Many of the worlds longest-lived people became the world's longest-lived people despite a history of what are considered to be poor lifestyle choices from the perspective of long term health. Amongst their number are smokers, the overweight, and the sedentary - all items shown to cause great harm to health in the long term. Studies have shown that each of these considered in isolation can shave as much as a decade from your life expectancy, and that's quite aside from what they will do to your quality of life via an increased risk of suffering chronic and debilitating medical conditions.

So how is it that we see a fair proportion of extremely old people with such a poor track record for basic good health choices over the course of their lives? So far it looks like that can be attributed to fortunate genes:

People who live to 95 or older are no more virtuous than the rest of us in terms of their diet, exercise routine or smoking and drinking habits ... Overall, people with exceptional longevity did not have healthier habits than the comparison group in terms of BMI, smoking, physical activity, or diet. For example, 27 percent of the elderly women and an equal percentage of women in the general population attempted to eat a low-calorie diet. Among long-living men, 24 percent consumed alcohol daily, compared with 22 percent of the general population. And only 43 percent of male centenarians reported engaging in regular exercise of moderate intensity, compared with 57 percent of men in the comparison group.

...

In previous studies of our centenarians, we've identified gene variants that exert particular physiology effects, such as causing significantly elevated levels of HDL or 'good' cholesterol. This study suggests that centenarians may possess additional longevity genes that help to buffer them against the harmful effects of an unhealthy lifestyle. ... Although this study demonstrates that centenarians can be obese, smoke and avoid exercise, those lifestyle habits are not good choices for most of us who do not have a family history of longevity. We should watch our weight, avoid smoking and be sure to exercise, since these activities have been shown to have great health benefits for the general population, including a longer lifespan.

Why rely on having a genetic buffer against subtle forms of self-harm when the odds are good that you have no such thing? The only reliable ways to ensure that you live for a long, long time in good health will come from progress in medical technology aimed at engineering greater human longevity: repair biotechnologies capable of reversing the known forms of cellular and molecular damage that cause aging. That progress in turn depends on the degree to which we choose to support and advocate rejuvenation research today.

Singularity Hub here looks at some of the research work that will lead to the ability to generate blood as needed: "Researchers [have] found a way to hunt down and isolate the stem cells from which your entire blood supply is derived. Until now, these hematopoietic stem cells (HSC) have been remarkably hard to track and isolate ... researchers were able to identify the CD49f protein as a key surface marker for hemotopoietic stem cells. Single CD49f HSCs were placed inside immunosupressed mice, and monitored to see how they developed. The entire spectrum of blood cells were produced, and just as important: they were self-renewing. The CD49f HSC wasn't just creating blood, it was creating an expanding and sustaining blood supply that should theoretically survive long term in the body." This will lead to a number of potential ways to generate sufficient quantities of blood to remove the need for blood donations, and ultimately will allow a patient's own cells to be used to generate blood on demand.

Link: http://singularityhub.com/2011/08/03/scientists-bag-and-tag-the-stem-cell-that-may-create-an-endless-supply-of-blood/

A recent long Popular Science article looks at Sierra Sciences and its founder, a group that has been working on telomere biology and its role in aging for some years. Alongside a number of other research groups, the Sierra crowd believe that telomeres are a lynchpin portion of our biochemistry and manipulating them might significantly extend life.

Make poor lifestyle choices, and you're likely to die of heart disease or cancer or something well before your telomeres would otherwise become life-threateningly short. But for the aerobicized Andrews, for anyone who takes reasonable care of himself, a drug that activates telomerase might slow down the baseline rate at which the body falls apart. Andrews likens the underlying causes of aging, free radicals and the rest, to sticks of dynamite, with truncated telomeres being the stick with the shortest fuse. "I believe there's a really good chance that if we defuse that stick," he says, "and the person doesn't smoke and doesn't get obese, it wouldn't be surprising if they lived to be 150 years old. That means they're going to have 50 more years to be around when somebody solves the other aging problems."

Telomeres, you might recall, are the frayed ends of our chromosomes, there in order to prevent problems during cellular replication - though more correctly they might be thought of as one portion of a more complex and regulated system that touches upon many cellular processes. You can't consider telomeres in isolation from the behavior of the telomerase enzyme that acts to rebuild telomere length, for example. Telomeres appear to erode away over a lifetime in many tissues, and their length in immune cells correlates decently with general health and levels of stress, shortened telomeres go hand in hand with increased cancer risk, and there's some interesting interplay between telomere length and levels of mitochondrial damage - both implicated in aging, and we might suspect these two things to be aspects of the same underlying process, though that remains a theory that can be argued either way at this time.

It would be hard to argue that telomeres are anything other than connected to aging - but are they a lynchpin that can be manipulated alone, in absence of other therapies, to significantly extend life? I am a skeptic on that count in the sense that I don't think the evidence presently in hand wholly supports that view. If you look at the most beneficial example of telomere manipulation in mice, a 50% life extension was achieved by combining genetic manipulation of p53 and telomerase levels together - but telomerase has a range of other potential effects on metabolism beyond affecting telomere length. I am not aware at this time of a study that categorically shows benefits accruing because of telomere length versus because of any other effects of telomerase - such as, for example, acting to protect mitochondrial DNA from damage, which in turn protects telomeres from shortening.

The bottom line for me is that this is certainly a line of research worth chasing further - there are a range of experiments that show benefits from telomerase therapies, such as improved immune system function, for example. But is the telomeres, or is it something else that's the important underlying mechanism? Either way, Sierra Sciences ran out of money for research in the end and now seems to be removing itself from the game through a mechanism we've sadly seen before, which is to get into bed with the supplement industry. I cannot think of a small company that has done this and remained a serious contender in advancing the state of medical science - the end result more often looks like the protandim debacle, in which whatever interesting scientific work once existed is abandoned and its echoes used to promote herbal compounds sold with a garnishing of lies. From the Popular Science article:

The stock-market crash of 2008 nearly wiped out two investors who had until then been his primary funders. Without the money to continue refining the nearly 40 telomerase-activating chemicals he and his team had already discovered, Andrews made the decision last September to cut a deal with John W. Anderson, the founder of Isagenix, an Arizona-based "network marketing" supplement company. This month, Isagenix will launch an anti-aging product containing several natural compounds that Sierra Sciences has verified to have "telomere-supporting" properties.

