27. January 2015 · Comments Off · Categories: Health, Neuroscience

Book Review: The SharpBrains Guide to Brain Fitness: How to Optimize Brain Health and Performance at Any Age by Alvero Fernandez

Of all the organs in the human body, a cryonicist should be most concerned about the health and integrity of his or her brain. Thousands of books have been written about physical health and fitness, but very few address the topic of how to keep the brain fit and healthy. Happily, interest in brain fitness, once relegated to academics and gerontologists, is now taking root across America and the world.

The importance of lifelong learning and mental stimulation as a component of healthy aging has long been recognized and touted as a way to stay mentally alert and to stave off dementia in old age. As with physical exercise, “use it or lose it” appears to apply to our brains too. And now that scientists are learning more about neuroplasticity and how brains change as a result of aging, they have begun to test the effects of various factors on brain health and cognitive ability across the lifespan.

Unfortunately, like much health-related research, the results reported by the media have often been convoluted, confusing, and even contradictory. Products developed by overzealous entrepreneurs make outlandish claims and frequently don’t deliver the purported results. Consumers and professionals alike are left wondering what works and what doesn’t when it comes to maintaining our brains in optimal working condition.

To aid all those navigating the murky waters of brain fitness, enter SharpBrains—a company dedicated to tracking news, research, technology, and trends in brain health and to disseminating information about the applications of brain science innovation. In so doing, they “maintain an annual state-of-the-market consumer report series, publish consumer guides to inform decision-making, produce an annual global and virtual professional conference,” and maintain SharpBrains.com, a leading educational blog and website with over 100,000 monthly readers.

Most recently, SharpBrains has published a book on brain fitness called The SharpBrains Guide to Brain Fitness: How to Optimize Brain Health and Performance at Any Age. A compilation and condensation of information accumulated over the lifespan of the company, The SharpBrains Guide to Brain Fitness emphasizes credible research and goes to great lengths to provide the most up-to-date research results in specific areas of brain fitness, followed by interviews with scientists doing work in those fields. The goal of the guide is to help the reader begin to “cultivate a new mindset and master a new toolkit that allow us appreciate and take full advantage of our brain’s incredible properties…[by] providing the information and understanding to make sound and personally relevant decisions about how to optimize your own brain health and performance.”

The Guide begins by emphasizing that the brain’s many neuronal networks serve distinct functions including various types of memory, language, emotional regulation, attention, and planning. Plasticity of the brain is defined as its lifelong capacity to change and reorganize itself in response to the stimulation of learning and experience—the foundation upon which “brain training” to improve cognitive performance at any age, and to maintain brain health into old age, is predicated.

The difficulty of making sense of the scientific findings on brain health and neuroplasticity is discussed at length, with the finger of blame pointed squarely at the media for reporting only fragments of the research and for often reporting those results which are not most meaningful. The authors stress that “it is critical to complement popular media sources with independent resources, and above all with one’s own informed judgment.”

The following chapters go on to review what is known today about how physical exercise, nutrition, mental challenge, social engagement, and stress management can positively affect brain health. Along the way they provide dozens of relevant research results (as well as the design of each study) to support their recommendations. Reporting on all of those experiments is beyond the scope of this review, so if you are interested in examining them (and you should be!) please obtain a copy of the Guide for yourself or from your local library.

Physical exercise is discussed first because of the very strong evidence that exercise—especially aerobic, or “cardio,” exercise slows atrophy of the brain associated with aging, actually increasing the brain’s volume of neurons (i.e., “gray matter”) and connections between neurons (i.e., “white matter”). While much of the initial research supporting the effects of exercise on the brain came from animal studies, the authors report that “several brain imaging studies have now shown that physical exercise is accompanied by increased brain volume in humans.”

Staying physically fit improves cognition across all age groups, with particularly large benefits for so-called “executive” functions such as planning, working memory, and inhibition. A 2010 meta-analysis by the NIH also concluded that physical exercise is a key factor in postponing cognitive decline and/or dementia, while other studies have found physical exercise to lower the risk of developing Parkinson’s disease, as well.

But don’t think that just any moving around will do the trick. When it comes to providing brain benefits, a clear distinction is drawn between physical activity and physical exercise. Only exercise will trigger the biochemical changes in the brain that spur neurogenesis and support neuroplasticity. It doesn’t need to be particularly strenuous, but to be most beneficial it should raise your heart rate and increase your breathing rate.

Of course, adequate nutrition is also imperative in obtaining and maintaining optimal brain health. The SharpBrains Guide to Brain Fitness primarily highlights the well-known benefits of the Mediterranean diet, which consists of a high intake of vegetables, fruit, cereals, and unsaturated fats, a low intake of dairy products, meat, and saturated fats, a moderate intake of fish, and regular but moderate alcohol consumption. But I think it is safe to say that the jury is still out on the best diet for the brain, as evidenced by the recent popularity of the Paleo diet among life extentionists. And, of course, ethnicity and genetics are important, too. The authors do stress the importance of omega-3 fatty acids and antioxidants obtained from dietary sources, stating firmly that “to date, no supplement has conclusively been shown to improve cognitive functioning, slow down cognitive decline, or postpone Alzheimer’s disease symptoms beyond placebo effect.” This includes herbal supplements such as Ginko biloba and St. John’s wort.

Beyond what we normally do to keep our bodies healthy, the Guide also discusses the relative effectiveness of different forms of “mental exercise.” Perhaps you’ve heard that doing crossword or Sudoku puzzles will keep you sharp and alert into old age, or that speaking multiple languages is associated with decreased risk of Alzheimer’s disease. The good news is that these things are true—to a degree. The part that is often left out is that it’s the challenge of these activities that is important. As with physical activity vs. physical exercise, mental exercise refers to the subset of mental activities that are effortful and challenging.

Puzzles and games may be challenging at first, but they (and other mental exercises) can quickly become routine and unchallenging. In order to reap the most benefit from mental exercise, the goal is to be exposed to novelty and increasing levels of challenge. Variety is important for stimulating all aspects of cognitive ability and performance, so excessive specialization is not the best strategy for maintaining long-term brain health. If you are an artist, try your hand at strategybased games. If you’re an economist, try an artistic activity. Get out of your comfort zone in order to stimulate skills that you rarely use otherwise.

The SharpBrains Guide states that “lifelong participation in cognitively engaging activities results in delayed cognitive decline in healthy individuals and in spending less time living with dementia in people diagnosed with Alzheimer’s disease.” This is hypothesized to be because doing so builds up one’s “cognitive reserve”—literally an extra reservoir of neurons and neuronal connections—which may be utilized so that a person continues to function normally even in the face of underlying Alzheimer’s or other brain pathology. This observation raises another important point on which neuroscientists and physiologists do not yet fully agree. Will we all eventually get dementia if we live long enough without credible brain rejuvenation biotechnologies? This is a topic I would like to return to in a future installment of Cooler Minds Prevail.

