08. August 2016 · Comments Off on How Uniform Are The Uniform Anatomical Gift Acts? · Categories: Cryonics, Society

“SECTION 11. PERSONS THAT MAY RECEIVE ANATOMICAL GIFT; PURPOSE OF ANATOMICAL GIFT”

Thus begins a very important section of a very important piece of legislation. Except it isn’t actually legislation at all, though it does look the part. It is the Revised Uniform Anatomical Gift Act (2006) [“UAGA”]. UAGA is model legislation, and in that form it does not have the force of law.

The model act continues:

(a) An anatomical gift may be made to the following persons named in the document of gift:

(1) a hospital; accredited medical school, dental school, college or university; organ procurement organization; or other appropriate person, for research or education;

Crucially, this section tells us under what, if any, authority we may direct that a cryonics service provider take custody of our bodies after legal death. Whether on plain meaning, or act-specific definition, cryonics service providers are not hospitals, medical or dental schools, colleges or universities. In some circumstances, Alcor and/or Suspended Animation behave like organ procurement organizations — insofar as brains are organs — but that term is defined in UAGA so as to require designation by the Secretary of the US Department of Health and Human Services. Subsection 2 (not reproduced above) is specific to organ transplantation, and subsection 3 pertains to eye banks and tissue banks, neither of which are good “homes” for a cryonics service provider.

So, for the time being we are left with “or other appropriate person, for research or education.” It isn’t much — but it’s home, and on that point at least one court agrees, namely the Court of Appeals of Iowa in Alcor Life Extension Foundation v Richardson. [1] But wait — how does a court in Iowa even begin to consider the meaning and effect of UAGA if it isn’t really law? Well, because the Iowa Legislature looked at the model uniform act, decided it liked it (mostly), and made it into state law. In fact, the Iowa Legislature made some changes to the model, but it left in the “other appropriate person” clause, and that is very good, because when Alcor sued Orville Richardson’s brother and sister for custody of Orville’s body, the Court of Appeals of Iowa agreed that Alcor was an “appropriate person for research” for the purposes of Iowa’s UAGA. [2]

Thus, we can see how important these words are. As the name implies, UAGA is an attempt to promote uniformity in an area of law which could otherwise vary considerably from state to state, making the procurement and transfer of life-saving organs and other tissues for transplant very difficult. So the Uniform Law Commission [3] came along and drafted UAGA for enactment in all states. Of course, this process is voluntary on the part of the states, and does not require wholesale adoption of the model act without modification — and that is where potential for trouble creeps in. Human cryopreservation is obviously not the intended subject of the act; even generally, gifts for research and education are only a secondary focus. In most states (Arizona being a conspicuous exception) there is no cryonics lobbyist at the table when state legislators are deliberating whether and how to enact the newest incarnation of UAGA; hence, they are not thinking about us or our unique interests when they consider whether to pass the model act with the words “or other appropriate person, for research or education” intact.

Now, section 24 of UAGA does state that “[i]n applying and construing this uniform act, consideration must be given to the need to promote uniformity of the law with respect to its subject matter among states that enact it.” But of course, the force of that section depends on whether or not it was itself legislated with the rest of the Act. However, assuming it was, this provision still cannot outweigh clear evidence of a legislature’s intent to diverge from the model by removing or materially altering particular language. That is to say, if the “other appropriate person” clause is left out of one state’s enactment of UAGA, a court has no discretion to read it in. [4] Where the uniformity provision does help is if Alcor ever has to go to court again in a state with a UAGA substantially similar to Iowa’s — then the Iowa case should carry significant persuasive force. [5] Happily, a majority of states’ UAGAs contain the “other appropriate person” clause, unaltered. [6] A few others have adopted different language that is equally or maybe even more applicable to cryonics organizations [7], and two states may even provide additional points of entry for cryonics service providers. [8] However, nine states present problematic aberrations from the mold. In Oklahoma, the State Anatomical Board gets to designate who is an “other appropriate person.” [9] Likewise, the Virginia Transplant Council is in charge of authorizing “other appropriate persons” in Virginia [10], and in the District of Columbia this is the domain of the mayor. [11] The remaining six states lack the “other appropriate person” clause entirely, and any other equivalent entry point: these are California, Florida, Maryland, New York, Texas, and Washington. [12] It is a little surprising to see some current (and in Texas’ case, future [13]) hubs of cryonics activity on this list.

At this stage, I feel I should point out that anatomical gift legislation is only one mechanism for making legal provisions for transference of custody of one’s body after legal death. The other (arguably more traditional) method is the “final disposition of human remains” method. Thus, the mere fact that a state’s anatomical gift legislation does not permit donations to cryonics organizations doesn’t rule out  legally enforceable cryonics arrangements. The nine states mentioned above all have some statutory provision for the disposition of human remains route, though Florida stands out for lack of clarity. Maryland and Oklahoma both provide the right to direct the disposition of one’s body after death. [14] Written preferences are likewise binding in California, District of Columbia, New York, Texas, and Washington, which states also provide the right to designate a person who will supersede the spouse or next of kin’s default authority to control disposition (though they would be bound by the decedent’s written instructions in any case). [15] Virginia allows for designation in writing of a person who will control disposition (over a surviving spouse or other next of kin), but the relevant statute does not expressly state that the decedent’s instructions are binding — though it could be argued that it is implied.[16] Florida’s statutes are not explicit as to who controls the disposition of human remains after death, nor whether written preferences of the deceased are legally binding, though case law has generally supported this result. [17]

However, even if the nine states whose anatomical gift statutes apparently preclude donation to cryonics organizations still provide legally enforceable final disposition rights, mightn’t a document that uses language around “anatomical donations” for this second purpose present somewhat of a red herring? For example, Alcor’s success in the Richardson case relied in part on the fact that Iowa’s UAGA takes precedence over its final disposition provisions, which would have favoured Orville’s brother and sister to control disposition. [18] But when an anatomical gift under UAGA fails for lack of a valid donee, the gift doesn’t fail, but passes instead “to the appropriate procurement organization” (which would not include the cryonics service provider).[19] Would this aspect of UAGA prevail over the cryonicist’s clear intent, just because he or she used the words “anatomical donation”? This result seems inconceivably formalistic, but illustrates the (potential) problem with blending legal categories. On the other hand, because we cannot necessarily control which anatomical gift legislation will ultimately apply to us (as it will be the law of whichever jurisdiction we die in, whenever that happens to be), a hybrid, one-size-fits-most solution has clear utility.

As a Canadian, my interest in UAGA was actually initially focused north of the border. I noticed that Cryonics Institute’s standard issue emergency necklace has “UNIFORM ANATOMICAL GIFT ACT” on the back, and I wondered what Canadian medical personnel might make of that, since we have no such named legislation. However, the intent of CI’s “Uniform Donor Form” [20] is fairly clear, and the majority of Canadian provinces have broadly empowering legislation for making “human tissue gifts.” [21] This is especially good because English-Canadian common law never developed the deferential approach taken by US judges to decedents’ preferences for final disposition — such preferences were only ever considered morally binding on executors and next of kin, and not legally so. [22] However, Alberta’s Human Tissue and Organ Donation Act only permits body donations to university medical, dental or related health programs. [23] This limitation expressly refers to “a body donated under this Act” as opposed to “any tissue, organ or body donated under this Act,” so it could be argued that Alcor neuropatients may still be transferred using the anatomical gift mechanism — but this may not reflect the intent of legislature, and as such may not be a sustainable reading. Unfortunately, this would mean that Albertans (or at minimum, Albertan whole-body patients) are hit doubly — they have no legally binding mechanism for transfer of custody of their bodies to their cryonics organization under either the anatomical gift or final disposition route.

