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The Rational Argumentator’s Fifteenth Anniversary Manifesto

The Rational Argumentator’s Fifteenth Anniversary Manifesto

The New Renaissance Hat
G. Stolyarov II
August 31, 2017
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As of today The Rational Argumentator has been in publication continuously for fifteen years – half of my lifetime to date. The more time passes, the more the value of continuity is reinforced for me, and so I hope that these fifteen years have only been an auspicious beginning for The Rational Argumentator. TRA shall continually endeavor to improve and expand in new directions, but always by building upon the old and by remaining rooted in a core identity – the championing of the principles of Reason, Rights, and Progress – the ideas that made Western civilization great. These ideals will hopefully be applied to forge a new global, universal human (and transhuman) civilization which we – all reasonable and decent people who wish to join this effort – can assemble by picking up the pieces of the wreckage of our unfortunate, downward-spiraling moment in history.

We live today in what Robert Heinlein prognosticated in his science fiction as the “Crazy Years”, which he described as exhibiting “Considerable technical advance during this period, accompanied by a gradual deterioration of mores, orientation, and social institutions” – gradual deterioration that became quite sudden and cataclysmic in 2016 and 2017. The climate of contemporary societies and political systems, particularly that of the United States, evokes William Butler Yeats’s famous lines:

  Things fall apart; the centre cannot hold;
Mere anarchy is loosed upon the world,
The blood-dimmed tide is loosed, and everywhere
The ceremony of innocence is drowned;
The best lack all conviction, while the worst
Are full of passionate intensity.

The deterioration cannot be attributed to any particular individual or even faction (these are, at most, symptoms), but rather to the fraying general fabric of contemporary Western, particularly American, life. Those who have regularly read the pages of The Rational Argumentator will not be surprised at my view that the deterioration is primarily due to the abandonment of upward aspiration both within mainstream culture and among various subcultures – a rejection of 18th-century Enlightenment meliorism and an embrace of postmodern aimlessness. To reverse this tendency, now, more than ever, it is essential to emphasize the importance of rational inquiry, civil discourse, and the mindset of building a civilization – as opposed to militant subjectivism (where a person considers his or her feelings to be unquestioned dogma – and woe to those who challenge them!), coarse crudity in manners, riotousness, and the mindset of “tearing down the system” in a futile attempt to start from scratch. We cannot and must not start over – for the primitive state of humankind is far worse than our admittedly deeply imperfect morass of institutions and norms. But we can – and we must – repair and build upon the achievements of the past, combining them with new technologies and insights to forge the next great era of our civilization, a project I outline briefly in a two-party video series, “The Great Transhumanist Game”.

Amid the turmoil, I was pleased to see that The Rational Argumentator has gained notice and achieved significant increases in its visitation, receiving 1,087,149 total page views during its fifteenth year, as compared to 823,968 page views the year prior. Cumulative lifetime TRA visitation stands at 10,979,785 page views, and I am confident that the 11-million mark will be exceeded in September 2017. Perhaps more readers are seeking an antidote to the Crazy Years. Reason is that antidote, and these pages provide it in abundance.

During its fifteenth year, TRA published 140 features. While this was a lower rate of publication than the 208 to 314 features published per year in the preceding five years, TRA has at the same time become allied with the United States Transhumanist Party, of which I became Chairman in November 2016. The U.S. Transhumanist Party website has been brimming with new content, contributed by a wide variety of forward-thinking minds, and I am proud that this young but steadily growing organization has published 105 features during my tenure as Chairman thus far. I am also proud of the cadre of volunteer Officers that the U.S. Transhumanist Party has assembled – a team of dedicated advocates for the future, which will hopefully greatly expand with time and become the core of a movement that will transform and redirect society and culture back toward the ideals of reason and amelioration.

Thus, for the upcoming year, I pose an ambitious task for The Rational Argumentator and its readers. Let us make sure that Yeats’s words remain a warning rather than the ever-present reality. The center must hold, and we must ensure that it holds. Each of us can participate in this project. We must become the center upon which human civilization depends for its survival, continuity, and growth. Through both great endeavors and small, routine maintenance tasks; through creation of elevated and noble works, as well as everyday kindnesses to the people in our lives; through the rhetoric that inspires great aspirations and the decorum that conveys respect and uplifts our sentiments into the realm of good will – we must be the agents of cultural transformation – a New Renaissance, a Re-Enlightenment, indeed, a Recivilization to follow the Crazy Years. One of my most inspired moments of the past year has been seeing the finished painting of the City of New Antideath, which I commissioned from artist Ekaterinya Vladinakova. I invite you to gaze upon this colossal cityscape to gain glimpses at an era where all of our major aims – the return of reason as the paradigm for life, the attainment of indefinite longevity, the liberation of humankind from privation and conflict – have been attained. May it inspire you to go forth and take the many necessary incremental steps toward such a world.

This essay may be freely reproduced using the Creative Commons Attribution Share-Alike International 4.0 License, which requires that credit be given to the author, G. Stolyarov II. Find out about Mr. Stolyarov here.

U.S. Transhumanist Party Interview with Bobby Ridge

U.S. Transhumanist Party Interview with Bobby Ridge

The New Renaissance Hat
Gennady Stolyarov II and Bobby Ridge
July 8, 2017
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Gennady Stolyarov II, Chairman of the United States Transhumanist Party, interviews Bobby Ridge, a researcher into transhumanist philosophy and the scientific method and the new Secretary-Treasurer of the United States and Nevada Transhumanist Parties.

Watch this conversation regarding the subjects of Mr. Ridge’s research, the scientific method, and transhumanism more generally.

Bobby Ridge has a Bachelor’s Degree in Biomedical Science from California State University of Sacramento (CSUS) and is striving to achieve his MD in Neurology. He only recently became a Transhumanist. He conducts research for CSUS’s Psychology Department and his own personal research on the epistemology and Scientiometrics of the Scientific Method. He also co-owns Togo’s in Citrus Heights, CA. Mr. Ridge considers transhumanism to describe the future of humanity taking its next steps in evolution, which are both puissant and daunting. With the exponential increase in information technology, Mr. Ridge considers it important for us to become a science-based species to prevent a dystopian-type future from occurring.

Visit the website of the U.S. Transhumanist Party at http://transhumanist-party.org/.

Become a member of the U.S. Transhumanist Party for free by filling out this form.

Critical Thinking Doesn’t Mean What Most People Think – Article by Sanford Ikeda

Critical Thinking Doesn’t Mean What Most People Think – Article by Sanford Ikeda

The New Renaissance Hat
Sanford Ikeda
July 4, 2017
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Academics like to say that we teach “critical thinking” without thinking too critically about what it means to think critically.