So you're basically looking at the genesis of another set of worthless products and magical thinking that apes the scientific method while rejecting everything that makes it work - just like most of the rest of the "anti-aging" marketplace. And beside that, another set of names who might have gone on to do good work will instead never be taken seriously again. Which is sad, given that they had a better vision of the necessary strategy for longevity science than most of the scientific community.

Changes in stem cell biology and capabilities are considered important in age-related degeneration. For example: "A decline in cellular homeostasis in older individuals underlies age-related pathologies like osteoporosis and osteoarthritis. [Researchers] report key differences in the patterns of expressed mRNAs in bone-marrow mesenchymal stem cells (bmMSCs) of young donors compared with old human donors. The distinct subsets of expressed genes associated with glycobiology are consistent with the underlying age-related decline in bone marrow function. ... It is now well established that in older individuals stem cells can become 'aged' and thus incapable of renewing surrounding tissues and organs as efficiently as young individuals. Experimental and clinical evidence has revealed the importance of stem cell aging in bone marrow transplants, as recipients of bone marrow from older donors do not fare as well as recipients of bone marrow from younger donors. However, the molecular mechanisms governing stem cell aging are not well understood. An important first step towards this goal is to delineate the gene expression differences between stem cells from young and old individuals. Bone marrow stem cells are particularly well suited for such studies, as they are relatively easy to purify to homogeneity. ... bmMSCs showed age-increases in the expression of genes associated with the degradation of N-glycans and glycosaminoglycans and with the biosynthesis of glycosphingolipids. These results reveal major differences in the glycobiology and glycan compostion of young and old bmMSCs, associated with age-related changes in the cellular responses to autocrine and paracrine signals. The difference in glycan pathways may not be limited to bmMSCs or even to stem cells, but could be more widely prevalent among other cell types."

Link: http://impactaging.com/papers/v3/n7/full/100356.html

Depressed Metabolism here notes the existence of a double standard when it comes to the science and practice of cryonics - actually one you'll find exists for all serious endeavors in life extension, such as SENS research: "One of the most predictable features of public debates about cryonics is that those arguing in favor of cryonics are held to more rigorous standards than those seeking conventional medical treatment. Advocates of cryonics do not just have to prove that cryonics will work, they are also supposed to solve problems like overpopulation and the presumed boredom arising from expended lifespans. To some, people who make cryonics arrangements have an inflated perception of their own importance and should just forgo such selfish attempts to extend their lives. The default position seems to be that people should not exist and that life needs justification. Could you imagine such antinatalist rhetoric being employed when a person seeks conventional medical treatment to extend their life? We can't, and such responses are quite indicative of the fact that people are not interested in serious evaluation of the cryonics argument."

Link: http://www.depressedmetabolism.com/2011/07/29/the-double-standard-about-cryonics/

Up until comparatively recently the scientific consensus was that neurogenesis, the process by which new neurons are created and assimilated into the workings of the brain, simply didn't happen in adults to any significant degree. Fortunately we are supplied with a modest flow of new brain cells as life goes on, and this post is a reminder that, amongst all the other benefits caused by calorie restriction, it also increases neurogenesis. Eat fewer calories whilst still obtaining an optimal amount of nutrients and you gain more functional brain cells as a result:

Adult neural stem cells in the dentate gyrus of the hippocampus are negatively and positively regulated by a broad range of environmental stimuli that include aging, stress, social interaction, physical activity, and dietary modulation. Interestingly, dietary regulation has a distinct outcome, such that reduced dietary intake enhances neurogenesis, whereas excess calorie intake by a high-fat diet has a negative effect.

This has actually been known for at least a decade, as you'll see if you look back into the scientific archives. For example, this from 2000:

We found that maintenance of adult rats on a DR regimen results in a significant increase in the numbers of newly produced neural cells in the dentate gyrus of the hippocampus ... The increase in neurogenesis in rats maintained on DR appears to result from decreased death of newly produced cells, rather than from increased cell proliferation. We further show that the expression of brain-derived neurotrophic factor, a trophic factor recently associated with neurogenesis, is increased in hippocampal cells of rats maintained on DR. Our data are the first evidence that diet can affect the process of neurogenesis, as well as the first evidence that diet can affect neurotrophic factor production. These findings provide insight into the mechanisms whereby diet impacts on brain plasticity, aging and neurodegenerative disorders.

Or this from 2002:

We now report that neurotrophin expression and neurogenesis can be modified by a change in diet. When adult mice are maintained on a dietary restriction (DR) feeding regimen, numbers of newly generated cells in the dentate gyrus of the hippocampus are increased, apparently as the result of increased cell survival. The new cells exhibit phenotypes of neurons and astrocytes.

So what exactly does a modest increase in the creation of new functional brain cells mean for humans? That remains to be determined in detail, and seems to boil down to quantifying the effects of increased plasticity in the brain. There is the expectation in the scientific community that increased plasticity will be shown to be beneficial in a range of ways, but to date few lines of research have managed to definitively link changes in plasticity with cognitive ability, resistance to age-related neurodegenerative diseases, and so forth. That would seem to be just a matter of time, however.

Meanwhile, the benefits of calorie restriction are so broad and large - on a par with exercise in humans, and thus still better for healthy people than any presently available medical technology - that it would seem foolish not to give serious thought to trying it.

From the Washington Post: "The machine looks like the offspring of an Erector Set and an inkjet printer. The 'ink' feels like applesauce and looks like icing. As nozzles expel the pearly material, layer by layer, you imagine the elaborate designs this device could make on gingerbread cookies. But the goo is made of living cells, and the machine is 'printing' a new body part. These machines - they're called three-dimensional printers - work very much like ordinary desktop printers. But instead of just putting down ink on paper, they stack up layers of living material to make 3-D shapes. The technology has been around for almost two decades, providing a shortcut for dentists, jewelers, machinists and even chocolatiers who want to make custom pieces without having to create molds. In the early 2000s, scientists and doctors saw the potential to use this technology to construct living tissue, maybe even human organs. They called it 3-D bioprinting, and it is a red-hot branch of the burgeoning field of tissue engineering. ... The possibilities for this kind of technology are limitless. Everyone has a mother or brother or uncle, aunt, grandmother who needs a meniscus or a kidney or whatever, and they want it tomorrow. ... The promise is exciting. The goal is not to squash that excitement, but to temper it with the reality of what the process is. ... The reality for now is that making such things as vertebral disks and knee cartilage, which largely just cushion bones, is far easier than constructing a complicated organ that filters waste, pumps blood or otherwise keeps a body alive. Scientists say the biggest technical challenge is not making the organ itself, but replicating its intricate internal network of blood vessels, which nourishes it and provides it with oxygen. Many tissue engineers believe the best bet for now may be printing only an organ's largest connector vessels and giving those vessels' cells time, space and the ideal environment in which to build the rest themselves; after that, the organ could be implanted."

