First published in Cryonics magazine, January-February, 2012
By Aschwin de Wolf
Many people who have made cryonics arrangements tend to think of it as a “back-up plan” in case hoped-for breakthroughs in rejuvenation will be too late to help them or as protection against lethal accidents. Their confident hope is that, if other workarounds don’t pan out, they will die from an age-related disease or accident and be cryopreserved in great fixable shape, ready for an easy resuscitation when appropriate techniques are developed. We need to recognize that not all cryonics members are likely to be that “lucky.”
In this article I want to discuss one of the most dreadful scenarios of all: the occurrence of an incurable brain-threatening disorder. I will distinguish among four scenarios:
- A member suffers an insult that produces acute damage to the brain.
- A member has a genetic mutation that produces an early-onset brain threatening disorder.
- A member is at higher genetic risk for a late-onset brain-threatening disorder.
- A member is diagnosed with a brain threatening disorder.
Insults and accidents
Absent not being cryopreserved at all, one of the worst things that can happen to a person with cryonics arrangements is to suffer an unexpected cerebral insult which produces instant brain damage and progressive neural death while the patient remains alive. Such insults could be caused by sudden cardiac arrest, severe strokes, or traumatic brain injury. In many circumstances, the patient is not aware of the insult and its consequences and is completely dependent on the paperwork he executed before the event and/or the judgment of legal representatives and medical professionals.
If cryonics were available as an elective medical procedure such cases would not present a major medical challenge. The patient could be stabilized at cryogenic temperatures in anticipation of more advanced treatment options, before delayed neuronal death could run its course. Currently, such an option is not available and there is great risk that a patient who has suffered a major cerebral insult will lose most of his identity-critical information in the days following the accident.
Forward-looking cryonicists can take measures to deal with such scenarios by executing paperwork that forbids medical professionals from instituting artificial life support after such events. Such paperwork can be complemented with a ‘Do Not Resuscitate’ order. To complicate matters, DNRs are a doubled edged sword for cryonicists because resuscitation can literally be a life-saver when a person suffers a brief period of cardio-respiratory arrest without comorbidities (for example, during surgery), but can also substantially increase brain damage if resuscitation is attempted when progressive damage is likely to occur afterward (for example, after prolonged cardiac arrest or severe head trauma). The challenge is to design a legally valid DNR order that distinguishes between “good” and “bad” resuscitations.
Since such accidents are hard to predict, there is little proactive planning that a cryonics organization member can do except to optimize his legal paperwork and ensure that those who will make decisions have a strong interest in avoiding destruction of identity-critical information while the member is alive. On a more abstract level, it can still be argued that there is an element of prevention involved here, too. For example, unhealthy eating habits and dangerous recreational activities can be avoided to reduce the probability of such events.
In medicine it is common to distinguish between genes that increase or decrease the probability of a patient developing a certain condition and single-gene mutations that invariably produce a certain condition. A good example of the latter is early-onset Alzheimer’s disease, which often runs in a family. Symptoms can start between the ages of 30 and 60. As with Alzheimer’s more generally, there are no known cures and treatment usually consists of assisting the victim and family members reactively as the disease progresses.
Prior to the availability of gene-testing, the existence of early-onset Alzheimer’s (or any kind of debilitating heritable disease) could produce severe anxiety and uncertainty in affected families, such as excessive sensitivity to normal memory lapses. Gene-testing can eliminate this uncertainty by determining whether the particular gene has been inherited from one of the parents. Not all people prefer to know if they will get an incurable disease. Cryonicists, however, are in a different situation because they can use this knowledge to take steps aimed at preventing destruction of personhood by expediting clinical death through voluntary abstention from food and drink or, in some countries like the Netherlands, to utilize assisted-suicide laws during the early stages of the disease.
Early-onset Alzheimer’s is not the only single-gene mutation heritable disease. Cryonics members with a family history of early-onset dementia, Parkinson’s, cardio-vascular problems, or accelerated aging would be well advised to have themselves genotyped or should request gene-specific tests to determine whether they are at risk too.
