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Problems Posed by Antibiotic-Resistant Tuberculosis Bacteria (2004) – Article by G. Stolyarov II

Problems Posed by Antibiotic-Resistant Tuberculosis Bacteria (2004) – Article by G. Stolyarov II

The New Renaissance Hat
G. Stolyarov II
July 26, 2014
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Note from the Author: This essay was originally written in 2004 and published on Associated Content (subsequently, Yahoo! Voices) in 2007.  The essay earned over 1,200 page views on Associated Content/Yahoo! Voices, and I seek to preserve it as a valuable resource for readers, subsequent to the imminent closure of Yahoo! Voices. Therefore, this essay is being published directly on The Rational Argumentator for the first time.  
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~ G. Stolyarov II, July 26, 2014

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How Evolution Complicates the Fight Against Infectious Disease

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Tuberculosis (TB) has been successfully fought with antibiotics for decades, but the emergence of antibiotic-resistance TB bacteria has resulted in numerous complications in the battle against this disease.

Misuse of antibiotics via their frequent introduction into an individual’s body may destroy certain weaker strains of the TB bacteria, but will leave in place the few bacteria that have by chance been born with the ability to resist the antibiotics used. These bacteria will then have no obstacle toward proliferating and thus contributing to the evolution of a strain almost fully resistant to that particular antibiotic. The resistant bacteria are naturally selected to survive and multiply as the fittest under such conditions.

When an environment rich in bacteria for a particular disease exists, it may be possible for several afflicted persons to be treated with a different antibiotic each and for those persons to develop strains of bacteria immune to that particular antibiotic. Due to frequent contact between these individuals, the various specifically immune strains can transfer from one individual to another. Within a given individual’s body a strain immune to antibiotic A is free to undergo genetic recombination with a strain immune to antibiotic B, thus sometimes transferring immunity to two or more antibiotics to a given set of bacterial organisms, whose multiplication can bring about a populous multi-resistant strain.

An example of environments where antibiotic-resistant bacteria mutate readily is the Russian prison system, which remains alarmingly overcrowded. Inmates live in constant close contact with one another, facilitating a rapid rate of infectious disease proliferation. The TB bacteria, often latent in healthy individuals, more frequently manifests itself in the malnourished prisoners, many of whom additionally undermine their health via alcoholism. Whenever they cough or speak, the bacteria can infect those nearby. Moreover, antibiotics, especially second-line drugs for treating resistant strains, are in short supply. Thus there exists no real barrier to the spread of tuberculosis within the prison network and beyond.

Transportation, a key factor in the global economy, can also be an agent for the spread of a particular infectious disease on a worldwide scale, as travelers from an epidemic-stricken part of the world can transmit the bacteria a continent away. In cities near the Siberian prisons, many college students have already become afflicted with lung consumption, while trains carry the disease to Moscow, where some Russian travelers to the United States can reach any destination in the world, including the United States, by airplane. In New York, strains of the Tomsk TB bacteria have already been discovered.

An understanding of evolution in bacteria may cause doctors to be more prudent in prescribing antibiotics to patients and compel them to realize that such drugs have their limitations and must not be over-indulged in. Antibiotics may be used for treating severe cases of a disease, whereas milder manifestations should be suppressed by other means. Also, second-line drugs, which are currently expensive and dangerous, can be researched in greater depth, seeing as they provide a resort when resistant strains have already developed. If a mass-manufacturing industry for those drugs develops, their abundance will increase, and thus their prices will drop, rendering them available to quell epidemics within populations, such as the Siberian inmates, which do not possess optimal purchasing power.

Scientists can also keep a step ahead of the bacteria by artificially breeding strains resistant to known antibiotics in lab cultures and developing new antibiotics that would eliminate those strains based on studies of the organisms’ physiological systems and weaknesses. In this manner, future mutations can be anticipated and cures made available to preempt the spread of the mutant strain in the early stages of its development. If most future mutations are likewise suppressed, it may be possible to stagnate the general trend toward emergence of more resistant bacteria.

Commonly Misunderstood Concepts: Health Care (2009) – Article by G. Stolyarov II

Commonly Misunderstood Concepts: Health Care (2009) – Article by G. Stolyarov II

The New Renaissance Hat
G. Stolyarov II
Originally Published October 12, 2009
as Part of Issue CCXI of The Rational Argumentator
Republished July 24, 2014
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Note from the Author: This essay was originally published as part of Issue CCXI of The Rational Argumentator on October 12, 2009, using the Yahoo! Voices publishing platform. Because of the imminent closure of Yahoo! Voices, the essay is now being made directly available on The Rational Argumentator.
~ G. Stolyarov II, July 24, 2014
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It is an odd society indeed where such a seemingly simple idea as health care is so severely misunderstood. Health care, as the constituents of the term suggest, is simply caring for one’s health, where health – of course – is the physical integrity and unobstructed functioning of one’s body. A healthy person is one whose body is not breaking down, one who is not in constant pain, one who is going to live for a long time unless some unforeseen external peril – such as an accident or an assault – violates the integrity of one’s body from without.

