surgeon, Paolo Macchiarini, who worked first at Karolinska and then at Kazan Federal University. He claimed that he had developed a technique for transplanting an artificial trachea containing stem cells – allegedly the organ takes root and does not cause an immune response in the patient's body. Later it turned out that the technique was not tested on animals, did not work in any case, and Macchiarini condemned several patients to severe surgery and the associated suffering without the slightest hope of improvement.

Another, perhaps the most important of the critics' arguments was of an absolutely practical nature. The demand for donor organs significantly exceeds the supply. On average, 20 people die every day without waiting for their turn. At the same time, the situation is not getting better: the waiting list for transplantation is growing faster than the number of available organs. Is it reasonable to use a donor body to save (with scanty chances of success) one life, instead of using these organs to save and improve the lives of 10-15 patients?

A modest result

However, time passed, and conversations remained conversations. Canavero, who received funding from the Chinese government, works with Ren Xiaoping. The recent publication is the result of their joint work. But we are no longer talking about a head transplant: the work is being carried out within the framework of a project for the treatment of spinal cord injuries. Although at the end of 2017, Canavero sent out victorious press releases about a successful head transplant, the operation was performed on a corpse. Meanwhile, Valery Spiridonov cooled down to the idea of becoming the first volunteer for such an operation, got married and moved to live in Florida. According to foreign media reports, his beautiful wife gave birth to a healthy child.

Expert opinion

I would treat this job with caution. Canavero's group published articles almost two years ago in which they said that it is already possible to perform a head transplant operation and there is a test subject - that Russian programmer. And only now the first article appears, which substantiates what could have been implemented two years ago. In standard practice, the opposite happens: first you get a theoretical basis, then you conduct experiments in vitro, then in vivo, and only after that you start talking about the possibility of human operations.  The theoretical basis on which this study is based is insufficient.
If you look at the list of references in the article, it is very small, and mostly the authors refer to themselves, to their research, and this is always alarming, as well as the size of the article.  The magazine itself, let's just say, is not the top in the world.
If this article had been published with a list of 60-100 references in Cell or Lancet, I would have had more confidence in it.  It is important that Canavero and his colleagues were the initiators of the idea of using polyethylene glycol – it allegedly prevents the formation of a scar between nerve tissues and promotes recovery.
But there is no independent confirmation of this.  And this statement itself is doubtful: nerves do not germinate into each other not only because a scar is formed there, but also because they have, in principle, a low regenerative capacity.
If we take into account that the same article itself says that it was not possible to detect a significant difference in the formation of a scar, then the mechanism of action of polyethylene glycol becomes completely incomprehensible.  Many groups are working on spinal cord repair methods.
In particular, electrical stimulation gives interesting results, there is evidence that electrical stimulation below the level of damage leads to accelerated growth, moreover, there are cautious attempts to apply this on a person. There is a research group of Martin Schwab, who is studying the possibilities of the Nogo-A family of proteins for stitching the spinal cord. But these works last for decades. It does not happen that you have written a four-page article and you can already apply it to a person.  I'm not saying that the Canavero group is cheating.
But we need longer studies, evaluation on large groups of animals. And it's strange that they start with the spinal cord, and not with simpler models, such as nerves.  Alexey Kashcheev, neurosurgeon, employee of the Scientific Center of Neurology.

However, Canavero is unlikely to be satisfied with modest work on everyday medical problems. In recent interviews, he claimed that a head transplant for him is yesterday. Now Canavero is going to move on to the second stage of the project – brain transplantation into a donor body and promises to perform this operation on a human in the next 3-5 years. I want to believe that this time he will limit himself to corpses.

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