Link: http://www.washingtonpost.com/national/science/2011/04/21/AFJM0WbG_print.html

News of another potential way to manipulate mitochondrial function to slow aging: "Mitochondria are the body's energy producers, the power stations inside our cells. Researchers [have] now identified a group of mitochondrial proteins, the absence of which allows other protein groups to stabilise the genome. This could delay the onset of age-related diseases and increase lifespan. ... When a certain MTC protein is lacking in the cell, e.g. because of a mutation in the corresponding gene, the other MTC proteins appear to adopt a new function. They then gain increased significance for the stabilisation of the genome and for combating protein damage, which leads to increased lifespan. These studies also show that this MTC-dependent regulation of the rate of aging uses the same signalling pathways that are activated in calorie restriction - something that extends the lifespan of many different organisms, including yeasts, mice and primates. Some of the MTC proteins identified in this study can also be found in the human cell, raising the obvious question of whether they play a similar role in the regulation of our own aging processes. It is possible that modulating the activity of the MTC proteins could enable us to improve the capacity of the cell to delay the onset of age-related diseases. These include diseases related to instability of the genome, such as cancer, as well as those related to harmful proteins, such as Alzheimer's disease and Parkinson's disease. At the moment this is only speculation, and the precise mechanism underlying the role of the MTC proteins in the aging process is a fascinating question that remains to be answered."

Link: http://www.sciencedaily.com/releases/2011/05/110510074433.htm

This paper suggests that the relationship between mitochondrial DNA variants and longevity is complex: "There is substantial evidence that mitochondria are involved in the aging process. Mitochondrial function requires the coordinated expression of hundreds of nuclear genes and a few dozen mitochondrial genes, many of which have been associated with either extended or shortened life span. Impaired mitochondrial function resulting from mtDNA and nuclear DNA variation is likely to contribute to an imbalance in cellular energy homeostasis, increased vulnerability to oxidative stress, and an increased rate of cellular senescence and aging. The complex genetic architecture of mitochondria suggests that there may be an equally complex set of gene interactions (epistases) involving genetic variation in the nuclear and mitochondrial genomes. Results from Drosophila suggest that the effects of mtDNA haplotypes on longevity vary among different nuclear allelic backgrounds, which could account for the inconsistent associations that have been observed between mitochondrial DNA (mtDNA) haplogroups and survival in humans. ... We hypothesize that aging and longevity, as complex traits having a significant genetic component, are likely to be controlled by nuclear gene variants interacting with both inherited and somatic mtDNA variability."

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20601194

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

A study conducted by researchers from the Ohio State University found that selenium can reduce specific markers that increase the risk of prostate cancer.

The Dreaded Prostate Cancer

The average age of prostate cancer diagnosis is 67 years old.  This is according to the National Cancer Institute Surveillance and Epidemiology and End Results Center; this is based on the incidence of prostate cancer in the United States from 2003 to 2007. Based on the same data, more than 16 percent of men will be diagnosed with prostate cancer in their lifetime. In the United States alone, it is estimated that more than 210,000 men will be diagnosed of prostate cancer and over 32,000 will die of the dreaded condition.

There are no assured means of preventing prostate cancer. But making smart choices in the foods that you eat and avoiding the risk factors associated with it can help in preventing the disease. Like other types of cancer, prostate cancer starts when cells begin to behave abnormally. It is clear that this behavior of the cells is caused by the mutation of the genes but researchers are still trying to better understand what causes and what triggers the mutation.

Lowering the risk of prostate cancer will take a little more than just diet modification. Taking bigger steps like changing your lifestyle and avoiding cancer-inducing habits may help in reducing your risk. Studies show that lifestyle intervention is the best approach in preventing prostate cancer and other diseases for people with heightened risk.

Natural Ways to Lower Your Risk

The nutritional guidelines for preventing prostate cancer is yet to be established. But so far, studies show that specific eating habits are linked to a lowered risk of developing the disease. Eating a variety of fruits and vegetables can supply the body with essential nutrients that helps in preventing different kinds of cancer.  Food sources rich in cancer-fighting substances like folate, vitamin B complex and diindolylmethane, which is found in cruciferous vegetables like kale, cabbage and broccoli, are well-recommended.  Sensible eating means balancing your calorie intake according to your body’s requirement.

The incidence of prostate cancer varies in different countries. Studies show that the highest rate appears in populations with the highest intake of fat. Foods rich in saturated fats, like those found in red meats, can increase the risk of developing prostate cancer. Eating whole-grain foods like whole-wheat breads and brown rice while limiting the consumption of refined sugar and white flour can also help in preventing the disease.

Eating foods rich in omega-3 fatty acids is also linked to a lower risk of developing prostate cancer. Omega-3 is found in salmon, mackerel, herrings and other cold-water fishes. Although there are mixed scientific evidence regarding the potency of omega-3 in lowering the risk of developing cancer, adding foods rich in the nutrient into your daily diet offers other health benefits like the prevention of cardiovascular disease.

Soybean products and other legumes are rich in phytoestogens, an enzyme found in plants that act like estrogen in the body. These chemicals can help reduce the risk of prostate cancer. A good evidence for this is the low incidence of prostate cancer in Asian countries where soybeans and soybean products are popular food choices.

Green tea contains various antioxidants like polyphenols that has been found to lower the risk of developing cancer. Vitamin D, on the other hand, has also showed strong potential in lowering the risk of developing prostate cancer. Foods rich in vitamin D are egg yolks, and fish liver oil. Exposing the skin to the sun for a few minutes a day will also trigger the production of vitamin D in the body.

The high incidence of prostate cancer drives state and privately-funded studies to determine better ways to prevent the disease. Researchers are also looking at the potency of some nutrients in fighting prostate cancer risk. A study conducted by researchers from the Ohio State University found that the supplementation of selenium can lower the levels of prostate cancer markers such as prostate specific antigen (PSA) and help in reducing the risk of the disease.