Being Critical, Not Thinking Critically 

Too often in practice, people equate critical thinking with merely being skeptical of whatever they hear. Or they will interpret it to mean that, when confronted with someone who says something that they disagree with, they either:

a) stop listening (and perhaps then start shouting),

b) find a way to squeeze the statement into our pre-existing belief system (if we can’t we stop thinking about it), or

c) attempt to “educate” the speaker about why their statement or belief system is flawed. When this inevitably fails we stop speaking to them, at least about the subject in question.

Ultimately, each of these responses leaves us exactly where we started, and indeed stunts our intellectual growth. I confess that I do a, b, and c far too often (except I don’t really shout that much).

To me, critical thinking means, at a minimum, questioning a belief system (especially my own) by locating the premises underlying a statement or conclusion, whether we agree with it or not, and asking:

1) whether or not the thinker’s conclusions follow from those premises,

2) whether or not those premises are “reasonable,” or

3) whether or not what I consider reasonable is “reasonable” and so on.

This exercise ranges from hard to excruciatingly uncomfortable – at least when it comes to examining my own beliefs. (I’ve found that if I dislike a particular conclusion it’s hard to get myself to rigorously follow this procedure; but if I like a conclusion it’s often even harder.)

Teaching Critical Thinking

Fortunately, people have written articles and books that offer good criticisms of most of my current beliefs. Of course, it’s then up to me to read them, which I don’t do often enough. And so, unfortunately, I don’t think critically as much as I should…except when I teach economics.

It’s very important, for example, for a student to critically question her teacher, but that’s radically different from arguing merely to win. Critical thinking is argument for the sake of better understanding, and if you do it right, there are no losers, only winners.

Once in a while, a student speaks up in class and catches me in a contradiction – perhaps I’ve confused absolute advantage with comparative advantage – and that’s an excellent application of genuine critical thinking. As a result we’re both now thinking more clearly. But when a student or colleague begins a statement with something like “Well, you’re entitled to your opinion, but I believe…” that person may be trying to be critical (of me) but not in (or of) their thinking.

It may not be the best discipline for this, but I believe economics does a pretty good job of teaching critical thinking in the sense of #1 (logical thinking). Good teachers of economics will also strategically address #2 (evaluating assumptions), especially if they know something about the history of economic ideas.

Economics teachers with a philosophical bent will sometimes address #3 but only rarely (otherwise they’d be trading off too much economic content for epistemology). In any case, I don’t think it’s possible to “get to the bottom” of what is “reasonable reasonableness” and so on because what ultimately is reasonable may, for logical or practical reasons, always lie beyond our grasp.

I could be wrong about that or indeed any of this. But I do know that critical thinking is a pain in the neck. And that I hope is a step in the right direction.

Sanford (Sandy) Ikeda is a professor of economics at Purchase College, SUNY, and the author of The Dynamics of the Mixed Economy: Toward a Theory of Interventionism. He is a member of the FEE Faculty Network.

This article was published by The Foundation for Economic Education and may be freely distributed, subject to a Creative Commons Attribution 4.0 International License, which requires that credit be given to the author. Read the original article.

Ayn Rand’s Heroic Life – Article by Jeffrey A. Tucker

Ayn Rand’s Heroic Life – Article by Jeffrey A. Tucker

The New Renaissance HatJeffrey A. Tucker
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I first encountered Ayn Rand through her nonfiction. This was when I was a junior in high school, and I’m pretty sure it was my first big encounter with big ideas. It changed me. Like millions of others who read her, I developed a consciousness that what I thought – the ideas I held in my mind – mattered for what kind of life I would live. And it mattered for everyone else too; the kind of world we live in is an extension of what we believe about what life can mean.

People today argue over her legacy and influence – taking apart the finer points of her ethics, metaphysics, epistemology. This is all fine but it can be a distraction from her larger message about the moral integrity and creative capacity of the individual human mind. In so many ways, it was this vision that gave the postwar freedom movement what it needed most: a driving moral passion to win. This, more than any technical achievements in economic theory or didactic rightness over public-policy solutions, is what gave the movement the will to overcome the odds.

Often I hear people offer a caveat about Rand. Her works are good. Her life, not so good. Probably this impression comes from public curiosity about various personal foibles and issues that became the subject of gossip, as well as the extreme factionalism that afflicted the movement she inspired.

This is far too narrow a view. In fact, she lived a remarkably heroic life. Had she acquiesced to the life fate seemed to have chosen for her, she would have died young, poor, and forgotten. Instead, she had the determination to live free. She left Russia, immigrated to the United States, made her way to Hollywood, and worked and worked until she built a real career. This one woman – with no advantages and plenty of disadvantages – on her own became one of the most influential minds of this twentieth century.

So, yes, her life deserves to be known and celebrated. Few of us today face anything like the barriers she faced. She overcame them and achieved greatness. Let her inspire you too.

Kudos to the Atlas Society for this video:

The Only Good Politics Are Boring Politics – Article by J. Andrew Zalucky

The Only Good Politics Are Boring Politics – Article by J. Andrew Zalucky

The New Renaissance HatJ. Andrew Zalucky
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If 2016 has taught us anything, it’s that boring politics are the best politics. A staid political culture is a sign of a healthy society, as it allows humanity’s passions to flourish outside of the coercive and violent realm of political power. Those who say we should look to our leaders to inspire us, or that politics should be the engine of “progress,” are unwittingly calling for the destruction of civil society.

The Joy of Boredom

Since the end of the Cold War, for example, the political climate of northern and western Europe has been characterized by the yawn-inducing push and pull between liberal democracy and social democracy (with a side of Christian conservatism here, a dash of old-school leftism there). Both sides share a broad commitment to stability and market economics, but may have marginal scuffles over the size of the welfare state and the extent of government regulation. Political factions are more likely to fight about numbers and the wording of a law than engage in grand, sweeping oratory over revolutionary manifestos. Prior to the migrant crisis, this order was rarely disturbed – even by the troubles within the Eurozone.

While this doesn’t get the blood rushing in the way that romantic mass-movements did in the past, it’s also a good backstop against the bloodletting that those movements produced. People here exercise their passions through sports, music, and entertainment. Nods to historical glories and national myths are safely cordoned off in powerless, symbolic royal families, rather than ecstatic throngs yearning for a “dear leader.” While political life in this “end of history” scenario doesn’t make for epic storytelling, it helps to produce the world’s happiest societies.

For the most part, this reality exists in the “Anglosphere” as well, as Canada, New Zealand, and Australia all enjoy a situation similar to that of the Eurasian peninsula. And yes, even Great Britain and the United States broadly share this state of affairs. We can tell when this order has been disrupted in the wrong way. I remember hearing pundits and journalists decry the 2012 election as “bitter” and “divisive.” Well, here we are in 2016. We’ve seen America’s own centre-right party swallowed whole by a candidate’s cynical campaign of nationalism and a narcissistic cult of personality. Meanwhile, factions of our centre-left party have shown an affinity for unilateral executive power and ideologies that should have crumbled with the Berlin Wall. The most awful political campaign of our lifetimes makes 2012 look like the pinnacle of sane, democratic discourse.

