Biological Repair Technologies

While I believe it is very hard to irreversibly destroy information, I had become quite concerned that the earliest presentation about future cell repair technologies for cryonics patients might have become lost forever. Jerome “Jerry” White’s paper, “Virus-Induced Repair of Damaged Neurons with Preservation of Long-Term Information Content,” was frequently referred to in papers on the topic of revival technologies, but I had never seen the actual paper and was curious and determined to find it. When I discovered that even the people in cryonics who usually own (or can access) a wealth of historical cryonics materials (Mike Perry, Mike Darwin, Steve Bridge, etc.) were not able to track down a copy I became progressively pessimistic and even started questioning whether the presentation was actually transcribed at all. I wrote a column about the missing paper in which I put forward the sad possibility that the paper was lost to us forever. I never gave up though. Then, in September 2014, Mike Perry wrote me to tell that Alcor member Art Quaife was in possession of the paper and would send a copy to him. After receiving the paper, a PDF copy was soon produced and Mike also spent considerable time creating an editable text version.

The premise of White’s paper is straightforward but ingenious (especially considering the fact that it was presented in 1969). We already know of biological “machines” that can enter the body of the patient and make modifications to cells and DNA. They are called viruses. When this is recognized it is not too far fetched to recognize the possibility of separating the virus as a biologically active delivery vehicle from its adverse health effects. The idea of using viruses to deliver genetic material has now become fully established in modern gene therapy. For example, the virus responsible for causing HIV and AIDS can be stripped of these properties but can still be used as a vehicle to modify genes within a cell. In his paper on biological cell repair, White proposed to modify viruses to engage in information gathering, gene modification, and cell repair.

Space does not permit me here to analyze the paper in detail but I would like to briefly discuss two issues concerning the feasibility of biological cell repair for the revival of cryonics patients, namely, capabilities and temperature.

Modifying a virus to change genes is one thing, but rebuilding damaged cell membranes and intracellular organelles is another and it is not fully clear how a virus can be modified to accomplish this. In addition, for non-neural cells a case could be made that it is often more time- and cost-effective to simply destroy and remove cells and cell structures with severe damage (after gathering sufficient information about the cells and their organization). For brain cells there is a special difficulty in that the ultrastructure appears to be identity-critical in a way not expected in non-neural tissue. So the conservative approach here would dictate repairing these cells instead of replacing them. The challenge is that although human physiology already has endogenous mechanisms to maintain DNA integrity and repair damaged DNA, the human genome does not encode for wholesale repair of cells (including their genomic content) that have sustained substantial damage. This, I should add, combined with only limited neurogenesis in the brain, may explain why aging and dementia are strongly correlated. One of the challenges of viral-induced repair of cells is that inserting new genetic information that allows for novel endogenous repair capabilities is itself dependent on the existence of viable cells in the body of the patient. This challenge is also identified in White’s paper when he proposes to create artificial viruses that “carry out degrees of repair greater than those the cell in its damaged condition would itself provide.”

An even bigger challenge for biological repair is temperature limitations. While it has been established that some enzymes still function (albeit at a slower pace) at low or even subzero temperatures, the temperatures that cryonics patients are stored at are substantially lower than that. This would seem to require that we first thaw the patient before conducting repairs. This course of action could create serious problems for the average cryonics patient. In the case of frozen patients, the ice will turn to water again and (damaged) biomolecules that were locked into place could dissolve into solution (which may constitute irreversible loss of identity-critical information). In the case of vitrified patients, ice nuclei that formed during the descent to cold temperatures (or continued forming during intermediate temperature storage) can organize themselves into ice during thawing. Another problem with conducting repairs after thawing is that ischemia will be permitted to continue, causing more damage. While White stipulates that “repair proceed faster than deterioration, whatever the temperature” it is not likely that credible future repair scenarios will permit substantial deterioration to occur during, or prior to, repair.

Does this close the door on biological cell repair? Not necessarily. We can imagine breakthroughs in cryoprotectant design that reconcile negligible toxicity with extreme resistance to ice formation. Patients cryopreserved with such agents could be thawed without risk of ice damage. When temperatures are raised to a point where meaningful enzymatic activity is possible, various biological strategies (metabolic inhibition, reversible fixation) could be used to allow time for repairs. Another idea is to pursue a hybrid strategy in which (crude) nano-size mechanical machines are used to access and open the circulatory system while disrupting nucleation and/ or delivering anti-nucleating molecules. After completing this task at cryogenic temperatures, the patient can be thawed and biological cell repair technologies introduced.

This discussion of the (potential) limitations of biological repair technologies draws attention to the relationship between cryopreservation technologies and repair technologies. We tend to think of preservation and repair technologies as independent endeavours but it has been shown here that the choice of cryoprotectant technology can influence the choice of the most effective repair technology. For example, if a cryoprotectant is just a moderately strong glass former, ice formation upon warming should be expected and mechanical repair technologies may be necessary for conducting the initial steps of repair (preventing ice formation). Or consider intermediate temperature storage. If we store patients just below the glass transition temperature of the vitrification solution, nucleation may still continue, which would favor ice formation upon warming, and thus, again, the need for initial mechanical cell repair technologies to stabilize the patient during the initial stages of repair. Some people think that biological cell repair is an inefficient and impractical (if not impossible) task and the resuscitation of cryonics patients will require mechanical nanoscale repair devices. This may very well turn out to be the case, but demonstrating the technical feasibility of biological cell repair would further strengthen the case for cryonics. Let us hope that Jerry White, who is currently cryopreserved, will be one of the beneficiaries of such powerful technologies.

Originally published as a column in Cryonics magazine, October, 2014