Selenium to Lower the Risk of Prostate Cancer

A study published in the Nutrition Research journal showed that selenium glycinate can improve the activities of plasma enzymes and reduce the levels of prostate cancer markers. The researchers from the Ohio State University said that the regular supplementation of selenium in a group of 30 middle-aged Americans resulted to a reduced risk of developing prostate cancer. They added that their study contradicts the popular notion that selenium cannot improve the activity of blood glutathione peroxides and lower the risk of prostate cancer.

Head researcher Dr Robert DiSilvestro of the Department of Human Nutrition and his co-authors said that if selenium has the ability to lower prostate-specific antigens in study participants, it can also lower the risk of prostate cancer.  This could be better achieved by introducing the nutrient in daily diet. They used a certain form of selenium called selenium glycinate which has not been used in previous studies. The researchers added that selenium glycinate has significantly high bioactivity.

The researchers reported that the supplementation of selenium raised the levels of erythrocyte and plasma activities in study participants. They also found that cancer risk marker serum PSA was lowered by selenium glycinate. But they added that the reduction in prostate cancer markers does not necessarily mean a lower risk of developing the disease.

Health Benefits of Selenium

Selenium is a mineral present in the soil and which appears in small amounts in some foods and in water. The nutrient plays an important role in metabolism and recent studies show that selenium has strong antioxidant properties. Although there are some evidences suggesting that high levels of selenium can increase the risk of skin cancer, regulated levels of the nutrient can result to a lower risk of developing various diseases. Population studies show that selenium deficiency is rare in healthy people.

The Recommended Dietary Intake of selenium for adults and children aged 14 years and above is 55 to 70 micrograms in a day. For the prevention of prostate cancer, men can take as much as 200 micrograms a day. But the threshold for selenium intake should be no more than 400 micrograms; anything beyond this is considered an overdose. Selenium has been used as a treatment for asthma, infertility and arthritis. But more importantly, selenium can act as an antioxidant which neutralizes cancer-causing free radicals and at the same time improve the potency of other antioxidants.

Sources
nutraingredients.com
webmd.com
webmd.com
mayoclinic.com
seer.cancer.gov

Discuss this post in Frank Mangano’s forum!

LysoSENS is the SENS Foundation initiative to build a platform for medical bioremediation capable of breaking down the damaging byproducts of metabolism that build up in old cells and degrade their ability to recycle garbage. The short of is that we know that out there somewhere are bacteria that can eat these compounds, such as the lipofuscin that contributes to many age-related conditions. There is no buildup of prominent components of lipofuscin in graveyards, for example - so something is consuming it. That bacterial something will be armed with enzymes, biological knifes and saws that might be turned into a therapy to destroy lipofuscin if identified and introduced into the human body.

You might recall that the early LysoSENS volunteers ran a contest for soil samples from obscure locations back in 2006, the better to get a good mix of bacterial origins for analysis.

The search for bacterial enzymes that can safely attack lipofuscin in the body presently gets the lion's share of research funding at the SENS Foundation, and, appropriately, they are hiring in the Bay Area, California:

SENS Foundation is hiring for our research center located in Mountain View, CA. We are seeking a team lead for our LysoSENS project, which contains both intra- and extramural components.

Qualified candidates will have an MS, or Ph.D. in the chemical/biological sciences and at least 5 years of work experience that must include prior project management experience. Duties will include the preparation of grant proposals, internal and external progress reports, individual and collaborative publication. The project lead will develop, interpret and implement standards, procedures, and protocols for the LysoSENS research program and may collaborate on determining strategic directions in the research program. Candidates must have a proven ability to lead other professionals.

Seems like the community has come a long way from the turn of the century, doesn't it? Raising enough money for formal hires is always a big organizational milestone, and congratulations are due to the SENS Foundation staff and volunteers who have worked hard to get to this point.

Some of what the body does in response to injury, especially in the nerves and brain, is in fact counterproductive in the long term: "Stroke is the leading cause of adult disability, due to the brain's limited capacity for recovery. ... Researchers interested in how the brain repairs itself already know that when the brain suffers a stroke, it becomes excitable, firing off an excessive amount of brain cells, which die off. The UCLA researchers found that a rise in a chemical system known as 'tonic inhibition' immediately after a stroke causes a reduction in this level of excitability. But while this 'damping down' initially helps limit the spread of stroke damage, the increased tonic inhibition level and reduced brain excitability persists for weeks, eventually becoming detrimental to the brain's recovery. ... It was surprising to find that the level of tonic inhibition was increased for so long after stroke and that there was an inflection point where the increased level eventually hindered the brain from recovering. It was also surprising that we could easily manipulate tonic inhibition in the brain after stroke to restore it back to a normal, 'non-stroke' level and, in doing this, enhance behavioral recovery. ... They found that by applying specific blockers of this inhibitory brain chemical, they could then 'turn off the switch.' The resulting enhanced brain excitability immediately improved behavioral recovery after stroke."

Link: http://www.eurekalert.org/pub_releases/2010-11/uoc--srw110110.php

Another step forward for the field of regenerative medicine: researchers have "discovered a novel way to convert human skin cells into brain cells ... Rather than using models made in yeast, flies or mice for disease research, all cell-reprogramming technology allows human brain, heart and other cells to be created from the skin cells of patients with a specific disease. The new cells created from the skin cells contain a complete set of the genes that resulted in that disease - representing the potential of a far-superior human model for studying illnesses, drugs and other treatments. In the future, such reprogrammed skin cells could be used to test both drug safety and efficacy for an individual patient with, for example, Alzheimer's disease.
... This technology should allow us to very rapidly model neurodegenerative diseases in a dish by making nerve cells from individual patients in just a matter of days - rather than the months required previously. ... used two genes and a microRNA to convert a skin sample from a 55-year-old woman directly into brain cells. (MicroRNAs are tiny strands of genetic material that regulate almost every process in every cell of the body.) The cells created [exchanged] the electrical impulses necessary for brain cells to communicate ... Using microRNA to reprogram cells is a safer and more efficient way than using the more common gene-modification approach. In ensuing experiments, [the researchers hope] to rely only on microRNAs and pharmaceutical compounds to convert skin cells to brain cells, which should lead to more efficient generation of cells for testing and regenerative purposes."