Inspired into Misery

By contrast, look at the countries with the most passionate, ideologically-charged and “inspirational” political cultures. Chavismo-style socialism has led Venezuela into a grave economic crisis and turned one of the most resource-rich countries on Earth into a humanitarian disaster. There’s no need to exaggerate the effect of the Kim-dynasty cult in North Korea, with its toxic mix of Marxist-Leninism and the legacy of the Japanese Emperors: famine, malnutrition, and the stultification of the mind that comes with any closed society. Theocratic societies may do a great job at fulfilling humanity’s need for spirituality and transcendence, but are abysmal in terms of civil liberties, women’s rights, and any sense of pluralism.

To the extent that life has improved in places like China, it is due to the regime moving away from its motivating ideology, not a misplaced loyalty to it. Ideas like property rights, limited government, and sovereignty of the individual may seem mundane to those in the West who’ve been conditioned to take them for granted, but once people abandon these ideas for the sweeping romantic ecstasy of leader-worship, national supremacy, or prostration before a man-made god, they become more willing to see their fellow citizens as numbers or a means to a political end. It’s this ecstatic frenzy that makes people comfortable with deportations, torture, show trials, and mass murder.

Libertarians and classical liberals would do well to read the advice Alan Wolfe gives in The Future of Liberalism. Though Wolfe is a liberal more in the New Deal/Great Society sense of the word, he still provides valuable insight for maintaining a stable political culture:

On matters of the heart, romanticism touches on the deepest emotions, expands the human imagination, and produces world-class music and art. But however much romanticism can serve as a corrective to liberalism, it ought never to be a substitute for it. “Politics,” Max Weber wrote, “is a strong and slow boring of hard boards.” That does not sound very dramatic, but its undramatic quality is what makes politics a blessing in disguise. When liberal politics works – either at home or abroad – fewer people are killed in the name of a cause, and fewer lives are disrupted to serve as characters in someone else’s drama.

He’s right to note that romanticism can be a corrective, as ideas are still important, but he wisely splits the difference in showing that proceduralism must still prevail over lofty notions of “getting things done.” He goes on to say that liberals

… ought to be aware of the powerful attractions of militarism, nationalism, and ideology, and they ought to be strong enough to resist them. Let the passions reign in the museums and concert halls. In the halls of government, reason, however cold, is better than emotions, however heartfelt.

In much the same vein, Robert O. Paxton wrote in The Anatomy of Fascism that

Fascism rested not on the truth of its doctrine but upon the leader’s mystical union with the historic destiny of his people, a notion related to romanticist ideas of national historic flowering and of individual artistic or spiritual genius, though fascism otherwise denied romanticism’s exaltation of unfettered person creativity. The fascist leader wanted to bring his people into a higher realm of politics that they would experience sensually: the warmth of belonging to a race now fully aware of its identity, historic destiny, and power; the excitement of participating in a vast collective enterprise; the gratification of submerging oneself in a wave of shared feelings, and of sacrificing one’s petty concerns for the group’s good; and the thrill of domination.

We’re right to be worried at the impulses at work in this election cycle. As Adam Gopnik wrote in the New Yorker earlier this year, “The national psyche never gets over learning that its institutions are that fragile and their ability to resist a dictator that weak.” When examining the two major party candidates, the American electorate is indeed left with a terrible choice. Still, we can survive, resist, and undermine the inevitably bad outcome.

J. Andrew Zalucky

J. Andrew Zalucky is a Connecticut-based writer focused on politics, history and cultural issues. Since 2011, he has run his own website, For the Sake of Argument. In addition, he writes about extreme music and is a regular contributor to Decibel and Metal Injection.

This article was originally published on FEE.org. Read the original article.

UNITY Biotechnology Raises $116M for Senescent Cell Clearance Development – Article by Reason

UNITY Biotechnology Raises $116M for Senescent Cell Clearance Development – Article by Reason

The New Renaissance HatReason
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The whispers of late have had it that UNITY Biotechnology was out raising a large round of venture funding, and their latest press release shows that this was indeed the case. The company, as you might recall, is arguably the more mainstream of the current batch of startups targeting the clearance of senescent cells as a rejuvenation therapy. The others include Oisin Biotechnologies, SIWA Therapeutics, and Everon Biosciences, all with different technical approaches to the challenge. UNITY Biotechnology is characterized by a set of high profile relationships with noted laboratories, venture groups, and big names in the field, and, based on the deals they are doing, appear to be focused on building a fairly standard drug development pipeline: repurposing of apoptosis-inducing drug candidates from the cancer research community to clear senescent cells, something that is being demonstrated with various drug classes by a range of research groups of late. Senescent cells are primed to apoptosis, so a nudge in that direction provided to all cells in the body will have little to no effect on normal cells, but tip a fair proportion of senescent cells into self-destruction. Thus the UNITY Biotechnology principals might be said to be following the standard playbook to build the profile of a hot new drug company chasing a hot new opportunity, and clearly they are doing it fairly well so far.

UNITY Biotechnology Announces $116 Million Series B Financing

Quote:

UNITY Biotechnology, Inc. (“UNITY”), a privately held biotechnology company creating therapeutics that prevent, halt, or reverse numerous diseases of aging, today announced the closing of a $116 million Series B financing. The UNITY Series B financing ranks among the largest private financings in biotech history and features new investments from longtime life science investors ARCH Venture Partners, Baillie Gifford, Fidelity Management and Research Company, Partner Fund Management, and Venrock. Other investors include Bezos Expeditions (the investment vehicle of Jeff Bezos) and existing investors WuXi PharmaTech and Mayo Clinic Ventures. Proceeds from this financing will be used to expand ongoing research programs in cellular senescence and advance the first preclinical programs into human trials.

The financing announcement follows the publication of research that further demonstrates the central role of senescent cells in disease. The paper, written by UNITY co-founders Judith Campisi and Jan van Deursen and published today, describes the central role of senescent cells in atherosclerotic disease and demonstrates that the selective elimination of senescent cells holds the promise of treating atherosclerosis in humans. In animal models of both early and late disease, the authors show that selective elimination of senescent cells inhibits the growth of atherosclerotic plaque, reduces inflammation, and alters the structural characteristics of plaque such that higher-risk “unstable” lesions take on the structural features of lower-risk “stable” lesions. “This newly published work adds to the growing body of evidence supporting the role of cellular senescence in aging and demonstrates that the selective elimination of senescent cells is a promising therapeutic paradigm to treat diseases of aging and extend healthspan. We believe that we have line of sight to slow, halt, or even reverse numerous diseases of aging, and we look forward to starting clinical trials with our first drug candidates in the near future.”

