Cryonics: Using low temperatures to care for the critically ill
By Aschwin de Wolf
In contemporary medicine terminally ill patients can be declared legally dead using two different criteria: whole brain death or cardiorespiratory arrest. Although many people would agree that a human being without any functional brain activity, or even without higher brain function, has ceased to exist as a person, not many people realize that most patients who are currently declared legally dead by cardiorespiratory criteria have not yet died as a person. Or to use conventional biomedical language, although the organism has ceased to exist as a functional, integrated whole, the neuroanatomy of the person is still intact when a patient is declared legally dead using cardiorespiratory criteria.
It might seem odd that contemporary medicine allows deliberate destruction of the properties that make us uniquely human (our capacity for consciousness) unless one considers the significant challenge of keeping a brain alive in a body that has ceased to function as an integrated whole. But what if we could put the brain “on pause” until a time when medical science has become advanced enough to treat the rest of the body, reverse aging, and restore the patient to health?
Putting the brain on pause is not as far fetched as it seems. The brain of a patient undergoing general anesthesia has ceased being conscious. But because we know that the brain that represents the person is still there in a viable body, we do not think of such a person as “temporarily dead.”
One step further than general anesthesia is hypothermic circulatory arrest. Some medical procedures, such as complicated neurosurgical interventions, require not only cessation of consciousness but also complete cessation of blood flow to the brain. In these cases the temperature of the patient is lowered to such a degree (≈16 degrees Celsius) that the brain can tolerate a period without any circulation at all. Considering the fact that parts of the human brain can become irreversibly injured after no more than five minutes without oxygen, the ability of the brain to survive for at least an hour at these temperatures without any oxygen is quite remarkable.
Again, because we know that in such cases the brain that represents the person is still there in a viable body, we do not think of such a person as “temporarily dead.” These examples illustrate that the medical community already recognizes and accepts the fact that a medical procedure that produces loss of consciousness, and even loss of circulation, does not constitute irreversible death.
Unfortunately, general anesthesia and hypothermic circulatory arrest cannot be used to pause the brain long enough to find a treatment for a person who has been declared legally dead by cardiorespiratory criteria. A person under general anesthesia may require tens, if not hundreds, of years of artificial circulation to keep the brain viable until medical science is able to return him to health. Leaving financial considerations aside, artificial circulation of an organ, let alone such a vulnerable organ as the brain, will produce increasing brain injury over time, and ultimately, destruction of the person.
Hypothermic circulatory arrest eliminates the need for metabolic support of the brain, but only for a limited period of time. Current research into hypothermic circulatory arrest indicates that the brain might tolerate up to 3 hours of complete circulatory arrest if the temperature is lowered close to the freezing point of water (zero degrees Celsius). This is not nearly long enough to put the brain on pause to allow the patient to reach a time where his current medical condition may be treatable. In light of these limitations, it is understandable that no serious attempts are currently being made to continue long-term care for a patient whose body has stopped functioning as an integrated organism.
But if low temperatures can extend the period that the brain can survive without circulation, much lower temperatures should be able to extend this period even further. At -196 degrees Celsius molecular activity has become so negligible that it can be said that the brain has been put on pause in the literal sense of the word. This allows the patient to be “transported” to a time when more advanced medical technologies are available, even if this would require hundreds of years. Advocates of human cryopreservation argue that long-term care at cryogenic temperatures offers a rational alternative to the current practice of burial and cremation of persons no longer treatable by contemporary medicine.
Contrary to popular views of cryonics, cryonics is not about preserving dead people but about long-term care of critically ill patients. The objection that cryonics is an attempt to resuscitate dead people reflects a misunderstanding of the rationale behind cryonics. The arguments supporting human cryopreservation are not radically different than the already established arguments behind general anesthesia and hypothermic circulatory arrest; it merely introduces lower temperatures and longer care. Therefore, the difference between contemporary medicine and cryonics is quantitative, not qualitative, in nature. Likewise, the relationship between cryonics and religion is not qualitatively different than that between contemporary medicine and religion. In both cases medical technology is used to preserve life.
But does the procedure of cooling a patient to cryogenic temperatures not cause injury in itself? Most of the human body consists of water and lowering the body below the freezing point of water will produce massive ice formation. For this reason, patients who present for cryonics are protected from ice damage by using a cryoprotective agent to reduce, or even eliminate, ice formation. Conventional extracorporeal bypass technologies are used to circulate the solution throughout the body. When enough water is replaced with the cryoprotective agent the patient is maintained at cryogenic temperatures for long-term care. Historically the cryoprotective agents that were used in cryonics are mainstream cryoprotective agents such as DMSO and glycerol. High concentrations of glycerol or DMSO can significantly reduce ice formation, but cannot eliminate it altogether.
A better alternative to conventional cryoprotection is vitrification. Vitrification offers the prospect of cooling an organ to cryogenic temperatures without ice formation. Although vitrification of pure water requires extremely high cooling rates, these cooling rates can be greatly reduced if high concentrations of cryoprotective agents and “ice blockers” are added. Ice blockers are synthetic variants of naturally occurring anti-freeze proteins used by hibernating animals to protect themselves from freezing injury. The vitrification agent is introduced within a so-called “carrier solution” which includes molecules to prevent cell swelling, support metabolism, maintain physiological pH, and prevent oxidative damage. The vitrification agent is introduced in a gradual fashion to prevent excessive volume changes in cells. During the final stages of cryoprotectant perfusion the temperature is dropped below zero degrees Celcius to protect the cells from toxicity caused by high concentrations of the vitrification agent at higher temperatures.