Link: http://www.sciencedaily.com/releases/2011/07/110728123107.htm

From Wired: "Blood drawn with a simple needle stick can be coaxed into producing stem cells that may have the ability to form any type of tissue in the body, three independent papers report... The new technique will allow scientists to tap a large, readily available source of personalized stem cells. ... Because taking blood is safe, fast and efficient compared to current stem cell harvesting methods, some of which include biopsies and pretreatments with drugs, researchers hope that blood-derived stem cells could one day be used to study and treat diseases. ... Three research groups used similar methods to prod certain immune cells in human blood to become induced pluripotent stem cells. Because they are reprogrammed adult cells, these stem cells share many of the same regenerative abilities as true embryonic stem cells but may not have as much versatility. ... Scientists' manipulations turned the stem cells in the new studies into several types of mature blood cells, including infection-fighting T cells. What's more, all the groups showed that a batch of the stem cells implanted into mice developed into the three main types of progenitor cells found in human embryos."

View the Article Under Discussion: http://www.wired.com/wiredscience/2010/07/stem-cells-from-human-blood-can-be-reprogrammed/

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Daniel Perry of the Alliance for Aging Research was kind enough to send over an article written in conjunction with Brian Kennedy of the Buck Institute for Research on Aging. I take this as a sign that various conjunctions are imminent in the moving spheres of government funding of aging research and the broader pressures on the economy. Organizations like these two have their own cycles of publicity and outreach that ebb and flow in time with potential shifts in public funding:

Bette Davis was right - old age is not for sissies.

One hundred years ago most of us didn't have the luxury of old age. Today, life expectancy is almost 80 years. But while we've gotten very good at adding life-years, we've yet to master how to keep those years healthy and vigorous. Eighty percent of seniors have at least one major chronic condition and half have two or more. Chronic diseases of later life are costing the nation more than $1 trillion per year - a figure expected to increase to $6 trillion by the middle of this century.

Scientists who study aging are in general agreement that the process isn't set in stone - the aging process can be sped up by genetics or poor lifestyle choices, but it can also be slowed down. With sufficient funding and focus, research that slows aging has the potential to do what no drug, surgical procedure, or behavior modification can do - add healthy years of life, and simultaneously postpone the costly and harmful conditions of old age.

Age is the common denominator and number one risk factor to virtually every chronic disease we face. Scientists know that alterations in cell replacement and repair, stress response, and inflammation are the key influencers to the development of cancer, heart disease, diabetes, and other debilitating (and costly) conditions later in life. These are also the essential changes taking place in our aging bodies.

There are currently 10,000 Americans a day turning 65; by 2030, about one in five Americans will be past that age. To afford the eldercare costs that lay ahead our country must invest now in the prevention and postponement of age-related illness. New realities of population aging and chronic disease call for new thinking how we fund biomedical research. The great majority of federal medical research funds goes to studies of diseases of aging such as cancer, heart ailments and diabetes in isolation from each other and largely divorced from the underlying aging processes that lead to all of them. Less than one percent of the National Institutes of Health's (NIH) annual budget funds research into the underlying biology of aging and its role in age-related disease.

Meanwhile privately funded research centers such as the Buck Institute for Research on Aging in California and other centers in universities across the U.S. are probing new understanding of aging in order to defeat diseases from cancer to Alzheimer's. And the private non-profit Alliance for Aging Research is pressing a 'Healthspan Campaign' pointing out the large social and economic rewards to be gained by increasing the federal investment in medical research with a greater focus on the underlying biology of aging.

Already the National Institutes of Health, which is mostly organized by various disease research programs, has initiated a cross-cutting interest group involving 17 separate NIH Institutes to pursue 'geroscience,' a new term for understanding our aging bodies so we might experience more healthy years of life. At a time when even medical research is feeling a funding squeeze, for multiple research institutes to pool expertise and resources in order to confront the mammoth health challenge of an aging population, this is a prudent course and a sound public investment for America's future.

This week, the Director of the NIH, Dr. Francis Collins, will testify before the Senate subcommittee that determines future appropriations. We are encouraged that the promise of more coordinated research into aging will be set before important members of Congress who help determine research priorities. As we have learned from the experience with polio and HIV/AIDS, significant federal investment in biomedical research can have a profound impact on not only reducing mortality and morbidity, but on reducing healthcare costs.

The evidence is strong that the single most effective strategy in "bending the cost curve" on health care is preventing age-related chronic diseases in the first place. It will require courageous and innovative policy-making to step outside the traditional way medical research priorities have been established. Just as old age is not for sissies, neither is forward-looking public policy.

---

Daniel P. Perry is President and CEO of the Alliance for Aging Research.
Brian K. Kennedy, Ph.D. is President and CEO of the Buck Institute for Research on Aging.

It's possible to agree with everything said above about aging and the need for action, and then completely disagree that a wise use of time is chasing tax dollars and playing the lobbying game - putting money into the pockets of politicians and their cronies rather than research institutions. Government funding comes with government regulation and government values: it corrodes everything it touches, destroys the incentives to create progress, blocks clinical applications of research, and turns even the most ambitious ideals into staid jobs programs for the connected that win ever more money by failing to achieve any of their goals.

My view of the ideal future for the funding of medical research is closer to that of Peter Thiel - venture philanthropy, crowdsourcing for research, radical distribution of research collaboration between regions of the world, open biotechnology and science, and big financial risks put on programs like the Strategies for Negligible Engineered Senescence that have massive payoffs on achieving success. This is a future in which the connectivity of the Internet, dirt-cheap biotechnology, crowdsourcing, cheap air travel, and medical tourism combine to make every present institution in medical research irrelevant.

So avoid like the plague the incremental, aim-for-one-little-bit-better, money-chewing philosophy of government expenditures and near-sighted goals, that's what I say. Political culture is unable to look past the present and unable to avoid corruption. If you leave progress up to politicians and the regulatory capture collective that is Big Pharma, all you'll get is waste, "progress" that is one step short of stasis, and the building of institutions that - like the FDA - are incentivized to prevent the future, not unleash it.