So this, I think, bodes very well for the next few years of rejuvenation research. It indicates that at least some of the biotechnology venture community understands the likely true size of the market for rejuvenation therapies, meaning every human being much over the age of 30. It also demonstrates that there is a lot of for-profit money out there for people with credible paths to therapies to treat the causes of aging. It remains frustrating, of course, that it is very challenging to raise sufficient non-profit funds to push existing research in progress to the point at which companies can launch. This is a problem throughout the medical research and development community, but it is especially pronrounced when it comes to aging. The SENS view of damage repair, which has long incorporated senescent cell clearance, is an even tinier and harder sell within the aging research portfolio – but one has to hope that funding events like this will go some way to turn that around.

From the perspective of being an investor in Oisin Biotechnologies, I have to say that this large and very visible flag planted out there by the UNITY team is very welcome. The Oisin team should be able to write their own ticket for their next round of fundraising, given that the gene therapy technology they are working on has every appearance of being a superior option in comparison to the use of apoptosis-inducing drugs: more powerful, more configurable, and more adaptable. When you are competing in a new marketplace, there is no such thing as too much validation. The existence of well-regarded, well-funded competitors is just about the best sort of validation possible. Well-funded competitors who put out peer-reviewed studies on a regular basis to show that the high-level approach you and they are both taking works really well is just icing on the cake. Everyone should have it so easy. So let the games commence! Competition always drives faster progress. Whether or not I had skin in this game, it would still be exciting news. The development of rejuvenation therapies is a game in which we all win together, when new treatments come to the clinic, or we all lose together, because that doesn’t happen fast enough. We can and should all of us be cheering on all of the competitors in this race. The quality and availability of the outcome is all that really matters in the long term. Money comes and goes, but life and health is something to be taken much more seriously.

Now with all of that said, one interesting item to ponder in connection to this round of funding for UNITY is the degree to which it reflects the prospects for cancer therapies rather than the prospects for rejuvenation in the eyes of the funding organizations. In other words, am I being overly optimistic in reading this as a greater understanding of the potential for rejuvenation research in the eyes of the venture community? It might be the case that the portions of the venture community involved here understand the market for working cancer drugs pretty well, and consider that worth investing in, with the possibility of human rejuvenation as an added bonus, but not one that is valued appropriately in their minds. Consider that UNITY Biotechnology has partnered with a noted cancer therapeutics company, and that the use of drugs to inducing apoptosis is a fairly well established approach to building cancer treatments. That is in fact why there even exists a range of apoptosis-inducing drugs and drug candidates for those interested in building senescent cell clearance therapies to pick through. Further, the presence of large numbers of senescent cells does in fact drive cancer, and modulating their effects (or removing them) to temper cancer progress is a topic under exploration in the cancer research community. So a wager on a new vision, or a wager on the present market? It is something to think about.

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.
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.
An Example of the Glaring Lack of Ambition in Aging Research – Post by Reason

An Example of the Glaring Lack of Ambition in Aging Research – Post by Reason

The New Renaissance HatReason
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The mainstream of aging research, at least in public, is characterized by a profound lack of ambition when it comes to treating aging as a medical condition. Researchers talk about slightly altering the trajectory of aging as though that is the absolute most that is possible, the summit of the mountain, and are in many cases ambivalent when it comes to advocating for even that minimal goal. It is this state of affairs that drove Aubrey de Grey and others into taking up advocacy and research, given that there are clear paths ahead to rejuvenation, not just a slight slowing of aging, but halting and reversing the causes of aging. Arguably embracing rejuvenation research programs would in addition cost less and take a much shorter span of time to produce results, since these programs are far more comprehensively mapped out than are efforts to produce drugs to alter the complex operations of metabolism so as to slightly slow the pace at which aging progresses. It is most frustrating to live in a world in which this possibility exists, yet is still a minority concern in the research community. This article is an example of the problem, in which an eminent researcher in the field takes a look at a few recently published books on aging research, and along the way reveals much about his own views on aging as an aspect of the human condition that needs little in the way of a solution. It is a terrible thing that people of this ilk are running the institutes and the funding bodies: this is a field crying out for disruption and revolution in the name of faster progress towards an end to aging.

How can we overcome our niggling suspicion that there is something dubious, if not outright wrong, about wanting to live longer, healthier lives? And how might we pursue longer lives without at the same time falling prey to quasiscientific hype announcing imminent breakthroughs? In order to understand why aging is changing, and what this means for our futures, we need to learn more about the aging process itself. As a biologist who specializes in aging, I have spent more than four decades on a quest to do exactly this. Not only have I asked why aging should occur at all (my answer is encapsulated in a concept called disposability theory), but I have also sought to understand the fastest-growing segment of the population – those aged 85 and above. The challenges inherent in understanding and tackling the many dimensions of aging are reflected in a clutch of new books on the topic. Are these books worth reading? Yes and no. They take on questions like: Can we expect increases in human longevity to continue? Can we speed them up? And, on the personal level, what can we do to make our own lives longer and healthier? If nothing else, these books and their varied approaches reveal how little we actually know.

To find out more about factors that can influence our individual health trajectories across ever-lengthening lives, my colleagues and I began, in 2006, the remarkable adventure of the still ongoing Newcastle 85+ Study, an extremely detailed investigation of the complex medical, biological, and social factors that can affect a person’s journey into the outer reaches of longevity. For each individual, we determined whether they had any of 18 age-related conditions (e.g., arthritis, heart disease, and so on). Sadly, not one of our 85-year-olds was free of such illnesses. Indeed, three quarters of them had four or more diseases simultaneously. Yet, when asked to self-rate their health, an astonishing 78 percent – nearly four out of five – responded “good,” “very good,” or “excellent.” This was not what we had expected. The fact that these individuals had so many age-related illnesses fit, of course, with the popular perception of the very old as sadly compromised. But the corollary to this perception – that in advanced old age life becomes a burden, both to the individuals themselves and to others – was completely overturned. Here were hundreds of old people, of all social classes and backgrounds, enjoying life to the fullest, and apparently not oppressed by their many ailments.

As for my stake in the enterprise, I began investigating aging when I was in my early 20s – well before I had any sense of my own body aging. Quite simply, I was curious. What is this mysterious process, and why does it occur? Everything else in biology seems to be about making things work as well as they can, so how is it that aging destroys us? Now that I am growing older myself, my research helps me understand my own body and reinforces the drive to live healthily – to eat lightly and take exercise – though not at the cost of eliminating life’s pleasures. For all that I have learned about aging, my curiosity remains unabated. Indeed, it has grown stronger, partly because as science discovers more about the process, it reveals that there is ever more to learn, ever greater complexity to unravel, and partly because I am now my own subject: through new physical and psychological experiences in myself, I learn more about what older age is really like. I know all too well that the next phase of my life will bring unwelcome changes, and of course it must end badly. But the participants of the Newcastle 85+ Study have shown me that the journey will not be without interest.

