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A Polite List of Requests to the FDA – Article by Dan Elton

A Polite List of Requests to the FDA – Article by Dan Elton

Daniel C. Elton, Ph.D.


A List of Requests to President Joseph R. Biden, Jr.,
HHS, FDA, and Congress: 

Approve the following vaccines for emergency use immediately: 


Give people the right to try the following vaccines: 

Seriously study and consider these actions: 

  • Allow hospitals and pharmacies to start stockpiling unapproved vaccines so they can be rapidly disseminated upon approval. 
  • Allow Moderna to give fractional doses. Data from Moderna’s clinical trials have illustrated that people between ages of 18 and 55 who received two 50-microgram doses showed an identical immune response to the standard of two 100-microgram doses.
  • Allow all age groups to get the vaccine. Research published in the journal Science indicates that as of October 2020, “individuals aged 20-49 are the only age groups sustaining resurgent SARS-CoV-2 transmission with reproduction numbers well above one”. Thus, targeting vaccines at these groups may accelerate the end of the pandemic and save more lives than continuing to restrict the vaccines to the elderly and vulnerable.
  • Consider making “First Doses First” national policy.


The FDA has not moved fast enough given the gravity of the situation we face. Consider the following: 

  • Pfizer sent its paperwork to the FDA on November 22, 2020, but rather than immediately convening its panel of experts, the FDA scheduled a review meeting for December 10. During that three-week wait, 27,000 Americans died of COVID-19. According to Dr. Marty Makary, a professor of public health policy at the Johns Hopkins Bloomberg School of Public Health who has conducted over a hundred clinical studies during his career, the FDA “could have done the approval in 24-48 hours without cutting any corners”.  The slow rollout that followed after the FDA approved the vaccine on December 11 was not due to delays in production – Pfizer had millions of doses produced and sitting in cold storage at the time of the approval. 
  • While Americans were waiting for the Pfizer vaccine that millions of their taxpayer dollars had been invested in, the FDA went dark for 4 days during the Thanksgiving holiday, with almost all of its 17,000 employees taking that time off, including those working on critical COVID-19-related work. 
  • Moderna sent its paperwork to the FDA on November 30, 2020. As with the Pfizer vaccine, the FDA needlessly delayed the approval by scheduling the review meeting for December 17. 
  • The FDA’s equivalents in the EU, Canada, Switzerland, UK, Israel, and Singapore all use rolling reviews, evaluating data as it becomes available for the sake of efficiency. The FDA does not. 
  • The Sputnik V vaccine was approved September 4, 2020, over 150 days ago. In a paper in The Lancet, phase III results indicate it has an effectiveness of 91.6% and excellent safety profile. 
  • China began administering the CanSino Biologica vaccine to its military in June after Phase I and Phase II clinical trials established safety and immune response. (The phase II results were published in The Lancet on July 20th, 2020). China approved the vaccine for their public on December 24, 2020. 


Here’s what public-health experts are saying:
 


“The F.D.A. needs to catch up to the science… They are inadvertently killing people by not following the science.” – Michael Mina, Epidemiologist, Immunologist, Physician, Harvard Medical School.

“We’ve gone from ‘Operation Warp Speed’ to develop a vaccine to ‘Operation Turtle Speed’ to review it… The FDA needs to stop playing games and authorize the Oxford-AstraZeneca vaccine.  It’s safe, cheap ($2-$3 a dose), and is the easiest vaccine to distribute.”Marty Makary, M.D., a professor of health policy at the Johns Hopkins University School of Medicine. 

I do think we’ve been too conservative… companies that potentially make public health diagnostic tests did not feel that there was, for example, a pathway to get those approved at the F.D.A.”Vivek Murphy, President Biden’s nominee for Surgeon General.

“We’ve already bought 300 million doses of the AstraZeneca-Oxford vaccine. We’ve paid for it — over a billion dollars — so let’s use it… I know we have some of that vaccine stockpiled.”Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine and the lead developer of a COVID-19 vaccine being produced in India.


More quotes from notable public figures: 

“For years the FDA was focused on, don’t repeat thalidomide. Drugs must be safe. AIDS forced a hard reckoning. The people who are dying while you wait matter. But this is a third, even harder conceptual change. Stopping the spread of the disease matters. And the FDA does not have the years it took to make the AIDS change of mindset.”John Cochrane, Senior Fellow at the Hoover Institution. 

The new strains spread quickly. The speed of our countermeasures will decide our fate. What feels like reasonable delays in our normal experience of time — a few weeks here for Congress to debate a bill, a few weeks there for the F.D.A. to hold meetings — could lead to the kind of explosive infections that overwhelm our hospitals and fill our morgues.”Ezra Klein, co-founder of Vox.

