X-Message-Number: 9647 Date: Fri, 8 May 1998 03:16:04 -0400 From: Mike Darwin <> Subject: Halperin's proposal RE: Halperin's proposal Jim Halperin has asked for comments and criticisms of his proposal. I'll start by saying that I agree almost completely with much of the previous criticism. I think most of the commentary has been thoughtful and on-point. Of course, I'll add a few points of my own, but I don't expect them to count for much with Mr. Halperin (for reasons I'll get to near the end of this post). First the more straightforward ones: One problem I've observed over the years in attempts to increase both organ and tissue donation is the barrier that inhibition of the free market represents. When I started work as a dialysis tech I was used as a scout to scour the ICUs and CCCUs for potential donors for harvest. I also participated in some harvests when I worked at Methodist Hospital in Indianapolis. I knew Lynne Driver and Larry Lloyd (the transplant coordinators) very well, and Larry was my immediate supevisior for some years. Methodist had one of the highest organ procurement rates in the region, indeed in the U.S. There were many reasons for this which I won't go into, but suffice it to say I've observed that other centers are STILL only now learning the lessons that Lynne and his team had long ago learned. The point of this digression was that a point of law got in the way of a _lot_ of harvesting, especially from lower class urban minority patients who constitute the largest untapped pool: who else gets hit on the head with a baseball bat or shot in the head so much???? That point of law is a very touchy one which states in effect "I (the person making the gift) have received no remuneration whatsoever in conjunction with making this anatomical donation." The law specifically charged the recipient organization with paying the donor's usual and customary funeral costs, but that was it. Any attempt to do more (offer a glitzier funeral, pay other expenses, offer medical care, or even benefit potential donors during their lifetimes with access to better medical care or other advantages was vigorously attacked. I know this still to be the case because 21CM has been preparing research protocols for CPR-related work where chest morphology demands that humans be used for suction cup type thumpers (CPR machines) and we have been extensively advised on the sensitivity of this issue. Since these negotiations are ongoing with several institutions, I raised Jim's idea with their legal counsel; they were of the opinion that offering an incentive like the one Jim proposes constitutes a violation of the specially enacted congressional ban against the "selling of human organs or tissues" and that it would violate the no compensation provisionms of Uniform Anatomical Gift Act (which is anything but "uniform") in most states. Another problem is that solid organ donors, which are those most desperately needed (heart , kidney and other thoracic and abdominal organs) excluding the minorities problems mentioned above, are most often lost because of the following reasons: 1) First and foremost is inadequate preservation technologies. Most hearts are not even harvested from the same donor who provides kidneys. We just didn't bother with most of them because the preservation time is only 4 hours to 6 hours MAXIMUM. The logistics of transport and the need to closely match the SIZE of the organ to the recipient frustrated harvesting. 2) Lungs are damn near impssible to preserve well. They also don't do well on transplant, but that's mostly because they preserve so poorly that the donor literally has to be "beating heart" and in the next OR for the harvest. This means that clinicians haven't gained experience overcoming the surgical problems attendant tolung transplantation (bronchial non-unions and infection) largely through lack of opportunity to hone their skills because so few transplants are done. Lungs also experience re-implantation injury which complicates their acute function (which is essential to the survival of the recipient). This is largely an immune-inflammatory response problem which is rapidly being solved by pharmacological intervention in the researh lab; but the preservation and transportation problems remain. 3) By far the largest untapped pool of donors are DOAs', people who arrest shortly AFTER arriving at the hospital and who cannot be or are not GOOD candidates for resuscitation. A recent issue of the Lancet reports on post-mortem transplant of such kidneys with good success. Ischemia-reperfusion treatment protocols promise to open up this huge pool of donors. But again, preservation technologies are critical since most organs are harvested with many hours or days of notice and with tissue typing starting BEFORE harvesting, buying much needed time. The exception is the heart. Because preservation times are so short hearts are matched ONLY for ABO and Rh blood groups; there is NO tissue typing for hearts. As a result, hearts are rejected far more frequently than other organs. 4) Thomas Starzl, M.D. is the man who single-handedly pounded liver transplants into reality (please, read his book Puzzle People for a clear, lay-level and honest account of the herculean animal research effort and clinical paradigm shift required) to achieve this. Starzl recently discovered that donors who don't reject their grafts long-term have chimeric immune systems. In other words, the immune system from the donor hitches a ride in the transplanted organ and colonizes the host! Starzl has demonstrated that in cases where you have a number of weeks you can frequently produce such a state of chimeric tolerance in recipients, bringing the number of organs rejected to vanishingly small levels and almost eliminating the need for the quality of life degrading drugs used to control rejection. Keep in mind a significant number of organs "wasted" are re-transplants where an organ has been rejected (needlessly) because good preservation technologies were not available to allow for optimal immunological preparation of the recipient. The catch is, of course, you neeed TIME. The future holds the prospect of transgenic transplantation of genetically engineered animal organs and I think the prospects for the heart and a few other organs are good using this technology (not so for the liver which makes to many custom, workable only in human proteins: thus only human livers will do for replacements). This means that transplantion will shift increasingly to quality of life organs; putting human-source organs in either the oldest or youngest patients, the best or the worst (depending upon how good the transgenic organs turn out to be). Better preservation technologies would also open up transplanting tissues like limbs, hands, breasts, penises, scalp