So, more than most, Albertan cryonicists might want to reconsider the wisdom of where they live. That said, while other readers may think themselves lucky to live in a state or province I didn’t mention, laws change [24], and I have just learned all-too-personally how many fifty states are to monitor. We must each be vigilant in ensuring our various cryonics legal documents are valid for their intended purposes.

Endnotes:

1 785 NW (2d) 717 (Ill Ct App 2010).

2 Ibid at 725.

3 http://www.uniformlaws.org

4 UAGA’s choice of law provision (section 19) states that a document of anatomical gift will be valid if it is executed in accordance with either (i) the law of the forum (i.e. the UAGA where the document is sought to be used), (ii) the law of the state/country where it was executed, or (iii) the law of the state/country where the person was domiciled, had a place of residence or was a national when the document was executed. However, the interpretation of the document of gift is governed by the forum law.That is to say, a document of anatomical gift to a cryonics service provider which is formally valid in the forum by merit of its validity under the laws of the state/country where it was executed, etc., may yet be ineffective under the laws of the forum.

5 The Richardson decision also included a tentative, but nonetheless authoritative finding that Orville’s payment to Alcor to preserve his body, and less-than-perfectly-altruistic motives did not move the transaction outside the legal category of “gift.”  Again, this finding and the uniformity provision should go a long way to deciding the issue if it comes up again in another state.

6 For ease of reference: Alabama, Alaska, Arkansas, Arizona, Connecticut, Georgia, Hawaii, Idaho, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Massachusetts, Michigan, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, North Carolina, North Dakota, Ohio, Oregon, Rhode Island, South Carolina, South Dakota, Tennessee, Utah, Vermont, West Virginia, Wisconsin, Wyoming.

7 Minnesota replaces “other appropriate person” with “non-profit organization in medical education or research.” Minn Stat § 525A.10. Delaware, Illinois, and Pennsylvania still use language from older incarnations of the UAGA, which lack “other appropriate person” but define “any bank or storage facility” in such a way that so long as the cryonics service provider is recognized as a permissible donee in its home state, it should qualify under the Delaware/Illinois/Pennsylvania statutes. 16 Del Code § 2712, 755 ILCS § 50/5-10, 20 Pa C S § 8612.

8 Alcor’s own lobbying efforts resulted in the inclusion of the comparatively broadly defined “procurement organization” in Arizona’s ARS §36-850; Missouri has provision for “cadaver procurement organization[s]”. Mo Rev Stat § 194.255.

9 63 OS §2200.11A.

10 Va Code § 32.1-291.11

11 DC Code §7-1531.10.

12 Cal Health & Safety Code § 7150.50; Fla Stat § 765.513; Md Code, Est & T §4-509; NY PBH Law §4302; Texas Health & Safety Code § 692A.011; RCW § 68.64.100.

13 Comfort, Texas is home to the Timeship project.

14 Md Code, Health §5-509; 21 OS § 1151.

15 Cal Health & Safety Code §7100.1; DC Code §3-413; NY PBH Law §4201.2(c); Texas Health & Safety Code § 711.002; RCW § 68.50.160.

16 Va Code §54.1-2825.

17 Fla Stat § 497.005(37) sets out an apparent order of priority in a definitions section, without elsewhere stating that that priority grants any particular rights; § 732.804 uses permissive language instead of imperative. See also Leadingham v. Wallace, 691 So (2d) 1162 (Fla 5th DCA 1997).

18 Supra note 1 at 727.

19 Uniform Anatomical Gift Act (2006), § 11(c)(4).

20 http://www.cryonics.org/documents/Uniform. html

21 These are largely derived from various iterations of the Uniform Human Tissue Gift Act proposed by the Uniform Law Conference of Canada.

22 Quebec and British Columbia are the only provinces which provide statutory rights to direct disposition of one’s own human remains: art 42 CCQ and Human Tissue Gift Act, RSBC 1996 c 211 s 4.

23 SA 2006 c H-14.5 s 3.

24 For example, the 2006 revision of UAGA was introduced in the Pennsylvania Legislature this year.

First published as a regular column called In Perpetuity in Cryonics Magazine, February 2013

01. July 2016 · Comments Off on Advances in Cryoprotectant Toxicity Research · Categories: Cryonics, Science

There is little disagreement among cryobiologists that the biggest limiting factor to reversible organ cryopreservation is cryoprotectant toxicity. It is actually not that hard to create vitrification solutions that completely inhibit ice formation at even the slowest cooling rates. The problem is that such highly concentrated vitrification solutions are too toxic to permit recovery of complex tissues. The least toxic vitrification solution for complex mammalian organs as of writing is M22. M22 is the culmination of many years of experimental and theoretical work by cryobiologist Greg Fahy and colleagues using rabbit kidney slices. Studying selected cryoprotectant mixtures on rabbit kidney slices, Fahy and colleagues came to the following conclusions:

1. High concentrations of a cryoprotective agent (or a mixture of different cryoprotective agents) can prevent ice formation during cooldown and warming.

2. The toxicity of some cryoprotectants can be neutralized by combining them with other cryoprotective agents.

3. The non-specific toxicity of a  cryoprotectant solution can be predicted by calculating a quantity (“qv*”) which is intended to measure the average hydrogen-bonding strength of the cryoprotectant polar groups with the water molecules in the solution.

4. Within limits, non-penetrating agents can reduce the exposure of cells to toxic amounts of cryoprotectants without reducing vitrification ability.

5. Synthetic “ice blockers” can be included in a vitrification mixture to reduce the concentration of toxic cryoprotective agents necessary to achieve vitrification.

While M22 is a low toxicity solution, its toxicity profile still necessitates minimizing exposure time and introduction and removal at low (subzero) temperatures. If we had a better understanding of the mechanisms of cryoprotectant toxicity, vitrification solutions with no toxicity at all could be introduced at higher temperatures and exposure times could be increased to optimize complete equilibration of the tissue with the cryoprotectant. It would also allow safer storage at intermediate temperature temperatures (around -130 degrees Celsius) because ultra-stable vitrification solutions could be used that are less prone to de-vitrification upon re-warming. This would be of particular interest for the cryopreservation of large organs or even whole organisms (with applications such as suspended animation and cryonics).

Two major reviews of cryoprotectant toxicity were published in the last 5 years; Gregory Fahy’s “Cryoprotectant Toxicity Neutralization” (Cryobiology, 2010) and Benjamin Best’s “Cryoprotective Toxicity: Facts, Issues, and Questions” (Rejuvenation Research, 2015).