“The US failure to authorize the AstraZeneca vaccine in the midst of a pandemic when thousands are dying daily and a factory in Baltimore is warmed up and ready to run is a tragedy and dereliction of duty of epic proportions. The AZ vaccine should be given an EUA immediately and made available in pharmacies for anyone who wants it while continuing to prioritize Moderna and Pfizer for the elderly and essential workers.”Alex Tabarrok, Bartley J. Madden Chair in Economics, George Mason University. 

“It’s amazing that not only is this vaccine (AstraZeneca) not approved, there’s no political pressure to approve it.”Matthew Yglesias, author of One Billion Americans: The Case for Thinking Bigger.

“The UK has authorized #AstraZeneca vaccine for #CV19 but #FDA won’t “because of questions about its efficacy among older people.”
Then authorize its use for younger people!
Dear FDA: Get out of the way!
Over 7,000 Americans died of CV19 in the past two days!
You are murdering us!”
– @Robert Zubrin on Twitter, author of The Case for Mars and The Case for Space.

Further reading: 

Dan Elton, Ph. D., is Director of Scholarship for the U.S. Transhumanist Party.  You can find him on Twitter at @moreisdifferent, where he accepts direct messages. 

How We Can Judge the Safety and Efficacy of New Vaccines Prior to Phase III Data and Why We Must – Article by Dan Elton

How We Can Judge the Safety and Efficacy of New Vaccines Prior to Phase III Data and Why We Must – Article by Dan Elton

Daniel C. Elton, Ph.D.


A common refrain we hear from public intellectuals about vaccines prior to Phase III data is “we don’t know anything about the safety or efficacy of vaccine X”. This attitude is both false and misleading to the public, instilling uncertainty and fear about vaccines. To see why it is false, consider if a normal vaccine safety study was done, but by coincidence all of the vaccines were given in hospital rooms that were painted blue. Could we conclude on the basis of such a study whether the vaccine would be safe if administered in rooms painted red? Yes, we can, and we should. We can utilize two forms of reasoning to conclude that the vaccine is safe if given in red rooms, even though we have no data on the matter.

The first form of reasoning roughly approximates the way an ideal Bayesian statistical reasoner would function to compute what is called a “prior probability distribution”. Under this form of reasoning, we consider the millions of doses of similar vaccines (called the “reference class”) that have been administered. For instance, we might consider the vaccines developed for very similar coronaviruses like SARS and MERS.  We note that if the color of paint did affect the safety of those vaccines, this would have likely been detected over the course of prior studies and over the course of millions of doses given previously. Of course, there is a chance the correlation might have been missed. To figure out how big that is, we can go a level deeper and consider a reference class of “things people might notice or fail to notice in medical studies”. We can conclude that for prior vaccines, if such correlations existed they would generally be picked up. On the basis of this and the fact that no such correlation was ever discovered in the reference class of prior vaccines we can conclude that the probability of vaccines like the COVID-19 vaccine being dependent on the color of paint is very small. 

The second type of reasoning, which happens to be much more straightforward in this situation, is what the physicist David Deutsch calls “reasoning from our best explanation of the world”. According to the philosopher of science Karl Popper, we should reason using our explanatory theories of the world which have survived the most rounds of attempted falsification, and which have the highest degree of falsifiability (this rules out non-testable explanations like “vaccines work via invisible ghosts”). In more prosaic terms, this simply means reasoning using the best scientific theories which make predictions in the domain under consideration. We note that our best theories of vaccine function do not anywhere depend on the color of paint in the room. Instead they depend on things like T-cells, binding affinities of molecules, the concentrations of certain molecules in the body, etc. So, we decide that the vaccine is safe regardless of the color of paint in the room where it is administered. 

Both of these forms of reasoning are valid and both are foundational to science, rationality, and human progress. Both of these types of reasoning can be used to say that vaccines under development are likely to be safe and effective before any data comes in. It’s why a reporter who interviewed numerous top scientists reported that they all told him that “they expected the vaccines were safe and effective all along.” Yet instead of proudly sharing this important knowledge with the public, we rarely hear scientists say publicly that they expect the vaccines are safe and efficacious. Instead, they hedge, saying “we have to wait until the data comes in”. This is unethical both on Kantian grounds (they are lying) and on consequentialist grounds, because it leads to undue caution and the public being afraid of vaccines. 

Unfortunately, there is little incentive for scientists to tell the truth about what the likely risks and benefits are with new vaccines before full Phase III data is published. If, for instance, one or two people suffer severe side effects in a Phase III trial (which is rare, but has happened) a scientist who said they suspected it was “very safe” might receive harsh criticism for making a premature assessment. On the other hand, the same scientist will get no pushback for saying “we need to wait for data to make a judgement”. Indeed, they are likely to even be praised for exhibiting the virtues of “caution, prudence, and scientific skepticism”. Moreover, under no scenario should someone be allowed to get a vaccine until the full data comes in, even though it’s fine to allow people to sign up for studies where they have a 50-50 chance of getting the vaccine. Not very consistent, eh?