Social engagement also appears to provide brain benefits. The NIH meta-analysis mentioned earlier concluded that higher social engagement in mid- to late life is associated with higher cognitive functioning and reduced risk of cognitive decline. Brain imaging studies indicate an effect of social stimulation on the volume of the amygdala, a structure that plays a major role in our emotional responses and which is closely connected to the hippocampus, which is important for memory.

Yet again, not all activity is equal. When it comes to social stimulation, “you can expect to accrue more benefits within groups that have a purpose (such as a book club or a spiritual group) compared to casual social interactions (such as having a drink with a friend to relax after work).” To keep socially engaged across the lifespan, seek out interactions that naturally involve novelty, variety, and challenge such as volunteering and participating in social groups.

“The lifelong demands on any person have changed more rapidly in the last thousand years than our genes and brains have,” The SharpBrains Guide explains in the intro to the chapter on stress management. The result? It has become much more difficult to regulate stress and emotions. It is great that we have such amazing and complex brains, but humans are among the few animals that can get stressed from their own thoughts. And while there are some (potentially) beneficial effects of short bursts of stress, high and sustained levels of stress can have a number of negative consequences. Those of note include: increased levels of blood cortisol which can lead to sugar imbalances, high blood pressure, loss of muscle tissue and bone density, lower immunity, and cause damage to the brain; a reduction of certain neurotransmitters, such as serotonin and dopamine, which has been linked to depression; and a hampering of our ability to make changes to reduce the stress, resulting in General Adaption Syndrome (aka “burnout”).

Research-based lifestyle solutions to combat stress include exercise, relaxation, socialization, humor and laughter, and positive thinking. In particular, targeted, capacity-building techniques such as biofeedback and meditation are recommended to manage stress and build resilience. Mindfulness Based Stress Reduction (MBSR) programs have provided evidence that meditative techniques can help manage stress and research shows that MBSR can lead to decreases in the density of an area of the amygdala which is correlated with reduction in reported stress.

So it appears that multiple approaches are necessary to develop a highly fit brain capable of adapting to new situations and challenges throughout life. “Consequently,” The SharpBrains Guide to Brain Fitness states, “we expect cross-training the brain to soon become as mainstream as cross-training the body is today, going beyond unstructured mental activity in order to maximize specific brain functions.”

There is growing evidence that brain training can work, but in evaluating what “works” we are mostly looking at two things: how successful the training program is (i.e., does it actually improve the skill(s) being trained?) and the likelihood of transfer from training to daily life. Building on an analysis of documented examples of brain training techniques that “work” or “transfer,” SharpBrains suggests the following five conditions need to be met for brain training to be likely to translate into meaningful real world improvements (condensed excerpt):

  1. Training must engage and exercise a core brain-based capacity or neural circuit identified to be relevant to real-life outcomes.
  2. The training must target a performance bottleneck.
  3. A minimum “dose” of 15 hours total per targeted brain function, performed over 8 weeks or less, is necessary for real improvement.
  4. Training must be adaptive to performance, require effortful attention, and increase in difficulty.
  5. Over the long-term, the key is continued practice for continued benefits.

Meditation, biofeedback, and/or cognitive therapy in concert with cognitive training to optimize targeted brain functions appear to be winning combinations in terms of successful techniques facilitating transfer from training to real life benefits. Top brain training software programs, based on SharpBrains’ analysis and a survey of their users, include Lumosity, Brain games, brainHQ, Cogmed, and emWave.

In the end, brain fitness needs are unique to each individual and brain fitness claims should be evaluated skeptically. SharpBrains recommends asking several questions when evaluating brain fitness claims, particularly whether there is clear and credible evidence of the program’s success documented in peer-reviewed scientific papers published in mainstream scientific journals that analyze the effects of the specific product.

Of course, your own individual experience with the product is ultimately the most important evaluation of all. If you are ready to take the plunge into the emerging brain fitness market, The SharpBrains Guide to Brain Fitness is a good place to start, and I’m sure they’d appreciate your feedback as this field continues to develop.

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

26. January 2015 · Comments Off · Categories: Health, Neuroscience, Science

After a few articles considering Alzheimer disease from several angles, I would like to switch gears this month and talk more generally about the interaction between the immune system and aging.

In his 2012 paper[1], Caleb E. Finch documents the evolution of life expectancy in the course of human history. The life expectancy at birth of our shared ape ancestor 6 millions years ago is hypothesized to approximate that of a chimpanzee, 15 years. The first Homo species appeared 1-2 million years ago and had a life expectancy of ~20 years, while H. sapiens came onto the scene ~100,000 years ago and could expect about 30 years of life. But starting around 200 years ago, concurrent with industrialization, human life expectancy jumped rapidly, to somewhere between 70 and 80 years today.

As many readers are likely aware, the huge recent increases in life expectancy are commonly attributed to improvements in hygiene, nutrition, and medicine during the nineteenth and twentieth centuries that reduced mortality from infections at all ages. Finch hypothesizes, generally, that early age mortality over the course of human history is primarily due to (acute) infection, while old age mortality is primarily due to (chronic) inflammation. Further analysis of mortality rates over the last several hundred years leads him to further hypothesize that aging has been slowed in proportion to the reduced exposure to infections in early life. These hypotheses are supported by twentieth century examples which strongly demonstrate influences of the early life environment on adult health, such as the effects of prenatal and postnatal developmental influences (e.g., nutrition, exposure to infection) on adult chronic metabolic and vascular disorders as well as physical traits and mental characteristics. This leads Finch to suggest “broadening the concept of ‘developmental origins’ to include three groups of factors: nutritional deficits, chronic stress from socioeconomic factors, and direct and indirect damage from infections.”

Finch also considers the effects of inflammation and diet on human evolution, proposing several environmental and foraging factors that may have been important in the genetic basis for evolving lower basal mortality through interactions with chronic inflammation, in particular: dietary fat and caloric content; infections from pathogens ingested from carrion and from exposure to excreta; and noninfectious inflammagens such as those in aerosols and in cooked foods. He hypothesizes that exposure to these proinflammatory factors, which one would expect to shorten life expectancy, actually resulted in humans evolving lower mortality and longer lifespans in response to highly inflammatory environments.

A means for this, he argues, was the development of the apoE4 genotype. Noting that the apoE4 allele favors advantageous fat accumulation and is also associated with enhanced inflammatory responses, Finch argues that heightened inflammatory response and more efficient fat storage would have been adaptive in a pro-inflammatory environment and during times of uncertain nutrition. As has been discussed in prior articles in Cooler Minds Prevail, the apoE alleles also influence diverse chronic non-infectious degenerative diseases and lifespan. “Thus,” Finch concludes, “the apoE allele system has multiple influences relevant to evolution of brain development, metabolic storage, host defense, and longevity.”