In a society where there exists advanced scientific medical knowledge, it is possible to benefit one’s health by consulting with certain individuals who specialize in aspects of this knowledge. These individuals are also useful in detecting diseases or other malfunctions that are not obvious to the intelligent layman, and they also do a commendable job in researching cures for diseases that have hitherto been without remedy. Most doctors are to be praised for the excellent work they do, and I am confident that any doctor worthy of his M.D. degree would strongly concur with the fundamental understanding of health care that I posit here.

Most people will recognize that doctors play an important and sometimes necessary role in the provision of health care. What many people today fail to recognize, however, is that doctors are never a sufficient part of genuinely effective health care. Doctors can indeed often detect signs of illness and recommend remedies, but to expect a doctor to perform all of your health care for you is just like expecting a teacher to perform all of your education for you. Doctors and teachers can both help and can even at times make the difference between success and failure, but without your participation and your vigilance, failure is inevitable.

What are other crucial components of health care? They are not esoteric, and they do not require specialized knowledge. They include eating in moderation, exercising regularly, avoiding harmful substances, practicing at most monogamy, keeping one’s surroundings clean, and avoiding risks to life and limb as much as possible. There are also numerous over-the-counter medications and first aid practices, that, if used intelligently, can enable individuals to recover from many minor and even some major perils. These habits are not just little frills added on to the body of health care; they are that body, and without them, one will be quite dead quite soon – but not before racking up absurd amounts of medical expenses. I will note that in the 20th century, human life expectancy in the West surged from the mid-to-late forties to the late seventies. Although medical advances were phenomenal during that time, the vast majority of the increase can be attributed to improvements in overall cleanliness of infrastructure and healthier habits. With the advent of sanitation, regular dental hygiene, automatic washers and dryers, and efficient household cleaning supplies, a lot of infectious diseases that formerly wiped out millions were kept at bay – mostly not by doctors, but by ordinary laypersons living their lives in a superior manner to that of their ancestors. New technologies motivated new behaviors, and these everyday behaviors are our first and so far our best line of defense against disease and decay.

Of course, some people who lead their lives in the most health-conscious manner possible can still be afflicted by catastrophic diseases for reasons that are none of their fault. As far as medical science is aware, many cancers do not appear to be caused by any active human behavior; indeed, some are an unfortunate product of poor genes. And, of course, there is the ultimate killer – senescence – which afflicts all humans, given the current level of medical technology. It is imperative that these perils be eradicated as soon as possible, and the best doctors, scientists, and media advocates are needed to enable a victory over what can justly be called the greatest threats to humans everywhere. I will add that it is a matter of justice that a person who suffers from a disease which he did not cause receive prompt, efficacious, and affordable care. But the vital question – and the question many people today neglect to consider – is how this just state of affairs can possibly come about.

Reality only works in certain ways, in accord with immutable natural laws. Wishing for a good outcome will not make it so, and even acting toward that outcome will only work if the right actions are undertaken. Any reasonable, moral person will agree that it is preferable for all reasonable, moral people to be healthy rather than not. What many people fail to recognize is that any process of improvement takes time, and that surrogate measures that attempt to bring about the improvement instantaneously are not only illusory but can also be severely counterproductive.

As a case in point, I bring forth the oft-encountered contemporary confusion of health care with health insurance. Too many people today believe that it is not taking care of oneself and visiting doctors when necessary that constitutes good health care, but rather the presence ofhealth insurance, which – at least in theory – promises to pay for some of the medical attention one receives from doctors. These individuals see statistics stating that millions do not have health insurance, and they mistakenly assume that these individuals do not have adequate health care. But it is entirely possible for a person to have healthy habits and – especially if this person is young – to not require extensive or expensive medical attention. It is also possible for a person to be sufficiently wealthy to afford to pay for the doctors he wishes to visit. Moreover, it is possible for a person to rely on the charity of doctors in providing any medically necessary attention – as was the case for centuries before health insurance came about, when most doctors would treat all patients but would charge them differential rates based on their ability to pay. In effect, with these traditional doctors, the rich voluntarily subsidized the poor on a largely free market, in a manner beyond the wildest dreams of the advocates of socialized medicine today.