As US Transhumanist Party Chairman Gennady Stolyarov II has described in detail in an an earlier publication on this site, all of this is the result of a deeply flawed and deadly ethical principle called the precautionary principle, which unfortunately many people have fallen under the sway of. The principle originates in the environmentalist movement but is widely applied in medicine, and was instrumental in decisions such as the Bush administration’s ban on stem-cell research and decisions to ban life-saving GMO technologies such as golden rice. It has been formulated to varying degrees in several different ways. The United Nations World Charter for Nature (1982) issued one version of the principle, stating: 

Activities which are likely to pose a significant risk to nature shall be preceded by an exhaustive examination; their proponents shall demonstrate that expected benefits outweigh potential damage to nature, and where potential adverse effects are not fully understood, the activities should not proceed. 

The principle starts off OK but dives into serious error in the last line. The issue is that the precautionary principle only focuses on the potential adverse effects of proceeding and ignores the potential adverse effects of not proceeding, i.e., the effects of delay. As should now be clear in the case of the COVID-19 vaccines, not proceeding can sometimes be much more deadly than proceeding! There is often a high but unclear risk to not proceeding, and a low but unclear risk to not proceeding. (Picture two probability distributions, both wide (unclear) but one with a mean that is distinctly higher than the other). That’s where the precautionary principle throws expected utility theory (cost-benefit analysis) out and says we cannot proceed. The Nobel Prize-winning physicist Freeman Dyson stated the issue as follows: 

The Precautionary Principle says that if some course of action carries even a remote chance of irreparable damage to the ecology, then you shouldn’t do it, no matter how great the possible advantages of the action may be. You are not allowed to balance costs against benefits when deciding what to do.” — Freeman Dyson, Report from the 2001 World Economic Forum

Imagine an alternative world in which our society and government was not under the sway of the precautionary principle. In this alternative world, scientists would give their truthful assessment of new vaccines to the public, stating that they are likely safe and effective, using one or both of the reasoning methods mentioned above. In such a world, given the clear potential harms of inaction, the public would be allowed to purchase new vaccines if they wanted, if the companies manufacturing them were comfortable doing so, and if they were fully informed prior to their decision that they were taking an unapproved product that carries potential risks but also potential benefits. Initially, only a few people would purchase the vaccines, perhaps on the basis of Phase I results. These would be folks like those who injected themselves with a DIY vaccine over the summer, and the tens of thousands who were willing to participate in clinical trials as early as last spring. Companies would be incentivized to survey those who took the vaccine and collect self-reported data on their outcomes, which is very cheap and easy to do. After a few months going by without any of those people keeling over and dying, and with very few (likely none) of those people getting hospitalized for COVID-19, more people would feel comfortable getting the vaccine. Things would quickly snowball, with more and more people becoming willing to get the vaccine. During this time the distribution system would have been stood up and become operational, with on-site stockpiles building up ahead of the FDA’s Emergency Use Authorization (currently, the FDA does not allow hospitals to stockpile unapproved vaccines ahead of their EUA). To present this case in its strongest form, in a future post I plan to estimate how many lives would have been saved, assuming many vaccines had become available to those who wanted them last March or August. However, I hope it’s easy to see that thousands of lives would have been saved in this alternative world.  

For more on the transhumanist alternative to the precautionary principle, the proactionary principle, see Max More’s excellent book chapter as well as the Wikipedia article and references therein.

Dan Elton, Ph. D., is Director of Scholarship for the U.S. Transhumanist Party.  You can find him on Twitter at @moreisdifferent, where he accepts direct messages. 

Reject the Deadly Precautionary Principle: Approve All COVID-19 Vaccines Immediately! – Article by Gennady Stolyarov II

Reject the Deadly Precautionary Principle: Approve All COVID-19 Vaccines Immediately! – Article by Gennady Stolyarov II

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Gennady Stolyarov II


It should be a mild relief that vaccination efforts against COVID-19 are finally beginning in the United States, but they are beginning eleven months too late, while the pandemic surrounds us and most of us must wait months longer to receive vaccinations. Over 300,000 Americans have already died needlessly and preventably from COVID-19; hundreds of thousands more are likely to die in the coming months, even though the exact same vaccine from Moderna that is even today still undergoing Food and Drug Administration (FDA) review already existed in its current form by January 13, 2020. As David Wallace-Wells writes in New York Magzine, in an article entitled “We Had the Vaccine the Whole Time” (dated December 7, 2020):