With the general relationship between inflammation and the evolution of human aging and life expectancy in mind, let us now consider immune system involvement in more detail, and the relationship between HIV and immunosenescence more specifically.

Immunosenescence refers to the ageassociated deterioration of the immune system. As an organism ages it gradually becomes deficient in its ability to respond to infections and experiences a decline in long-term immune memory. This is due to a number of specific biological changes such as diminished self-renewal capacity of hematopoietic stem cells, a decline in total number of phagocytes, impairment of Natural Killer (NK) and dendritic cells, and a reduction in B-cell population. There is also a decline in the production of new naïve lymphocytes and the functional competence of memory cell populations. As a result, advanced age is associated with increased frequency and severity of pathological health problems as well as an increase in morbidity due to impaired ability to respond to infections, diseases, and disorders.

It is not hard to imagine that an increased viral load leading to chronic inflammatory response may accelerate aging and immunosenescence. Evidence for this is accumulating rapidly since the advent of antiretroviral therapies for treatment of HIV infection. An unforeseen consequence of these successful therapies is that HIV patients are living longer but a striking number of them appear to be getting older faster, particularly showing early signs of dementia usually seen in the elderly. In one study, slightly more than 10% of older patients (avg = 56.7 years) with wellcontrolled HIV infection had cerebrospinal fluid (CSF) marker profiles consistent with Alzheimer disease[2] – more than 10 times the risk prevalence of the general population at the same age. HIV patients are also registering higher rates of insulin resistance and cholesterol imbalances, suffer elevated rates of melanoma and kidney cancers, and seven times the rate of other non-HIV-related cancers. And ultimately, long-term treated HIV-infected individuals also die at an earlier age than HIV-uninfected individuals[3].

Recent research is beginning to explore and unravel the interplay between HIV infection and other environmental factors (such as co-infection with other viruses) in the acceleration of the aging process of the immune system, leading to immunosenescence. In the setting of HIV infection, the immune response is associated with abnormally high levels of activation, leading to a cascade of continued viral spread and cell death, and accelerating the physiologic steps associated with immunosenescence. Despite clear improvements associated with effective antiretroviral therapy, some subjects show persistent alterations in T cell homeostasis, especially constraints on T cell recovery, which are further exacerbated in the setting of co-infection and increasing age.

Unsurprisingly, it has been observed that markers of immunosenescence might predict morbidity and mortality in HIV-infected adults as well as the general population. In both HIV infection and aging, immunosenescence is marked by an increased proportion of CD28- to CD57+, and memory CD8+ T cells with reduced capacity to produce interleukin 2 (IL-2), increased production of interleukin 6 (IL-6), resistance to apoptosis, and shortened telomeres. Levels of markers of inflammation are elevated in HIV infected patients, and elevations in markers such as high-sensitivity C-reactive protein, D-dimer, and interleukin 6 (IL-6) have been associated with increased risk for cardiovascular disease, opportunistic conditions, or all-cause mortality[4].

But even as we are beginning to identify markers that appear to be associated with risk of poor outcome in HIV infection, it is still unclear how patients should be treated on the basis of this information. To that end, several trials are underway to evaluate the effects of modulation of immune activation and inflammation in HIV infection. At the same time, clinicians at the forefront of advancing knowledge and clinical care are performing research aimed at optimizing care for aging HIV patients.

The implications for such research may be far-reaching. In fact, many HIV clinicians and researchers think that HIV may be key to understanding aging in general. Dr. Eric Verdin states, “I think in treated, HIV-infected patients the primary driver of disease is immunological. The study of individuals who are HIV-positive is likely to teach us things that are really new and important, not only about HIV infection, but also about normal aging.”

Dr. Steven Deeks stresses the collaborative efforts of experts across fields. “I think there is a high potential for tremendous progress in understanding HIV if we can assemble a team of experts from the world of HIV immunology and the world of gerontology,” he says. “Each field can dramatically inform the other. I believe HIV is a well described, well studied, distinct disease that can be used as
a model by the larger community to look at issues of aging.”

References

[1] Finch, C (2012). Evolution of the Human Lifespan, Past, Present, and Future: Phases in the Evolution of Human Life Expectancy in Relation to the Inflammatory Load. Proceedings of the American Philosophical Society, 156:1, 9-44.

[2] Mascolini, M (2013). Over 10% in Older HIV Group Fit Alzheimer’s Biomarker Risk Profile. Conference Reports for NATAP: 20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013.

[3] Aberg, X (2012). Aging, Inflammation, and HIV Infection. Topics in Antiviral Medicine, 20:3, 101-105.

[4] Deeks, S, Verdin, S. and McCune, JM (2012). Immunosenescence and HIV. Current Opinion in Immunology, 24: 1-6.

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

23. January 2015 · Comments Off · Categories: Neuroscience, Science

Last month this column considered current and future progress in Alzheimer Disease (AD) diagnosis, management, and treatment. Because AD is a terrible brain disease with an increasing rate of prevalence with age, and because it represents one of – if not the – worst conditions that can afflict a person with cryopreservation arrangements, I would like to continue our consideration of this well-known and widely-feared neurodegenerative disease. Specifically, our focus will be on apolipoprotein E (apoE) and research regarding its role in the modulation of physiological responses to certain viral infections.

ApoE protein is primarily synthesized peripherally in the liver and mediates cholesterol metabolism systemically, but it is also made in the central nervous system by astroglia and microglia (non-neuronal cell types) where it transports cholesterol to neurons. In the CNS, neurons express receptors for apoE that are part of the low density lipoprotein receptor gene family. Historically, apoE has been recognized for its role in lipoprotein metabolism and its importance in cardiovascular disease. Of course, apoE carrier status is also widely known as the major factor determining one’s risk of developing late-onset Alzheimer disease (AD). But more recent research has indicated that the various isoforms of apoE may also have significant immunological impact by conferring different susceptibilities to other diseases, as well.

The human apoE gene is located on chromosome 19 and is composed of 79 individual single nucleotide polymorphisms (SNPs). The three major alleles of apoE, named Epsilon-2 (Ɛ2), Epsilon-3 (Ɛ3), and Epsilon-4 (Ɛ4), are determined by differences in SNPs s429358 and rs7412. The products of these alleles are the protein isoforms apoE2, apoE3, and apoE4, which differ only by a single amino acid at two residues (amino acid 112 and amino acid 158). These amino acid substitutions affect noncovalent “salt bridge” formation within the proteins, which ultimately impacts on lipoprotein preference, stability of the protein, and receptor binding activities of the isoforms (see Table 1).