Greg Fahy’s paper is a rigorous exposition of experimental results concerning the phenomenon of cryoprotectant toxicity neutralization. The paper is mostly limited to the discovery that DMSO can block the toxic effects of amides such as formamide. The combination of DMSO and formamide (or other amides such as urea and acetamide) is indeed one of the building blocks of M22 but this combination cannot be used without limit and the paper includes data that indicate the maximum molar concentrations (and ratios) that still permit full viability. In theory, if two (or more) cryoprotectants would completely neutralize each other’s toxicity they could be the sole components of a vitrification solution. But as the formulation of M22 shows, it is still necessary to add weak glass formers such as ethylene glycol, extracellular CPA’s, and “ice blockers” to supplement the toxicity neutralization obtained with formamide and DMSO. An important finding in Fahy’s paper is that n-methylation abolishes toxicity neutralization for amides and combining methylated amides also does not lead to toxicity neutralization between them. In fact, Fahy found that the presence of n-methylated compounds renders even small amounts of DMSO toxic. The remainder of the paper discusses the mechanisms of cryoprotectant toxicity and Fahy now favors protein denaturation as a plausible mechanism of (non-specific) toxicity. While other cases of toxicity neutralization have been reported in the literature, no rigorous studies have been done to produce a body of knowledge that is comparible to what we know about amide-DMSO interactions.

Benjamin Best’s paper is more general in scope but presents a lot of experimental data and also critically discusses Fahy’s work on cryoprotectant toxicity. As Ben Best points out, different (and seemingly contradictory) results do not necessarily mean that cryoprotectant toxicity is a species or cell-type dependent phenomenon. One could imagine a meta-analysis of cryobiology data in which variables such as concentration, loading- and unloading protocols, exposure temperature, exposure time, and the type of viability assay are matched to ensure methodological consistency. It is also important to compare cryoprotectants at their minimum concentration to vitrify to make meaningful toxicity comparisons. If the work at 21st Century Medicine is an indication, universal low-toxicity cryoprotective solutions should be feasible. Perhaps the most interesting part of the paper is where Best offers a critique of Grag Fahy’s “qv* hypothesis of cryoprotectant toxicity”, which aims to show that non-specfic toxicity concerns the degree to which cryoprotectants leave water available to hydrate macromolecules. This discovery allowed for the substitution of ethylene glycol for propylene glycol in Fahy’s lower toxicity vitrification solutions, despite the resulting higher CPA concentrations. Best observes, “it seems contradictory that water remains available for hydration, but not available for ice formation.” A potential rejoinder to this observation is that so called “bound water” does not participate in ice formation but can be disturbed by strong glass formers. Best also suggests a potential refinement of qv* that allows for more precise calculation of the hydrogen bonding strength of the polar groups that are used to calculate qv*. It is conceivable that such a refinement would eliminate the few remaining outliers in the data that support the qv* hypothesis. The paper also draws attention to the possibility of kosmotropic co-solvents and changes of pH and microenvironment polarity to mitigate cryoprotectant toxicity.

Neither of the papers discusses cryopreservation of the mammalian brain, but there is good reason to believe that in the case of this organ modification of low-toxicity vitrification solutions is required. Conventional cryoprotective agents such as PG, EG, and DMSO have poor blood brain barrier (BBB) penetration and the brain may not tolerate the CPA exposure times that other organs do. For example, while M22 can be used for cryopreservation of the brain, many of its component have poor BBB penetration and PVP and the ice blockers (X-1000 and Z-1000) are assumed not to cross the (non-ischemic) BBB at all. One potential solution is to (reversibly) open the BBB with so- called BBB modifying agents like detergents or perhaps to search for cryoprotective agents that can cross the BBB.

The most fundamental question in the design of vitrification solutions remains whether it is possible at all to introduce high concentrations of cryoprotectants without creating any kind of irreversible molecular and ultrastructural adverse effects. Understanding what specific and non-specific cryoprotectant toxicity exactly is should enable us to answer this question.

Originally published as a column (Quod incepimus conficiemus) in Cryonics magazine, September-October, 2016

09. February 2016 · Comments Off on Groundbreaking Scientific Results Prove that the Proposition of Human Medical Biostasis has Potential and Needs to be Brought into Mainstream Scientific and Medical Focus · Categories: Cryonics, News

Breaking News [Media Press Package with additional detail]

A team from 21st Century Medicine has developed a technology that has been independently verified to enable near-perfect, long-term structural preservation of a whole intact mammalian brain.

This new breakthrough just won the Brain Preservation Prize – five years after it was launched by the Brain Preservation Foundation (BPF).

“One of the, if not THE, most important scientific results in the history of medical biostasis and cryonics has been accomplished” Aschwin de Wolf, President of The Institute for Evidence-Based Cryonics

According to the BPF, 21st Century Medicine narrowly beat a team led by Dr. Shawn Mikula at the Max Planck Institute of Neurobiology (published last year in Nature Methods).

In addition to proof of this accomplishment and the full 21st Century Medicine “Aldehyde-Stabilized Cryopreservation” protocol recently being published in the journal Cryobiology, it was also independently verified by the BPF through extensive electron microscopic examination.

 

 

 

 

 

The prize was independently judged by neuroscientists Dr. Sebastian Seung, Professor at Princeton University and Dr. Kenneth Hayworth, President of the BPF.

“Imagine being able save, and at low temperatures, indefinitely preserve people who can no longer be sustained by contemporary medicine so that future medicine can both revive them and restore their health – these results provide strong support of that being possible”

Dr. JP de Magalhães, Chair of the UK Cryonics and Cryopreservation Research Network

This follows recent scientific evidence that long-term memory is not modified by the process of whole organism cryopreservation and revival in simple animal models.

As the two leading think-tanks/scientific networks in cryonics we share here a brief with both more color and our perspectives on what this important breakthrough means and – does not mean – for cryonics. 

In the words of Dr. Ken Hayworth, President of the Brain Preservation Foundation, and one of the prize judges:

“Every neuron and synapse looks beautifully preserved across the entire brain. Simply amazing given that I held in my hand this very same brain when it was a vitrified glassy solid… This is not your father’s cryonics”

09. February 2016 · Comments Off on Recent developments relevant to cryonics · Categories: Cryonics, Neuroscience

A lot of interesting pieces related to cryonics have appeared over the last few months that I thought I would share:

Four professors conclude in MIT Technology Review that there is significant and growing body of evidence in support of human cryopreservation: “The Science Surrounding Cryonics” 

New York Times Cover story by Pulitzer Prize winning journalist on “A Dying 23 Year Young Woman’s Hope in Cryonics and a Future”

Skeptic Michael Sherman writes a piece in Scientific American called  “Can Our Minds Live Forever?”

Here are three recent important peer reviewed papers:

Dr. Greg Fahy and Robert McIntyre of 21st Century Medicine describe here a new cryobiological and neurobiological technique, aldehyde-stabilized cryopreservation (ASC), which demonstrates the relevance and utility of advanced cryopreservation science for the neurobiological research community. The ASC technology is now also competing against Dr Mikula at Max Planck in he brain preservation prize.

The Grand Challenges of Organ Banking and It’s Potential is described by large group of the worlds leading cryobiology scientists:  The first Organ Banking Summit was convened from Feb. 27 – March 1, 2015 in Palo Alto, CA, with events at Stanford University, NASA Research Park, and Lawrence Berkeley National Labs. Experts at the summit outlined the potential public health impact of organ banking, discussed the major remaining scientific challenges that need to be overcome in order to bank organs, and identified key opportunities to accelerate progress toward this goal. Many areas of public health could be revolutionized by the banking of organs and other complex tissues, including transplantation, oncofertility, tissue engineering, trauma medicine and emergency preparedness, basic biomedical research and drug discovery – and even space travel.