You may be surprised to learn that of the trio of long-awaited coronavirus vaccines, the most promising, Moderna’s mRNA-1273, which reported a 94.5 percent efficacy rate on November 16, had been designed by January 13. This was just two days after the genetic sequence had been made public in an act of scientific and humanitarian generosity that resulted in China’s Yong-Zhen Zhang’s being temporarily forced out of his lab. In Massachusetts, the Moderna vaccine design took all of one weekend. It was completed before China had even acknowledged that the disease could be transmitted from human to human, more than a week before the first confirmed coronavirus case in the United States. By the time the first American death was announced a month later, the vaccine had already been manufactured and shipped to the National Institutes of Health for the beginning of its Phase I clinical trial. This is — as the country and the world are rightly celebrating — the fastest timeline of development in the history of vaccines. It also means that for the entire span of the pandemic in this country, which has already killed more than 250,000 Americans, we had the tools we needed to prevent it.

As has been demonstrated time and again during this pandemic, scientists and doctors have been the true heroes in their rapid and immensely creative responses, whereas institutions and their processes have failed massively, and our egregiously broken society and culture have precipitated abysmal mass-scale reactions and behaviors as well. But the major reason why now almost 300,000 Americans died who did not need to die at all, is the Precautionary Principle – a cornerstone of contemporary “bioethics” which is, in fact, deeply unethical. The Precautionary Principle is the fundamental reason why new medical treatments, including vaccines, are required in the United States to undergo extensive safety and efficacy testing before they are allowed to be provided to patients, even willing patients who may knowingly accept the risks of experimental medicines. Essentially, unless safety and efficacy can be rigorously demonstrated first, along with a sufficient lack of adverse consequences, adherents of the Precautionary Principle believe that no action should be taken to implement an innovation. Those who espouse the Precautionary Principle completely ignore, of course, the costs and risks of inaction – which, in the case of a global pandemic, can be measured in more than 1.62 million lives worldwide, but which have also resulted in far greater numbers of deaths from more “routine” otherwise terminal illnesses, whose victims might have been saved by new treatments whose approval the FDA delayed, sometimes for a decade or more while billions of dollars were spent on hyper-expensive efficacy testing.

While laudable efforts were made in the United States to greatly accelerate the review timeframe for COVID-19 vaccines – hence the now well-known “Operation Warp Speed” – those efforts did not come in time for the hundreds of thousands who died and the hundreds of millions who now live in fear of death every day as the pandemic’s spread has become all-encompassing. Cutting the approval timeline from the typical unconscionable 4-5 years to 9 months is an improvement, but not nearly enough. Much more should have been done right away. Approval for the vaccines should have been granted as soon as they were developed, and instead of putting review roadblocks in the way, governments should have actively aided in vaccine production and distribution of all serious candidate vaccines from day one.

While New York Magazine’s David Wallace-Wells made the seemingly obligatory (during this tragically precautionary era) disclaimer that “To be clear, I don’t want to suggest that Moderna should have been allowed to roll out its vaccine in February or even in May, when interim results from its Phase I trial demonstrated its basic safety” (and Wallace-Wells still faced considerable vitriol for the quite modest observations he sought to make) – I do want to suggest exactly that. Indeed, I would go further and insist that it was a moral imperative to approve and facilitate the mass production and distribution of vaccines such as Moderna’s mRNA-1273 to willing members of the general population as soon as those vaccines were available.

Transhumanists reject the Precautionary Principle and instead follow the Proactionary Principle, which, per the description of Max More (Extropy Institute, 2004), “urges all parties to actively take into account all the consequences of an activity – good as well as bad – while apportioning precautionary measures to the real threats we face, in the context of an appreciation of the crucial role played by technological innovation and humanity’s evolving ability to adapt to and remedy any undesirable side-effects.” The Proactionary Principle does not ignore the potential for adverse consequences of an activity, but recognizes that there are situations when the benefits can greatly outweigh any potential adverse effects.

Imagine how, in an alternate history, a Transhumanist administration would have dealt with the COVID-19 crisis. Suppose, for instance, that Zoltan Istvan had been elected President in 2016 and thus was the President who faced the COVID-19 pandemic in 2020. Or suppose that Charlie Kam, the U.S. Transhumanist Party (USTP) Presidential nominee in 2020, had held the country’s highest executive office. The U.S. Transhumanist Party Platform contains 21 sections specifically addressing COVID-19 responses – proposals that were adopted by USTP members in late March 2020, and would have saved most of the lives of the COVID-19 victims had they been expeditiously implemented by governments. These proposals, indeed, are applications of the Proactionary Principle to the COVID-19 pandemic. Section CIII of the USTP Platform specifically states that “The United States Transhumanist Party supports the rapid research into effective cures and vaccines for COVID-19 and the harnessing of synergies from this research to also develop a cure for the common cold and more effective vaccination against influenza. Such research should proceed with no barriers, subject to the researchers’ expression of ethical intentions, and any regulations or processes that would delay the progress of such research should be immediately waived or repealed. In the effort to accelerate progress in this field, the United States Transhumanist Party advocates for an immediate $100 billion funding package for the rapid development of a COVID-19 vaccine, with all volunteers being accepted into human trials as soon as practicable.”