Isoform Amino acid 112 Amino acid 158 Relative charge Lipoprotein preference LDL receptor binding ability

apoE2

cysteine

cysteine

0

HDL

low

apoE3

cysteine

arginine

+1

HDL

high

apoE4

arginine

arginine

+2

VLDL, chylomicrons

high

Table 1. ApoE isoform amino acid differences and resulting chemical and physiological changes.

There are also two minor alleles, Epsilon-1 (Ɛ1) and Epsilon-5 (Ɛ5), which are present in less than 0.1% of the population. The three major alleles are responsible for three homozygous (Ɛ2/Ɛ2, Ɛ3/Ɛ3, Ɛ4/Ɛ4) and three heterozygous (Ɛ2/Ɛ3, Ɛ2/Ɛ4, Ɛ3/Ɛ4) genotypes. [I will pause to mention here that it is now quite easy to determine one’s genotype through services such as 23andme.com.]

An interesting document in the field is the literature review by Inga Kuhlman, et al. (Lipids in Health and Disease 2010, 9:8) which assesses hepatitis C, HIV and herpes simplex disease risk by ApoE genotype. An important finding is that the Ɛ4 allele is found less frequently in populations as they age (e.g., 14% of the general German population vs. 5% in centenarians), indicating that Ɛ4 is a major mortality factor in the elderly. This is assumed to be a result of the Ɛ4 allele’s well-known predisposition to Alzheimer and cardiovascular diseases.

The authors explain that “apoE4 carriers have a tendency for 5-10% higher fasting total cholesterol, LDL-cholesterol and triglyceride levels relative to homozygote Ɛ3/Ɛ3” and that this tendency towards higher lipid levels is probably responsible for the 40-50% greater cardiovascular disease risk in Ɛ4 carriers. They also point out that “although the molecular basis of the pathology is poorly understood, and likely to be in part due to apoE genotype associated differences in brain lipid metabolism, an apoE4 genotype has been highly consistently associated with the risk of an age-related loss of cognitive function, in an allele dose fashion.” This means, of course, that Ɛ4/Ɛ4 carriers are at greatest risk for cognitive dysfunction with increasing age.

In the field of immune regulation, a growing number of studies point to apoE’s interaction with many immunological processes. In their article, Kuhlman, et al., summarize the impact of the Ɛ4 allele on the susceptibility to specific infectious viral disease. The authors review a number of studies of the effects of apoE4 genotype on hepatitis C (HCV), human immunodeficiency virus (HIV), and herpes simplex (HSV) infection and outcome in humans.

In general, apoE4 was found to be protective against hepatitis C infection vs. (Ɛ3/Ɛ3) controls. Though the exact mechanisms of apoE genotype-specific effects on HCV life cycle remain uncertain, apoE seems to be involved because “available data indicate that the outcome of chronic HCV infection is better among Ɛ4 carriers due to slower fibrosis progression.”

Concerning the possible influence of apoE genotype on HIV infection and HIV-associated dementia, the authors call attention to the fact that “cholesterol is a crucial component of the HIV envelope and essential for viral entry and assembly.” Given that apoE is essential for cholesterol transport, they hypothesize that apoE genotype influences HIV-induced effects on neurological function. Subsequent review of available research suggests that the 4 allele is associated with higher steady-state viral load and faster disease progression due to accelerated virus entry in 4 carriers, but a correlation between apoE4 and HIV-associated dementia “remains controversial and needs to be clarified by further studies.”

Lastly, a review of the literature regarding the effects of apoE4 genotype on herpes simplex virus (HSV)-1 infection and outcome in humans indicates that apoE4 enhances the susceptibility for HSV-1 “as well as the neuroinvasiveness of HSV-1 compared to other apoE variants” (i.e., HSV-1 is found in more frequently in the CNS of 4 carriers). Importantly, the authors also note that “the combination of apoE4 and HSV-1 may lead to a higher risk of Alzheimer disease (AD) than either factor in isolation.”

Due to its generally being associated with higher risk of cardiovascular disease, dementia, and increased susceptibility to and/or accelerated progression of various viral infections, one may wonder why the 4 allele has not been eliminated by evolutionary selection. This may be explained, in part, by the protective and beneficial effects it exhibits in certain harmful infectious diseases, as demonstrated for hepatitis C.

The exact mechanisms of apoE influence on susceptibility to and course of viral infection remain shrouded. Because the mechanisms of HCV, HIV, and HSV infection are quite similar (i.e., all three viruses compete with apoE for cell attachment and receptor binding), it is interesting to find differences in receptor binding among them.

Involvement or interaction between the immune system, cognition, and brain diseases such as AD is an as-yet widely untouched field of inquiry. Further elucidation of the mechanisms by which apoE may influence the pathogenesis of infectious viral diseases can lead to new developments in the treatment of disease based on an individual’s apoE genotype.

Aside from the role that ApoE plays in susceptibility and progression of infectious disease, there is growing interest in the role that infection or a compromised immune system plays in the development of dementia. For example, despite the successful management of HIV with antiretroviral drugs, some patients are showing signs of memory impairment and dementia at a relatively young age. Interestingly, these people seem to show accelerated aging, too, which raises important questions about the relationship between the immune system, immunosenescence, and aging.

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

14. November 2014 · Comments Off · Categories: Health, Neuroscience

Any terminal illness is a terrible thing; but to a cryonics member, a brain-destroying neurodegenerative disease is the worst contemporary medical “death sentence” one can receive. There are several flavors of neurodegenerative disorders, many of which primarily affect the patient’s movement, strength, coordination, or the peripheral nervous system. And there are numerous contributory mechanisms in the causation of neurodegeneration, including prion infection and toxin related disease. But the most common – and the most feared – neurodegenerative disease is one that affects not movement, but cognition.

Of course, I am speaking of Alzheimer disease (AD). Originally described in a 51- year old woman by the Bavarian psychiatrist Alois Alzheimer in 1906, neuropathologists have increasingly recognized that AD is also the most common basis for latelife cognitive failure. Culminating in neuronal dystrophy and death leading to the progressive loss of memory and other cognitive functions (i.e., dementia), and affecting individuals of both sexes and of all races and ethnic groups at a rate of occurrence in the U.S. ranging from approximately 1.3% (age 65-74) to 45% (age 85-93), it is easy to see why AD has generated so much intense scientific interest in recent years.

In the recently published work “The Biology of Alzheimer Disease” (2012), most of what is known about AD today is described in detail in the various chapters covering topics such as the neuropsychological profile and neuropathological alterations in AD, biomarkers of AD, the biochemistry and cell biology of the various proteins involved in AD, animal models of AD, the role of inflammation in AD, the genetics of AD, and treatment strategies. The editors’ selection of contributions has resulted in the most up-to-date compendium on Alzheimer disease to date.