Persistence of Long-Term Memory in Vitrified and Revived Caenorhabditis elegans. Two scientists ask the question:  “Can memory be retained after cryopreservation?” and then demonstrate that a form of long-term memory in C. elegans is not been modified by the process of vitrification or slow freezing.

06. January 2016 · Comments Off on Who speaks for the dead? · Categories: Cryonics, Society

Do the dead have rights, in the proper sense of the word? That is to say, when someone is obligated to do something with a dead person, like bury them, for whose benefit are they doing it? For the dead? Or for the living?

You might well ask, is this really important? In short, yes. The person to whom the obligation is owed is the person who may sue for enforcement of that right, and their identity may also determine the remedies which are available to them (be it money, compulsory performance of or abstinence from a particular act). So, the question of whose rights are engaged in dealing with the dead is fundamentally important from the cryonics patient advocate’s perspective.

An illustration: If you make a contract with someone, both of you intending that a substantial portion of what you have promised to do will only be done after (and in fact as a result of) your legal death, and vice versa that a substantial portion of what they have promised to do will likewise only be done after your legal death: who has promised what to whom?

While you remain alive, the answer seems quite obvious. But once you are dead, you are no longer a person. You, sadly, are not an entity recognized by law. You are your estate. Your estate has legal personality of a kind, but it is probably better to think of your estate as a medium. And, as such, it really isn’t about you anymore — it’s about your stuff, and who gets it. Yes, you can (and should, and hopefully do) have a will that references your cryonics arrangements, but practically speaking, the interest that your estate has in that contract you made for things to be done for you after you died, is the fact that something about that contract could result in more stuff for the estate’s beneficiaries. That’s really all the estate can care about, because the real, live person who was capable of having immaterial (or better still, “non-pecuniary”) interests in the contract is now gone.

But wait? How can the cryopreservation agreement (cat’s out of the bag — that contract was about cryonics after all) result in more stuff for the estate? Your cryonics service provider (CSP) didn’t promise to give anything, or pay anything. You, the patient promised to give something, and in fact cleverly entered into other contracts with other people to automatically transfer money to your CSP upon your legal death. So how could the cryopreservation agreement possibly represent a source of “stuff ” for the estate? Well, that’s because there were really two layers of promises — two sets of obligations in every contract. The top layer, or primary obligations, are what you actually bargained for. The secondary obligations are what the other party must do (or rather, pay) if they do not perform their primary obligations. These secondary obligations are the damages, and they are a part of the contract from the very beginning without anything being written about them.

So, the potential pecuniary ($) interest your estate has in the cryopreservation agreement, since your estate is just a medium that can only really have an interest in things and stuff, is in the failure of your CSP to do what it promised to do for you. And unfortunately for you, in cryonics there are no do-overs.

Hence why it is important to know who speaks for you when you are dead. The beneficiaries of your will, however friendly to your arrangements and well-intentioned they are, have no vested, personal, legal interest in the CSP’s performance of its primary obligations to you under the cryopreservation agreement. The executor of your will, on the other hand, has certain obligations to carry out promises made by you when you were alive, and (sometimes) to ensure that your body is dealt with as you directed by will or other instrument. The executor may even have an obligation to ensure that you remain interred as directed. But how long must they keep vigil? When they, too, are dead, does their executor now watch over the both of you? At a certain point (if not right away) this clearly becomes impossibly impractical. Alternately, if your CSP’s custody of your body was effected by a consent to body donation for research (which is the more robustly enforceable method, generally), even your executor has essentially no standing with respect to your body. And this is good, because above all else we trust that our CSPs want the same thing we want — and I have no reason to believe that is anything but true. But what if, someday down the road when your executor and next-of-kin are now in the dewar next to you, your CSP’s performance dips demonstrably below the threshold of “good faith best efforts”? Is there anyone who can claim authority to move you or to enforce performance of your CSP’s primary obligations under the cryopreservation agreement?

The above is not an exhaustive analysis by any measure. I write it hoping only that it will illustrate how peculiarly vulnerable cryonics patients are under the laws currently applying to them. What I plan to do with this column is explore intersections of law and cryonics & life extension (and there are many), and one theme I expect to visit frequently is cryonics patient advocacy. This is the issue of “who speaks for the dead” adverted to above, though in truth it starts long before legal death, and is more about how the dead or incapacitated can speak for themselves through legally recognized documentary evidence of their intentions: wills, trusts, powers of attorney (financial and health care), advance directives, consents to body donation, etc. However, all of these need agents to carry them out, and others still may seek to tear them down, so the more complex questions deal with how to build checks and balances into your supplementary cryonics documents and otherwise incentivize compliance of possible threats.

One specific topic I plan to look at soon: Just how uniform is the Uniform Anatomical Gift Act in its implementation by the various States? Are body donation consent forms executed under the authority of the UAGA enforceable outside America?

Another, somewhat related question: If a cryonicist executes a valid will in Oregon, moves to California, and dies there without executing a new will, but the original will does not comply with the formalities of execution applying in California, is the will valid — and if so, is it valid for all purposes, or only some? This is the domain of private international law, aka “conflict of laws,” which refers to how one legal jurisdiction deals with foreign legal elements: foreign parties, parties asking for application of foreign law, or foreign judgments. This is a particularly complicated area, but one which cannot be ignored, since so many cryonicists do not live in the same legal jurisdiction as their cryonics organization.

Another theme I will be exploring in this column is access to cryonics and other forms of life extension. In the case of cryonics, impediments to access can take the very blatant form of a law directly prohibiting it, or essential procedures thereof, or else operate indirectly, like mandatory autopsy provisions. Access to cryonics is also context-specific — taking on a very different meaning for someone diagnosed with a brain-threatening disorder, for instance. As such, the availability of legal assistance in dying is a topic which might be dealt with under this heading, and whether the practical benefits accruing to those patients outweighs the risks, both individually and to cryonics generally. How the law defines death, and public policy debates over whether to move to new definitions for reasons quite separate from cryonics, also fall neatly here.

Access to life extension, more generally, is also interesting to examine from a legal perspective. Are the current models of regulation applying to drug development sufficiently flexible to accommodate the advent of SENS-type rejuvenation therapies? One could say that cryonics aspires to being ordinary health care someday, at which time we can expect that it will be subject to some form of regulation. What should it look like? And how can cryonics organizations today best self-monitor and self-regulate to ease that eventual transition?

Finally, constitutional rights instruments have immense potential as tools for securing meaningful access to cryonics and other forms of life extension. However, the content and implementation of these fundamental rights documents vary throughout the world. Cryonics has fairly deep roots in America, but are we certain there is no better soil on Earth in which it might flourish?

All of the above areas of law overlap and interact, and there are other relevant ones that I have not mentioned (insurance law, notably), and no doubt a few I am not yet even aware of. I also plan to report on live cases of interest, as they arise.

One last, but significant point: due to variations between the laws of different jurisdictions (even within a single nation) you cannot simply assume that paperwork designed to work in one jurisdiction will work as intended in yours. You need to find a cryonics-friendly advisor where you live and have them review your cryonics arrangements, and revise them if necessary to work in your home jurisdiction. You are fighting for your life — you cannot afford to wear ill-fitting armor.

