The problem with ethics as a profession is exactly that it has become a profession: the salaried ethicist knows that his continued employment depends upon finding problems with research and development. Money, even modest amounts of the stuff, is a powerful incentive. So where there are no problems, there are still groups of people who are effectively being paid to invent problems - and you wonder why medical science isn't moving as fast as it might be.

This form of institutional corrosion is well entrenched throughout the Western world now, of course, and so you'll see plenty of things like this open access whine-slash-justification-for-a-paycheck:

Optimistic predictions of the feasibility and effectiveness of life extension should be critically reviewed in the light of their ethical and social implications. Some anti-aging scientists claim that arguments against anti-aging medicine will simply be dismissed by research outcomes. We would claim that the problem is not with the availability of results, but with defining the nature of what we consider "results".

The idea that life extension research will necessarily translate into what some judges interpret as a result (i.e. the cure of aging) is problematic, because the translational process from potential life extension interventions into reality is not only a matter of science. Suppose we have laboratory advances that are promising for the future translation of laboratory work to the clinic. This result would matter scientifically, but would not solve the ethical and social questions of life-extending interventions. Even if we should succeed in the laboratory, the problems of equitable access to such interventions, the impacts of the future implementation of life extension on health care systems, the risk of pressure to make use of life extension techniques - all these issues will still be with us. Here, more than ever, it must be stressed that the "nature" of what we consider "results" matters not only scientifically, but also ethically and socially. Ethical and social debate on these issues is therefore much needed, along with scientific research and discussion.

Roughly translated: "I don't actually know enough about contemporary longevity science to write about it comprehensively or well, but I do know how to write successful grants. Please pay me and my colleagues more money rather than putting those resources to work on actual research." The middle section of the paper is particularly offensive on that count, an incomplete overview that plays up the bad and the unknown while failing to mention important topics such as SENS, systems biology, tissue engineering, and so on and so forth. There are admittedly far worse things going on in the world these days than the efforts of a legion of minor parasites who've manage to redirect research funding to build an industry that actively opposes research, but the noisy parasitism of the ethics profession manages to be more aggravating than its cost should make it.

Strange things happen to cultures when they lose sight of what matters, begin to value abstractions such as "society" over real individuals, and empty talk over tangible progress. I'd say it's a form of collective cabin fever brought on by the shrinking world and the absence of a frontier: with no hard-to-reach destination for the best, brightest, and most motivated to head for when matters become less than tolerable, there is no escape valve to prevent a network of diverse cultures from nonetheless degenerating in lockstep. The only form of protest that really matters in the long term - when it comes to applying pressure for change - is emigration to a remote region in order to build better lives. The sooner that the next new frontier is opened by technological progress in orbital flight the better in my view.

Another of the observed effects of calorie restriction in lower animals is shown to exist in humans as well: "Reduction of body temperature has been proposed to contribute to the increased lifespan in calorie restricted animals and mice overexpressing the uncoupling protein-2 in hypocretin neurons. However, nothing is known regarding the long-term effects of calorie restriction (CR) with adequate nutrition on body temperature in humans. In this study, 24-hour core body temperature was measured every minute by using ingested telemetric capsules in 24 men and women consuming a CR diet for an average of 6 years, 24 age- and sex-matched sedentary (WD) and 24 body fat-matched exercise-trained (EX) volunteers, who were eating Western diets. ... Mean 24-hour, day-time and night-time core body temperatures were all significantly lower in the CR group than in the WD and EX groups ... Long-term CR with adequate nutrition in lean and weight-stable healthy humans is associated with a sustained reduction in core body temperature, similar to that found in CR rodents and monkeys. This adaptation is likely due to CR itself, rather than to leanness, and may be involved in slowing the rate of aging."