Link: https://lareviewofbooks.org/article/want-live-longer-complicated-relationship-longevity/

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.
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.
Criticizing Programmed Theories of Aging – Article by Reason

Criticizing Programmed Theories of Aging – Article by Reason

The New Renaissance HatReason
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Today I’ll point out an open-access critique of programmed aging theories by the originator of the disposable soma theory of aging, one of the modern views of aging as accumulated damage rather than programming. The question of how and why we age is wrapped in a lot of competing theory, but of great practical importance. Our biochemistry is enormously complex and incompletely mapped, and thus the processes of aging, which is to how exactly our biochemistry changes over time, and all of the relationships that drive that change, are also enormously complex and incompletely mapped. Nonetheless, there are shortcuts that can be taken in the face of ignorance: the fundamental differences between young and old tissue are in fact well cataloged, and thus we can attempt to reverse aging by treating these changes as damage and repairing them. If you’ve read through the SENS rejuvenation research proposals, well, that is the list. The research community may not yet be able to explain and model how exactly this damage progresses, interacts, and spreads from moment to moment, but that effort isn’t necessary to build repair therapies capable of rejuvenation. You don’t need to build a full model of the way in which paint cracks and peels in order to scrub down and repaint a wall, and building that model is a lot most costly than just forging ahead with the painting equipment.

The engineering point of view described above, simply getting on with the job when there is a good expectation of success, is somewhat antithetical to the ethos and culture of the sciences, which instead guides researchers to the primary goal of obtaining full understanding of the systems they study. In practice, of course, every practical application of the life sciences is created in a state of partial ignorance, but the majority of research groups are nonetheless oriented towards improving the grand map of the biochemistry of metabolism and aging rather than doing what can be done today to create rejuvenation therapies. Knowledge over action. If we had all the time in the world this would be a fine and golden ideal. Unfortunately we do not, which places somewhat more weight on making material progress towards the effective treatment of aging as a medical condition – ideally by repairing its causes.

But what are the causes of aging? The majority view in the research community is that aging is a process of damage accumulation. The normal operation of metabolism produces forms of molecular damage in cells and tissues, a sort of biological wear and tear – though of course the concept of wear and tear is somewhat more nuanced and complex in a self-repairing system. This damage includes such things as resilient cross-links that alter the structural properties of the extracellular matrix and toxic metabolic waste that clutters and harms long-lived cells. As damage accumulates, our cells respond in ways that are a mix of helpful and harmful, secondary and later changes that grow into a long chain of consequences and a dysfunctional metabolism that is a long way removed from the well-cataloged fundamental differences between old and young tissues. An old body is a complicated mess of interacting downstream problems. In recent years, however, a growing minority have suggested and theorized that aging is not caused by damage, but is rather a programmed phenomenon – that some portion of the what I just described as the chain of consequences, in particular epigenetic changes, are in fact the root cause of aging. In the programmed view of aging, epigenetic change causes dysfunction and damage, not the other way around. That these two entirely opposite views can exist is only possible because there is no good map of the detailed progression of aging – only disconnected snapshots and puzzle pieces. There is a lot of room to arrange the pieces in any way that can’t be immediately refuted on the basis of well-known past studies.

There are two ways to settle the debate of aging as damage versus aging as evolved program. The first is to produce that grand map of metabolism and aging, something that I suspect is at the least decades and major advances in life science automation removed from where we stand now. The other is to build therapies that produce large degrees of rejuvenation, enough of a difference to put it far beyond argument that the approach taken is the right one. That is not so far away, I believe, as the first SENS rejuvenation therapies are presently in the early stages of commercial development. I think that, even with the comparative lack of funding for this line of development, ten to twenty years from now the question will be settled beyond reasonable doubt. Meanwhile, the programmed-aging faction has become large enough and their positions coherent enough that the mainstream is beginning to respond substantially to their positions; I expect that this sort of debate will continue all the way up to and well past the advent of the first meaningful rejuvenation therapies, which at this point look to be some form of senescent cell clearance.

Can aging be programmed? A critical literature review – by Axel Kowald and Thomas B. L. Kirkwood

Quote:

Many people, coming new to the question of why and how aging occurs, are attracted naturally to the idea of a genetic programme. Aging is necessary, it is suggested, either as a means to prevent overcrowding of the species’ environment or to promote evolutionary change by accelerating the turnover of generations. Instead of programmed aging, however, the explanation for why aging occurs is thought to be found among three ideas all based on the principle that within iteroparous species (those that reproduce repeatedly, as opposed to semelparous species, where reproduction occurs in a single bout soon followed by death), the force of natural selection declines throughout the adult lifespan. This decline occurs because at progressively older ages, the fraction of the total expected reproductive output that remains in future, on which selection can act to discriminate between fitter and less-fit genotypes, becomes progressively smaller. Natural selection generally favours the elimination of deleterious genes, but if its force is weakened by age, and because fresh mutations are continuously generated, a mutation-selection balance results. The antagonistic pleiotropy theory suggests that a gene that has a benefit early in life, but is detrimental at later stages of the lifespan, can overall have a net positive effect and will be actively selected. The disposable soma theory is concerned with optimizing the allocation of resources between maintenance on the one hand and other processes such as growth and reproduction on the other hand. An organism that invests a larger fraction of its energy budget in preventing accumulation of damage to its proteins, cells and organs will have a slower rate of aging, but it will also have fewer resources available for growth and reproduction, and vice versa. Mathematical models of this concept show that the optimal investment in maintenance (which maximizes fitness) is always below the fraction that is necessary to prevent aging.

In recent years, there have been a number of publications claiming that the aging process is a genetically programmed trait that has some form of benefit in its own right. If this view were correct, it would be possible experimentally to identify the responsible genes and inhibit or block their action. This idea is, however, diametrically opposed to the mainstream view that aging has no benefit by its own and is therefore not genetically programmed. Because experimental strategies to understand and manipulate the aging process are strongly influenced by which of the two opinions is correct, we have undertaken here a comprehensive analysis of the specific proposals of programmed aging. On the principle that any challenge to the current orthodoxy should be taken seriously, our intention has been to see just how far the various hypotheses could go in building a convincing case for programmed aging.

This debate is not only of theoretical interest but has practical implications for the types of experiments that are performed to examine the mechanistic basis of aging. If there is a genetic programme for aging, there would be genes with the specific function to impair the functioning of the organism, that is to make it old. Under those circumstances, experiments could be designed to identify and inhibit these genes, and hence to modify or even abolish the aging process. However, if aging is nonprogrammed, the situation would be different; the search for genes that actively cause aging would be a waste of effort and it would be too easy to misinterpret the changes in gene expression that occur with aging as primary drivers of the senescent phenotype rather than secondary responses (e.g. responses to molecular and cellular defects). It is evident, of course, that genes influence longevity, but the nature of the relevant genes will be very different according to whether aging is itself programmed or not.