Of course, the presence of health insurance cannot avert the need to seek the attentions of doctors. Indeed, a well-known concept in insurance, moral hazard, suggests that in some cases, an insured individual may actually be more likely to fall victim to a peril than an uninsured individual, because the insured individual is shielded from some of the financial consequences of the loss. Insurance can make life easier for some people in some cases, and it can also be a good safeguard for catastrophes, but it is neither necessary nor sufficient for proper health care. Indeed, the manner in which health insurance has developed in the United States is one of the contributing factors to the astronomically increasing prices of specialized medical care. Health insurance in the U. S. is not provided on a largely free market like most forms of property insurance. Instead, it is mostly tied to one’s employment by virtue of the market-distorting tax breaks that employers receive for providing health insurance. One does not need to worry about what happens with one’s car insurance if one loses a job, but losing one’s job can severely damage one in the realm of health insurance.

Since employers began to receive favorable treatment from the federal government for providing health insurance in the 1940s, the health insurance snowball has continued to embroil more people in a crisis of increasing proportions. The people who got the subsidized insurance had an incentive to spend more money than they usually would on doctors – often an outcome of hypochondria rather than of a reasonable concern for health. As demand for medical services rose, so did the cost, and so the people who did not have insurance – especially the elderly and unemployed – found it more difficult to afford even basic services. The federal government’s solution? Medicare and Medicaid, which put the elderly and unemployed in the same position to spend more freely that the previously insured had. This, of course, further increased the demand for and price of specialized medical services. With the recent vast expansion of Medicare under the Bush administration, it is no surprise that prices have further skyrocketed.

Now, because so many people have subsidized health insurance, it has become extremely difficult to afford medical care for catastrophic situations without it. This is not a necessary component of health care in a quasi-advanced society; it is a creation of bad policies that incrementally expanded the scope of the present crisis. An even worse policy is on the horizon; it is not socialized healthcare yet, but in some respects it may even be worse. The Obama administration and its supporters in Congress threaten to require everyone to purchase health insurance and to eliminate the aspect that makes it insurance – selection and pricing on the basis of the risks posed by the insureds. Forcing people to purchase health insurance and prohibiting discrimination on the basis of pre-existing conditions are the same as making the healthy subsidize the ill and charging everyone roughly the same general rates. With this kind of incentive system in place, it is only logical to assume that many people who otherwise would have lived spectacularly would begin to demand medically unnecessary attention simply to be net beneficiaries of the system where everyone ostensibly subsidizes everyone else. This cannot continue indefinitely, as resources are finite, and the inevitable recourse by the government will be the rationing of medical services – a political selection of who lives and who dies. This scenario – so common in many countries in the West today, including Britain and Canada – is the opposite of genuine health care. Indeed, denying care to an individual who could afford it and placing that individual on a waiting list on which he dies is nothing short of murder.

Only a massive shift in public opinion and government policy can extricate us from the entanglement of health care with health insurance and return us to the direct relationship between patients and doctors, as well as the optimal amount of motivation for each individual to care for his own health. Until then, stay healthy and try to make sure that you do not need the care that gets rationed – if you can.

Read other articles in The Rational Argumentator’s Issue CCXI.

Advancing Pharmaceutical and Medical Technology Does Not Depend on Patents – Article by Nathan Nicolaisen

Advancing Pharmaceutical and Medical Technology Does Not Depend on Patents – Article by Nathan Nicolaisen

The New Renaissance Hat
Nathan Nicolaisen
January 1, 2014
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Pharmaceutical drug manufacturers are often regarded as the successes of the intellectual property regime. It is assumed that their willingness to take risks by investing heavily in R&D is justified by the awarding of patents over their lifesaving discoveries. Proponents of intellectual property claim that without patents many lifesaving drugs would not exist. They assert that generic drug manufacturers would diminish profit margins and dissipate the original manufacturer’s market share and innovation would come to a virtual standstill. Further, manufacturers once willing to create new drugs will no longer do so without sufficient returns on investment. Research into the matter suggests, however, that patent protection may not be required for medical advances.

Unpatented Medical Technologies

The notion that unpatented medical technologies are not feasible is historically false. Surveys of important medical breakthroughs provide insight into whether patents are absolutely necessary and conducive to innovation in medicine. In 2006, the British Medical Journal challenged its readership to submit a list of the most noteworthy medical and pharmaceutical inventions throughout history. The original list contained over 70 different discoveries before being narrowed down to 15. The list goes as follows in no particular order: penicillin, x-rays, tissue culture, ether anesthetic, chlorpromazine, public sanitation, germ theory, evidence-based medicine, vaccines, the pill, computers, oral rehydration therapy, DNA structure, monoclonal antibody technology, and smoking health risk. Of these discoveries, only two of them have remotely anything to do with patents, chlorpromazine and the pill.[1] In another survey conducted by the United States Centers for Disease Control the results are strikingly similar. Of the ten most important medical discoveries of the twentieth century, none of them had anything to do with patents.[2]