The spectacular decrease in the cost of genome sequencing will bring whole genome sequencing within the reach of most cryonicists within 5 years. As we write, it is already possible to have yourself genotyped (though not fully sequenced) at a company like 23andMe for around $200. Customers will not only be able to learn about common health risks and traits but such services can also be used for genetic genealogy and finding relatives. Since our ability to interpret all the results lags the amount of data that can be produced, even the most informed consumer is faced with a bewildering confusion of possibilities for certain diseases and traits.
Interestingly, a gene that is associated with susceptibility to late-onset Alzheimer’s disease is one of the most robust findings in biomedical science. In short, there are three variants (alleles) of the apolipoprotein E (APOE) gene: APOE2, APOE3, and APOE4. The APOE3 gene is the most common variant among humans, followed in order by APOE4 and APOE2. Of the three alleles, APOE4 is associated with an increased risk of Alzheimer’s disease and APOE2 is associated with a decreased risk. Since all people inherit one copy of the APOE gene from their father and one from their mother, the range of possibilities vary from E2/E2 to E4/E4 (nine combinations in all), with carriers of the former having the lowest risk and carriers of the latter having the highest risk. As a matter of fact, one recent review of Alzheimer’s disease claims that there are no known cases of elderly autopsied E4/E4 humans without physical correlates of the disease, whereas these markers are virtually absent in people with E2/E2.
This does not mean that all people with high susceptibility will actually get the disease as they age. Medical examiners and researchers often find amyloid-beta plaques and tau protein (common indicators of Alzheimer’s) in autopsied patients who did not show evidence of impaired brain function during life. Presumably, the neurophysiological requirements for the development of Alzheimer’s disease need to reach a certain threshold or can be inhibited by such features as structural organization, neuron count, the presence of “good” genes, etc. Nevertheless, the APOE gene has been found to be a reasonably good predictor for the susceptibility to late-onset Alzheimer’s disease and cryonicists will benefit from knowing their status.
As old as diagnosing disease is the propensity of humans to procrastinate in going to the doctor to obtain a formal verdict. In the case of brain-threatening disorders such procrastination could be equivalent to a death sentence for a cryonicist. Although a 100% accurate diagnosis of Alzheimer’s disease can only be made upon autopsy, a combination of gene tests, mental tests, blood and fluid samples, and PET scans can now be used to render a positive Alzheimer’s diagnosis in many cases. Such tests can also differentiate different kinds of (age-related) dementia. For people with a single-gene mutation, or APOE4 homozygotes, with a strong family history of Alzheimer’s disease, it is prudent to have periodic mental and physical testing to detect very early manifestations of the disease.
Similarly, people who have a strong genetic and/or family history of traits and diseases that produce (acute) brain-threatening disorders can benefit from frequent testing.
Window of opportunity
From a cryonics perspective, the progressive nature of neurodegenerative diseases presents a “window of opportunity” to prevent (further) destruction of the brain. In reality such vigilance is rare. Most people who have stated that they would never allow themselves to be consumed by Alzheimer’s disease ultimately succumb to it and end life in a vegetative state. For obvious reasons, cryonicists would strongly like to avoid such a fate.
There are a number of obstacles that prevent people from taking advantage of this window of opportunity. The biggest problem is lack of a formal diagnosis. This is not necessarily the result of fearing to see a doctor. In many cases, the disease has progressed enough to numb the level of analytical thinking and determination needed to seek a diagnosis. This is especially a risk for people who live alone. In a way, one could say that neurodegenerative diseases manifest themselves as the inability to clearly recognize the situation. For many patients this is not necessarily a bad thing because it still enables them to continue a meaningful life. For a cryonicist, such a scenario is a source of great fear as the outcome may annihilate the prospect of meaningful resuscitation of the original individual after cryopreservation (if cryopreservation is even attempted).
The personality changes that accompany brain threatening disorders can also be abused by family members and third parties who stand to gain from a person not being cryopreserved. For this reason, it is strongly recommended to ensure that relatives and third parties will not benefit if a person is not cryopreserved, irrespective of the condition of the patient or the quality of the cryopreservation. It should be obvious that for people with hostile partners and family members, brain threatening disorders can present an even a greater challenge.