For various programmed theories of aging, we re-implemented computational models, developed new computational models, and analysed mathematical equations. The results fall into three classes. Either the ideas did not work because they are mathematically or conceptually wrong, or programmed death did evolve in the models but only because it granted individuals the ability to move, or programmed death did evolve because it shortened the generation time and thus accelerated the spread of beneficial mutations. The last case is the most interesting, but it is, nevertheless, flawed. It only works if an unrealistically fast-changing environment or an unrealistically high number of beneficial mutations are assumed. Furthermore and most importantly, it only works for an asexual mode of reproduction. If sexual reproduction is introduced into the models, the idea that programmed aging speeds up the spread of advantageous mutations by shortening the generation time does not work at all. The reason is that sexual reproduction enables the generation of offspring that combine the nonaging genotype of one parent with the beneficial mutation(s) found in the other parent. The presence of such ‘cheater’ offspring does not allow the evolution of agents with programmed aging.

In summary, all of the studied proposals for the evolution of programmed aging are flawed. Indeed, an even stronger objection to the idea that aging is driven by a genetic programme is the empirical fact that among the many thousands of individual animals that have been subjected to mutational screens in the search for genes that confer increased lifespan, none has yet been found that abolishes aging altogether. If such aging genes existed as would be implied by programmed aging, they would be susceptible to inactivation by mutation. This strengthens the case to put the emphasis firmly on the logically valid explanations for the evolution of aging based on the declining force of natural selection with chronological age, as recognized more than 60 years ago. The three nonprogrammed theories that are based on this insight (mutation accumulation, antagonistic pleiotropy, and disposable soma) are not mutually exclusive. There is much yet to be understood about the details of why and how the diverse life histories of extant species have evolved, and there are plenty of theoretical and experimental challenges to be met. As we observed earlier, there is a natural attraction to the idea that aging is programmed, because developmental programming underpins so much else in life. Yet aging truly is different from development, even though developmental factors can influence the trajectory of events that play out during the aging process. To interpret the full complexity of the molecular regulation of aging via the nonprogrammed theories of its evolution may be difficult, but to do it using demonstrably flawed concepts of programmed aging will be impossible.

Given that the author here has in the past been among those who dismissed the SENS initiative as an approach to treating aging by repairing damage, it is perhaps a little amusing to see him putting forward points such as this one: “despite the cogent arguments that aging is not programmed, efforts continue to be made to establish the case for programmed aging, with apparent backing from quantitative models. It is important to take such claims seriously, because challenge to the existing orthodoxy is the path by which science often makes progress.” Where was this version of the fellow ten years ago?

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.
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.
The Rational Argumentator’s Fourteenth Anniversary Manifesto: Who Is the Western Man?

The Rational Argumentator’s Fourteenth Anniversary Manifesto: Who Is the Western Man?

The New Renaissance Hat
G. Stolyarov II
August 31, 2016
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Who Is the Western Man?

On the fourteenth anniversary of The Rational Argumentator, it is fitting to consider the tagline that has been featured on TRA since its founding: “A Journal for Western Man”. But who is this Western Man for whom The Rational Argumentator is intended? In 2002, the answer to that question seemed rather apparent for at least a substantial segment of then-prevalent libertarian, conservative, and Objectivist thinkers who, each in their own way, understood the Western Man to stand for the general cultural ideals and noblest aspirations of Western civilization.

Unfortunately, the decade of the 2010s and the past two years especially have seen the rise of a noxious and fundamentally anti-Western, anti-modern, and anti-civilization movement known as the “alt-right”, which has attempted to appropriate the rhetoric of Western culture and even of the Renaissance for itself. The Rational Argumentator will not allow this appropriation to remain unchallenged. TRA stands resolutely in opposition to all forms of bigotry, racism, nativism, misogyny, and any other circumstantially rooted intolerance – all of which are contrary to the ideals of high Western civilization. But at the same time, The Rational Argumentator also cannot cave to the “social justice” campus activism of the far Left, which would have even the very identification of Western culture and civilization banished, lest it offend the ever-more-delicate sensibilities of firebrand youths who resolutely refuse to let knowledge of the external world get in the way of their “feelings” and subjective experiences. TRA will not abandon the Western Man, but will continue to explain what it is that the Western Man represents and why these principles are more important and enduring than any tumultuous, ephemeral, and most likely futile and self-defeating activist movements of our era.

So who is the Western Man? It is a not a particular man from the West. It is not a descriptor limited to a particular subset of individuals based on their birth, skin color, national origin, or even gender. Indeed, my original intent behind the “Western Man” descriptor was specifically to salvage the generic term “man” – meaning an archetypical representative of humankind – from any suggestions that it must necessarily be gender-specific. This subtitle was meant transparently to imply, “Of course, ‘Western Man’ includes women, too!”  Some of the greatest and most courageous Western Men – from Hypatia of Alexandria to Mary Wollstonecraft to Ayn Rand to Ayaan Hirsi Ali – have been women.

A Western Man can have been born anywhere, have any physical features, any age, any gender (or lack of gender identity), any sexual preferences (or lack thereof), any religion (or lack thereof) – as long as he/she/it is a thinking being who accepts the valuable contributions of Western culture and civilization and seeks to build upon them. If self-aware, rational artificial intelligences are developed in the future, or if an intelligent alien species comes into contact with us, these beings could potentially be Western Men as well.

A Western Man will respect and seek to learn from the great philosophy, literature, art, music, natural and social sciences, mathematics, and political theory that flourished in Western societies throughout the past three millennia – although by no means is a Western man required to focus exclusively on ideas that originated in the West. Indeed, Western culture itself has unceasingly interacted with and absorbed the intellectual contributions of Egyptian, Mesopotamian, Arabic, Persian, Indian, Chinese, Korean, and Japanese thinkers and creators – to provide just a few examples. Likewise, a great deal of hope for the future of Western civilization can be found among entrepreneurs in Asia, Africa, and Latin America who have endeavored, with notable success, to spread the technologies of the digital age, construct great buildings, and lift billions of people out of abject poverty and into humane and respectable living standards accompanied by ever-increasing longevity.

A Western Man is someone who embraces the ideal of cosmopolitan universalism – a rejection of circumstantially defined tribalism, of the casting of people as “one of us” or “the other” based on attributes that they did not choose. This cosmopolitan universalism is the product of both a long-evolving philosophical framework and the material abundance that enabled the broadening of what Adam Smith termed our circles of sympathy to encompass ever more people.