The book culminates in a chapter called Alzheimer Disease in 2020, where the editors extol “the remarkable advances in unraveling the biological underpinnings of Alzheimer disease…during the last 25 years,” and yet also recognize that “we have made only the smallest of dents in the development of truly disease-modifying treatments.” So what can we reasonably expect over the course of the next 7 years or so? Will we bang our heads against the wall of discovery, or will there be enormous breakthroughs in identification and treatment of AD?

Though a definitive diagnosis of AD is only possible upon postmortem histopathological examination of the brain, a thorough review of the book leads me to believe that the greatest progress currently being made is in developing assays to diagnose AD at earlier stages. It is now known that neuropathological changes associated with AD may begin decades before symptoms manifest. This, coupled with the uncertainty inherent in a clinical diagnosis of AD, has driven a search for diagnostic markers. Two particular approaches have shown the most promise: brain imaging and the identification of fluid biomarkers of AD.

Historically, imaging was used only to exclude potentially surgically treatable causes of cognitive decline. Over the last few decades, imaging has moved from this minor role to a central position of diagnostic value with ever-increasing specificity. The ability to differentiate AD from alternative or contributory pathologies is of significant value now, but the need for an earlier and more certain diagnosis will only increase as disease-modifying therapies are identified. This will be particularly true if these therapies work best (or only) when initiated at the preclinical stage. Improvements in imaging have also greatly increased our understanding of the biology and progression of AD temporally and spatially. Importantly, the clinical correlations of these changes and their relationships to other biomarkers and to prognosis can be studied.

The primary modalities that have contributed to progress in AD imaging are structural magnetic resonance imaging (MRI), functional MRI, fluorodeoxyglucose (FDG) positron emission tomography (PET), and amyloid PET. Structural MRI, which is used to image the structure of the brain, has obvious utility in visualizing the progressive cerebral atrophy characteristic of AD. Such images can be used as a marker of disease progression and as a means of measuring effective treatments (which would slow the rate of atrophy). Functional MRI, on the other hand, measures changes in blood oxygen leveldependent (BOLD) MR signal. This signal, which can be acquired during cognitive tasks, may provide the clinician with a tool to compare brain activity across conditions in order to assess and detect early brain dysfunction related to AD and to monitor therapeutic response over relatively short time periods.

FDG PET primarily indicates brain metabolism and synaptic activity by measuring glucose analog fluorodeoxyglucose (which can be detected by PET after labeling it with Fluorine-18). A large body of FDG-PET work has identified an endophenotype of AD – that is, a signature set of regions that are typically hypometabolic in AD patients. FDG hypometabolism parallels cognitive function along the trajectory of normal, preclinical, prodromal, and established AD. Over the course of three decades of investigation, FDG PET has emerged as a robust marker of brain dysfunction in AD. Imaging of β-amyloid (Aβ) – the peptide that makes up the plaques found in the brains of AD patients – is accomplished via amyloid PET to determine brain Aβ content. Historically, this has only been possible upon postmortem examination, so the utility of amyloid imaging is in moving this assessment from the pathology laboratory to the clinic. Because amyloid deposition begins early on, however, amyloid PET is not useful as a marker of disease progression.

The well-known hallmarks of AD, the plaques and neurofibrillary tangles first described by Alouis Alzheimer in 1906, were discovered in 1985 to be composed primarily of β-amyloid and hyperphosphorylated tau protein, respectively. Advances in our knowledge of Aβ generation and tau protein homeostasis have led to substantial research into disease-modifying drugs aimed at decreasing overall plaque and tangle load in an effort to halt neurodegeneration. Such treatments will likely be most effective if started early in the disease process, making sensitive and accurate fluid biomarkers of Aβ and tau especially important.

Outside of imaging, progress in AD diagnostics stems primarily from the assessment of fluid biomarkers of AD. These biomarkers are generally procured from the cerebrospinal fluid (CSF) and blood plasma and include total tau (T-tau), phosphorylated tau (P-tau) and the 42 amino acid form of of β-amyloid (Aβ42). These core biomarkers reflect AD pathology and have high diagnostic accuracy, which is especially useful in diagnosing AD in prodromal and mild cognitive impairment cases.

Because the CSF is in direct contact with the extracellular space of the brain, biochemical changes in the brain can be detected in the CSF. Assays to detect Aβ42 led to the discovery that Aβ42 in AD is decreased to approximately 50% of control levels, making the measurement of Aβ42 a useful clinical tool. Measurements of T-tau (around 300% of control in AD patients) and P-tau biomarkers (a marked increase in AD patients) in combination with Aβ42, however, provide an even more powerful diagnostic assay.

Fluid biomarkers for AD other than Aβ and tau have been posited, but positive results have been difficult to replicate. Novel biomarkers with the most promise inlcude the amyloid precursor proteins sAPPβ and sAPPα, β-site APP cleaving enzyme-1 (BACE1), Aβ oligomers, and other Aβ isoforms. Additionally, neuronal and synaptic proteins as well as various inflammatory molecules and markers of oxidative stress may prove valuable as CSF biomarkers. Studies of plasma biomarkers such as those investigating plasma Aβ have yielded contradictory results, but promising novel blood biomarkers for AD may be found in certain signaling and inflammatory proteins.

Taken together, progress in brain imaging and identification of fluid biomarkers hold great promise in improved diagnosis of AD cases. When combined with expected drug therapies we may be able to delay the onset of neurodegeneration and associated cognitive impairment significantly. In the meantime, early diagnosis is helpful in stratifying AD cases, monitoring potential treatments for safety, and monitoring the biochemical effect of drugs. For cryonicists, early diagnosis can help guide treatment and end-of-life care decisions in order to optimize cryopreservation of the brain.

So – back to the original question. What can we predict about the AD landscape in 2020?

Besides continued progress in early diagnosis through brain imaging and fluid biomarkers, the authors anticipate that advances in whole-genome and exome sequencing will lead to a better understanding of all of the genes that contribute to overall genetic risk of AD. Additionally, improved ability to sense and detect the proteins that aggregate in AD and to distinguish these different assembly forms and to correlate the various conformations with cellular, synaptic, and brain network dysfunction should be forthcoming in the next few years. Lastly, we will continue to improve our understanding of the cell biology of neurodegeneration as well as cell-cell interactions and inflammation, providing new insights into what is important and what is not in AD pathogenesis and how it differs across individuals, which will lead, in turn, to improved clinical trials and treatment strategies.