Natural Market Advantages and Trade Secrecy

Contrary to popular belief, large pharmaceutical companies may maintain significant market share advantages after the introduction of generics through the help of natural barriers to entry. Large pharmaceutical companies have a first-mover advantage and an established internal and external structure that competitors, large and small, do not. Regardless of how fast competitors can manufacture a generic drug (never mind the fact that they must hire new labor, train new employees, buy raw materials, establish suppliers, organize logistics, create a marketing and advertising plan, and set up competitive shelf space), it can be extremely difficult to make a dent in the market dominance of an already-established drug. Competition data from India suggests that it takes approximately four years for generic drugs to enter the market.[3] In addition, the Congressional Budget Office calculated that an original drug manufacturer could still maintain a market share of more than 20 percent after the introduction of generics. Expanding the scope of research beyond pharmaceutical drugs, a survey of R&D labs and company managers revealed that between 23 percent and 35 percent believe a patent is an effective way of getting a return on investment. At the same time 51 percent believe trade secrets to be an effective way of ensuring returns.[4]

The Truth about R&D Costs and Generic Drugs

Pharmaceutical drug manufacturers enjoy large margins in spite of large R&D. The claim that R&D for pharmaceuticals is high is not unfounded. The cost to bring a new drug to market varies between estimates of $402 million on the lower end and $800 million on the upper end.[5],[6] Regardless of high R&D costs, drug companies still command high margins. For the past two decades pharmaceutical drugs have been one of the most profitable industries in the United States, never dropping below third place.[7] The profitability of pharmaceuticals can be explained away under the assumption that people are living longer and consuming more pharmaceutical drugs. It may also be suggested that the human population is less healthy than in the past and the demand for pharmaceutical drugs is inelastic. But, analysis of the profit margin on pharmaceutical drugs and lack of any serious innovation suggests that this is not always the case.

The pharmaceutical industry globally maintains about a 25 percent operating margin as opposed to 15 percent for consumer goods. In the United States, this number achieved its zenith at almost 35 percent. The high margin on the drugs may not be due directly to high R&D costs, either. As of 2006, the ratio of R&D to sales revenue was about 0.19.[8] Further, the top 30 pharmaceutical firms in the world incur costs for promotions and advertising that are nearly double the costs of R&D. This is not to imply that there is a perfect amount of R&D spending each firm must do, rather it is to show that the inability to recoup R&D costs is greatly exaggerated.

Generic drugs are not just manufactured by small companies that seek to ride on the coattails of the giants. It is believed that generics add nothing innovative to the realm of lifesaving drugs, they merely manufacture competing drugs that are already in the public domain; the real innovation comes from the companies willing to invest in research and development. The National Institute of Health Care Management conducted a survey of drugs that received approval from the FDA from 1989 to 2000 with revealing results. Just over half the drugs in the survey, 54 percent, were using active ingredients that were already in use in the market. Of the drugs that were approved by the FDA, 23 percent were given a priority rating on the basis that they were a sufficient clinical improvement compared to existing alternatives. As a corollary, 77 percent of the approved drugs did not exhibit any kind of significant clinical improvement.[9] In other words, these drugs are functionally generic drugs, offering no kind of advantage over existing treatments. Large drug companies are ironically engaging in the kind of behavior they abhor by developing functionally generic drugs while wasting valuable R&D resources.

Conclusion

In a truly free market, whoever has the resources to manufacture an invention is permitted to do so, and the firms that enter the market first with a new drug enjoy a significant advantage. Moreover, the fact remains that the best way to protect an idea is to keep it a secret, which is why the trade-secret method remains effective. The federal government, however, has made it profitable to conclude that the best way to protect an idea is twisting the wrists and shoulders of one’s competitors with government force. Yet in spite of overwhelming federal-government intervention, innovation and ingenuity prevail, even if to a lesser degree.

Nathan Nicolaisen is a senior at Luther College in Decorah, Iowa studying business management and mathematics. 

This article was published on Mises.org and may be freely distributed, subject to a Creative Commons Attribution United States License, which requires that credit be given to the author.

Notes

[1] This means that the inventions were not patented, due to some previous patent, or discovered out of desire to obtain a patent. Michele Boldrin and David K. Levine, Against Intellectual Monopoly, (Cambridge University Press, January 2010), 258, 259.

[2] ibid, 259.

[3] ibid, 266

[4] ibid, 186

[5] $402 million is in 2000 dollars. James Bessen and Michael J. Meurer, Of Patents and Property, Boston University Shool of Law, 2008), http://object.cato.org/sites/cato.org/files/serials/files/regulation/2008/11/v31n4-4.pdf

[6] $800 million is in 2000 dollars. Michele Boldrin and David K. Levine, Against Intellectual Monopoly, (Cambridge University Press, January 2010), 241.