Link: http://www.impactaging.com/papers/v3/n4/full/100280.html

Economies of scale apply to all endeavors, including the production of human tissue: "The high-tech production lines of [a] laboratory in Germany began moving this week turning out a unique product - human skin. Nicknamed 'The Flesh Factory' by the boffins who work at the Stuttgarter Fraunhofer-Institute, it aims to produce 5,000 circles of skin as big as a one-euro cent every month. Costing around 45 pounds each, when the skin circles are perfected they will be sold to hospitals and clinics around the world for life-saving operations. Project leader Professor Heike Walles, 48, has devoted her whole life to the goal of reproducing human skin on an industrial scale - to save human life and protect animals; it can be used for the kind of testing currently requiring the sacrifice of live creatures. ... Until now, methods of culturing tissue like that used for skin transplants have been very expensive. Most of the steps are carried out manually, which means that the process is not particularly efficient. ... The new production line is entirely mechanical and controlled by computers. ... The process works like this; a biopsy - a sample of human tissue - is checked for sterility. A gripper arm then transports the biopsy into an automated cutting device. The machine snips the biopsy into small pieces, isolates the different cell types, stimulates their growth, and mixes the skin cells with collagen. A three-dimensional reconstruction of the different skin layers is produced with the aid of a special gel matrix - and the skin is ready. In the final step, the machine packages the cells for shipment. Alternatively, the tissue can be cryopreserved - that is, deep-frozen and stored for later use."

Link: http://germanherald.com/news/Allan_Hall's_Germany/2011-04-13/647/The_Flesh_Factory_goes_online

The Vegas Group is a yet-to-be-built community initiative intended to bring longevity science to the open biotechnology and DIYbio communities - and from there reverse engineer and make ready for human use the most promising longevity-enhancing technologies demonstrated in mice in the laboratory. We are entering an age of medical tourism, and the clinics and laboratories of Asia will be happy to accept business and open source biotechnologies generated by DIYbio work in the US. At this stage, I'm still thinking through the project: breaking it down into manageable chunks, and considering what I should work on first:

The path to this future involves networking and community building in a whole new and different direction from that taken by much of the longevity advocacy community - and the construction of a codex of information, a how-to manual of recipes for replicating specific products of the formal research community in longevity science. ... any step one for me will involve considering the codex: what it is, and how it will be constructed, maintained, and made useful to the seeds of what will be the Vegas Group - however that organization ultimately comes about, and whatever form it ultimately takes.

As the cost of biotechnology falls, so is the door opened to much wider development and innovation, wherein lab cooperatives host a mix of hobbyists, moonlighting professionals, and semi-professionals who collaborate on a range of their own projects. Ultimately, low-cost desktop biotech toolkits will be developed and a community of tens or hundreds of thousands of developers will contribute from their homes - just as is the case for open source software development today. With computers in mind, a good historical analogy for the present state of the small DIYbio community is in fact the Homebrew Computer Club in the mid 1970s, prior to the introduction of the first popular personal computer kit. Some small but enthusiastic individuals and groups are designing, building, and selling biotech hardware - such as PCR machines - that will ultimately be the components of a home laboratory, but matters are not yet at that stage of take-off that will see dozens of companies founded and many more people join the community in a short period of years. That lies ahead. The wave is coming, in its own time, and I would like to be positioned to take advantage of it.

All journeys start with the first steps, and I'm in favor of incremental approaches to development. Make something small, a minimum viable product that is the most elementary building block that can stand on its own and still contribute to the ultimate goal. Release it, obtain feedback, and then start on the next building block - and repeat that process until you have as fully as possible realized your initial vision. There will be much to learn along the way, and small building blocks coupled with "release early, release often" make that learning less painful.

Given a large idea, the challenge is often finding that starting point. From the broad high level outline of the Vegas Group, I focused on the codex: the necessary how-to documents and body of knowledge that will enable people to participate. As a general rule, technical communities are terrible at documentation - and that lack of documentation is a real hurdle to recruitment and growth. It could be argued that the DIYbio community isn't yet at the point where it could benefit greatly from a codex: there are other tasks to be completed first relating to hardware. But time is ticking, and progress is being made. The period of being too early won't last forever, and establishing even the skeleton of a practical longevity science codex at hobbyist or non-profit speed will be a process that takes years.

The codex itself is a very large project: something large enough to found a company on in and of itself. There are any number of questions: how best to discover the business models that work to efficiently produce accurate reverse engineering from published papers on longevity-related biotechnology; how best to structure the information presented; how to organize writers and researchers; how to even assemble and prioritize the list of materials needed; and so on ad infinitum.

Thus a fairly narrow initial project for the codex must be identified, so that the first group of volunteers to work on it can run into all the brick walls and fall into all of the potholes without risking a great deal if it all fails. Small projects are easy to scrap, rework, and start over if necessary - and that is a tremendous advantage when you don't yet know the detailed recipe for success. Along the way the volunteers will come to an understanding of how best to make assembly of the broader codex work as a process.

