2007-10-14

7th Alcor Conference, October 5-7, 2007 Part II

Sunday

First up was a panel discussion and question-and-answer on cryonics and critical care with David Crippen, M.D., a prominent critical care physician, Leslie Whetstine, Ph.D., a bioethicist, and Tanya Jones, of Alcor, moderated by Alcor's Aschwin de Wolf.

The first two panelists did not seem much familiar with cryonics, and they and the audience had some heated discussion, but out of it all came some interesting information and at least the recognition of the emotional difficulty of these issues.

David noted that because physicians can keep brains alive for a long time, it is often not clear when a person is "dead". Hospitals can maintain the heartbeat, breathing, body warmth, and most metabolic functions of a patient indefinitely. Brain death is decided by fulfillment of a checklist of objective criteria, but brain death is more of a process than event; it may not be something that happens all at once.

Normally, brain death is required for organ donation, but if cardiac function has ceased, if there is no request to resuscitate, and progression to death is inevitable, organ donation may proceed. Since cryopreservation is ideally begun on patients who are NOT brain dead, but only dead by cardiac criteria, as with organ donation, there may be serious controversy about whether the patient in this case ought to be considered dead.

David reminded the audience that surgeons scoffed at hand-washing before surgery, until it became REALLY obvious that it would save countless lives. Medical professionals tend to be very conservative, reluctant to change, and they tend to be convinced only by the "gold standard" of peer-reviewed, published medical research. If cryonicists can produce some of this, they may change minds over time. Right now, cryonics operates "under the wire" and the courts have not yet become involved.

Eventually, we may be sure, the courts will become involved, when there is a significant legal challenge.

The legal status quo, reflecting a long-standing social objection to suicide and euthanasia, is that "a person cannot agree to be dead at a particular time." Consent of the patient is irrelevant. This notion ruffled the feathers of many of the strong-willed, freethinking members of the audience, but it is an honest assessment of present legal and social opinion.

Nevertheless, Hugh Hixon captured the applause of the audience when he noted, in regard to the panelists' concern about a 'slippery slope', that if public policy completely ignored the wishes of the patient, they were already AT the bottom of a slippery slope.

Cryonicists, I would say, are caught in a difficult position. They theoretically admit and support the notion that when the patient's brain is 'alive', the patient is alive or at least possibly alive (able in theory to be resuscitated or reconstituted). But they want cryopreservation to be able to be conducted on these 'live' persons, at least when they are 'legally dead'. So cryonicists must support, in practice, the cardiac criteria they do not accept, in theory. Legal, ethical, and medical technology are developing in ways that are driving cryonics toward a confrontation with the rest of society, a demand for a demonstration of their fundamental claim: that their patients ARE potentially alive, both before AND after cryopreservation.

Tanya Jones noted that Alcor makes sure hospital staff are told of the anatomical donation arrangements of the standby patients. The staff are asked NOT to wait for brain death. Alcor has never had a patient declared brain dead. Cannulae can be placed before death pronouncement, even some medicines may be supplied.

Eventually there will be a transition when the brain is considered viable through cryopreservation, so that cryopreservation will have to become a medical procedure, not performed by Alcor, and not in the context of anatomical donation. Tanya said she would like to see Alcor take a more active approach in framing the legal debate of the future rather than waiting passively for legal challenges of others to frame the debate.

Leslie Whetstine maintained her doctoral dissertation's point that "cardiac arrest is a prognosis not a diagnosis, of death. All real death is brain death." The heart can beat in a brain dead body.

Leslie admitted to being confused by cryonicists' position. Cryonicists admit patients aren't really dead, yet they want the legal definition of death applied, transferring the patients' legal rights. On the other hand, where was the ethical controversy? Whole human embryos can be cryopreserved alive legally, so why can whole adults not be?

She argued that whole brain death need not be considered a necessary criterion for brain death. Rather, she said, loss of consciousness, or personhood, should be considered sufficient. Persistent vegetative state would qualify in this sense.

Aschwin wondered whether cryonics might someday be incorporated into long-term critical care medicine.