[7] ibid, 256

[8] ibid, 255

[9] ibid, 261

23andMe and the FDA’s Travesty of Justice – Video by G. Stolyarov II

23andMe and the FDA’s Travesty of Justice – Video by G. Stolyarov II

Mr. Stolyarov explains that the US Food and Drug Administration has hit a new low in warning the genetic testing service 23andMe to halt sales of its $99 testing kits. The kits are not a drug or medical treatment; they merely provide information and violate no one’s rights. The irrationality of some people is used as an excuse to deny everyone else potentially life-saving information while establishing artificial barriers that would prevent declines in the cost of medical care.

References
– “FDA warns Google-backed 23andMe to halt sales of genetic tests” – Toni Clarke – Reuters – November 25, 2013
23andMe Website
Petition to “overrule the FDA’s decision to bar 23andMe from selling their potentially life-saving diagnostic kits”

SENS or Cryonics?: My Answer to a Hypothetical Choice – Video by G. Stolyarov II

SENS or Cryonics?: My Answer to a Hypothetical Choice – Video by G. Stolyarov II

If Mr. Stolyarov had $1 billion to donate to life extension, would he donate it to SENS (Strategies for Engineered Negligible Senescence) or cryonics? Find out his answer.

References:
– “How Can I Live Forever?: What Does and Does Not Preserve the Self” – Essay by G. Stolyarov II
– “How Can I Live Forever?: What Does and Does Not Preserve the Self” – Video by G. Stolyarov II
SENS Research Foundation Website
– “Kim Suozzi Cryogenically Preserved After Battle With Brain Cancer” – Huffington Post – January 22, 2013

The Last Generation to Die – Article by Reason

The Last Generation to Die – Article by Reason

The New Renaissance Hat
Reason
September 27, 2013
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The last generation whose members will be forced into death by aging is alive today. It won’t be the youngest of us, born in the past few years – they, most likely, have thousands of years ahead of them. It won’t be the oldest of us either, as even under the plausible best of circumstances we are twenty to thirty years away from a widespread deployment of rejuvenation therapies based on the SENS research program. As to the rest of us, just who is left holding the short straw at the end of the day depends on the speed of progress in medical science: advocacy, fundraising, and the effectiveness of research and development initiatives. Persuasion and money are far more important at this early stage than worrying about how well the researchers are doing their jobs, however.

We live in a world in which the public is only just starting to come around to the idea that aging can be treated, and demonstrations of rejuvenation in the laboratory could be achieved in a crash program lasting ten to twenty years, at a comparatively small cost. But still, most people don’t care about living longer, and most people try not to think about aging, or the future of degeneration and sickness that awaits. They think it is inevitable, but that is no longer true. If you are in early middle age today in the first world, then you have a good shot at living for centuries if the world suddenly wakes up tomorrow and massive funding pours into rejuvenation research. You will age and die on a timescale little different from that of your parents if that awakening persistently fails to happen.

So, roll the dice, or help out and try to swing the odds in your favor. Your choice.

Crowdfunding on Kickstarter and related sites is still the new new thing, the shine not yet worn off. One of the truths that this activity reinforces is that it is far, far easier to raise funding for the next throwaway technological widget than for medical research projects aimed at the betterment of all humanity. Research crowdfunding is a tiny, distant moon orbiting the great mass of comics, games, and devices on Kickstarter, Indiegogo, and others. Hell, it’s easier to crowdfund a short film that points out how close human rejuvenation might be to the present day than it is to crowdfund a project to actually conduct a portion of that research. Is this a reflection of rationality? You decide, though it could be argued either way regarding whether a dollar given to raising awareness is more valuable than a dollar given to the researchers at this point in time. Both research and persuasion need to happen.

The Last Generation To Die – A Short Film

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Set in the future when science first begins to stop aging, a daughter tries to save her father from natural death. The story takes place roughly 30 years in the future at the moment when science has first figured out how to stop aging through genetics. It is framed around the gulf between generations that would occur with the first release of this technology. A daughter who works for a company called Aperion Life – the first to bring this new technology to the public – wants to save her aging father. She starts him on the trials but he soon stops coming. The film continues with the conflict rising between them as she wants him to live on with her while he feels a natural ending is more human.The film centers itself around the natural conflict that would exist at this divide. Upon developing this story, I’ve asked many people and I’ve found a pretty even 50/50 divide of opinions strongly on one side or the other- either they want to die naturally and believe there is beauty in finality, or they want to see what the future holds and have more time to explore and learn more in life. I’d like to turn the question to you… Which side are you on? Would you want to live on or die naturally?