The current generation of vitrification agents can preserve the fine details (ultrastructure) of the brain without requiring unfeasible cooling rates. Although electrical activity has recently been demonstrated in vitrified rabbit brain slices, reversible vitrification of the human brain without loss of cellular viability is currently not possible. The current research objective, therefore, is to improve on these vitrification agents to allow for reproducible vitrification and recovery of organs with complete long-term viability. Such a breakthrough would not only lead to cryogenic organ banking for transplantation and research but would remove the most fundamental obstacle to suspended animation of humans.
Brain death and cryonics
Although a vitrified patient cannot be rewarmed and restored to health with contemporary technologies, the extremely low temperatures at which a patient is maintained permit possible resuscitation of a patient in the future without any risk of deterioration during long-term care. In this sense it compares favorably to procedures such a hypothermic circulatory arrest which allow for only a few hours to treat a patient. This not only offers the option to treat patients who cannot be treated with contemporary medical technologies, it also offers the possibility to treat medical conditions where successful resuscitation is possible but higher brain function will be lost if care is resumed at normal body temperature.
A good example of this is cardiac arrest. Patients who have suffered more than 5-7 minutes of cardiac arrest can often be resuscitated, but some of the most vulnerable cells in the brain (such as the hippocampal CA1 neurons) will die within days of the insult. There are currently no effective medical interventions or neuroprotective agents that will prevent such damage. As a result, today’s medicine can restore viability to such patients, but only by losing some, or most, higher brain functions.
If one believes that the objective of medical care is not just to preserve life in the sense of integrated biological function, but also to preserve the person, then one would agree that such patients might be better served by interventions that place them under long-term care in the form of cryonics. Although there is no guarantee that such patients will be restored to full functionality in the future, the certainty of higher brain death is an alternative that many people would prefer to avoid.
Cryonics does not involve the freezing of dead people. Cryonics involves placing critically ill patients that cannot be treated with contemporary medical technologies in a state of long-term low temperature care to preserve the person until a time when treatments might be available. Similar to such common medical practices as general anesthesia and hypothermic circulatory arrest, cryonics does not require a fundamental paradigm shift in how conventional medicine thinks about biology, physiology, and brain function. Although current cryopreservation methods are not reversible, under ideal circumstances the fine structure that encodes a person’s personality is likely to be preserved. Complete proof of reversible vitrification of human beings would be sufficient, but is not necessary, for acceptance of cryonics as a form of long-term critical care medicine. The current alternative is death; or for persons who are at risk of suffering extensive brain injury, loss of personhood.
For very old and fragile patients, meaningful resuscitation would require reversal of the aging process. Obviously, the objective of cryonics is not to resuscitate patients in a debilitated and compromised condition, but to rejuvenate the patient. Ongoing research in fields such as biogerontology, nanomedicine, and synthetic biology inspire optimism that such treatment will be available in the future. The fortunate thing for cryonics patients is that even if fundamental breakthroughs in these fields will be the result of long and painstaking research, the cold temperatures allow them time — a lot of time.
“We’ll look back on this 50 to 100 years from now — we’ll shake our heads and say, “What were people thinking? They took these people who were very nearly viable, just barely dysfunctional, and they put them in an oven or buried them under the ground, when there were people who could have put them into cryopreservation. I think we’ll look at this just as we look today at slavery, beating women, and human sacrifice, and we’ll say, “this was insane — a huge tragedy.” Alcor CEO Max More, Ph.D.
The first minutes after “death”
As currently practiced, cryonics procedures can only be started after legal death has been pronounced by a medical professional. To prevent brain injury between pronouncement of legal death and long-term care in liquid nitrogen all major cryonics organizations offer standby services to ensure that the time of circulatory arrest is minimized. In ideal circumstances the cryonics organization of which the patient is a member will deploy a standby team consisting of cryonics professionals to stabilize the patient immediately after pronouncement of legal death.
A mechanical device is used to restart blood circulation and ventilate the patient. Because the objective of this intervention is not to resuscitate but to stabilize the patient this is called cardiopulmonary support (CPS). At the same time the patient is lifted into a portable ice bath to induce hypothermia to slow metabolic rate. A number of medications are also given to support blood flow to the central organs, reverse and prevent blot clotting, restore physiological pH, prevent edema, and protect the brain from ischemic injury.
If the patient is pronounced legally dead at a remote location an additional step to this protocol is added and the patient’s blood is washed out and replaced with an organ preservation solution to preserve viability of the tissue during transport at low temperatures. The organ preservation solution that is currently used by cryonics organizations is similar to the cold organ preservation solutions that are used in conventional medicine (such as Viaspan) to preserve organs for transplantation.
At the cryonics organization the patient’s blood (or the organ preservation solution) is replaced with the vitrification agent to prevent ice formation during cooldown to liquid nitrogen temperatures for long-term care.