Next up was Steve Harris, M.D., of Critical Care Medicine, discussing liquid ventilation, the new method ensuring the fastest cooling of patients. The heart-lung machine is faster, but it requires more time to set up, thus making it practically slower. Liquid ventilation can cool 5 degrees in 5 minutes in dog experiments, once the airway ventilation is set up.

There are 300,000 cardiac arrests per year in the U.S., and up to 50% will have moderate or severe brain damage. There is a 67% survival rate after 5.5 minutes down, and it takes paramedics about 5-10 minutes at least to get to the patient. Damage after 10 minutes is enough to reduce non-vegetative survival to essentially zero. Most of the good effects of cooling (clinically induced post-resuscitation mild hypothermia) disappear after 15 minutes.

Liquid ventilation with perfluorocarbons was discovered in 1965, but recent FDA trials were disappointing. (Steve and Mike Darwin from the audience disagreed over the reasons why the trials failed, so I, for one, don't know what to conclude.) The volume, pressure, and other factors must be carefully controlled to prevent damage to the lungs (which can be lethal).

The next speaker was Calvin Mercer, Ph.D., a religious studies professor at East Carolina University. It was refreshing to see a discussion of religious, and specifically Christian, concerns about cryonics, since it is likely that religious people, an overwhelming majority of the U.S. (and world) population, will be decisively influential in how or whether cryonics will be studied, funded, researched, or implemented.

Already, there have been signs of the conservative objections to this new-fangled and unsettling idea, muted only (I would suppose) because of the widespread perception of its infeasibility. But even more disturbing is the rejection by the liberal, 'progressive' religious.

Calvin noted that complete scientific support of cryonics (even if cryonics got it!) wouldn't help if the general public doesn't give cryonics a place in the cultural arena of religion. Religious opinions on cryonics should be important to cryonicists because they will affect membership, legislative support, funding, and legal climate. He said his speech would focus on American Christians since they predominate in the area where cryonics is unfolding.

Calvin noted that SYMBOLS are very important to religious people; they are how religious people construct their identity in the world. Conservative Christians have historically been closed-minded to new science, but religion can, and has, evolved with culture over time. He believes that in the future, when it becomes clear that life extension is inevitable, both 'bioconservatives' and life extension enthusiasts will be found among both religious conservatives and religious liberals.

Religious liberals tend to be anthropocentric, this-wordly, pragmatic, and revisionist. That makes them friendly to science. But they are worried about fairness and access to new technologies for less privileged people. Their support for cryonics will depend on how the issue of justice is addressed by cryonics. How will cryonics affect "the least of these"? The poorest, the least educated?

This is certainly a concern I, for one, share.

Conservative Christians may be evangelicals or fundamentalists (the latter defined as "evangelicals who are angry about something"). They tend to be theocentric; they have a very low view of humans as sinful and weak. Their otherworldly emphasis is on supernatural realms and beings. They value religious understanding handed down from previous generations, unchanging. They hold dogmatic beliefs not open to debate.

Conservatives' longstanding suspicion of science will play some part in their attitudes towards cryonics. But Calvin believes some significant segment of conservative Christians may embrace life extension. They may, for example, think of life extension as a way of avoiding Hell and preparing to be sure they will go to Heaven. They may also be strongly convinced by the notion that cryonics preserves life (note their general pro-life stance). Resuscitation is not raising the really dead, only the apparently dead, they might argue. Resuscitation does not result in spiritual transformation, the way resurrection would. The soul might not 'leave the body' unless the person is really dead.

Christine Petersen of the Foresight Institute gave a quick review of everyday life extension practices such as diet, exercise, adequate quality sleep, and stress-avoidance, and humor. She wisely noted that one should not take just any supplement that MIGHT help since substances in the body may interact in undesirable ways. Authorities disagree on the number and type of supplements that would be advisable (from most conservative to most liberal: doctors, the FDA, RealAge.com, Kronos, Ray Sahelian, Ray Kurzweil, and the Life Extension Foundation). People should rearrange their lives if necessary to avoid "toxic" stress from bosses, commutes, coworkers, spouses, etc. Males benefit from greater quantity of sex, while females benefit from greater quality of sex. Most of her recommendations were of the sort, obviously, that the audience was not quick to object to!