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

10. November 2014 · Comments Off · 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

20. October 2014 · Comments Off · Categories: Neuroscience, Science

Cryonics Magazine, February 2013

This is the first entry in a new series of short articles about neuroscience and its implications for the field of human cryopreservation and life extension. In this article I discuss the relationship of the brain to consciousness and knowledge acquisition before venturing into more specific and practical topics

What is consciousness? Most of us understand the word in context, but when asked to define it we are suddenly at a loss for words or at best we offer a description that seems wholly inadequate. Scientists, philosophers, and religious scholars have debated the source, meaning, and nature of consciousness for all of recorded history. But with the rise of neuroscience over the past few decades, it now seems as though explaining the nature and mechanisms of conscious experience in neurobiological terms may be an attainable goal.

The recent work on consciousness by neuroscientists has left certain philosophers more frustrated than ever before, including the likes of Thomas Nagel and David Chalmers. They suspect that consciousness may be quite different and separate from the brain circuitry proposed to underlie it.

Consciousness has appeared to be a strange and undefinable phenomenon for a very long time. Daniel Dennett captured the feeling very nicely in the 1970s:

“Consciousness appears to be the last bastion of occult properties, epiphenomena, immeasurable subjective states — in short, the one area of mind best left to the philosophers. Let them make fools of themselves trying to corral the quicksilver of “phenomenology” into a respectable theory.”(1)

Consciousness no longer appears this strange to many researchers, but the philosophers just mentioned continue to hold that it may not be reduced to brain processes active in cognition. A common philosophical complaint is that any neurobiological theory of consciousness will always leave something out. What it will always leave out is the feeling itself — the feeling of what it is like to be aware, to see green, to smell flowers, and so on (Nagel 1974; Chalmers, 1996). These are so-called qualia — the experiences themselves — and these are what are important about consciousness. The philosopher making this argument may go on to conclude that no science can ever really explain qualia because it cannot demonstrate what it is like to see green if you have never seen green. Ultimately, they argue, consciousness is beyond the reach of scientific understanding.

By contrast, neuroscientists take for granted that consciousness will be domesticated along with the rest of cognition. Indeed, this work tends to assume that neuroscience will not only identify correlates of consciousness, but will eventually tell us what consciousness is. By and large, these neuroscientific efforts have been directed toward cortical regions of the brain, cortical pathways, and cortical activity. This is due, in part, to the prevalence of clinical studies of human patients with region-specific cortical lesions that are correlated with deficits in specific kinds of experiences. This tendency to focus on the cortex may also reflect the common knowledge that humans possess the highest level of consciousness of all animals and have proportionally more cortex than our closest relatives (and — so the supposition goes — therein lies the difference in levels of consciousness).

Another theory of consciousness, offered by Dr. Gerald M. Edelman, aims to resolve this “divorce” between science and the humanities over theories of consciousness. The premise of Edelman’s theory is that the field of neuroscience has already provided enough information about how the brain works to support a scientifically plausible understanding of consciousness. His theory attempts to reconcile the two positions described earlier by examining how consciousness arose in the course of evolution.

In his book on the topic, Second Nature: Brain Science and Human Knowledge, Edelman says:

“An examination of the biological bases of consciousness reveals it to be based in a selectional system. This provides the grounds for understanding the complexity, the irreversibility, and the historical contingency of our phenomenal experience. These properties, which affect how we know, rule out an all-inclusive reduction to scientific description of certain products of our mental life such as art and ethics. But this does not mean that we have to invoke strange physical states, dualism, or panpsychism to explain the origin of conscious qualia. All of our mental life, reducible and irreducible, is based on the structure and dynamics of our brain.

In essence, Edelman has attempted to construct a comprehensive theory of consciousness that is consistent with the latest available neuroanatomical, neurophysiological, and behavioral data. Calling his idea Neural Darwinism, Edelman explains that the brain is a selection system that operates within an individual’s lifetime. Neural Darwinism proposes that, during neurogenesis, an enormous “primary repertoire” of physically connected populations of neurons arises. Subsequently, a “secondary repertoire” of functionally defined neuronal groups emerges as the animal experiences the world. A neural “value system,” developed over the course of evolution and believed to be made up of small populations of neurons within deep subcortical structures, is proposed to assign salience to particular stimuli encountered by the animal in order to select patterns of activity.

For example, when the response to a given stimulus leads to a positive outcome the value system will reinforce the synaptic connections between neurons that happened to be firing at that particular moment. When a stimulus is noxious, the value system will similarly strengthen the connections between neurons that happened to be firing at the time the stimulus was encountered, thus increasing the salience of that stimulus. When a stimulus has no salience, synaptic connections between neurons that fired upon first exposure to that stimulus will become weaker with successive exposures.

Importantly, the mapping of the world to the neural substrate is degenerate; that is, no two neuronal groups or maps are the same, either structurally or functionally. These maps are dynamic, and their borders shift with experience. And finally, since each individual has a unique history, no two individuals will express the same neural mappings of the world.

This brings us to the three tenets of Edelman’s theory:

1. Development of neural circuits leads to enormous microscopic anatomical variation that is the result of a process of continual selection;

2. An additional and overlapping set of selective events occurs when the repertoire of anatomical circuits that are formed receives signals because of an animal’s behavior or experience;

3. “Reentry” is the continual signaling from one brain region (or map) to another and back again across massively parallel fibers (axons) that are known to be omnipresent in higher brains.

Edelman thus believes that consciousness is entailed by reentrant activity among cortical areas and the thalamus and by the cortex interacting with itself and with subcortical structures. He suggests that primary consciousness appeared at a time when the thalmocortical system was greatly enlarged, accompanied by an increase in the number of specific thalamic nuclei and by enlargement of the cerebral cortex — probably after the transitions from reptiles to birds and separately to mammals about a quarter of a billion years ago. Higherorder consciousness (i.e., consciousness of consciousness), on the other hand, is due to reentrant connections between conceptual maps of the brain and those areas of the brain capable of symbolic or semantic reference — and it only fully flowered with hominids when true language appeared. Regarding language and its relationship to higher-order consciousness, Edelman explains:

“We do not inherit a language of thought. Instead, concepts are developed from the brain’s mapping of its own perceptual maps. Ultimately, therefore, concepts are initially about the world. Thought itself is based on brain events resulting from the activity of motor regions, activity that does not get conveyed to produce action. It is a premise of brain-based epistemology that subcortical structures such as the basal ganglia are critical in assuring the sequence of such brain events, yielding a kind of presyntax. So thought can occur in the absence of language….

The view of brain-based epistemology is that, after the evolution of a bipedal posture, of a supralaryngeal space, of presyntax for movement in the basal ganglia, and of an enlarged cerebral cortex, language arose as an invention. The theory rejects the notion of a brainbased, genetically inherited, language acquisition device. Instead, it contends that language acquisition is epigenetic. Its acquisition and its spread across speech communities would obviously favor its possessors over nonlinguistic hominids even though no direct inheritance of a universal grammar is at issue. Of course, hominids using language could then be further favored by natural selection acting on those systems of learning that favor language skills.”