I feel this is a film that needs to be made. Asking these questions in the form of art and story will help start the discussion. Our world is changing very fast and the rate of technology is speeding up. What does all of this mean for humanity? Everything we know, from a book to a play to a song, ends… What does it mean when there is no ending? Would we be more complacent? Would life be as meaningful? Is there more of a beauty in the way it has always been with our passing or is there more beauty in our bodies and minds staying fresh and alive for many, many years to come? What about social justice and overpopulation? Would life become boring after living on indefinitely or would you find it exhilarating to have time to learn new languages, instruments, subjects – to read more books, to love more – to live several lifetimes? Would it be worth it if some of your most loved friends or relatives passed on and wouldn’t live on with you? Are you interested in seeing what the future brings in technology and social evolution or are you happy to have contributed and be a part of it for a short time?

Tim Maupin’s Film, ‘The Last Generation to Die’, to Explore Longevity and Life Extension

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Chicago filmmaker Tim Maupin launched a Kickstarter for a short film titled, “The Last Generation to Die.” Maupin thinks now is a great time to start a conversation about life extension. And he’s right. The idea that within decades a genetic fountain of youth may plausibly reverse the aging process, even indefinitely stave off death, seems to be rising up in pop culture. Maupin’s Kickstarter has so far raised over $15,000 – $6,000 more than its initial funding goal. Encouraged by the positive response, they’re dreaming bigger and hope to fund a stretch goal of $25,000 in the last 10 days of the campaign.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.  

This work is reproduced here in accord with a Creative Commons Attribution license.  It was originally published on FightAging.org.

Editor’s Note from G. Stolyarov II: I am proud to have donated $50 to help make the film The Last Generation to Die a success. I encourage all readers to donate during the remaining nine days in which the Kickstarter project is open to accepting funds.

Aubrey de Grey Comments on the “Hallmarks of Aging” Paper – Article by Reason

Aubrey de Grey Comments on the “Hallmarks of Aging” Paper – Article by Reason

The New Renaissance Hat
Reason
September 8, 2013
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The Hallmarks of Aging paper was published earlier this year. It is an outline by a group of noted researchers that divides up degenerative aging into what they believe are its fundamental causes, with extensive references to support their conclusions, and proposes research strategies aimed at building the means to address each of these causes. This is exactly what we want to see more of in the aging research community: deliberate, useful plans that follow the Strategies for Engineered Negligible Senescence (SENS) model of approaching aging.

Read through the Hallmarks of Aging and you’ll see that it is essentially a more mild-mannered and conservative restatement of the SENS approach to aging – written after more than ten years of advocacy and publication and persuasion within the scientific community by SENS supporters. To my eyes, the appearance of such things shows that SENS is winning the battle of ideas within the scientific community, and it is only a matter of time before it and similar repair-based efforts aimed at human rejuvenation dominate the field. Rightly so, too, and it can’t happen soon enough for my liking. SENS and SENS-like research is the only way we’re likely to see meaningful life extension technologies emerge before those of us in middle age now die, so the more of it taking place the better.

Aubrey de Grey, author of the original SENS proposals and now Chief Science Officer of the SENS Research Foundation that funds and guides rejuvenation research programs, is justifiably pleased by the existence of the Hallmarks of Aging. See this editorial in the latest Rejuvenation Research, for example:

A Divide-and-Conquer Assault on Aging: Mainstream at Last

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On June 6th, a review appeared concerning the state of aging research and the promising ways forward for the field. So far, so good. But this was not any old review. Here’s why: (a) it appeared in Cell, one of the most influential journals in biology; (b) it is huge by Cell’s standards – 24 pages, with well over 300 references; (c) all its five authors are exceptionally powerful opinion-formers – senior, hugely accomplished and respected scientists; (d) above all, it presents a dissection of aging into distinct (though inter-connected) processes and recommends a correspondingly multi-pronged (“divide and conquer”) approach to intervention.

It will not escape those familiar with SENS that this last feature is not precisely original, and it may arouse some consternation that no reference is made in the paper to that prior work. But do I care? Well, maybe a little – but really, hardly at all. SENS is not about me, nor even about SENS as currently formulated (though a depressing number of commentators in the field persist in presuming that it is). Rather, it is about challenging a profound, entrenched, and insidious dogma that has consumed biogerontology for the past 20 years, and which this new review finally – finally! – challenges (albeit somewhat diplomatically) with far more authority than I could ever muster.

Aging has been shown, over several decades, to consist of a multiplicity of loosely linked processes, implying that robust postponement of age-related ill-health requires a divide-and-conquer approach consisting of a panel of interventions. Because such an approach is really difficult to implement, gerontologists initially adopted a position of such extreme pessimism that all talk of intervention became unfashionable. The discovery of genetic and pharmacological ways to mimic [calorie restriction], after a brief period of confused disbelief, was so seductive as a way to raise the field’s profile that it was uncritically embraced as the fulcrum of translational gerontology for 20 years, but finally that particular emperor has been decisively shown to have no biomedically relevant clothes.