This is exactly what would have been done by a Transhumanist administration with the Moderna, Pfizer, AstraZeneca, and any other vaccines, including do-it-yourself experiments such as that undertaken by Josiah Zayner. The Transhumanist administration would have asked the vaccine developer one question: “Do you intend to apply this candidate vaccine in an ethical manner when offering it to the general public?” After giving an affirmative answer to that question, the vaccine developer would have the full legal right to test, give away, or sell its product to any volunteers capable of giving informed consent – provided that the recipients understood that the vaccine was experimental and had not passed the typical safety and/or efficacy tests. Receiving any vaccine would always remain entirely voluntary. Individuals who were uncertain or concerned about side effects – or even motivated by pseudoscientific, anti-scientific, or religious objections – would maintain the right not to get vaccinated. However, those who chose to get vaccinated would be shown clearly and quickly to have far lower incidence of COVID-19, and the statistical disparity in infection rates between the vaccinated and the un-vaccinated would grow too large in just a few months for reasonable people to ignore. Those who become vaccinated would be free to lead their everyday lives and participate in economic activities as usual, and massive disruptions to the economy and to people’s livelihoods would have been completely avoidable. The multifaceted advantages of vaccination under this approach would become abundantly clear in a relatively short time.

Testing would not be eliminated by the Transhumanist administration. Indeed, it would be accelerated and fully funded via the $100 billion emergency package (and likely via other resources as well), so that vaccine developers would need to pay absolutely nothing out of pocket for any compliance with testing protocols. However, testing would occur in parallel with mass distribution of the vaccines, and as much data as possible would be collected from vaccine recipients in the general population, to greatly augment the samples of tested patients. If any specific side effects manifested themselves in a statistically significant portion of the population, protocols for administering the vaccine would be adjusted in real time. For example, if a specific group of people were found to be particularly vulnerable to certain side effects, members of that group would quickly receive additional disclosures and warnings and would be able to make informed decisions in light of this information.

Could there conceivably be adverse side effects or even deaths of certain patients under this approach of mass distribution in parallel with testing? Of course, that is a possibility. However, the scale of such side effects and deaths would surely be orders of magnitude less than the all-encompassing devastation that the current sequential review-and-approval process has allowed to happen. So far nobody has died specifically from any COVID-19 vaccine. At least 1.62 million people in the world have died from COVID-19. Numerous others have died because of the fallout of the restrictive measures taken to contain the spread of COVID-19. Even if the vaccines had been far more dangerous than they actually are, it is absolutely impossible for them to have caused anywhere near the death toll inflicted by the disease itself and the societal havoc that it and responses to it have wreaked. This basic insight, whose evidence is all around us, is precisely what the Precautionary Principle misses. By placing all of the burden of proof on the innovation, the Precautionary Principle gives a free pass to the wantonly murderous status quo. Inaction is not safety. Inaction is quite frequently the greatest danger – and at no time is that truer than during a global pandemic. If we do nothing, any of a vast array of perils will befall us rather quickly.

The United States has already lost more people to COVID-19 than it had to all but one of its historical wars. The novel coronavirus is the enemy here to be sure, but the Precautionary Principle is an even more pernicious and insidious foe. The Precautionary Principle is responsible for the hundreds of thousands of American dead just as much as the novel coronavirus itself, since it prevented an implementation of an existing off-the-shelf solution that could have saved the vast majority of their lives. Every war in history has resulted in unacceptable death tolls because of fundamentally flawed premises – ideas and practices that brought about the war because people accepted them as commonplace and justified. Slavery, religious intolerance, jingoistic nationalism, and totalitarianism have all stemmed from deep moral errors that caused colossal loss of life – and fortunately most of humanity has recognized the great evil that these notions entail and has resoundingly rejected them. The Precautionary Principle, when implemented in institutions that have the power to make life-or-death decisions, is in that same league of moral errors; it will be remembered decades and centuries hence as the greatest destroyer of lives in our epoch.