Next up was Chris Heward, Ph.D., president of Kronos Science Laboratory, which has conducted many large population studies on aging. All the while not having any clear definition of what aging IS. Apparently, it may be many different, but interacting, biochemical processes. There are no yet accepted biomarkers for 'aging'. Kronos pays close attention to signs of oxidative stress, but there is significant (huge) variation across time in single individuals.

Life expectancy has increased in recent times, but mainly only due to decreases in infant mortality. Life expectancy increases after 65 years have not been impressive. The 'downward' slope of aging begins around 20 years old. Premature aging of one element of the body is usually responsible for premature death. The top 3 killers in the U.S. are cardiovascular disease, cancer, and cerebrovascular disease.

Alzheimer's disease is increasing, and not entirely because of increasing diagnosis. Five percent of people aged 65-74 will be affected. By age 85, the risk will rise to near 50%. Such figures are obviously disturbing to those of us who wish to extend our natural lifespans, while at the same time preserving our personal identity. Alzheimer's disease, and all forms of age-related dementia, amount to a terrible conflict in our plans. Should we try to live longer, and run greater risk of dementia? Or should we lean wholly on cryonics, a completely unproven technology? One can be sure there are no easy answers.

2007-10-13

7th Alcor Conference, October 5-7, 2007 Part I

Another wonderful Alcor conference!! Congratulations and thanks to all the organizers, speakers, and panelists. It was great meeting life extensionists and cryonicists from all over the world.

Friday
Arizona lobbyist Barry Aarons gave the welcome address. It is good to see Alcor's continuing political engagement, which Alcor needs to survive. But this time, there was a hint of something more than just survival expected from current elected leaders ... trying to get Alcor recognized as part of the biotechnology industry in Arizona.

Saturday
Susan Klein emceed. It was great seeing Bruce and Susan Klein, founders of the Immortality Institute, active at this event.

Steve Bridge, former Alcor president, spoke first. He introduced the tone and scope of the conference, clearing up misconceptions for those new to cryonics. We are not interested in cryonics because we are a hare-brained cult, or because we have an obsession with high technology or science fiction. We are interested in cryonics because we seriously want to preserve life.

Steve noted that fewer than 20 scientists in the world are working on cryonics today. Perhaps, as he noted, this is because early cryonicsts did not try hard enough to convince scientists to work on it. I think, however, scientists would have made up their own minds anyway. After it became clear that resuscitation from extremely low temperatures would not be easy, it was obviously not 'low hanging fruit.'

Scientists find big-goal projects intractable. How many cancer researchers think of their research as about a cure for cancer? At most, modestly, they think of their research as perhaps a small brick on the path toward a cure for cancer. They think of their research as positioned in the context of a more immediately tractable problem, of either a theoretical or a practical kind, a sub-goal.

What is a sub-goal for cryonics? Freezing organs for transplantation comes to mind, and it is here that most of the work so far has been done. Yet decades of failure have convinced the organ transplant field not to expect extremely long-term, extremely low-temperature storage of most organs any time soon. Yet there is the possibility that continuing advances in medicine and biology and biophysics will uncover possibilities for new approaches.

Steve also noted that the word 'dead' should be reserved for information-theoretic death, a point that was echoed throughout the conference by other speakers. But if we accept this consensus, what word should we use for the condition in which we would expect biostasis to be applied? In the case of terminal, incurable degenerative brain disorders, this does not even correspond to the fiction of legal death. Inevitable Impending Identity-Critical Information Loss? That would make an awkward acronym. :)

Steve also reminded us that we still do not know if cryonics preserves people. How do we know we are preserving identity? How do we know long-term memories and personality are being preserved? What are the physical correlates of identity in the brain? These questions are really the most fundamental of all. Even if low-temperature biostasis were reversible, if resuscitation from such a state were possible, would the patient be amnesiac? brain-damaged? insane? Information-theoretic criteria are not yet able to be framed in biological terms.