What is this first codex project, though? I propose that reverse engineering and documentation of mitochondrial protofection is a good candidate. This is a technique by which mitochondrial DNA is replaced throughout an individual's cells, and was first demonstrated in mice back in 2005. As you might know, progressively accumulated damage to mitochondrial DNA is one of the causes of aging, as described by the mitochondrial free radical theory of aging. Future rejuvenation biotechnology must include a way to either permanently work around this form of damage, such as through the methodology advocated by the SENS Foundation, or periodically repair it - say once every two to three decades.

Why protofection? In a nutshell:

• It is comparatively easy to explain to a non-technical audience.
• It fits with the SENS vision for rejuvenation biotechnology.
• It has already been demonstrated to work, so at least one group of researchers knows exactly how to do it.
• It is old enough that this and related knowledge may have spread somewhat, making it more amenable to reverse engineering.

Protofection works in mice, but since that demonstration six years ago next to nothing has been heard of it - just a few publications indicative of a slow exploration in search of possible FDA-approved applications. The FDA does not consider aging a disease, however, and therefore its regulators will not approve any treatment that aims to intervene in aging or achieve rejuvenation. That unfortunate fact is well known, and thus there is little funding available for attempts to treat aging: potential technologies are instead subverted into the development of limited treatments for late stage age-related diseases. The silence regarding protofection is probably another good example of the way in which the present regulatory apparatus holds back progress, as developing protofection for safe general human use is an obvious course of action based on the weight of evidence linking mitochondrial DNA damage and aging. Yet it isn't happening.

Given that a number of years have passed since the viability of protofection was demonstrated, it should be an easier target for reverse engineering and documentation of processes than more recent developments. By which I mean that it should be easier to find researchers and post-graduates unconnected with the work who nonetheless know enough to write on the topic.

Protofection is also (I hope) narrow enough not to generate a true mountain of supporting needs in terms of how-to documents. Part of the process of discovery is to understand how to develop the initial list of documents required for the codex, starting from a high-level goal like "let's reverse engineer protofection, make reproducing it comprehensible to the semi-professional DIYbio volunteer, and release that documentation under a Creative Commons license" and working all way down to the brass tacks and petri dishes. Protofection, while something that can be explained in a few short sentences, stands at the top of a sizable pyramid of techniques and knowledge in biotechnology: how to work with DNA, how to manage your own laboratory equipment, how to keep cell cultures, and so on for a long list of topics.

If this takes a few years to get right, that's fine by me. It will provide a blueprint for doing the same to other areas of biotechnology, and by that time there should be more people interest in helping out - both for longevity science and for their own areas of interest.

Here is an example of a research commentary that misses the forest for the trees: "Vegetarians experience a 36 percent lower prevalence of metabolic syndrome than non-vegetarians, suggests new research ... Because metabolic syndrome can be a precursor to heart disease, diabetes, and stroke, the findings indicate vegetarians may be at lower risk of developing these conditions. Metabolic syndrome is defined as exhibiting at least three out of five total risk factors: high blood pressure, elevated HDL cholesterol, high glucose levels, elevated triglycerides, and an unhealthy waist circumference. ... while 25 percent of vegetarians had metabolic syndrome, the number significantly rises to 37 percent for semi-vegetarians and 39 percent for non-vegetarians. The results hold up when adjusted for factors such as age, gender, race, physical activity, calories consumed, smoking, and alcohol intake. ... On average, the vegetarians and semi-vegetarians were three years older than non-vegetarians. Despite their slightly older age, vegetarians had lower triglycerides, glucose levels, blood pressure, waist circumference, and body mass index (BMI). Semi-vegetarians also had a significantly lower BMI and waist circumference compared to those who ate meat more regularly." Given the broader context of what is known about the effects of body fat on long-term health, the plausible mechanism here looks to be related to the amount of visceral fat rather than anything to do with diet per se.

Link: http://www.eurekalert.org/pub_releases/2011-04/llua-vmb041311.php

Progress in tissue engineering: "scientists have created human kidneys from stem cells ... The artificial organs were created in a laboratory using human amniotic fluid and animal foetal cells. They are currently half a centimetre in length - the same size as kidneys found in an unborn baby. [Scientists] hope they will grow into full-size organs when transplanted into a human. ... It sounds a bit science fiction-like but it's not. The idea is to start with human stem cells and end up with a functioning organ. We have made pretty good progress with that. We can make something that has the complexity of a normal, foetal kidney ... The research team hope that doctors will eventually be able to collect amniotic fluid, which surrounds the growing embryo in the womb, when a baby is born. This will then be stored by scientists in case that person develops kidney disease later in life. The fluid can then be used to create a matching kidney. Creating an organ using a patient's own stem cells solves the problem of having to use powerful immunosuppressant drugs to stop the body rejecting a another person's kidney. ... the technology could be ready for use on humans in around 10 years." By which time it will probably be unnecessary to collect amniotic fluid, as the signals and chemicals it provides will be understood and reproduced.