Such a theory is attractive because it does not simply concentrate on conscious perception, but it also includes the role of behavior. We do well to keep in mind that moving, planning, deciding, executing plans, and more generally, keeping the body alive, is the fundamental business of the brain. Cognition and consciousness are what they are, and have the nature they have, because of their role in servicing behavior.

An important element of Edelman’s theory that consciousness is entailed by brain activity is that consciousness is not a “thing” or causal agent that does anything in the brain. He writes that “inasmuch as consciousness is a process entailed by neural activity in the reentrant dynamic core it cannot be itself causal.” This process causes a number of “useful” illusions such as “free will.”

Edelman’s theory of consciousness has further implications for the development of brain-based devices (BBDs), which Edelman believes will be conscious in the future as well. His central idea is that the overall structure and dynamics of a BBD, whether conscious or not, must resemble those of real brains in order to function. Unlike robots executing a defined program, the brains of such devices are built to have neuroanatomical structures and neuronal dynamics modeled on those known to have arisen during animal evolution and development.

Such devices currently exist — such as the “Darwin” device under development by The Neurosciences Institute. Darwin devices are situated in environments that allow them to make movements to sample various signal sequences and consequently develop perceptual categories and build appropriate memory systems in response to their experiences in the real world.

And though Edelman recognizes that it is currently not possible to reflect the degree of complexity of the thalmocortical system interacting with a basal ganglia system, much less to have it develop a true language with syntax as well as semantics, he nevertheless suggests that someday a conscious device could probably be built.

More ambitiously, Edelman also thinks that contemporary neuroscience can contribute to a naturalized epistemology. The term “naturalized epistemology” goes back to the analytical philosopher Willard Quine and refers to a movement away from the “justification” (or foundations) of knowledge and emphasizes the empirical processes of knowledge acquisition. Edelman is largely sympathetic towards Quine’s project, but provides a broader evolutionary framework to epistemology that also permits internal states of mind (consciousness).

1 Daniel C. Dennett, “Toward a Cognitive Theory of Consciousness,” in Brainstorms: Philosophical Essays on Mind and Psychology (Montgomery, VT: Bradford Books, 1978).

26. September 2011 · Comments Off · Categories: Cryonics, Health · Tags: , , , ,

As every modern consumer knows, smartphones are today’s go-to portable technology. Everything from GPS navigation to finding a good deal on your next meal or haircut right NOW to a wide variety of games and applications may be had at the touch of a button. But developers of smartphone applications (i.e, “apps”) are only just beginning to realize the true capabilities of having so much computing power in the palm of your hand. Indeed, the possibilities for health monitoring applications in combination with GPS location bodes well for cryonicists.

Until cryonics-specific apps become available, there are several existing applications useful to cryonics members and organizations. Here are some of the most interesting from the Android Market:

ICE (In Case of Emergency):   Emergency personnel look for ICE information in patient mobile phones. This ICE app has a couple of widget options and can be accessed even when the phone is locked. My favorite feature is the ability to put any special instructions (like the protocol from your Alcor bracelet) on the main screen. The app acts primarily as an emergency contact list. Your cryonics service provider should be #1, followed by family and friends who support your cryonics arrangements. Additionally, you may enter your vital stats, medical and dental insurance information, and any known allergies, conditions, and/or medications.

For those with “dumb phones,” just create a contact called “ICE” and enter your cryonics organization’s emergency number. Additional information about placing ICE  numbers in your cell phone may be found in this article by Fred and Linda Chamberlain.

Emergency Button: Emergency Button sends a distress signal with your coordinates to a defined recipient when pressed. This has obvious utility for all matters of personal safety, and can be used to alert your cryonics organization to emergency health situations as soon as they emerge.

Google Latitude: Latitude is a GPS location tracking app. It allows for various privacy settings and can be configured to share only with specific people. A cryonics organization could, with its members’ permission, use such an app for real-time location tracking.

These are just three basic apps that are commonly available and useful to cryonicists now. I hope to be updating this list as improvements in smartphone technology continue.

david_croftDavid Wallace Croft is an Alcor member in the Dallas area where he lives with his wife Shannon and five children, Ada, Ben, Tom, Abe, and Ted.  He is employed as a Java software developer and is a part-time doctoral student.  His contact information and his weblog are available at www.CroftPress.com.

1. How did you first learn about cryonics?

I first learned about cryonics from the Extropians.  I think I first learned of the Extropians from “Wired” magazine.  I really liked what I read in the Extropian Principles so I dug into this subculture online.  I was a volunteer Webmaster for the Extropy Institute for a brief period.

2. When did you join Alcor and what motivated you to become a member?

Along with every other techie, I was swept into the Silicon Valley dot com boom during the late 90’s.  I worked next to Xerox PARC so I would sometimes wander over to attend their guest lectures including a slideshow on the subject of cryonics presented by Dr. Ralph Merkle.  I had a chance to attend local cryonaut dinners and meetings including a meeting at the Shaw-Merkle residence.  Actually signing up remained on my to-do list for a few years until I saw an ad on the back of the shirt of insurance agent Mr. Rudi Hoffman at an Extropian conference.  I approached him and he helped me make it happen.

3. How does your membership impact your life plans or lifestyle?

My Alcor membership has given me some peace of mind with regard to the terror of impending death.  I lost my faith in the supernatural afterlife at an early age and I struggled with the ramifications.  Now that I am middle-aged with five children, death is less frightening but I still think about my dwindling days with some despair.  My cryonics hope keeps me functional.

I am currently in Dallas but my long-term plan is to find a job in Phoenix, possibly in academia, so that I can establish my retirement residence near Alcor.

4. What do you consider the most challenging aspect(s) of cryonics?

Even amongst my atheist allies, cryonics is considered crazy.  When I read Humanist literature, I see a “mortalist” attitude where an acceptance of death is considered the rational alternative to belief in a supernatural afterlife.

5. Have you met any other Alcor members?

I have enjoyed my fellowship with members over the years, most recently at the Alcor conferences.  Awhile back, we had a cryonauts dinner here in the Dallas area with Dr. Scott Badger, Chana de Wolf, and Todd Huffman; I note that all four of us are involved in the study of the mind and brain.  I had the opportunity to attend one of the annual get-togethers hosted by Max and Natasha More in nearby Austin.  I also sample the CryoNet, Society for Universal Immortalism, and Venturists electronic mailing lists.

6. What areas of Alcor’s program would you like to see developed over the next 5-10 years?

I would like to see more Alcor conferences.  I would also like to see Alcor establish a second operational center in another location.