How much senseless loss of life needs to occur before we recognize that our institutions, based on the Precautionary Principle, are wantonly negligent in allowing our fellow humans to die and are still withholding life-saving solutions from them? It is time to reject the Precautionary Principle once and for all and to institute the truly humane policy of allowing all rationally capable individuals to assess the risks and benefits of emerging medical treatments for themselves. This would not only save colossal numbers of lives in the immediate term, but also greatly accelerate medical discovery and technological progress – since innovators would be able to obtain data rapidly and iterate upon their approaches. The arrival of cures for cancer, dementia, diabetes, and biological aging itself will depend on how free medical innovators are to offer their treatments and how free patients are to accept them. Extensive and expensive pre-distribution review processes kill many more people than they save. End them now!

Gennady Stolyarov II is the Chairman of the United States Transhumanist Party. 

Breaking the Bottleneck: A Synergy of Technology and Medicine – Article by Zach Richardson

Breaking the Bottleneck: A Synergy of Technology and Medicine – Article by Zach Richardson

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Zach Richardson


In March of 2019, I began to have a very strange problem. I was breathing normally, but felt like I was suffocating. The problem became much worse when lying down, but seemed to come and go arbitrarily. Some days it would be really bad, and on others I didn’t even notice it. This happened twice in a week, and I checked with a doctor. He assured me I had anxiety and gave me a prescription for some anxiolytic medicine. I couldn’t breathe, and his solution was Xanax. I stupidly trusted him.

In May 2019, I ended up in the hospital. My body was turning yellow, and my liver, kidneys, and heart were failing. The cause was idiopathic; none of the 7 specialists knew why I was having congestive heart failure. A couple of drugs were tried, but in the end the only solution they said would save my life was the implantation of a mechanical device that would help my heart pump: a Ventricular Assist Device, or VAD.

I was lucky enough to be selected as a perfect candidate for a clinical trial, partially due to being particularly young for having Congestive Heart Failure (CHF). A new version of an already cutting-edge technology would be tested on my body, and the results would be recorded for their study. The machine they implanted was called the Heartmate 3, and it saved my life.

The VAD is currently used either as “bridge” or “destination” therapy, with “bridge” meaning that it is used only temporarily until one can get a heart transplant, and “destination” meaning that one is ineligible for transplant at all, and will have the VAD for the rest of one’s life. Some of the contraindications for VAD implantation being bridge therapy include being obese or over 65 years of age. Luckily, I am not either of those two, and therefore am eligible for a transplant. However, there are two factors that are going to lead to it likely being an extremely long time before a donor heart is available. One is that I am a larger man, standing at 6 feet tall, meaning I require a larger-than-average heart. The other is that I have Type O blood, which is the hardest from the standpoint of receiving an organ donation.

This puts me in a very interesting situation, where I am a young man who may have many years still ahead of him with an implanted device. It may be 7 years from now when I get the call for transplant, or it may be tomorrow. If it happens 7 years from now, there may be therapies that will have been developed that would allow me to regrow my heart, or clone one from my stem cells, and thereby avoid having to be on a cocktail of immunosuppressants indefinitely. Unfortunately, even Athersys only has CHF treatments in the preclinical stage, which means I may have to wait a while. I intensely wish those trials weren’t being constrained like they are.

Having set significant life extension towards the very top of my hierarchy of values, I am extremely grateful that I live in a society where these technologies are available to me. I have a highly personal interest in seeing a society of scientists and biomedical engineers emerge to help develop these technologies! However, part of my situation was just me getting lucky: I had the treatment I needed approved just months before receiving it, and happened to have top-notch insurance.

One unfortunate side effect of having a centralized regulatory system is that the Food and Drug Administration (FDA) is only held responsible for what are known as “Type I Errors”. A Type I error is where the FDA passes an unsafe drug or treatment, leading to harm to an individual or group. Unfortunately, this means that FDA officials do not seem to care at all about “Type II Errors”, where they do not pass a life-saving treatment or drug in time to save someone’s life. The FDA is so terrified of having another Vioxx incident, that FDA officials are overly cautious in approving the use of radically innovative and breakthrough technologies. The fact that these technologies carry some risk is something of no worry to someone who is going to die if they don’t get the treatment. It is much harder to blame the FDA for being too safe than it is to blame them for being reckless.

This is why I am proud to be a member of the U.S. Transhumanist Party (USTP), where science and technology are put at the forefront of American politics. The current bottleneck those like me with CHF face is regulatory hurdles. Article VI, Section VI, of the USTP Constitution states: “The United States Transhumanist Party upholds morphological freedom—the right to do with one’s physical attributes or intelligence whatever one wants so long as it does not directly harm others.” Right now what I and others with CHF would like to do is to get a stem-cell heart. We are being hindered not by direct legislation restricting morphological freedom, but by the far more pernicious hindrance of excessive regulatory burden. The treatments we want are being developed exponentially slower than they could be, because each step of the way has to adhere to draconian testing standards. This means a lot of Type II errors are being committed. We are not being told, “You cannot get this treatment.” Providers are being told, “You cannot provide this treatment.”