First published as a regular column called In Perpetuity in Cryonics Magazine, January 2013.

06. May 2015 · Comments Off on Cryonics as a measure of rationality? · Categories: Cryonics, Society

Most cryonics advocates are often frustrated by the amount irrationality, ignorance, and hostility when other people encounter the idea of human cryopreservation. It should not be surprising then that some of us have simply concluded that most people “just don’t get it.” Which raises an important question. Is making cryonics arrangements a strong measure of rationality? After all, a close examination of Alcor members indicates that most of them are highly educated, a disproportionate number of them have PhDs, and their backgrounds are often in fields where strong analytic skills are required; computer science, neuroscience, biochemistry, etc. Another indicator is that cryonics is relatively popular in communities with a high proportion of “nerds.” In fact, a number of “leaders” in the “rationality” community (Robin Hanson, Eliezer Yudkowsky) have cryonics arrangements and have made public arguments in favor of cryonics. In short, someone who has made cryonics arrangements is not prone to short term gratification and minimizes cognitive biases, one could argue.

The problem with this characterization of cryonics as a measure of rationality is that it does not explain why the overwhelming number of people who can be considered highly analytical or rational have not made cryonics arrangements. Many cryonicists are smart but most smart people are not cryonicists. To explain this we will have to look elsewhere.

The 18th century skeptic and analytical philosopher David Hume once wrote that “reason is a slave to the passions.” In the case of cryonics, no matter how smart a person is, if the person does not have a passion for life (and an aversion to death and aging) that person will not be primed for an enthusiastic personal endorsement of cryonics. Closely related to having a desire to live and to pursue life extension is a an optimistic temperament. A cryonicist is not necessarily “wildly” optimistic, but (s)he should at least think that life is worth living and not be prone to thinking about the future in dystopian terms. I am also inclined to think that such a person is prone to think “like an economist” (to use Bryan Caplan’s phrase). With this I mean that a person can think in a probabilistic manner, does not see the world as a “zero-sum game,” and sees developments like automation, computerisation and biotechnologies in a positive light.

Do these combined traits produce a favorable attitude towards cryonics? This still cannot be the complete story because the traits discussed so far are shared by many millions of people in the world and support for cryonics is extremely small. I want to single out two additional traits that are usually required to prime someone for cryonics. The person also needs to be a non-conformist of some kind. When cryonics is as small as it is, strongly endorsing cryonics makes someone stand out (to put it mildly). And this “standing out” is not comparable to just having a bizarre hobby or a strange sense of style. It can sometimes produce confusion or hostility in other people, which can turn even our most life-affirming friends and family into apologetic pro-mortalists.

The most important trait, in my opinion, and the one that really distinguishes the cryonicist from the non-cryonicist, is the ability to deal with vulnerability, uncertainty and the unknown — in some cases, to even welcome it. People who have been around in cryonics for awhile know that ultimately (that is, when you dig a little deeper) skeptics are really afraid to be resuscitated in a distant and unknown future. This should not be easily dismissed. Personal identity is not identical to the brain or the body (as a simplistic version of cryonics would have it) but extends to all the things and people that have become part of a person’s life. To many people, the cryonics proposal means  survival at the cost of losing everything that gives meaning to their lives.

If we look at the limited acceptance of cryonics from this perspective, does this inspire optimism in persuading more people? An immediate response would be negative because fundamental character traits are hard to change. Another approach, however, is to change the conceptualization and delivery of cryonics so that these fears are not triggered. In particular, it might serve a cryonics organization well to transition from an organization that just “stores” a human body or brain without specific resuscitation and reintegration scenarios to an organization that offers more comprehensive means of identity preservation. Such an organization puts a strong emphasis on the cryopreservation of families and friends. It will offer means of asset preservation and personal belongings. It develops specific resuscitation protocols which are updated and calibrated as our knowledge and technologies improve. And it makes serious efforts to provide a reintegration program which seeks to minimize adjustment to the time in which an individual is resuscitated.

Is endorsement of cryonics a measure of rationality? Yes, but without a desire to live, a reasonably optimistic attitude, an independent mindset, and, most of all, confidence in a cryonics organization to preserve all that is important to a person, being smart by itself is not going to do it.

This is a web-exclusive edition of the Quod incepimus conficiemus column that is published in Cryonics magazine but was omitted from the April 2015 issue.

20. January 2015 · Comments Off on Alcor vs Disintegration · Categories: Cryonics, Society

This article was previously published in Cryonics Magazine, May, 2013

In this short article I will discuss two distinct developments in contemporary cryonics that are setting the stage of how cryonics is going to be practiced in the foreseeable future.

First, there is the recognition that the most formidable obstacle for people to make cryonics arrangements is not scientific or technological, but psychological. We know this because people tell us so. It is a form of anxiety about the future and social alienation that is even a concern for people who have made cryonics arrangements. Ignoring this and/or telling people to “toughen up” is simply not an effective response.

Second, there is an increasing interest in long-term wealth preservation among people who have made cryonics arrangements and this interest is no longer confined to wealthy Alcor members. In addition, there is also a growing interest in preserving biographical information, ranging from personal memories to tangible objects. This development can reflect a desire to prevent “disintegration” (see Keegan Macintosh’s excellent article in this magazine) during cryostasis or may be motivated by the use of such information for damage repair or validation of resuscitation attempts.

It seems clear to me that these two developments are closely associated and that Alcor can address the desire of their members to preserve biographical information, remain “connected” and make cryonics a less anxiety-inducing choice at the same time.

In the April 2013 issue of Cryonics magazine Mike Anzis contributed a useful review of very long-term storage alternatives for personal information and materials and all these options have their pro’s and con’s. I suspect that many people not only have reservations about the long-term survival of many of the organizations and companies reviewed, but also have concerns about privacy and the alignment of the goals of these entities and the objective of personal survival.

While it is unrealistic to expect that Alcor can be involved in all matters concerning personal data storage and reintegration (there is an argument for diversification and redundancy, too) it seems rather obvious that Alcor has a more substantial role to play than it does today. It needs to play a substantial role if we want Alcor to be perceived as an organization that does not just see reversible cryopreservation and rejuvenation as a technical problem to be solved, but one that will also do its best to give its patients a face, maintain the social integration of its patients, and facilitate means to protect personal assets and personal information.

I cannot do justice to the practical aspects of this objective in this short article but let me conclude with a number of specific suggestions.

We do not know whether email in its current format will still exist in the future but we do know that Alcor owns a domain name and can issue email addresses to their cryopreservation members and provide secure storage of email messages.

We do not need to speculate as much about the nature and compatibility of very long-term data storage technologies if Alcor starts offering such services and will ensure to upgrade them as times change. In addition, Alcor can allow its members to securely edit their personal information and medical records to allow for a better response in time of need.

Alcor can hardly compete with social networking platforms such as Facebook and Google+ but we can make an effort to offer individual members the opportunity to create a private or public online profile that will be retained after cryopreservation of the member, and that can perhaps even be updated by Alcor, family, and friends.

The benefits of such changes are greater than just offering Alcor members more opportunities to retain personal information, prevent disintegration, and more strongly identify with their cryonics organization. By giving our members a visible place and the tools to remain relevant we will also communicate to the rest of the world that we are serious and that we will not let our members slide into oblivion – even during cryostasis.