The edifice of Western philosophical thought has been built upon by thinkers since the times of Thales, Socrates, and Aristotle – but its greatest intellectual breakthroughs were made during the 18th-century Age of Enlightenment. The Western Men who embraced these ideals were often personally flawed; they were men of their time and constrained by the practical realities and social mores that surrounded them. Some Western Men throughout history have, unfortunately, owned slaves, respected individual liberty only in some instances, or been improperly prejudiced against broad groups of people due to ignorance or gaps in the consistent application of their principles. Nonetheless, the legacy of their work – the notions of universal, inalienable individual rights and the preciousness of each person’s liberty and humanity – has been indispensable for later accomplishments, such as the abolition of slavery, women’s suffrage and liberation, civil and privacy rights, cultural and legal acceptance of homosexuality, and recognition of individual rights for members of religious minorities, atheists, and children. If we are able to see farther and know better than to repeat some of the moral errors of the past, it is because, to paraphrase Sir Isaac Newton, we stand on the shoulders of intellectual giants who paved the way for our embrace of the aforementioned great cultural achievements.

The ideals of peaceful commerce and cultural exchange – indeed, cultural appropriation (in an educated, informed, and deliberate manner) of the best elements of every time, place, and way of life – have resulted in a dramatic reduction in warfare, a general decline in nationalistic and tribal hatreds, and a widespread understanding of the essential humanity of our fellows in all parts of the world. Were it not for the intellectual achievements of Western civilization and the global commercial and industrial networks to which it gave rise, humankind would still be embroiled in a bitter, Hobbesian war of all against all. A Western Man is anyone who gives the essential achievements of modernity their well-deserved recognition and admiration, and who studies and offers justified respect to the forebears and authors of these achievements. A Western Man is also anyone who seeks to build upon these accomplishments and add his, her, or its distinctive bricks to the edifice of human progress.

A Western Man is not a fanatic or a bully, and sees fanatics and bullies as the threats to civilization that they are. A Western Man does not use ideology to stifle peaceful expression or compel others to dutifully “know their place” within some would-be totalitarian static social order. A Western Man knows that some people will disagree with him, her, or it, and they have the right to disagree peacefully. However, they do not have the right to be protected from attempts at persuasion or the presentation of diverse and possibly contrary views.

A Western Man embraces reason as the way to discover more about the external world and about human beings. Reason is not the exclusive province of any subset of people; anyone is capable of it, but it takes training and effort – and great respect for the intellect – to utilize consistently and properly. From reason stem the empirical scientific method, the deductive processes of formal logic and mathematics, and the application of empirical and logical truths to the development of technology which improves the human condition. A Western Man does not vilify technology, but rather sees it as a key driver of human progress and an enabler of moral growth by giving people the time and space which prosperity affords, making possible contemplation of better ways of living and relating to others – a prerogative only available to those liberated from hand-to-mouth subsistence.

The ideal of the Western Man is to maintain the great things which have already been brought into this world, and to create new achievements that further improve human life. There is thus both a conservative and a progressive motive within the Western Man, and they must combine to sustain a rich and vital civilization. A Western Man can go by labels such as “liberal”, “conservative”, “libertarian”, “progressive”, or “apolitical” – as long as they are accompanied by careful thought, study, discernment, work ethic, and an earnest desire to build what is good instead of, out of rage or spite, tearing down whatever exists. Conservation of great achievements and progress in creating new achievements are not antagonists, but rather part of the same essential mode of functioning of the Western Man – transcending petty and often false political antagonisms which needlessly create acrimony among people who should all be working to take civilization to the next level.

The next level of civilization – the unceasing expansion of human potential – is the preoccupation of the Western Man. This – not descending into contrived identitarian antagonisms – is the great project of our era. Building on the philosophical groundwork laid by Enlightenment humanism and its derivatives, a Western Man can explore the next stage of intellectual evolution – that of transhumanism, which promises to liberate humankind from its age-old shackles of death, disease, severe scarcity, Earth-boundedness, and internecine conflict.

Who is the Western Man? If you accept the challenge and the honor of supporting and building upon the great civilization which offers us unparalleled opportunities to create a glorious future for all – then the Western Man can be you.

TRA Statistics and Achievements During Its Fourteenth Year

TRA published 211 regular features during its fourteenth year, a rate of publication comparable to that of the eleventh and thirteenth years, while remaining below the extremely active tenth and twelfth years, as shown in the table below:

TRA Year Regular Features Published Page Views in Year
10th 306 1,302,774
11th 208 1,077,192
12th 314 1,430,226
13th 228 892,082
14th 211 823,968

With slightly less content published during the fourteenth year, and a similar average number of page views per published feature (3,905.06 in the fourteenth year versus 3,912.64 in the thirteenth year), it could be expected that total page views would decline slightly. While TRA did not reach the milestone of 10,000,000 cumulative page views during its fourteenth year, it did come the overwhelming majority of the way toward it. Total lifetime TRA visitation currently stands at 9,892,636 page views. However, I am confident that the 10-million page-view threshold will be exceeded within the next two months.

I have reason to expect that publication activity will again accelerate during TRA’s fifteenth year, although this may not occur immediately. Over the past year, I have been occupied with satisfying some of the last remaining requirements of my actuarial studies, and their successful completion is in sight. In the meantime, I collaborated with ACTEX Publications to produce a major 400-page commercial study guide, Practice Problems in Advanced Topics in General Insurance, for SOA Exam GIADV.

Several large-scale endeavors within the transhumanist and life-extensionist movements were pursued over the past year. TRA’s anniversary (August 31) coincides with the date of formation of the Nevada Transhumanist Party, a non-election-oriented, non-donation-accepting, policy-oriented party that advocates for the widespread adoption of emerging technologies, individual liberty, and the pursuit of indefinite life extension. The Nevada Transhumanist Party has grown to 107 members during its first year and has been a forum for numerous thought-provoking discussions. Nevada Transhumanist Party activities have occurred online via its Facebook page and its hosted video panels, such as the Panel Discussion on Hereditary Religion, a conversation among Transhumanist Libertarians and Socialists, and the panel for International Longevity Day, in collaboration with MILE – the Movement for Indefinite Life Extension – entitled “How Can Life Extension Become as Popular as the War on Cancer?” In-person activities of the Nevada Transhumanist Party included attendance at a university political lecture, a local Libertarian candidate’s campaign event, and RAAD Fest, the largest in-person gathering of life-extension supporters to date, where I personally met and spoke with such luminaries of the life-extension movement as Aubrey de Grey, Bill Andrews, and Zoltan Istvan.

Gradual but fundamental shifts are occurring that will contribute to more frequent and impactful activity on The Rational Argumentator’s pages during its fifteenth year. As the overview of the Western Man in this manifesto indicates, the importance of TRA’s work and ideals remains paramount. TRA will remain a bulwark of thoughtful consistency in an era where it seems entire societies have become unmoored from core principles that are integral to a successful civilization. We will steadfastly champion the virtues of reason and deliberation, discussion and civil debate, individualism and classical liberal tolerance, creation and maintenance. Even when the tumult of current events calls into question the foundations of civilized life, TRA will be here to reaffirm and uphold them.