Link: http://www.telegraph.co.uk/health/healthnews/8443740/Scientists-create-human-kidneys-from-stem-cells.html

Over at Chronosphere you'll find a weighty set of posts that aim to provide a foundation for critiquing cryonics at the organizational level of achieving consistently good cryopreservations, and the development of professional organizational cultures and processes - such as record-keeping - required to support that goal. All industries require ongoing initiatives that provide solid, constructive critiques of present practice, for otherwise how are the participants to progress and improve themselves?

You be the Judge: Understanding and Evaluating the Quality of Human Cryopreservations from Cryonics Organization Literature and Case Report Data, Part 1:

The goal of this series of articles is to equip the reader with the tools necessary to make an accurate assessment of the quality of care cryonics patients, both individually and as a group, are receiving from their respective cryonics organizations.

You be the Judge: Understanding and Evaluating the Quality of Human Cryopreservations from Cryonics Organization Literature and Case Report Data, Part 2:

In a very real sense, that care starts the moment the member/patient experiences his first contact with the cryonics organization that will ultimately cryopreserve him. The tenor of that first contact will likely determine the nature and course of the member's subsequent interaction both with cryonics and his cryonics organization. If cryonics is presented as a developed product that is costly but nevertheless fairly routine, say like buying a home or an automobile, that's very likely how it will be subsequently be treated. If, on the other hand, there is heavy emphasis on the lack of infrastructure to provide help in an emergency and the need to exercise both personal responsibility and personal preparedness, outcomes will likely differ - at least statistically, if not in each individual case.

You be the Judge: Understanding and Evaluating the Quality of Human Cryopreservations from Cryonics Organization Literature and Case Report Data, Part 3:

not only is it important that those caring for the patient know what is expected of them, the cryonics organization must also know what the family/caregiver's needs are, both logistically and psychologically. Cryonics is unfamiliar territory for family, and the procedures attending [the preparatory period immediately prior to cryopreservation] can perturb what in many cases will be a fragile emotional and psychological equilibrium in the patient's home life. Organizations that fail to establish rapport, and work to ascertain and meet the needs of the patient's family, risk non-cooperation, obstruction and even litigation. Seemingly small details, such as protecting flooring or furniture from water damage, or arranging for a few minutes of private "alone time" with the patient before he is removed from the home or care facility after acute stabilization, can mean the difference between heartfelt assistance, and bitter belligerence from the next of kin.

The quotes above hit some of the points I have had in mind in past years when discussing the need for cryonics organizations to (a) become more professional in character, and (b) form up a better product offering for customers, one that provides more in the way of service and guidance than is presently the case. That theme continues into the last of the four posts, linked below.

You be the Judge: Understanding and Evaluating the Quality of Human Cryopreservations from Cryonics Organization Literature and Case Report Data, Part 4:

Nevertheless, the real solutions to the problems discussed here are not easy, because they demand the acquisition of professionalism, knowledge, and skill in the context of cryonics as medicine. I personally believe that Jerry Leaf and I came very close to doing that in the decade between 1981 and 1991. But we failed. Why we failed will be discussed at a later time. Suffice it to say that the problem of maintaining professionalism is a nettlesome one in medicine, engineering and other demanding disciples that are vastly more developed than cryonics is today, and there will be no quick fixes.

"No quick fixes" is a conclusion I agree with. Nothing worthwhile is quick and painless to achieve, and even small industries change slowly when it comes to company cultures. The only reliable path to faster change involves money, as change follows rapid growth in the number of paying customers in any human endeavor. Unfortunately that growth remains elusive for cryonics providers, just as it has throughout that past decades. From where I stand, I'd say that the best near-term path to the goal of transformative growth in revenue lies in developing spin-off technologies in cryobiology and related fields - but that's an opinion offered without any great insight into the inner workings of the industry as it exists today. It is simply taken from the standard business texts: if you've consistently failed to achieve good growth with option A, then perhaps it's time to try options B, C, and D.