So in conclusion, I see folk like the authors above to be in some ways rather like the A4M business leaders, for all that their politics couldn't be any more different. By that I mean that their hearts are in the right place, they have an enthusiasm for the cause of really, actually doing something about aging, but are heading down the wrong road when it comes to achieving significant, game-changing progress in longevity science by the only metric that matters - how long we all live.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

A thesis on culture and the urge to longevity is discussed by Ronald Bailey at Reason Magazine:

Cave's fascinating new book, Immortality, posits that civilization is a major side effect of humanity's attempts to live forever. He argues that our sophisticated minds inexorably recognize that, like all other living things, we will one day die. Simultaneously, Cave asserts, "The one thing that these minds cannot imagine is that very state of nonexistence; it is literally inconceivable. Death therefore presents itself as both inevitable and impossible. This is what I will call the Mortality Paradox, and its resolution is what gives shape to the immortality narratives, and therefore to civilization."

...

Cave identifies four immortality narratives that drive civilizations over time which he calls; (1) Staying Alive, (2) Resurrection, (3) Soul, and (4) Legacy. Cave gracefully marches through his four immortality narratives citing examples from history, psychology, and religion up to the modern day. "At its core, a civilization is a collection of life extension technologies: agriculture to ensure food in steady supply, clothing to stave off cold, architecture to provide shelter and safety, better weapons for hunting and defense, and medicine to combat injury and disease," he writes.

Cave is something of a deathist, at first glance looking like he believes that progress means overcoming the primal urge to immortality of the self and the fear of death, but at least he is a deathist who has produced an interesting work on our deep cultural heritage. It should go without saying that history is silent when it comes to the choices we make now in building the future - it can only persuade, not veto. Preferences on life, death, and the quest for rejuvenation biotechnology are personal choices.

But onwards: I think that it is useful to realize that much of our present culture - and that includes the culture of longevity science and its supporters - has very ancient roots indeed. Unbroken lines can be traced from the incentives and psychology of stone age shamans through to the magical thinking and oral fixations of today. Little but technology separates us from our ancestors of five or ten thousand years past, and what to what use do we put that technology? We use it to make our greatest myths real: we are building the world that our ancestors chose to imagine, and which we too imagine, driven by our shared human condition and neural physiology.

Spend a little time with ancient myth, and you'll soon see there is little fundamental difference between the tales of thousands of years past and the folktales of a few hundred years ago. Our present popular entertainments merely continue the theme, a thousand more frills but the same underlying psychology at work. We humans identify with a certain set of stories, and those stories are found repeated throughout our mythologies. In turn, mythology drives technology, as technology is, at heart, a way to satisfy human desires.

As to those parts of mythology that we haven't got to yet - such as unbounded longevity, enabled through biotechnology - well, give it time. We have managed flight, standing atop mountains, journeying to the moon, transmuting the elements, growing food in abundance beyond the wildest dreams of past centuries, changing the course of floods and rivers, and far more. Even the oldest myths will in due course be reconstructed in the real world, even if that means we will build cities in the clouds, cats that can talk, and spirits for companionship. Given sufficiently advanced biotechnology and an understanding of the fundaments of intelligence, the world of a century from now will be populated by people who do not age and disembodied machine intelligences - easily enough matched to the roles of hidden peoples and household spirits in legend.

Interestingly, in the past I have sketched more or less the opposite thesis to Cave above - that our heritage of myths surrounding progress, death, and mortality are a basis for the widespread knee-jerk rejection of longevity science observed in present day populations:

• Our Beauteous But Destructive Heritage of Myth, Legend, and Stories
• Dying to Live Forever
• "Every Story is the Story of the Fall"

"Every story is the story of the Fall" - except the one that matters, the one we're all writing together with quills of science, will and toil in the real world. That story is a grand arc of irresistible rise, of the defeat of obstacles and surpassing of limitations to our true potential. But you wouldn't know it from the myths that we find most comforting, as illustrated by their widespread nature.

...

The story of the Fall is an old and simple one; the world is one of shortages, pain, suffering and death, yet we humans can conceive of a world absent these troubles. Nostalgia is a part of the human condition also - we see earlier times in our own lives as better than they were, and it's a short leap from there to draw a line of decay from an imagined golden age to the imperfect present. The Fall is an alignment of the mythic world - a better, imaginary world - with the arrow of time; for a variety of reasons, we have come to put that mythic world in the past rather than the future.

...

This is an age of progress and biotechnology. Yet we folk who might be the first ageless humans stand atop a bone mountain. Its slopes are the stories of the dead, created, told, and appreciated by people who knew their own mortality. It is an enormous, pervasive heritage, forged by an army of billions, and no part of our culture or our endeavors is left untouched by it. This is one part of the hurdle we must overcome as we strive to convince people that a near future of rejuvenation biotechnology is plausible, possible, and desirable.

This dichotomy might be another facet of the difficulty in explaining modern attitudes towards longevity and aging. Why are people on the one hand so enthused by the "anti-aging" marketplace, and at the same time so quick to reject real and meaningful science aimed at extending the health human life span? I've thought on this for a decade and still have no satisfying answer.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

If we accept this, the path before us is very clear.