In my ideal world, regulatory agencies would work more like Underwriters Laboratories or Quality Assurance International. Leaving regulatory activity to the market, far from the fearmongering of producing dangerous and shoddy drugs and treatments, would instead invigorate the institutions as they would compete to certify the best products and treatments for consumers, since their names and reputations would be on the line.

I believe there needs to be a much stronger focus in regulatory institutions toward the elimination of Type II Errors, because there are a lot of sick people going untreated.

Zach Richardson is a Certified Supply Chain Professional and small-business co-owner producing respirator-style masks to help stem the tide of COVID-19’s spread. His website is isgmanufacturing.com. He is a member of the U.S. Transhumanist Party.

U.S. Transhumanist Party Meeting at RAAD Fest 2019 – October 6, 2019

U.S. Transhumanist Party Meeting at RAAD Fest 2019 – October 6, 2019

Gennady Stolyarov II
Johannon Ben Zion
Brent Reitze


On October 6, 2019, the U.S. Transhumanist Party / Transhuman Party held a meeting in Las Vegas at RAAD Fest 2019, with approximately 45 members of the public in attendance. USTP Chairman Gennady Stolyarov II, Presidential Candidate Johannon Ben Zion, and Director of Publication Brent Reitze provided an overview of the recent 2019 Electronic Primary and the lessons learned from it and solicited ideas from the attendees about how to improve public recognition of transhumanism and arrange for activism with similar impact to Zoltan Istvan’s 2016 Immortality Bus campaign. A vigorous but civil and thought-provoking discussion ensured for approximately 90 minutes. Watch the video recording of the meeting here.

References
U.S. Transhumanist Party 2019 Electronic Primary Results – Johannon Ben Zion Endorsed as Candidate for President of the United States
U.S. Transhumanist Party 2019 Primary Election Results and Johannon Ben Zion Acceptance Speech 

Join the U.S. Transhumanist Party / Transhuman Party for free, no matter where you reside. Click here to apply in less than a minute.

Not Classing Aging as a Disease is Not a Major Problem – Article by Steve Hill

Not Classing Aging as a Disease is Not a Major Problem – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by at the Life Extension Advocacy Foundation (LEAF) on July 19, 2018. In this article, Mr. Hill does an excellent job explaining why the lack of the definition of aging as a disease under the FDA is not so bad as is sometimes feared. Personally, I do not agree with this. Relying on off-label use is not a good idea because that is much slower of a process than doctors quickly seeing that a drug has FDA approval. Once the FDA considers aging as a disease, pharmaceutical companies will quickly enter this arena and make increasingly better drugs. Mr. Hill makes some excellent points, though, and I highly recommend this article. 

~ Bobby Ridge, Assistant Editor, June 29, 2019

A common concern in the community is that the FDA, the EMA, and other bodies, such as WHO, do not classify aging as a disease and that this poses a problem for developing therapies that target aging. However, this is not really as serious an issue as some people would suggest; today, we will have a look at why that is.

Why this will not stop progress

Aging is a variety of distinct processes, damages, and errors; therefore, simply treating aging in clinical terms is not a viable endpoint. For a clinical trial to be conducted, it requires a verifiable indication, and aging is too general for the FDA and EMA to classify it as a disease.

It also is not a major challenge for damage repair-based approaches, such as those proposed by SENS and the Hallmarks of Aging, as these approaches are not focused on an all-in-one therapy with the indication of “aging”. They are based on a strategy of dividing damages into manageable groups and developing a suite of rejuvenation therapies that addresses each of them.

No single therapy will reverse or halt all of the aging processes when used alone, nor will it prevent all age-related diseases that accompany them. So, to have aging as an indication in any clinical trial would be pointless for any damage repair therapy.

Researchers are free to target aging processes

That said, researchers are very well aware that the processes of aging, which lead to the familiar diseases of aging, are a problem, and this is where the focus lies. There has been considerable effort to classify these processes and precursors of pathology as diseases themselves.

A prime example is the inclusion of sarcopenia (frailty and muscle loss) in the World Health Organization International Classification of Diseases (ICD) a few years ago thanks to lobbying by members of our community. Adding more general codes to the ICD that include these aging processes and precursors is an ideal solution, as it could potentially make it easier to organize trials and develop drugs that target the aging processes.

Back in June 2018, the World Health Organization released the new International Classification of Diseases (ICD-11). The previous version, ICD-10, was published in 1983, and the new ICD-11 will likely be the standard for years to come. The new ICD-11 now includes the extension code “Ageing-Related” (XT9T) for age-related diseases, and this should go a long way towards making focusing on aging easier for future drugs and therapies. Again, this is thanks to work by members of our community, who have spent countless hours researching and pushing for change.