You might recall the identification of klotho as a longevity-related gene in mice and other lower animals in recent years. Here is a study on levels of klotho in humans: "The aging-suppressor gene klotho encodes a single-pass transmembrane protein that in mice is known to extend life span when overexpressed and resemble accelerated aging when expression is disrupted. It is not known whether there is a relationship between plasma levels of secreted klotho protein and longevity in humans. ... We measured plasma klotho in 804 adults, greater than or equal to 65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy. ... During 6 years of follow-up, 194 (24.1%) of the participants died. In a multivariate Cox proportional hazards model, adjusting for age, sex, education, body mass index, physical activity, total cholesterol, high-density lipoprotein cholesterol, cognition, 25-hydroxyvitamin D, parathyroid hormone, serum calcium, mean arterial pressure, and chronic diseases, participants in the lowest tertile of plasma klotho [had] an increased risk of death compared with participants in the highest tertile of plasma klotho ... In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans." Given the number of adjustments there, I'd like to see a confirming study - and for preference one that explicitly took into account calorie intake as well. Just because you see the expected result is no reason to abandon the usual level of caution needed when reading the output of the scientific method.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21474560

Even at older ages, exercise is a still very important - as demonstrated by the degree to which it influences ongoing health in later stages of life, just as it does in earlier stages in life. "It is not sufficient simply to live longer. One of the current priorities for public health is to how to maintain good quality of life for longer. This has given rise to the concept of 'successful aging' generating a turning point in our thinking about aging, which is no longer seen as an inevitable decline. ... Physical activity has a pleiotropic effect and is a significant factor in successful aging. This study aims to quantify the relationship between the physical activity of a 65-year-old cohort and the level of life satisfaction and self-rated health 7 years later. A total of 988 questionnaires were sent by mail to a representative sample of healthy pensioners. Life satisfaction and health status were estimated on two visual analogical scales in answer to the following questions: (1) How would you estimate your state of health? and (2) Are you generally satisfied with your life? The level of physical activity was estimated using a questionnaire which enabled us to calculate: Daily energy expenditure (DEE) [and] VO2 peak. ... Energy spent in activity and VO2 peak estimated from DEE, measured at the age of 65, appear to be strong predictors of well-being 7 years later."

Link: http://dx.doi.org/10.1089/rej.2010.1101

It remains plausible that many cancers will suddenly become curable at some point in the next decade or so - even in their later stages - through the identification and targeted destruction of the cancer stem cells that power the cancer's growth:

The promise - the hoped for possibility - of cancer stem cells is that they represent a small, manageable, less complex range of biochemical targets to prevent and destroy cancer. The biotechnology of this year and next can flip genetic switches and safely destroy cells with specific markers - if we just know where to look, what to destroy, what to change.

Over the past few years, researchers have started the long process of cataloging cancers with identifiable stem cells at their root, and the unique signatures of those cancer stem cells. Those biochemical signatures in theory provide a template for targeted cell destruction therapies currently under development: engineered viruses, nanoparticle assemblies, immune therapies, and so forth. Given a distinct cell type, researchers can deplete its population without harming other cells or damaging tissues elsewhere in the body - a far cry from the present brute force approach of chemotherapy, and something that has been demonstrated numerous times in the laboratory.

On this topic I noticed a good open access paper today that provides an introduction to - and overview of - the near future of this branch of medical research.

Therapeutics formulated to target cancer stem cells: Is it in our future?:

When discussing potential targets for the treatment of cancer today, the conversation will generally lean towards targeted therapy of cancer stem cells (CSCs). With the identification of potential defining characteristics for CSCs, there have also been more questions raised as to which of these characteristics may make better targets. For many years, research seemed to focus on isolating CSCs by specific identifying markers but the research has seemed to shift towards identifying the way in which these stem cells behave that make them different from bulk tumor cells. Limited efficacy has been seen with the use of cell surface markers in clinical trials; however, there have been recent advances that target other aspects such as signaling pathways or genetic alterations seen particularly in CSCs. The following is a review of what information is out there and what seem to be the most promising paths on this journey to identifying therapeutic targets of self-renewing CSC sub-populations.

For the other side of the debate on cancer stem cells, you might look back into the archives. Not all researchers think that cancer stem cells are a viable target for therapies, or that they are in fact a sustaining force for cancer:

• The Skeptical View of Cancer Stem Cell Research
• Another Blow To Cancer Stem Cells

From my outsider's perspective, the competing evidence for and against the cancer stem cell hypothesis might be resolved if it turns out that only some cancers have clearly identifiable stem cells at their root. But we shall see how it all turns out: the research community is certainly going to spend a great deal of time and money over the next decade trying to destroy cancer by identifying and targeting its stem cells.