Another obstacle to recognizing the window of opportunity is wishful thinking about treatments. One could easily imagine a life extensionist falling victim to a dangerous overoptimism. A person is diagnosed with Alzheimer’s disease but steadfastly believes that, for example, new stem cell treatments and pharmacological therapies will be able to halt or reverse the disease at a faster pace than the disease will progress. Undoubtedly, at some point in the future this will be the case, but is it prudent to believe it will happen to you?
Perhaps the hardest and most subtle problem is the tendency to delay action until the disease has progressed enough to seriously impair the quality of life but not enough to prevent self-awareness of the disease, its consequences, and the need to take action. This is often not a deliberate process but generally will manifest itself as a conjunction of the instinct to survive and day-to-day rationalizations. In reality, such attempts to let the disease progress and settle for the perfect time for cryopreservation will often fail. One reason for this is that the commitment to the idea of cryonics progressively weakens as mental faculties fail.
The aim of cryonics is to preserve the identity-encoding information in the brain (and any other organs) when contemporary medicine is not able to maintain the patient in good health. The prospect of clinical death is not encouraging, but the biggest threat to a cryonics member, absent not being cryopreserved at all, it is to succumb to a brain threatening disease while still alive.
One of the biggest challenges a cryonicist can face is to have an acute brain-threatening insult without being able to respond to it. Such a scenario can be somewhat decreased by making sensible lifestyle decisions (no extreme sports or dangerous errands in the home) and diet decisions. Executing smart advance directives and appointing the right medical surrogate can make a world of difference.
Having a single-gene mutation that virtually guarantees getting a brain-threatening disorder such as Alzheimer’s disease has one “good” aspect: certainty about one’s fate (absent near-term cures). This allows for (long-term) planning and execution of the right paperwork. Cryonicists who have a documented family history of such diseases will benefit from medical testing, even if they have decided to let nature take its course and just execute the right paperwork to ensure that the disease will not lead to cancellation of their cryonics arrangements.
The most complicated predicament is having a higher susceptibility to one or more brain-threatening disorders. In the case of Alzheimer’s and Parkinson’s it is now possible to get yourself genotyped to quantify such risks. What distinguishes susceptibility genes from “deterministic” genes is the role played by such things as lifestyle, diet, gender, ethnicity, exercise, stress, exposure to toxins, etc. There is no scientific consensus on the most appropriate diet or supplements to avoid dementia-inducing diseases, but this is an area where progress is conceivable. Elderly cryonicists who have a much higher susceptibility to brain-threatening disorders can benefit from routine testing.
Being diagnosed with a brain threatening disorder presents a concrete and actionable challenge. Not all cryonicists prefer to take heroic measures to ensure a timely cryopreservation, but for those who do, recognizing the existence of a window of opportunity and the dangers of procrastination is of great importance.
I conclude this article with four specific recommendations:
- Consult Rebecca Lively’s article, “How to Protect your Cryonics Arrangements from Interference by Third Parties,” and make sure that you have executed the right paperwork.
- Use genetic testing, genotyping, or whole genome sequencing to determine whether you have a single-gene mutation associated with a brain-threatening disease or increased susceptibility for late-onset brain-threatening disorders.
- Familiarize yourself with the nature and progression of the major brain threatening insults and disorders and how they affect decision making and personhood.
- Consult Mike Perry’s “Options for Elective Cryopreservation” (published in this issue) for your options in case of a brain-threatening disorder.
I am grateful for the suggestions and edits made my Mike Perry and Chana de Wolf.
Warning Signs of Alzheimer’s Disease
- Memory loss that disrupts daily life
- Challenges in planning or solving problems
- Difficulty completing familiar tasks at home, at work or at leisure
- Confusion with time or place
- Trouble understanding visual images and spatial relationships
- New problems with words in speaking or writing
- Misplacing things and losing the ability to retrace steps
- Decreased or poor judgment
- Withdrawal from work or social activities
- Changes in mood and personality
More detailed information on the website of the Alzheimer’s Association.