20. January 2015 · Comments Off on Cryonics and Natural Selection · Categories: Cryonics, Death, Society

“…it is not the strongest that survives; but the species that survives is the one that is able best to adapt and adjust to the changing environment in which it finds itself” so reads a quote that, in modified form, often has been mistakenly attributed to Charles Darwin but was in fact a description of Darwin’s views penned down by a Professor of Management and Marketing named Leon C. Megginson in 1963. But, surely, one reason for the popularity of this quote is that it captures the modern view of evolution quite well. In this column I would like to briefly reflect on what cryonics means in the context of evolution and natural selection.

Any cryonicist that has not kept his support of cryonics completely to himself must have found himself in a situation where even the most reasonable arguments seemed to leave someone else completely indifferent, or even hostile. Even in the case of family members or friends there comes a point where one cannot help thinking, “well, if you would rather die than think, fine, I am not going to stop you.” It appears, then, that people who make cryonics arrangements are part of an extremely small group of people that will escape the common fate of all humans (i.e. death), as a consequence of being extremely open-minded and adaptable.  But is this the “survival” that the theory of natural selection speaks of?

The modern theory of natural selection is essentially about reproduction. It is not necessarily the longest-lived species (the survivors) whose (genetic) traits will become more common in a population but the ones whose fitness leads to greater reproductive success. It can hardly be denied that cryonicists are extraordinarily capable of adapting to change (or ready to adapt to future change) but it has also been quite firmly observed that cryonicists (or life extentionists in general) are lagging the general population in terms of reproduction, either because of the higher number of single persons or because of the lower interest in having children. It is sometimes observed that whereas most people seek “immortality” by ensuring their genes will survive in future generations, cryonicists see immortality by seeking to survive themselves. In addition, even allowing for a growing interest in cryonics, the number of people making cryonics arrangements is simply too small to have a meaningful effect on the genetic and mental traits of future generations. At best, cryonicists may find themselves being perceived as independent, courageous, individuals that were simply more capable of anticipating the future of science and medicine.

It is tempting, indeed, to think of cryonicists as a homogeneous group of people who are extraordinarily analytic and adaptable but a closer inspection of the motives of people who make cryonics arrangements suggests something different. Indeed, if we look at the early days of cryonics, we see a disproportionate number of cryonicists who where extraordinary visionaries, sometimes independently arriving at the same conclusions (think of Robert Ettinger and Ev Cooper). As cryonics received more mainstream exposure, however, we see different reasons why people endorse cryonics. A partner has cryonics arrangements and the other person is persuaded to do so, too. Subcultures in which making cryonics arrangements is strongly endorsed (like transhumanism). A strong fear of death that prompts a person to do anything to not die, regardless of a dispassionate assessment of cryonics. In more recent times, even career considerations can be a factor as more “market-based” salaries are available in the field of cryonics. Still, despite the possibility that the personality type that chooses cryonics is increasingly getting more diverse, it still makes sense to talk about the demographics of cryonics for as long as the cryonics population is substantially different from the general population.

Where does all this leave us concerning cryonics and natural selection? Since natural selection is basically about reproductive success despite death it would not be correct to characterize the small group of cryonicists that will survive (where others do not) as an example of Darwinian evolution in action, I think. It may be tempting to use Darwinian terminology to characterize our situation but upon closer scrutiny there are problems with this. What might be said, though, is that (successful) cryonicists will be in the extraordinary situation to live for such a long time that they can see human evolution further unfold and even be in a position to consciously direct it through human enhancement.

This is a web-exclusive edition of the Quod incepimus conficiemus column that is published in Cryonics magazine but was omitted from the December 2014 issue.  

10. November 2014 · Comments Off on Ancient Brains · Categories: Cryonics, Neuroscience, Science

Cryonics seeks to preserve terminally ill humans in anticipation of future medical advances that may restore these patients to youthful vigor, cure their devastating diseases, and resuscitate them from cryopreservation itself. At the core of this mission lies the goal of preserving that which we know to be most important to continuity of the person him/herself: the brain.

Absent reversible cryopreservation of the brain (i.e., maintenance of viability), a cryonicist’s best hope for eventual resuscitation lies in preserving brain ultrastructure with as much fidelity as possible. Improvements in cryopreservation solutions, methodologies, and protocols from the field to the operating room have greatly enhanced our ability to meet this objective, as evidenced by microscopic evaluations of tissues vitrified in the lab. More recently, CT scans of patients after neuropreservation have provided valuable feedback as to the efficacy of cryoprotective perfusion in actual Alcor cases. Such progress bodes well for good patient outcomes.

But even our greatest attempts at optimal preservation are thwarted by issues such as long ischemic periods resulting in significant perfusion impairment or even the inability to perfuse at all. So how do we evaluate these patients in light of our objective?

Perhaps the best place to start is the extreme. Let us consider, for example, a prehistoric human brain discovered in 2008 at a construction site in York, UK. A paper published in 2011 in the Journal of Archaeological Science (“Exceptional preservation of a prehistoric human brain from Heslington, Yorkshire, UK”) provides gross and histological observations as well as preliminary results of chemical assays in order to determine the extent and cause of preservation of the brain. Low-powered reflected light microscopy and electron microscopy were performed to explore the surviving morphology and histology of the brain, while highly sensitive neuroimmunological techniques and proteomic analyses were employed to explore brain chemistry.

Examination of the skull indicated death by an abrupt trauma to the neck followed by deliberate dismemberment of the head between veretebrae C2 and C3. Significantly, the authors report “no trace of microbial activity, bacterial or fungal, with none of the porosity or ‘tunneling’ that is characteristic of putrefactive microorganisms.” Examination of the brain masses revealed recognizable sulci and gyri, but neither macroscopic nor CT evaluation could differentiate between grey and white matter.

Histological examination of the brain masses showed “a homogenous, amorphous substance that had not retained any cellular or matrix structure.” Transmission electronic microscopy (TEM) also did not detect any surviving cellular structure, although it did reveal what appeared to be “numerous morphologically degraded structures characteristic of the myelin sheath of nerve fibres.”

Preliminary biomolecular analysis found only 5% of the brain was detectable as hydrolysable amino acids, in contrast to fresh brain tissue of which proteins represent more than 1/3 of dry weight. When compared with a fresh brain, the Heslington brain was also depleted in polar amino acids and enriched in hydrophobic amino acids. Very little undegraded solventsoluble brain lipid was preserved (0.8%- 1.1% wet weight compared with 17.1% for rat brain). In addition, there was an almost complete absence of phospholipids and only a trace of cholesterol, while degradation products of a wide range of lipids were found in abundance.

Ultimately, the authors determined that the preservation of this brain was due to decapitation (thus eliminating the movement of putrefying bacteria from the gut to the brain) followed by inhibition of postmortem putrefaction achieved through rapid burial into fine-grained wet sediment. They go on to argue that this type of preservation is not as unusual as one might think, citing several similar examples of preserved prehistoric human brains, almost always found in wet burial environments.

While interesting in its own right, few would argue that the Heslington brain represents a state of preservation amenable to resuscitation. The ability to infer anything beyond gross macro structure has been obliterated and the normal chemical constituents of the brain have dissolved almost completely into the surrounding environment. Clearly, much of the look of a brain can be retained while none of the person’s identity remains (or is recoverable).