The first goal of medicine is to see to it that no one has to reach a hospital or a clinic. This is what I mean by prevention. [Technically called primary prevention; not of course ruling out the importance of secondary prevention (early detection and prompt treatment) and tertiary prevention (restoring function and reducing disability)]. This should be the very first goal, not the last; which means, health promotion/education activities along with clean water, nutritious food, clean and disaster free habitation, proper sanitation, control of pollution, poverty alleviation, empowerment of the deprived and disadvantaged, life-style modifications. A tall order, which involves multiple agencies, not in control of medicine and its movers. That is one prime reason why it is not top of the agenda, perhaps. And of course because it cuts at the very root of the justification for the medical establishment, and its proliferation. But medicine has as much a treatment orientation as a social perspective. For health is a means to well-being, and health can be achieved for all only when all are mobilized for health and become conscious of what should be its legitimate thrust (Singh and Singh, 2004). Moreover, prevention, understood as preventing a disease from occurring, also means, finding out vaccines, and other preventive measures, for all its diseases, not just the infectious. Let this stop sounding ludicrous. It is comforting to note that work on vaccines is underway, especially for diabetes (Phillips et al., 2008; Richardson et al., 2009), hypertension (Mitka, 2007; Ambhl et al., 2007; Phisitkul, 2009), cancers (especially cervical: Jenkins, 2008; Keam and Harper, 2008; Schwarz, 2008), and at least suggested for schizophrenia and other mental disorders (Tomlinson et al., 2009). And, related to this, it must research and highlight life style changes which prevent disease, and tackle diseases of poverty and of lifestyle (Singh and Singh, 2008). Some work in this field is already on, for example, in cancers (Anand et al., 2008), Type 2 Diabetes (Misra, 2009), cardiovascular disease (Pischke et al., 2008), ulcerative colitis (Langhorst et al., 2007); as also the beneficial effects of a vegetarian diet in lifestyle diseases (Segasothy and Phillips, 1999). Preventive psychiatry also needs a boost, for psychiatry, and overall for medicine, for do we not know that psychological distress is at the root of common medical problems that reach a primary care physician, and complicate many manifestations of other disorders at all levels of their manifestation. The complex relationships between gene-environment interactions, particularly the interplay of vulnerability and resilience factors within a persons biography need close scrutiny in individualized preventive psychiatry (Mller-Spahn, 2008), as does reduction of stigma in secondary prevention (Reeder and Pryor, 2008). The role of health psychology and the related field of behavioural medicine which focus on the interplay among biological dispositions, behaviour, and social context also need enthusiastic backing as a means to health promoting behaviours and preventing health damaging ones (Kaplan, 2009). Modern medicine must look closely at, and not pooh pooh, the claims of alternative and complementary medicine, including yoga, meditation and spirituality, just because one is put off by their tall sounding claims, and some charlatans in the group. Rather, it must submit their claims to rigorous scientific and experimental scrutiny. Some recent studies in yoga in general (Lipton, 2008; Bijlani, 2008; Corliss, 2001; Oken et al., 2006; Brown and Gerbarg, 2005; Shapiro et al., 2007; Flegal et al. 2007), and yoga in cancers (Culos-Reed et al., 2006; Bower et al., 2005; Smith and Pukall, 2009; Danhauer et al., 2009) are promising in this direction. Studies of meditation as an adjunct to modern medicine deserve special mention here. Some promising leads are in works on Longevity and health through yogic meditation (Bushell, 2009), and meditation in general (Bushell and Thiese, 2009); meditative practices for health (Ospina et al., 2007), and their clinical trials (Ospina et al., 2008); Sudarshan kriya in stress, anxiety and depression (Brown and Gerbarg, 2009); Transcendental Meditation and longevity (Alexander et al., 1989); meditation and slowing of aging, (Epel et al., 2009); mindfulness and distress (Jain et al., 2007); and mindfulness and well-being (Shapiro et al., 2008). Spirituality and its various scientific studies need a close scrutiny too. Some areas of spirituality which have interested researchers in recent times are positive emotions and spirituality (Vaillant, 2008), its neurobiology (Mohandas, 2008), healing presence (McDonough-Means et al., 2004), spiritual encounter and complementary treatment (Foster, 2006), spirituality and psychiatry (Mohr, 2006), health and spirituality in critical care (Puchalski, 2004), spirituality and critical care holistic nursing (Carpenter et al., 2008), difficulty in talking about spirituality in a medical setting (Molzahn and Sheilds, 2008) etc. To promote rigorous scientific scrutiny of claims in Complementary and Alternative medicine [CAM], laudable efforts are on by relatively new Journals in the field like Evidenced Based Complementary and Alternative Medicine (an Oxford Journal, since June 2004, http://ecam.oxfordjournals.org), BMC Complementary and Alternative Medicine (Published by BioMed Central, since 2001, http://www.biomedcentral.com/bmccomplementalternmed), Alternative Therapies in Health and Medicine (since 1995, first journal in the field of CAM to be indexed with NLM http://www.alternative-therapies.com), Journal of Alternative and Complementary Medicine (since 1995, Official Journal of the International society for Complementary Medicine Research, http://www.liebertpub.com/products/product.aspx?pid=26). Some notable relatively recent work in CAM in the field in anxiety and depression (van der Watt et al., 2008), depression in women (Manber et al., 2002), menopausal women (Kronenberg and Fugh-Berman, 2002), sleep disorders in the elderly (Gooneratne, 2008), osteoarthritis (Ernst, 2006), asthma (Pretorius, 2009) etc, should not go unnoticed. And while all this happens, the preventive and social medicine guys from mainstream medicine need to awaken and clean up their act. To stop being sidelined, and point out how they matter. And of course, to re-emphasize that prevention is better than cure (Phakathi, 2009, where it is in relation to child sexual abuse, but applicable elsewhere too).

The third is to closely study and report on longevity and well-being studies. Well-being implies the presence of (1) positive emotions and the absence of negative ones; (2) mature character traits, including self-directedness, cooperativeness, and self-transcendence; (3) life satisfaction or quality of life; and (4) character strengths and virtues, such as hope, compassion, and courage, all of which are now measurable by scales (Cloninger, 2008). Some relatively recent literature focuses on telomeres and longevity (Haussmann and Mauck, 2008); sex differences in longevity, (Franceschi et al., 2000); Immunology and longevity (Candore et al., 2006); psychosocial factors and longevity (Darviri et al., 2009) etc. The paradigm of Reorganizational healing [ROH] is an interesting recent work in the field of wellness, behaviour change, holistic practice and healing (Epstein et al., 2009). Anyone who has not visited a hospital and is over 60 years is a precious commodity to research. Anyone who has none of the lifestyle diseases till 60 is also similarly precious. All those who are 90 and active physically and mentally, even if diseased, form another very precious group. And all centenarians are the most precious group to study. It is fascinating to see the breadth of studies on this topic. There is a burgeoning research on centenarians in the last decade, some of promise and interest are in the areas of Centenarians and healthy aging (Engberg et al., 2009); antioxidants and healthy centenarians (Mecocci et al., 2000); nonagenarians and centenarians in China, (Ye et al., 2009); centenarians in Bama (Xiao et al., 1996); quality of life and longevity, (Jeune, 2002); Danish centenarians, not necessarily healthy but still autonomous (Andersen-Ranberg et al., 2001); and not necessarily having dementia, (Andersen-Ranberg et al., 2006); centenarians and their cognitive functions, (Silver et al., 2001); dementia free centenarians (Perls, 2004a, 2004b); centenarians being different (Perls 2006); cognitive states of Centenarians, (Luczywek et al., 2007); successful aging in centenarians: myths and reality, (Motta et al., 2005); physical activity and centenarians (Antonini et al., 2008); centenarians aging gracefully (Willcox et al., 2007) etc.

Read more here:
Modern Medicine: Towards Prevention, Cure, Well-being and ...