Next, Brian Wowk, Ph.D., from 21st Century Medicine, spoke. He reviewed the process of cryosuspension by vitrification and the theory behind it. The goal of vitrification is to prevent ice formation. In ideal cryonics cases, the brain may vitrify without ice formation, although ice may form elsewhere in the body (in a whole body case). In cryoprotection, 60% of the body's water is replaced by cryoprotectant ("anti-freeze" to prevent ice crystallization). Long-term potentiation (LTP), thought to be a mechanism involved in long-term memory, persists in vitrified brain slices, after rewarming, in an animal model. The machinery for forming memory, if not memory, survives vitrification.

Obstacles to reversing vitrification include cryoprotectant toxicity, ischemic damage, and fracturing. The latter could be solved by higher-temperature storage, though this would be more expensive, risky, and require more care. Methods for repairing damage at the cellular or tissue level (regeneration) need not require nanotechnology, and work on repairing or preventing cell/tissue damage is of course a continuing focus of mainstream medical research.

Stephen Van Sickle, current Alcor Executive Director, spoke next on Alcor's research. How do anti-ischemia drugs relate to cryoprotection? The Critical Care Research drug protocol has still not yet been verified with cryoprotection.

Alcor is setting up a cardiopulmonary bypass research lab with rats. Stephen noted that part of the biostasis protocol is already known to be reversible -- about 2 hours into blood washout and lowering of body temperature to around 2 degrees C. At some point during perfusion of cryoprotectant, though, the process becomes irreversible. It would be interesting to know when! And why. (note: cryoprotectant toxicity above).

Alcor is also continuing to develop intermediate temperature storage (ITS) to prevent fracturing. Unfortunately, fractures can occur well before safe long-term storage temperatures are reached. Sometimes fractures do NOT occur until almost liquid nitrogen temperatures, which suggest it is theoretically possible to avoid fractures with ITS. Alcor is now studying the problem with noninvasive visual imaging, as well as auditory detection. Alcor is also planning to use a fiber optic spectrometer to measure blood low (by near infrared/NIR) to try to measure perfusate volume and flow rate in brain, maybe modeling concentrations in the brain, and also perhaps to determine if there is ice formation in the brain by scattering from ice.

Next, Tanya Jones spoke. She emphasized the importance of stabilization (cooling, cardiopulmonary support, medications, and perfusion with organ preservation solutions). Only about half of Alcor's patients were stabilized. Those who were not were generally nonideal cases who were 'down' too long to initiate stabilization without causing more harm. This is a continuing problem -- that people don't get sick at convenient times and with plenty of advance warning! Stabilization buys between 24-48 hours worth of time to transport patient to Alcor for more cooling and longterm care.

Alcor is moving toward a largely automated whole body perfusion system with literal bells and whistles. Hopefully this will help prevent human error and assist in the gathering of high-quality data. Stabilization kits are also being reorganized, so that there are fewer boxes to fly out when necessary. Alcor continues to work on a stabilization network - working toward improved training and recruiting new medical personnel. About half of Alcor's U.S. patients are resident in California, with the rest mostly in Arizona, Florida, Texas, and New York. Alcor would eventually like to deploy 14 regional stabilization kits for the U.S. and worldwide, and conduct local training on the regional equipment.

Next, Ralph Merkle, Ph.D., spoke. He felt that cryonicists were being too conservative about cryopreservation preserving memory. (Why?) Ralph noted the slow pace of nanotechnology, but observed that resuscitation of cryonics patients was its most ambitious application. He estimated that it would be about 5 years before labs began experimental verification of some of the theoretical work he and Freitas have done. He said practical nanotechnology will result in a revolution in medicine. Cryonics revival will require mature nanotechnology, which in turn will require the funding of long-term system design, which is largely absent now. Almost all spending is on very near-term applications, he said. Nanotech research now is not focused on a goal, what to make with nanotechnology. Cryonics provides the answer, according to Ralph.