and craniofacial tissues whose destruction occur in staggering numbers anually and whose victims just have to "live" with the resultant mutilation and disability because a) there are no large banks of matchable tissues, and b) the risks of immunosupression currently poses too great a theat to life. Countless women undergo mutilating mastectomies and I've observed, in my own brief acute care clinical career no fewer than ca. 20 young men who have lost their penises due to thermal/chemical burns (everything from high tension line work to industrial accients and mechanical injury (largely industrial and vehicular) and cancer or the side effects of "localized" radiotherapy. The quality of theses men's lives is often devastated with, in my experience, wives and girlfiends frequently leaving them (something, oddly enough, I saw far more than with women undergoing mastectomies). Limb amputations and digit loses speak for themselves both in terms of commoness, visibility and disability. These tissues simply are not transplanted because good preservation technologies do not exist. 5) Tissue-engineering is BIG business and will help millions of people with horrible burns, missing ears and other seriously damaged peripheral tissues. Some companies have started to ship product already which will alleviate suffering from burns so profoundly there are no words to describe it. What is one of their major problems? You guessed it; lack of high quality preservation procedures. 6) In the 3rd world there are sharp limits to upregulating herd quality of indigenous animals used for food and work because artificial insemination (AI) techniques, to be effective, require cryopreserved sperm and, to be most effective, embryos too. Sperm cryopreservation alone has brought the average American dairy cow from producing a few hundreds of pounds of milk per year to producing tems of thousands of pounds! All on the same calorie intake. In fact, Steve Bridge's father ran an AI business that provided the frozen sperm that created the prize winning cow Ellen who, I believe, produced 250,000 pounds of high quality milk and cream in one year!!!!! The development of cryoprotectants that allow dry ice storage of sperm would revolutionize the quality of life in countries where high-tech LN2 freezing, storage and transport of sperm are not possible. LN2 exists in developed countries as a byproduct of a huge industrial infrastructure, producing liquified gases for industrial (metallurgical) and medical applications. Dry ice is, by contrast, cheap and easy to make and transport. The point I'm making here is that the way to maximize transplantation AND improve the number of people being cryopreserved is to improve the technology through research. And we are not talking theoretical research, but rather appllied research with direct technological application. No,. I am not foolish enough to believe that successful reversible cryoprerservation of the brain or clinically applied cryopreservation of the kidney, heart or liver will "sell" cryonics to the GENERAL public. No such thing. But, I do believe based on considerable prior experience that each one of these advances brings a new and higer quality cohort of people into cryonics. Already, cryonics groups have a disproportionate numbers of physicians as members. The number of physicians and other technically sophisticated and high quality minds will grow as the barriers to be overcome change from theoretical ones (Is the information REALLY there? Can nanotechnolgy be implemented in a reasonable time frame? Can it do what its theoriticians say it will?, etc.) to more purely technological ones: OK, the brain is sitting there intact and so are most of the organs. At least I'm still basically ME after they finish preserving me. One more big unnown eliminated, one more cohort persuaded. Ralph Merkle has a graph of Alcor's growth versus time. That growth begins about 6 months after I took over as President and continues until a short while after Jerry Leaf dies and and the split off of CryoCare. Jerry had been on scene for several years before I arrived, and he had critical technical and interpersonal skills (basically you didn't fuck with Jerry and everybody knew that--sorry, there is no other word to use). The combination of Jerry, Hugh Hixon , myself and later Saul Kent, Carlos Mondragon and BRENDA PETERS (with much off-site inpit from Steve Bridge who continued to edit CRYONICS during the my first few years running Alcor) STIMULATED rapid growth. As Saul has pointed out, a keystone of that growth was the provision of framework for research and progress which was palpable, exciting and, truly world changing. People could see methods improving by objective criteria they could understand, and they could easily be a part of it. Hell, we had secretaries (day job) doing OR work and computer people assisting with surgery. The atmosphere was like the model rocket societies of the 20's and 30's. Nanotechnology furthered that goal. What is NOT generally understood is that in the two years prior to writing Engines of Creation Drexler had a gift subscription to CRYONICS (given by Lee Gabriel of ACS, I believe). He has personally told me that those two years of getting CRYONICS were instrumental in his including his chapter on cryonincs in his book and on shaping his thinking about the feasibility of cryonics. Hugh Hixon and I both provided many pages of commentary on Drexler's orginal manuscript (entitled The Future By Design) and many of those comments CAN BE FOUND in Engines. At that time, I did not have the data I have now about how badly brain tissue (selectively, I might add) is injured by freezing, let alone thawing. At that time we were relying on fragmentary and, as it turned out, inappropriate studies done on not very relevant animal models (such as Suda's work, Pascoe's work, and the work of kidney and heart cryopreservationists). As it turns out, the injury to brains was far worse than I imagined possible under the worst of circumstances. But, we did not know that at the time. So, where is all this leading? To a conclusion I have found to be nearly useless: trying to persuade people to spend their money on something they don't really have their heart set on. To Jim Halperin I would say, your idea is the hard way to do what you want to do. There are lots of better ways to spend you money, many (believe it or not!) NOT involving 21CM which in my not so humble opinion will provide you with faster, lower resistance, higher yieldd pathways to success. However, I'll end by saying I've never changed anybody's idea about a pet project that they *believed in*. But you asked for a critique, and there, you got it :-). Good luck whatever course you choose. Mike Darwin Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=9647