Next up for discussions is the issue of "hyperonconicity." Just as cells require a certain "tonicity" (electrolyte concentration) to maintain their normal volume, tissues with capillaries require a certain concentration (and type) of large (macro-) molecules (colloid) to avoid accumulating water between the cells and becoming swollen, or edematous. Hyperonconicity refers to any solution that has more ability to hold water in the circulatory system (circulating blood or perfusate) than would be the case under NORMAL conditions. The key word there is NORMAL. The macromolecules that comprise colloids can be thought of as molecular sponges that hold water in the capillaries and prevent it from accumulating in between cells as a result of the hydrostatic pressure of perfusion.
This water holding ability is quite complex and nuanced and depends upon the condition of the junctions between the cells in the capillary, the charge of the colloid, the unique chemical properties of the colloid (poorly understood), the configuration of the colloid molecule, and so on.
Onconicity and hyperonconicity are thus in actual practice, relative terms - relative to the condition of the capillary membrane. It is quite possible to have a markedly hyperoncotic perfusate and still have massive edema due to accumulation of water and of the colloid in between the cells! This is so because injured capillary membranes do not behave the same way as healthy or intact ones do - they leak! They leak colloid and with the colloid goes water. Simply cooling the organs (or bodies) of non-hibernating animals results in increased capillary permeability and the leakage of colloid and water into the spaces between cells. There is currently not a complete understanding of why this happens, or why some colloids do not leak as much in the cold as do others. In fact, only a very few species of colloid have been shown to leak less in hypothermia.
Capillary injury and consequent leakage of colloid from ischemia is vastly worse than that induced by hypothermia alone, and no colloid has been identified which is effective at inhibiting this leak, or even reducing it enough in clinical settings to meaningfully change outcome. In the setting of serious ischemic injury in the presence of high concentrations of cryoprotectant, NO COLLOID OR OTHER MOLECULAR SPECIES HAS BEEN SHOWN TO SIGNIFICANTLY REDUCE EDEMA - INCLUDING the PEGs OF VARIOUS MOLECULAR WEIGHTS. CI's own research associates had reported this to CI prior to Ben's decision to do an ad hoc experiment on a human patient with absolutely no prior laboratory animal or even bench testing of the perfusate. The only thing more unconscionable than such an uninformed and reckless action is the continued denial that it was such, and that his "mistake did not have the disastrous consequences implied by Mike Darwin."
Here is what Ben Best says about the outcome for Curtis Henderson in terms of cryoprotective concentration at the end of perfusion:
" The refractive index of the effluent was 1.366 after six liters of VM−1 had been perfused, and was 1.3586 at the end. Intermediate values were as low as 1.3586 and as high as 1.3651, but this was a small range with no trend, and is indicative of random variation. These values are well below the values of 1.416 for 60% VM−1 and 1.4275 for 70% VM−1 — and they showed no trend."
Based on the reported refractive indexes of the venous effluent, I would estimate that Curtis Henderson had approximately 20% to 20% cryoprotectant in his brain - most of which was ethylene glycol. That would (again roughly estimating) equate to about 1.5M to 2.0 M glycerol in terms of colligative cryoprotective effect. I have not yet posted the electron micrographs (EMs) of the damage incurred when 3M glycerol is used as a cryoprotectant in the cat brain, but the histology is posted here: http://wp.me/p1sGcr-lt . I can tell you that the EM's are vastly worse than are the light micrographs.
I have provided a detailed, and I believe accurate, scientific rebuttal to Ben Best's claims. For onto a decade I have privately urged CI to either stop advertising that they are perfusing human patients under conditions which yield 86.1% viability +/- 5.8% (for a 55% concentration CI-VM-1 at - 20 deg C FOR TEN MINUTES, followed by cooling to and rewarming from -130 degrees C at 0.3 degrees C/min) brain tissue viability and ultrastructure, when in reality they are treating patients with 70% VM-1 delivered at +7 (or higher) to -7 deg C (rarely) over far longer periods of time (hours) and in the presence of ischemic insults that typically run to many hours, or even days!
This isn't about elegance of writing, it's about facts, most of which are derived from CI's own website.
I searched but did not find any discussion comparing the merits of the two major cryonics providers in the US, so I figured it might be productive to start such a discussion myself by posing the question to the community: which provider would you choose, all things being equal: Alcor or the Cryonics Institute?
From my research, Alcor comes across as the flasher, higher-end option, while CI seems more like a Mom-and-Pop operation, having only two full-time employees. Alcor also costs substantially more, with its neurosuspension option alone running ~$80k, compared with CI's whole-body preservation cost of ~$30k. While Alcor has received far more publicity than CI, much of it has been negative. The Ted Williams fiasco is probably the most prominent example, although the accuser in that case seems anything but trustworthy. However, Alcor remains something of a shadowy organization that many within the cryonics community are suspicious of. Mike Darwin, a former Alcor president, has written at length on both organizations at http://www.chronopause.com, and on the whole, at least based on what I've read, Alcor comes across looking less competent, less trustworthy, and less open than CI.
One issue in particular is funding. Even though Alcor costs much more, it has many more expenses, and Darwin and others have questioned the long term financial stability of the organization. Ralph Merkle, an Alcor board member and elder statesman of cryonics who has made significant contributions to other fields like nanotechnology, a field he practically invented, and encryption, with Merkle's Puzzles, has essentially admitted(1) that Alcor hasn't managed its money very well:
"Some Alcor members have wondered why rich Alcor members have not donated more money to Alcor. The major reason is that rich Alcor members are rich because they know how to manage money, and they know that Alcor traditionally has managed money poorly. Why give any significant amount of money to an organization that has no fiscal discipline? It will just spend it, and put itself right back into the same financial hole it’s already in.
As a case in point, consider Alcor’s efforts over the year to create an “endowment fund” to stabilize its operating budget. These efforts have always ended with Alcor spending the money on various useful activities. These range from research projects to subsidizing our existing members — raising dues and minimums is a painful thing to do, and the Board is always reluctant to do this even when the financial data is clear. While each such project is individually worthy and has merit, collectively the result has been to thwart the effort to create a lasting endowment and leave Alcor in a financially weak position."
Such an acknowledgement, though appreciated, is frankly disturbing, considering that members depend utterly on these organizations remaining operational and solvent for decades, perhaps even centuries, after they are deanimated.
Meanwhile, CI carries on merrily, well under the radar, seemingly without any drama or intrigue. And Ben Best seems to have very good credentials in the cryonics community, and Eliezer, one of the most prominent public advocates of cryonics, is signed up with them. Yet the tiny size of the operation still fills me with unease concerning its prospects for long-term survivability.
So with all of that said, besides cost, what factors would lead or have led you to pick one organization over the other?
1: http://www.alcor.org/Library/html/CryopreservationFundingAndInflation.html