The publication of so authoritative a commentary adopting the “paleogerontological” position, that aging is indeed chaotic and complex and intervention will indeed require a panel of therapies, but now combined with evidence-based optimism as to the prospects for implementing such a panel, is a key step in the elevation of translational gerontology to a truly mature field.

In essence, as de Grey points out, work on aging has been following the wrong, slow, expensive, low-yield path for a couple of decades: the path of deciphering the mechanisms of calorie restriction and altering genes and metabolism to slightly slow down aging. This path cannot result in large gains in life expectancy and long-term health, and it cannot result in therapies that will greatly help people who are already old. What use is slowing down the accumulation of the damage of aging if you are already just a little more damage removed from death, and frail and suffering because of it, and the treatment will meaningfully alter none of that? If we want to add decades or more to our healthy life spans before we die, then rejuvenation and repair of damage are what is needed: ways to reverse frailty, remove suffering, and restore youthful function.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.  

This work is reproduced here in accord with a Creative Commons Attribution license.  It was originally published on FightAging.org.

Mitochondrially Targeted Antioxidant SS-31 Reverses Some Measures of Aging in Muscle – Article by Reason

Mitochondrially Targeted Antioxidant SS-31 Reverses Some Measures of Aging in Muscle – Article by Reason

The New Renaissance Hat
Reason
May 26, 2013
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Originally published on the Fight Aging! website.

Antioxidants of the sort you can buy at the store and consume are pretty much useless: the evidence shows us that they do nothing for health, and may even work to block some beneficial mechanisms. Targeting antioxidant compounds to the mitochondria in our cells is a whole different story, however. Mitochondria are swarming bacteria-like entities that produce the chemical energy stores used to power cellular processes. This involves chemical reactions that necessarily generate reactive oxygen species (ROS) as a byproduct, and these tend to react with and damage protein machinery in the cell. The machinery that gets damaged the most is that inside the mitochondria, of course, right at ground zero for ROS production. There are some natural antioxidants present in mitochondria, but adding more appears to make a substantial difference to the proportion of ROS that are soaked up versus let loose to cause harm.

If mitochondria were only trivially relevant to health and longevity, this wouldn’t be a terribly interesting topic, and I wouldn’t be talking about it. The evidence strongly favors mitochondrial damage as an important contribution to degenerative aging, however. Most damage in cells is repaired pretty quickly, and mitochondria are regularly destroyed and replaced by a process of division – again, like bacteria. Some rare forms of mitochondrial damage persist, however, eluding quality-control mechanisms and spreading through the mitochondrial population in a cell. This causes cells to fall into a malfunctioning state in which they export massive quantities of ROS out into surrounding tissue and the body at large. As you age, ever more of your cells suffer this fate.

In recent years a number of research groups have been working on ways to deliver antioxidants to the mitochondria, some of which are more relevant to future therapies than others. For example gene therapies to boost levels of natural mitochondrial antioxidants like catalase are unlikely to arrive in the clinic any time soon, but they serve to demonstrate significance by extending healthy life in mice. A Russian research group has been working with plastinquinone compounds that can be ingested and then localize to the mitochondria, and have shown numerous benefits to result in animal studies of the SkQ series of drug candidates.

US-based researchers have been working on a different set of mitochondrially targeted antioxidant compounds, with a focus on burn treatment. However, they recently published a paper claiming reversal of some age-related changes in muscle tissue in mice using their drug candidate SS-31. Note that this is injected, unlike SkQ compounds:

Mitochondrial targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice

Quote:

Mitochondrial dysfunction plays a key pathogenic role in aging skeletal muscle resulting in significant healthcare costs in the developed world. However, there is no pharmacologic treatment to rapidly reverse mitochondrial deficits in the elderly. Here we demonstrate that a single treatment with the mitochondrial targeted peptide SS-31 restores in vivo mitochondrial energetics to young levels in aged mice after only one hour.

Young (5 month old) and old (27 month old) mice were injected intraperitoneally with either saline or 3 mg/kg of SS-31. Skeletal muscle mitochondrial energetics were measured in vivo one hour after injection using a unique combination of optical and 31 P magnetic resonance spectroscopy. Age-related declines in resting and maximal mitochondrial ATP production, coupling of oxidative phosphorylation (P/O), and cell energy state (PCr/ATP) were rapidly reversed after SS-31 treatment, while SS-31 had no observable effect on young muscle.