This essay may be freely reproduced using the Creative Commons Attribution Share-Alike International 4.0 License, which requires that credit be given to the author, G. Stolyarov II. Find out about Mr. Stolyarov here.

An Interview with Kelsey Moody of Ichor Therapeutics, Bringing a SENS Therapy for Macular Degeneration to the Clinic – Article by Reason

An Interview with Kelsey Moody of Ichor Therapeutics, Bringing a SENS Therapy for Macular Degeneration to the Clinic – Article by Reason

The New Renaissance HatReason
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As I mentioned last week, earlier this year Fight Aging! invested a modest amount in the Ichor Therapeutics initiative to develop a treatment for macular degeneration, joining a number of other amateur and professional investors in helping to get this venture started. The approach taken here is based on the results of research carried out at the Methuselah Foundation and SENS Research Foundation over much of the past decade, funded by philanthropists and the support of our community of longevity science enthusiasts. This is how we succeed in building the future: medical science in the laboratory leads to medical development in startup companies, each new stage bringing treatments capable of repairing specific forms of age-related molecular damage that much closer to the clinic.

Ichor Therapeutics is one of a growing number of success stories to emerge from the SENS rejuvenation research community. Young scientists, advocates, and donors involved in earlier projects – years ago now – have gone on to build their own ventures, while retaining an interest in stepping up to do something meaningful to help bring an end to aging. Back in 2010, Kelsey Moody worked on the LysoSENS project to find ways to break down damaging metabolic waste in old tissues; fast-forward six years, and he is the now the CEO of a successful small biotechnology company with a great team, taking that very same technology and putting it to good use. I recently had the chance to ask Kelsey a few questions about the future of SENS rejuvenation research, as well as how the Ichor scientists intend to construct a new class of therapy for macular degeneration, one based on removing one of the root causes of the condition.

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Who are the people behind Ichor Therapeutics? How did you meet and decide that this was the thing to do? Why macular degeneration as a target?

People have always been the focus of Ichor. Since day one we have worked to create a positive environment that cultivates a product-oriented research focus and emphasizes autonomy and personal accountability for work. As a result, ambitious self-starters tend to find their way to Ichor and remain here. However, we recognized early on that just filling a lab with a bunch of blue-eyed bushy tailed young up-and-comers is not sufficient to develop a robust, mature, translational pipeline. We have augmented our team with a number of critical staff members who are seasoned pharma operators, including our Quality Assurance Director and General Counsel.

Age-related macular degeneration (AMD) was chosen as a target because we believe it is the closest SENS therapy to the clinic. While we obviously have an interest in providing cures for the patients suffering from AMD and are attracted to the large market opportunities such a treatment could bring, our broader interest is in validating the entire SENS paradigm. We believe that Aubrey de Grey continues to receive excessive criticism because nothing spun out of SENS has ever made it into a legitimate pre-clinical pipeline, much less to the bedside. However, this does not mean he is wrong. Our goal is to be the first group to bring a SENS inspired therapy into the clinic and in doing so, silence critics and generate new energy and capital for this cause.

I understand there’s a lengthy origin story for the approach you are taking to treat AMD; it’d be great to hear some of it.

Our approach to treating AMD is based on the hypothesis that cellular junk that accumulates over the lifespan significantly contributes to the onset and progression of AMD. Our goal is to periodically reduce the burden of the junk so it never accumulates to levels sufficient to induce pathology. The strategy to accomplish this calls for the identification of enzymes that can break down the junk in a physiological setting, and the engineering of these enzymes such that they can break down the target in the correct organelle of the correct cell without appreciable collateral damage to healthy cells or tissue.

Methuselah Foundation and SENS Research Foundation did excellent work in establishing this program nearly a decade ago. They successfully identified a number of candidate enzymes that could break down the molecular junk, but reported that the targeting systems evaluated failed to deliver these enzymes to the appropriate organelles and cells. My group reevaluated these findings, and discovered that these findings were flawed. The delivery failure could be entirely attributed to a subtle, yet highly significant difference between how the target cells behave outside of the body as compared to inside the body. It turned out that the approach was in fact valid, it was the cell based assay that had been used that was flawed. This discovery was striking enough that SENS Research Foundation provided Ichor with funding and a material and technology transfer agreement to reassess the technology, and over $700,000 in directed program investments and grants have been received in the last year or two.

You recently completed a round of funding for the AMD work; what is the plan for the next year or so?

The new funds will allow us to develop a portfolio of enzyme therapy candidates to treat AMD. We will obtain critical data necessary to secure follow-on investment including in vitro studies (cell culture studies to confirm mechanism of action and cytotoxicity) and pivotal proof-of-concept in vivo studies, such as toxicity, PK/PD (how long the enzyme stays in the body and where), and efficacy. We will also be restructuring the company (reincorporating an IP holding company in Delaware, ensuring all contracts are up to date and audited) and ensuring our IP position is on solid footing (licensing in several related patents from existing collaborators, and filing several provisional patents from our intramural work). Collectively, we believe these efforts will position us to obtain series A for investigational new drug (IND) enabling pre-clinical studies.

You’ve been involved in the rejuvenation research community for quite some time now. What is your take on the bigger picture of SENS and the goal of ending aging?

This is a loaded question. What I can say is that the medical establishment has made great progress in the treatment of infectious disease through the development of antibiotics, vaccines, and hygiene programs. However, similar progress has not been realized for the diseases of old age, despite exorbitant expenditures. I have chosen to work in this space because I think a different approach is necessary, and it is here that I believe my companies and I can be the most impactful. I think SENS provides a good framework within which to ask and answer questions.

What do you see as the best approach to getting nascent SENS technologies like this one out of the laboratory and into the clinic?

We need more people who fully understand, in a highly detailed way, what a real translational path looks like. To take on projects like this, being a good scientist is not enough. We need people who can speak business, science, medicine, and legal, and apply these diverse disciplines to a well articulated, focused product or problem. There is no shortage of people who partially understand some of these, but the details are not somewhat important – they are all that matter for success in this space.

Another area is for investors. Some of the projects that come across my desk for review are truly abysmal, yet I have seen projects that are clearly elaborate hoaxes or outright scams (to anyone who has stepped foot in a laboratory) get funded to the tune of hundreds of thousands of dollars or more. While it is perfectly reasonable for high net worth individuals to gamble on moon shots in the anti-aging space (and I am ever grateful for the investors who have taken such a gamble on us) even aggressive development strategies should have some basis in reality. This is especially true as more and more high tech and internet investors move into the space.

If this works stupendously well, what comes next for Ichor Therapeutics?

I really want to get back into stem-cell research, but I basically need a blank check and a strong knowledge of the regulatory path to clinic before I feel comfortable moving into the space. A successful AMD exit would accomplish both of these goals, and position us to pivot to cell-based therapies.

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