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Putting death on ice: new hope for those dying from incurable diseases may come from cryonics research.

Benjamin Franklin, who predict" ed humans would one day live to be 1,000 years old, once said he would prefer to live one year every 100 years, so that he could peek into future centuries, even millennia. Modern-day cryonics may eventually fulfill that fantasy, and the United States, home of the world's most prominent cryonics facilities, is in the vanguard of this emerging science-investigating suspended animation to enable sick humans to hibernate at sub-zero temperatures for decades, even centuries, without damage to the cellular structures, and to be awakened when cures are found for them.

Since 1968, when the first human was cryonically suspended, the number has been steadily growing. There are now some 20 people worldwide in suspended animation, and hundreds have signed up.

But the technology of cryonics has not yet been perfected. Patients who are frozen with today's techniques cannot be thawed out and revived. The cryonic suspension procedure involves the lowering of body temperature to -196 degrees C, after having perfused protective chemicals through the circulatory system. (All experts agree that at liquid nitrogen's temperature of -196 degrees C, molecular motion is extremely slow and decay is essentially nonexistent. At this cold temperature, degeneration that would take one second at normal temperature would take 30 trillion years.) But the process also causes freeze damage. In fact, no vertebrate has ever been or can presently be revived after deep-freezing and thawing. So although cold can preserve, it can also destroy. At -20 degrees C most of the fluids in cells are frozen, causing the formation of ice crystals and possibly substantial damage.

Further, scientists are thus far unable to even estimate the extent of freeze damage occurring during a cryonics suspension performed at the time of clinical death because measurement of the damage would require thawing.

So those who have been frozen with current techniques will be thawed using advanced and improved technologies in the future. Death: A Process, Not a Moment

Cryonics is implemented at the time of clinical and legal death, defined as loss of cardiovascular activity and brain waves. And although many might argue that when you are dead, you are dead, this simply is not true. Leaders in cardiovascular physiology, and medical resuscitation experts such as Dr. Peter Safar at the University of Pittsburgh, agree that death is not a moment but a progressive pathophysiological process of systems shutting down-that it occurs over time. A patient is declared dead after his heart stops beating and the coordination of his body is absent. But the cells, tissues, and organs are still alive, and very much so. In fact, organs are now being used for transplantation after clinical death.

Thus, true death occurs when a person is pronounced dead and left at room temperature, causing the cells to deteriorate. Burial then permits the total destruction of the organism. Cooling and freezing prevents this normal progression. In fact, reversal of death in humans is currently possible within 5 to 20 minutes of onset. And people have survived as much as 22 minutes underwater and after hours of clinical death. Advances in resuscitation medicine are expected to enable the reversal of clinical death after even longer periods of time.

Encouraging progress is also being made by cryobiologists-scientists studying the effects of cold on single cells and on such human organs as hearts, livers, and kidneys in the hope that, one day, whole organs can be stored for transplantation. At present, hearts and livers can be stored for only a few hours and kidneys for only a couple of days.

As with whole human bodies, though, the problem with trying to keep organs frozen is that the very process of freezing tissue tends to destroy it. The spaces between cells are filled with water. When the temperature drops to 32 degrees F or below, this water freezes, forming ice crystals on the outside of the cells, which sever and tear the organs and can cause substantial damage.

The challenge, then, is either to avoid the formation of ice altogether, by freezing and thawing so fast that crystals do not have time to form, or to minimize ice formation by pumping high doses of glycerol or some other cryoprotectant into the organ. Although both techniques hold out much promise, rapid-thawing technologies are so far immature, and cryoprotectants are usually toxic.

One promising new approach to organ preservation is a technique called vitrification. Fluids in an organ are replaced by a cryoprotectant that, when cooled, becomes instantly hard as glass. The vitrifying solution seems to leave kidneys intact, experts at the American Red Cross say, but it is too soon to predict whether the organs will regain full function after transplantation.

Dramatic breakthroughs are taking place, however, in labs that are working with single, discrete cells. This work could impact on the large-scale preservation of bodies and organs. Free of the problem of damage from surrounding water crystals, individual cells such as ova and sperm are being rapidly frozen. In fact, many mammalian cell types and almost all human tissues can be frozen and cryopreserved with great success. Such tissues as human corneas, blood components, sperm, bone marrow, skin, intestines, lymphocytes, erythrocytes, teeth, kidney tissue, and embryos are routinely being frozen and stored in liquid nitrogen-and surviving the process. Although a great variety of cell types and tissues can be cryopreserved, it is not yet possible to reversibly freeze entire organ systems of appreciable size, or entire vertebrates.

Strong evidence suggests, however, that such technology is feasible. Many species of insects can tolerate deep, subzero temperatures, and insects are in fact highly complex organisms comprising many cell types in an organized array. Thus, nature demonstrates that the freezing of highly complex tissues is possible.