Let us then look at a situation that hits a little closer to home. Published in Forensic Science International in 2007, an article entitled “Autopsy at 2 months after death: Brain is satisfactorily preserved for neuropathology” provides us with considerable food for thought. In this example, a 77-year-old woman’s whole body was stored postmortem in a 3°C cooling chamber for 2 months prior to chemical fixation of her brain at autopsy.

The authors describe moderate autolysis of internal organs of the body, indicating the start of decomposition and putrefaction, as well as reduced tissue consistency and superficial areas of disintegration of the brain. Overall gross morphology was sufficiently preserved to allow macroscopic examination and application of neuropathological methods for diagnosis of neurological disorders. Importantly, they also report that “histologically, normal brain structures including all major parenchymal cell types (neurons, astrocytes, oligodendrocytes, microglia), neuropil, axons, and myelin sheaths were preserved.”

In this case, the use of cold temperatures (3°C) drastically slowed, but did not stop, deterioration of the brain. However, enough of the brain’s chemical constituents and physical structure remained to provide the basis for possible future resuscitation. And while this woman’s brain was preserved by chemical diffusion over the course of 9 weeks (allowing for continued degradation of subcortical tissues during the course of fixation), the use of cryogenic temperatures to quickly preserve her brain would also have been possible, as has been the situation for many “straight frozen” Alcor patients who were received in similar condition.

Exactly where the line between recoverability and non-recoverability — resulting in information-theoretic death — exists is yet to be determined. And while we push, rightfully, for ever greater preservation methods, we do well to remember that those preserved under lessthan- optimal conditions are by no means lost causes. Preserved information, even in fractured and distorted form, may well be adequate to infer the original state.

Originally published as an article (in the Cooler Minds Prevail series) in Cryonics magazine, March, 2013

16. October 2014 · Comments Off on Cryonics without Repair · Categories: Cryonics

Cryonics Magazine, August, 2013

Why Reversible Cryopreservation Matters

[The following is a text adaptation of a PowerPoint presentation given on Sunday, May 12, 2013 at the Resuscitation and Reintegration of Cryonics Patients Symposium in Portland, Oregon.]

Let’s start with the following definition of cryonics:

“Cryonics is the stabilization of critically ill patients at ultra-low temperatures to allow resuscitation in the future.”

As you can see, nothing in this definition says that repair is an intrinsic feature of cryonics. But is this a reasonable perspective? Let’s think about a number of aspects of cryonics that could be classified as “repair.”

• Critically ill patients are sick and will need medical treatment in the future.
• Most cryonics patients will require
rejuvenation.
• The cryopreservation process itself causes (irreversible) damage.

Yes, cryonics patients will require a second look at their condition by a future doctor who will have more advanced medical technologies at his/her disposal. This could conceivably be called “repair.” Most cryonics patients will also require rejuvenation biotechnologies. After all, it makes little sense to cure the patient’s disease but leave him/her in a fragile, debilitated state. This could be called “repair” too, in particular if you believe that aging is the progressive accumulation of damage. The repair that I want to discuss here is repair of the damage that is associated with the cryopreservation process itself. If we can eliminate this kind of damage, and the associated requirement of repair in the future, we will make the idea of cryonics a whole lot more attractive. What would be the advantages of being able to offer such “cryonics without repair?”

Perhaps the most obvious advantage is that cryonics could not be dismissed solely by pointing to the (irreversible) damage caused by the cryopreservation process itself. In essence, such a form of cryonics would be akin to putting a critically ill patient in a state of true suspended animation. This would strengthen the legal position of cryonics patients because a decision to abandon a patient in such a condition would be more akin to murder (or at least serious neglect). Another advantage would be that the absence of cryopreservation damage would increase the likelihood of the patient being restored to good health in the future. Less damage is also likely to translate into lower costs, too, and it is rather obvious that such an advantage can mean more security for the patient. Reversible cryopreservation may also lead to earlier treatment and resuscitation attempts, which may reduce challenges associated with re-integration. Cryonics without repair also matters in the here-and-now. Without the goal of reversible cryopreservation there are no objective, empirical criteria to evaluate the quality of care in a cryonics case. Last, but not least, we should do no harm. Allowing unnecessary injury of the patient because future advanced technologies should be able to fix it is a morally suspect gamble with a person’s life.

That is an impressive list of arguments in favor of offering reversible human cryopreservation. Now let’s try to be more specific about what cryonics without repair means. Clearly, the condition of the patient should not worsen relative to the critical condition the patient was in at the time of pronouncement of legal death. In fact, a rarely recognized possibility in a good cryonics case is that it might even be feasible to slightly improve the condition of the patient through the administration of cerebroprotective medications and washing out the blood, provided these procedures do not restore spontaneous circulation and consciousness, of course. A common perspective at Alcor to look at the objective of stabilization procedures is to say that these procedures should be aimed at maintaining viability of the patient by contemporary criteria. In the past I have characterized this objective as securing viability of the brain, but I think it would be better to aim for complete viability of the body unless there is a clear trade-off between viability of the brain (the most important organ in cryonics) and the rest of the body. Ultimately, though, we do not just want to be able to reverse the stabilization procedures but all cryonics procedures.

Before we walk through basic cryonics procedures to identify obvious and notso- obvious opportunities for cryonics procedures to produce additional damage, let’s look at circumstances in which the patient suffers additional damage that cannot be attributed to the cryonics organization. The most obvious situation is where there is a long delay between pronouncement of legal death and the start of cryonics procedures because hours go by before the patient is discovered or hospital administrators do not allow immediate access. It is important to recognize that the goal of maintaining viability can be defeated before we even start our procedures. Critics of cryonics often talk about compromising circumstances as if they are intrinsic aspects of cryonics instead of the result of tragic but avoidable events or hostile authorities. Reversible cryopreservation is only possible if the cryonics organization is notified in time and receives good cooperation from hospital administrators and other authorities.

The first real opportunity for a cryonics organization to “screw up” is to allow substantial periods of warm and cold ischemia. This can happen in a number of ways including, but not limited to, not restoring adequate circulation, inadequate ventilation, allowing blood pressure and cerebral perfusion to drop (restoring blood pressure does not guarantee good cerebral blood flow), suboptimal induction of hypothermia, or conducting surgery at high temperatures without metabolic support. In ideal circumstances a cryonics stabilization is conducted so that suboptimal results in one of these areas are offset by gains in the other protocols.

If a cryonics organization is able to provide metabolic support and rapidly cool down the patient to close to the freezing point of water the next challenges involve the cryopreservation process. The best known form of damage here is, of course, ice damage. While today’s vitrification agents are formulated to inhibit ice formation at realistic cooling rates, there are still a number of things that can go wrong. The distribution of cryoprotectant in the brain can be incomplete as a result of surgical errors or flaws during cryoprotective perfusion (e.g., vessels not properly cannulated, extremely low or high pressures, pumping air, etc.) The cryoprotectant can also be introduced at temperatures that are too warm or introduced too rapidly to allow the cells to maintain volume in an acceptable range. Even if none of these mistakes are made, we run into other challenges that cryonics organizations cannot successfully overcome yet.