7. What kind of lasting contribution would you like to make to cryonics?

I would like to help establish a democratic religion for cryonaut brights.  I was inspired by the 1933 “Humanist Manifesto” proposing Humanism as a new religion.  I am the Treasurer and a co-founder of the Society for Universal Immortalism (SfUI), formerly known as the Transhumanist Church, which requires cryonics suspension arrangements before becoming a voting member.  I have also created a website for my own personal micro-religion which I call “Optihumanism”.  In my “Optihumanist Principles”, I have attempted to blend Religious Humanism, Neo-Objectivism, and Immortalism in a concise statement of my beliefs.  Less seriously, I also have a webpage for my “Cryobaptist Church” which makes the tongue in cheek assertion that salvation can be achieved by a post-mortem baptism in liquid Nitrogen.

8. What do your friends and family members think about your cryopreservation arrangements?

In general, my friends and family think it is a bit eccentric.  I am attempting to plant seeds with my wife and children by introducing them to cryonics fiction.

9. What are your hobbies or special interests?

One of my special interests is church-state separation activism.  With the assistance of my Objectivist friend and attorney Dean Cook, my family has legal cases pending challenging the constitutionality of a couple of new laws involving religion in Texas public schools:  a mandatory moment of silence and adding “under God” to the state pledge.

I am also a part-time doctoral student in Cognition and Neuroscience at the University of Texas at Dallas.  Although my Bachelors is in Electrical Engineering, my two Masters degrees had a focus on neuroscience and neuromorphic systems.  As a programmer, I have been hired to work on a number of interesting projects including neural network chip design, intelligent software agents, peer-to-peer frameworks, and multiuser 3D environments.  My academic research could be described as pursuing artificial intelligence via a study of spiking neuronal networks.

10. What would you like to say to other members?

Many of my atheist, humanist, objectivist, and immortalist friends do not have children.  I recommend that you have them if you can.  Children are blessings we give to ourselves.

mammoth.jpg

In “Ice Baby” by Tom Mueller, the May 2009 issue of National Geographic announces the recent discovery of a 40,000 year old baby mammoth in Sibera. She is called Lyuba, named after the wife of the Nenet reindeer herder who found her, and is in near-pristine condition, having even her eyelashes. In fact, besides most of her wooly coat being gone, the only pieces missing (part of her tail and right ear) were destroyed after her recovery. Even so, she is undoubtedly the most complete specimen of mammoth to date.

Of course, paleontologists such as Dan Fisher, who has spent his entire life studying Pleistocene mammoths and mastodons, are excited by this find because Lyuba provides the most complete set of data it is possible to obtain, and all from one animal. Before, Fisher and his colleagues had been forced to infer certain states of health from fossils (primarily teeth) by comparing against similar findings in the mammoth’s closest relative, the elephant. But Lyuba was so well-preserved that Fisher was able to scan her, take tissue samples, and even retrieve stomach contents.

A three-day autopsy, during which Lyuba was allowed to partially thaw to facilitate more invasive procedures, indicated that Lyuba was a well-fed one-month old mammoth at the time of her death, indicating that death was accidental. Supporting these findings was a dense mix of clay and sand in her mouth and throat, which she likely inhaled after falling into riverbank mud, leading to suffocation, but also the probable cause of her excellent preservation. Dense mud would have sealed out oxygen and prevented aerobic microbes from decomposing her soft tissue, and then lactic acid-producing microbes colonized her tissues, effectively “pickling” her carcass. Later, the ground turned to permafrost, freezing her as well.

Following Lyuba’s article in National Geographic is another article entitled “Recipe for a Resurrection” (also by Tom Mueller), which discusses the possibilities for cloning extinct species such as mammoths and Tasmanian tigers. Pointing to the recent success of Teruhiko Wakayama’s team in cloning mice that had been frozen for 16 years, and the recent publishing of 70 percent of the mammoth genome by a team led by Webb Miller and Stephan C. Schuster, the article details the hurdles that still remain in accomplishing this long hoped-for feat.

Oddly enough, though cloning offers no hope of bringing back the same individual organism, the article ends with a  pro-death quote from Tom Gilbert, “an expert in ancient DNA at Copenhagen University who with Schuster and Webb pioneered the harvesting of mammoth DNA from hair,” who “questions both the utility and wisdom of cloning extinct species. —  ‘If you can do a mammoth, you can do anything else that’s dead, including your grandmother. But in a world in global warming and with limited resources for research, do you really want to bring back your dead grandmother?'”

The Field Museum in Chicago is planning an exhibition tour starring Lyuba in 2010, with assistance from the National Geographic Society.

Watch Waking the Baby Mammoth on National Geographic throughout the month of May (next airing May 6).

11. December 2008 · Comments Off · Categories: Health, Science · Tags: , ,

Nanotechnology idea-man Robert Freitas, Jr. has published an article in the January 2009 issue of Life Extension Magazine providing a tutorial in nanomedicine and documenting its progression toward real-world application.

In “Nanotechnology and Radically Extended Life Span,” Freitas describes several theoretical medical nanorobots, such as the microbiovore, which would “act like an artificial mechanical white cell, seeking out and digesting unwanted pathogens including bacteria, viruses, or fungi in the bloodstream.” In addition to fighting infection, medical nanorobots could invigorate old or diseased cells by replacing chromosomes with fresh new ones, correcting the cellular damage and mutations that lead to aging.

Freitas and colleagues have performed many analyses and simulations of the types of technologies and tools that will be necessary to create these nanoscale medical robots, filing two patents for the mechanosynthesis of nanorobots. Together with Ralph Merkle, Freitas founded the Nanofactory Collaboration to “coordinate a combined experimental and theoretical R&D program to design and build the first working diamandoid nanofactory.” This effort has involved many collaborations with researchers from nine different organizations and four countries, and has resulted in a dozen academic articles.

Now Freitas is eager to test his theories with the help of scanning probe microscopist Philip Moriarty, who is attempting to build several of Freitas’ mechanosynthesis tooltips. Presumably, the creation of working tooltips will lead directly to their intended purpose: the creation of nanorobots. Freitas hopes to manufacture medical nanorobots that can contribute to radical life extension therapies by the 2020s.

Of course, most cryonicists are of the opinion that nanotechnological interventions will be necessary for the reversal of aging and disease in cryopreserved patients. As we move closer to reversible cryopreservation with improved stabilization protocol and cryoprotectant solutions, perhaps the maturation of nanomedicine and cryonics will coincide.

In the past Alcor has supported Freitas’ work at the expense of supporting research that could improve the quality of its cryopreservation procedures for existing members. It is therefore encouraging to learn that the Life Extension Foundation has contributed money to support Freitas’ work on nanomedicine.