We are far from the first generation to have looked at the state of science and postulated that we can significantly extend human life span through some specific means - but we are the first generation to have possession of the necessary scientific knowledge to be correct in our evaluation. That we have this knowledge is why you can't just look at the long history of predictions of longevity and say "we're just another generation that will be disappointed - it's all more of the same." The past is a great place to look if you want to predict the future of politics, but a terrible resource for predicting the future of technology. There is an enormous difference between the state of life science of today and the nascent biotechnology of the 1970s and advocates like Timothy Leary - and not to mention the science of the early 20th century as is referenced in this article: "It might seem as if a magic [longevity-enhancing] pill isn't so far off. But before we get too cheery about the prospects for these discoveries, it's useful to be reminded of the many longevity 'breakthroughs' that have come and gone in the past. One such potential advance was hailed in the November 1929 issue of Technology Review, in an essay called 'Forestalling Death: The Cow's Contribution to Human Longevity' ... In the previous 125 years, Tobey observed, average life span had risen from the low 30s to the upper 50s. This was primarily due to reductions in infectious disease and in the infant death rate ... It wasn't enough to simply reduce a threat such as infectious disease - it was imperative that we find something we could add to our lives, or maybe simply increase our intake of something we were already consuming. He felt recent research might have uncovered just such a substance. ... He pointed to recent experiments at Columbia University, wherein one set of rats had been given an 'adequate diet' of one-sixth dried whole milk and five-sixths whole wheat. An 'optimal diet' group, meanwhile, received double the milk and less wheat. The average duration of life was almost exactly ten percent greater in those subjects receiving the optimal diet ... Is it possible that we have had the fountain of youth within our grasp throughout the ages that man has been seeking this liquid phantasm? Milk has always been recognized as the one most nearly perfect food ... but apparently it possesses hitherto undreamed of virtues." And so on: the end result is more of the oral fixation that seems to so dominate our culture - in the popular imagination everything of significance must be something that we put in our mouths and consume. Most important medicine, of course, is nothing of the sort.

Link: http://www.technologyreview.com/biomedicine/39630/

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

A billion people will die between now and the earliest plausible date for the first package of rough and ready but working rejuvenation therapies - say twenty years from now. Another few decades will pass for the technology to work its way out to global availability at low cost, and the deaths by aging will continue in less fortunate regions while this happens. Even after aging is completely conquered, there will be an ongoing toll of death due to accidents and whatever passes for disease in the age of medical nanotechnology. Death isn't going away completely for we biological folk, no matter how well we do in the field of medicine in the foreseeable future: medicine can't wave away falling rocks.

Thus will always be a role for what we might term post-mortem critical care: technologies and services to preserve the fine structure of the brain and the mind it contains following death, and keep them preserved until such time as that patient can be restored to life. At present the only post-mortem critical care option is cryonics, with what looks like a fair few years to wait for technology to advance to the point of restoration, and thus an unknown chance of eventual success for any individual - but a significantly greater chance than is offered by the grave, of course. In contrast, in a future in which the technology to restore a preserved person exists, cryonics and other preservation technologies like plastination will occupy a more dynamic position in the medical toolkit, and patients might expect to wait in a preserved state only for transport to the nearest major population center.

At last year's SENS5 conference, Max More, CEO of cryonics company Alcor, gave this presentation on the future of his industry:

Cryonics involves the cryopreservation of humans as soon as possible after legal and clinical "death". Legal and clinical death differ importantly from biological death or true (irreversible) cessation of function. It is therefore a mistake to portray cryonics as an alternative to cremation or burial. It is true that cryopreserved people are not alive but neither are they dead. Cryonics should be seen as part of the field of life extension. Cryonics enables the transport of critically ill people through time in an unchanging state to a time when more advanced medical and repair technologies are available. Even after "longevity escape velocity" has been attained and aging has been largely tamed, cryonics will continue to be needed for people who die of accidents or diseases for which there is no cure at the time.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The immune system is a powerful tool for the selective destruction of unwanted cells, and researchers are a fair way down the road of engineering the activity of the immune system to form therapies. You might look at granulocyte transplant therapy as an example of the sort of tools that are under development. Here is an article on another line of research that has just reached the stage of early tests in humans:

In the research published Wednesday, doctors at the University of Pennsylvania say the treatment made the most common type of leukemia completely disappear in two of the patients and reduced it by 70 percent in the third. In each of the patients as much as five pounds of cancerous tissue completely melted away in a few weeks, and a year later it is still gone.

...

the researchers removed certain types of white blood cells that the body uses to fight disease from the patients. Using a modified, harmless version of HIV, the virus that causes AIDS, they inserted a series of genes into the white blood cells. These were designed to make to cells target and kill the cancer cells. After growing a large batch of the genetically engineered white blood cells, the doctors injected them back into the patients. In similar past experimental treatments for several types of cancer the re-injected white cells killed a few cancer cells and then died out. But the Penn researchers inserted a gene that made the white blood cells multiply by a thousand fold inside the body. The result, as researcher June put it, is that the white blood cells became "serial killers" relentlessly tracking down and killing the cancer cells in the blood, bone marrow and lymph tissue.

An editorial and research paper are available if you are interested in delving further into the details. Unfortunately this work suffers from much the same problem as efforts to develop granulocyte transplant therapies, which is that there are next to no sources of funding for research groups at the cutting edge of immunotherapy. The article relates what is a sadly common story in this part of the scientific community:

So why has this remarkable treatment been tried so far on only three patients? Both the National Cancer Institute and several pharmaceutical companies declined to pay for the research. Neither applicants nor funders discuss the reasons an application is turned down. But good guesses are the general shortage of funds and the concept tried in this experiment was too novel and, thus, too risky for consideration. The researchers did manage to get a grant from the Alliance for Cancer Gene Therapy, a charity founded by Barbara and Edward Netter after their daughter-in-law died of cancer. The money was enough to finance the trials on the first three patients.

This is a good example of how philanthropy modeled on venture investment - backing a range of early stage, high risk, high reward projects - can help break up the log-jams that result from institutional reluctance to fund the cutting edge in any field. The larger an institution, the more they will tend towards only backing the safe choices, but by doing that they ensure that the backing of their resources has little chance of producing radical change. Hopefully other projects, such as work on granulocyte based therapies, can find the connections needed to benefit from similar sources of funding and vision.