Successful vitrification requires the use of high concentrations of organic solutes (such as DMSO and formamide) and non-penetrating polymers. While much progress has been made by cryobiology researchers Gregory Fahy and Brian Wowk to formulate solutions with low toxicity, and such solutions have been shown to successfully cryopreserve brain slices, our current understanding is that it is not likely that the brain of a cryonics patient remains spontaneously viable after being equilibrated with these agents. This is partly because the “blood brain barrier” leads to a situation in which solutes naturally present in the brain become concentrated during cryoprotective perfusion (dehydration) as discussed in the next paragraph. This causes cells inside whole brains to be cryoprotected by a mixture of natural solutes and some components of the perfused cryoprotectant solution rather than just the carefully-formulated cryoprotectant solution. Sometimes natural is not good.

It is sometimes said that eliminating cryoprotectant toxicity is the “holy grail” of cryonics research. While there is good empirical evidence to suggest that despite this toxicity good ultrastructure of the brain is still possible, true reversible human cryopreservation without reliance on sophisticated repair will require cryoprotectants with much lower toxicity. The need for less toxic cryoprotectants is especially tied into the problem of achieving concurrent and adequate distribution of cryoprotectant to all parts of the body that are vulnerable to freezing injury, which requires many hours of perfusion. In addition to cryoprotectant toxicity there are a number of other poorly-understood phenomena that could frustrate the ideal of cryonics without repair such as “chilling injury” and “thermal shock.”

An interesting form of injury that is not well known by the general public but that triggers a lot of discussion among cryonics researchers is dehydration of the brain. Without exception, a wellconducted cryopreservation of the brain with present technology produces severe shrinking. In fact, this shrinkage, and the corresponding increase in concentration of salts and proteins naturally present in the brain, appears to be a key mechanism by which whole brains vitrify despite limited permeability to perfused cryoprotectants. Evidence of substantial dehydration (obtainable by direct inspection of the brain inside the skull or via CT scans) is often considered an indicator of good care in cryonics. Of course, this leaves the question unanswered whether such a degree of dehydration is compatible with viability of the brain. Yuri Pichugin, the researcher who developed the Cryonics Institute’s current vitrification agent, VM-1, considered such extreme cerebral dehydration an obstacle to restoring viability after vitrification and identified a number of blood brain barrier modifiers that allowed him to recover brain slices after whole brain cryoprotective perfusion with improved viability. Whether such agents are of benefit or actually harmful is still an open research question.

Even if we could cryopreserve a human being without ice formation, toxicity, chilling injury, or other forms of injury associated with cryoprotection, there is still one remaining obstacle for reversible  cryopreservation: fracturing caused by thermal stress. While fracturing has been recognized as a problem and observed as an empirical phenomenon in patients as far back as the early 1980s, this form of injury has pushed itself to center stage (together with cryoprotectant toxicity and cerebral dehydration) since cryonics organizations started using vitrification agents aimed at eliminating ice formation altogether. If ice formation is eliminated, fracturing is the only mechanical form of damage left. While the significance of fracturing damage is sometimes downplayed by molecular nanotechnology experts, and fracturing at cryogenic temperatures doesn’t result in actual fragmentation, letting a human brain form fractures is not what most people would consider appropriate treatment of a critically ill patient.

What is striking, however, is how little we actually know about fracturing in cryonics patients. Fracturing has been observed in patients that were cryopreserved with (relatively) low concentrations of cryoprotectants. Such protocols produced ice formation and we should therefore not be surprised about observing cracking in those patients. Even in patients who have been cryopreserved using modern vitrification agents acoustic fracturing events (which may or may not correspond with actual fractures) have been detected above the glass transition temperature (Tg) of the pure vitrification solution. But even these observations have little relevance to the question of what we should expect in a good case. Many cryonics patients are perfused under sub-optimal conditions due to delays after clinical death. It is therefore likely that many of these fracturing events, if real, can be attributed to ischemia-induced perfusion impairment and ice formation. And that cooling frozen tissues to very low temperatures can cause fracturing is something we already know.

There are some encouraging preliminary research results suggesting that under ideal circumstances (i.e., good equilibration, controlled cooling) fracturing is not as serious a problem as it has been made out to be. The current practice of long term care at liquid nitrogen temperature may not be salvaged by such observations, but the intermediate temperature storage (ITS) systems that have been developed might be sufficient to eliminate this problem under good conditions at temperatures not too far below Tg. A related intriguing question is what the effect of severe cerebral dehydration is on the occurrence and frequency of fractures in the brain.

Let’s say that one agrees with the objective of “cryonics without repair” (or very limited repair), and the identification of the biggest scientific and technical obstacles to achieve this. What should our research and clinical objectives be? For starters, cryonics organizations should continue to cultivate an interest in personal alarm systems and securing good legal and logistical cooperation with providers of medical care. One technical development that deserves to be introduced is “field vitrification.” Strictly speaking, the phrase is a misnomer because we are not really talking about the patient being vitrified in a remote location; it is the cryoprotective perfusion part of the procedure that is done prior to transport to Alcor (in remote cases). Evidence from at least three labs indicates that perfusing the patient in the field with a vitrification solution and shipping on dry ice is safe, practical, and superior to blood substitution in most scenarios. While remote blood substitution (“washout”) is clearly demonstrated to be better than shipping the patient without removing the blood, it is not likely that hypothermic organ preservation solutions capable of keeping the brain viable for longer than 24 hours, and capable of inhibiting whole body edema, will be developed any time soon. Field vitrification is simply the next logical development in high-quality evidence-based cryonics. Other important improvements include better cooling efficiency (e.g., using cyclic cold lung lavage), improved cardiopulmonary support protocols, a renewed emphasis on monitoring during casework, and the introduction of intermediate temperature storage.

The most formidable challenge will be to develop what I call “brain-friendly” cryoprotectants. What needs to be accomplished? These agents should have no, or tolerable, toxicity, eliminate chilling injury and other poorly-understood forms of cryopreservation injury, allow safe and fracture-free storage at intermediate temperatures, and allow cryoprotective perfusion with greater penetration of agents into brain tissue with less dehydration so that results in whole brains can more closely match the high viabilities now obtainable in brain slices.

At my own company, Advanced Neural Biosciences, we have successfully developed a rat EEG model to screen for such brain-friendly cryoprotectants. As I write up this presentation, we have been successful in recovering integrated whole brain electrical activity after hypothermic circulatory arrest at 0° Celsius. Our next objectives are to recover EEG activity in the brain after cooling to subzero temperatures and to understand the relationship between cryoprotectants, the blood brain barrier, dehydration, and viability. It is too early to report any significant findings yet, but one thing that has become quite clear to us is that adequate ventilation during cool down is essential to recovery of whole brain activity. This is rather important because cryonics organizations have not been that concerned about meeting the brain’s demand for oxygen during stabilization, and during blood washout and blood substitution in particular. No doubt, if we continue this research we will learn other things that have direct relevance to the practice of cryonics.

The whole brain cryopreservation research project has been made possible by the generous support of the Life Extension Foundation. The author also wishes to thank the Immortalist Society, Cryonics Institute, Alcor, LongeCity, 21st Century Medicine, Alan Mole, York Porter, Jordan Sparks, David Ettinger, Ben Best, Mark Plus, Peter Gouras, James Clement, Luke Parrish, and John Bull for additional support.