The next speaker was Dr. Michael West, a gerontologist and COB of Advanced Cell Technology (a regenerative medicine company) and former CEO of Geron Corporation, without a doubt the most prominent person to address a cryonics conference since I have been going to them. Listening to Michael West was certainly one of the high points of the conference for me.

Interestingly, his presentation touched not only on the technical concepts behind his research, but also the deep cultural, even mythological framework, in which such research might be understood. Perhaps he has developed this approach because of the fierce controversy surrounding human embryonic stem cells, which he and his colleagues were the first in the world to isolate. (On one slides, Michael wryly noted one of his embryonic stem cell lines that President George W. Bush had "blessed".)

Michael reminded the audience that the modern biological distinction between germ (reproductive) cell lines and somatic (regular body) cell lines exposes a dualism that hints at the biological origin of aging and death.

Originally, we may presume, all early life cells were, or at least tried to be, immortal. These early cells were predecessors of today's germ cells (and their renegade imitators, cancer cells) in that they had no fixed lifespan, repaired themselves, and reproduced indefinitely. In one way of thinking about it, somatic cells evolved to help germ cells survive and reproduce, but somatic cells were denied immortality, and this gave rise to death, which continues to beset us multicellular organisms.

Michael compared the differences between germ and somatic lines to the difference between the Greek concepts Zoe and Bios. These are two words for life, one the eternal life of nature, the other the temporary life of an individual person. The mythological analogues of Zoe were Demeter and Dionysus, two gods of the eternal fecundity of nature (in grain and grape harvests). Nature performs the immortal renewal of life. "How do we transfer immortality to individuals?" Michael asked. "How do we conduct 'immortality transfer'?"

Cells can immortalize, he noted. Telomeres shorten in somatic cells over time, whereas germ cells' telomeres don't. Telomeres at the end of chromosomes are like fuses burning down. They cause cells to senesce. Michael again drew comparisons from Greek mythology, this time to the Fates who drew out, measured, and cut the thread of life at its predetermined limit.

Michael and his collaborators have in fact engineered immortal cells. The enzyme telomerase can rebuild the telomeres as they decrease, so that they become effectively immortal. Embryonic stem cells in laboratory petri dishes actually start to form tissues, even brain tissue (neocortex).

Michael dispelled the myth that the cloned sheep Dolly was born with prematurely old telomeres. Untrue, he said. In fact, cow somatic cells, by nuclear transfer cloning, caused cells to OVER-reset, giving them even longer lifespans than normal. Human therapeutic cloning is possible, Michael said. Wakayama et al. (2000) showed in a mouse model that mice clones could have lengthened lifespan. Mitochondria can also be rejuvenated by nuclear transfer, and cells can be cloned so that not they are not just nuclear but also mitochondrial clones.

No one has yet cloned human embryonic stem cells by nuclear transfer, mainly because it is difficult. It has been done in other animals, though. Medical work on embryonic stem cell therapy includes new approaches to macular degeneration and vascular disease. There are so many types of cells that researchers are still studying them to determine how they make complex somatic cells.

Michael's final slide, of Isis and Osiris, was quite moving. In the Egyptian myth, Osiris is killed, but his wife Isis searches until she finds a way to revive him using the Cord of Life. In other words, love conquers death.

The next speaker was Aubrey De Grey, who kindly provided a NEW TALK. The topic was how leaders in various scientific fields and especially publication editors like himself could do more to educate scientists about the legal fiction of death and the possibility of seeing cryopreservation as life-saving critical care. "We have a moral duty to demystify the 'yuck factor,'" he said. It will be difficult to demystify the topic, but Aubrey believes it is possible. "A logical, fair argument is easier to make and most likely to succeed eventually."

Aubrey's presentation was followed by a panel from Alcor's Board of Directors. The most contentious issue raised was the possibility of having Alcor's membership elect its Board (it is currently a self-perpetuating Board). The panel gave a good argument that many special-purpose nonprofits with large assets such as museums or hospitals have self-perpetuating Boards, and a quick show of hands indicated that the majority of the audience (although they may not have been all Alcor members), approved of keeping thing the way they were. 'If it ain't broke, don't fix it.'