These effects of SS-31 on mitochondrial energetics in aged muscle were also associated with a more reduced glutathione redox status and lower mitochondrial [ROS] emission. Skeletal muscle of aged mice was more fatigue resistant in situ one hour after SS-31 treatment and eight days of SS-31 treatment led to increased whole animal endurance capacity. These data demonstrate that SS-31 represents a new strategy for reversing age-related deficits in skeletal muscle with potential for translation into human use.

So what is SS-31? If look at the publication history for these authors you’ll find a burn-treatment-focused open-access paper that goes into a little more detail and a 2008 review paper that covers the pharmacology of the SS compounds:

Quote:

The SS peptides, so called because they were designed by Hazel H. Sezto and Peter W. Schiler, are small cell-permeable peptides of less than ten amino acid residues that specifically target to inner mitochondrial membrane and possess mitoprotective properties. There have been a series of SS peptides synthesized and characterized, but for our study, we decided to use SS-31 peptide (H-D-Arg-Dimethyl Tyr-Lys-Phe-NH2) for its well-documented efficacy.

Studies with isolated mitochondrial preparations and cell cultures show that these SS peptides can scavenge ROS, reduce mitochondrial ROS production, and inhibit mitochondrial permeability transition. They are very potent in preventing apoptosis and necrosis induced by oxidative stress or inhibition of the mitochondrial electron transport chain. These peptides have demonstrated excellent efficacy in animal models of ischemia-reperfusion, neurodegeneration, and renal fibrosis, and they are remarkably free of toxicity.

Given the existence of a range of different types of mitochondrial antioxidant and research groups working on them, it seems that we should expect to see therapies emerge into the clinic over the next decade. As ever, the regulatory regime will ensure that they are only approved for use in treatment of specific named diseases and injuries such as burns, however. It’s still impossible to obtain approval for a therapy to treat aging in otherwise healthy individuals in the US, as the FDA doesn’t recognize degenerative aging as a disease. The greatest use of these compounds will therefore occur via medical tourism and in a growing black market for easily synthesized compounds of this sort.

In fact, any dedicated and sufficiently knowledgeable individual could already set up a home chemistry lab, download the relevant papers, and synthesize SkQ or SS compounds. That we don’t see this happening is, I think, more of a measure of the present immaturity of the global medical tourism market than anything else. It lacks an ecosystem of marketplaces and review organizations that would allow chemists to safely participate in and profit from regulatory arbitrage of the sort that is ubiquitous in recreational chemistry.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.  

This work is reproduced here in accord with a Creative Commons Attribution license.  It was originally published on FightAging.org.

Get Your “Supporter of Indefinite Life Extension” Open Badge

Get Your “Supporter of Indefinite Life Extension” Open Badge

The Rational Argumentator is now offering a free Open Badge to any individual who supports the concept of indefinite human life extension. To claim the badge, click here.

This badge was designed by Wendy Stolyarov, whose art you can see here, here, and here.

If you would like to find out more about Open Badges and the empowering role they can have in producing a new Age of Enlightenment, read this essay.

You would need a free account with Mozilla Backpack to receive the badge. And, of course, you would need to think that indefinite human life extension is desirable. That is all!

You would receive the badge for being a supporter of extending human lifespans beyond any fixed limit. Indefinite human life extension includes the defeat of senescence and other diseases, and the achievement of indefinite youthfulness. While indefinite life extension would not make people indestructible and would not eradicate all causes of death, it would nonetheless lift the “inevitable” death sentence that currently hangs over us all.  Indefinite life extension could be achieved in the future through advances in medical technology, including biotechnology, nanotechnology, and information technology.

Even thinking favorably of indefinite life extension is a courageous, forward-thinking, and highly beneficial attitude to take. Enjoy your reward!

Computer Games, Distributed Computing, and Life Extension – Video by G. Stolyarov II

Computer Games, Distributed Computing, and Life Extension – Video by G. Stolyarov II

Imagine if it were possible to help cure disease and lengthen human lifespans simply by playing one’s computer games of choice. Here, Mr. Stolyarov describes a concept for doing just that, and he welcomes efforts from any of you to help bring it about.

Remember to LIKE, FAVORITE, and SHARE this video in order to spread rational discourse on this issue.

Support these video-creation efforts by donating here and here.

References
– “Computer Games, Distributed Computing, and Life Extension” – Article by G. Stolyarov II – The Rational Argumentator
Article and discussion on Transhumanity.net
Mr. Stolyarov’s Page of Distributed Computing Statistics
Rosetta@home
Folding@home
World Community Grid
Human Proteome Folding
Help Conquer Cancer
FoldIt
– “Public Solves Protein Structure” – Jef Akst – The Scientist – September 18, 2011
– “ALS Cause and Protein-Folding Prediction – Thoughts on Two Impressive Scientific Discoveries ” – Video by G. Stolyarov II – September 20, 2011