Also of great relevance to humans is the knowledge that some species of frogs can tolerate partial freezing during winter months in the northern United States and Canada, thus proving that nature already successfully practices cryopreservation. The frogs produce cryoprotective polyols (like glucose and glycerol) that allow them to survive temperatures of -9 degrees C, when nearly 50 percent of their bodies turns to ice. Likewise, golden hamsters can survive temperatures between O degrees C and -2 degrees C after their body water becomes up to 50 percent ice, but only for a period of about one hour. If the hamster can tolerate this extent of freezing without cryoprotectants, it is conceivable to assume that mammalian species might also be able to tolerate long-term storage in a partially frozen state if cryoprotectants could be administered and distributed throughout the body, as occurs naturally in frogs.

Medical Benefits

Strictly speaking, cryonics is considered the freezing of the human body in liquid nitrogen, in hopes that future medical and scientific progress will enable the thawing and revival of the patient. But the blood substitute and protocols developed in order to advance cryonics technology have immediate applications in low-temperature medicine. Such applications include multi-organ preservation; bloodless surgery; therapy for overcoming the blood-borne symptomatic infections that accompany AIDS; and specific, organ-directed, high-dose cancer chemotherapy. A number of surgical and experimental procedures can potentially be performed in an ice-cold, bloodless condition, thereby eliminating certain risk factors that accompany such operations at normal temperatures.

The blood substitute also has important implications for chilled, bloodless surgery, possibly allowing for major surgery that requires little or no donated blood for transfusion. (This is assuming a high degree of importance these days, given the risk of a patient's contracting AIDS from tainted blood during surgery.) The blood substitute can also be used at ice-cold temperatures to extend storage time for multi-organ transplant donors. Currently, the postmortem storage time of hearts, livers, lungs, and certain vital organs is limited to several hours.

The blood substitute can also be effectively used to maintain transplant recipients and other nearly terminal individuals over time spans of weeks or months until needed organs, tissues, machinery, or therapies become available. Thus, cryonics has the potential to become the backbone of space medicine, maintaining seriously ill or injured astronauts during prolonged missions.

One of the most important and immediate applications of low-temperature medicine, however, is the use of the blood substitute at ice-cold temperatures for specific, organ-directed, high-dose cancer chemotherapy. In this case, the cancer patient is chilled, blood-substituted, and cooled to the ice point. The organ bearing the tumor is selectively warmed and perfused with warmed, oxygenated blood containing very high concentrations of powerful anti-tumor agents, while the other tissues and organs are protected by the cold.

The chemotherapeutic agents selectively destroy the proliferating cancer cells, but dividing cells in other tissues and organs normally poisoned by such treatment (due to the high toxicity of the chemotherapeutic agents) are protected by the cold and the specificity of the organ receiving the antimetabolite.

After Life

Cryonics, however, is just the tip of the iceberg in the broader discipline of the life-extension sciences. Life-extension sciences include such areas as interventive gerontology, which involves trying to understand the aging process, hopefully slowing or halting it, and eventually reversing it; transplantation and artificial organs, in which unbelievable progress is being made; regeneration and biological repair; resuscitation, or the reversal of death; and cloning, creating whole organs and body parts genetically identical to our own using the nuclei and genetic material preserved in the suspended patient's cells. Scientists may also be on the verge of locating and tampering with the DNA-level biomechanisms that cause aging.

Yet, most of what is known conclusively about aging and life extension has been discovered only during the past few decades. It was only in the late 50s, for example, that Leonard Hayflick demonstrated that human cells-with the notable exception of cancer cells-replicate a maximum of 50 times. This phenomenon, known as the Hayflick limit, was major news to scientists, who had been clinging to the results of prior research, believing that human cells were immortal. Fifty replications roughly corresponds to 115 years, giving us a maximum life span and making us by far the world's longest-living mammals.

What remains a mystery is just how our cells know when they have hit 50 replications: even when frozen and thawed, they still "remember" what number they are on. Considerable effort has therefore gone into trying to locate the internal clock, since slowing it down would theoretically extend human life. Is it in the magically complex DNA molecule discovered only 30 years ago, or is it somewhere in the brain?

California Institute of Technology scientists are trying to find a way to keep DNA from deteriorating, allowing it to be kept in constant healthy replication. If this experiment succeeds, it could potentially slow the process of aging. And if this is done soon, we may be the last generation to die young," and our grandchildren may be the first to measure their lives in centuries.

Moreover, advances in our understanding of human aging may result in the ability to reverse age changes, which could permit the revival of old, cryonically suspended patients as young, healthy individuals.

Mortality and Life


Despite the fact that cryonicsts and life-extension scientists are on the cutting edge of major advances in the way life is sustained, cryonics is still a controversial science. Even some of the cryobiologists trying to deep-freeze single cells and whole organs think that cryonics is moving too fast.

It is entirely possible to understand such criticism without having to accept it. After all, what is seen as science fiction today may be the reality of tomorrow. Albert Einstein, perhaps the most creative mind of the 20th century, said that "imagination is more important than knowledge" and that aU great ideas and innovations have always encountered violent opposition from mediocre minds. " So we must reach out to grapple with the complex and eternal questions. Science must be daring and it must be innovative.
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Author:Ben-Abraham, Avi
Publication:Saturday Evening Post
Date:Apr 1, 1989
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