Most aging hallmarks are very clearly linked to specific age-related diseases, such as beta-amyloid protein and malformed tau in Alzheimer’s, lysosomal aggregates in foam cells in atherosclerosis, and alpha-synuclein in Parkinson’s disease. Companies are perfectly welcome to target these aging processes directly, and indeed more and more researchers and big institutions are doing just that in order to treat age-related diseases.

Therefore, not classifying aging itself as a disease poses few barriers to developing therapies that address aging; it’s simply a case of working within the existing framework. UNITY Biotechnology is a prime example; this company is targeting senescent cells and applying its method to multiple age-related diseases; as everyone gets senescent cells, these therapies will be broadly applicable once they become available, and off-label use is likely to expand rapidly.

Also, rejuvenation therapies could, at first, be licensed as treatments for genetic disorders, even though the root cause of the pathology underlying those diseases is not aging. An example of this is the inherited mitochondrial disorders, known as mitochondriopathies, many of which are caused by mutations in the mitochondrial DNA (mtDNA). While these mutations are inherited and are not the result of age-related, deleterious damage to the mtDNA, the same repair-based approach can be applied: the allotopic expression of the protein in the nucleus, as proposed by MitoSENS, could potentially be used to repair the mtDNA allowing normal cellular function to resume.

The majority of damage repair therapies, if not all, could be developed as therapies for diseases with accepted indications and verifiable endpoints, which should satisfy bodies such as the FDA and EMA. Therefore, whether regulatory agencies perceive aging as a disease or not is of no consequence to the development of rejuvenation biotechnologies that address the aging processes.

This does not mean regulatory changes are not needed

Even though classifying aging as a disease is unnecessary, significant reform in the regulatory system is still needed in order to encourage investors and companies to put the time and money into researching and developing rejuvenation therapies.

One area in need of reform is the establishment of aging biomarkers, which indicate the repair or removal of age-related damage, as acceptable endpoints for rejuvenation therapies. Studies that use these biomarkers would also need to include long-term follow-up studies to ascertain the effects of a therapy over a longer period of time.

This would deviate from regulators’ normal requirements that therapies have to prove an effect on hard outcomes to be approved. In an ideal situation, patients should get rejuvenation therapies long before they are in immediate danger and once diseases have manifested, but this makes trials more time consuming and more costly to run.

However, back in February 2018, the FDA published a new guidance document detailing how early-stage Alzheimer’s patients might be identified, which, if accepted, would represent a significant change in policy and a step in the right direction. The document suggests that the results of imaging tests or suitable biomarkers could be enough to consider Stage 1 Alzheimer’s patients as suitable subjects for clinical trials.

This is a positive move as it means that therapies can be tested on people in the very early stages of Alzheimer’s rather than on those who have already suffered considerable if not irreparable damage to the brain, damage that no therapy could hope to address alone. This could mean that these early-stage patients could enroll in a clinical trial and take a therapy that could potentially prevent the disease from ever progressing further or reaching the point where cognitive decline begins.

In the case of repair-based therapies, it would then be a case of demonstrating that the early stages of Alzheimer’s disease were improved via the removal or repair of the underlying age-related damage, and suitable biomarkers would show this.

Moving with the times

Another area where regulatory bodies have struggled is keeping up with the rapid march of technology and medicine. Technologies such as gene therapies have struggled to gain traction due to an antiquated regulatory framework struggling to cope with them. Thankfully, this is also being acknowledged, and the regenerative medicine advanced therapies (RMAT) framework published earlier this year seeks to address this issue and make large-scale changes to how its regenerative medicine policy framework operates as a whole.

According to new FDA regulations, a drug is eligible for designation as an RMAT if:

  • The drug is a regenerative medicine therapy, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except for those regulated solely under Section 361 of the Public Health Service Act and part 1271 of Title 21, Code of Federal Regulations;
  • The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and
  • Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition.

While the FDA created these new guidelines, we joined forces with the Niskanen Center to submit comments to the agency so that it would hear the voice of our community.

Conclusion

Aging not being classified as a disease by the FDA, EMA, etc. is not a major issue; the real need is for policy changes that make developing drugs and therapies that target the aging processes easier and more financially viable. It is good that changes are being made to current frameworks and that progress will almost certainly continue in these areas.

Meanwhile, we can continue to support the development of repair-based approaches to aging knowing that such therapies, if they work, will be approved even in the current regulatory landscape.

Steve Hill serves on the LEAF Board of Directors and is the Editor-in-Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Aubrey de Grey – Clinical Trials in Five Years – Interview by Laura Sanz Olacia

Aubrey de Grey – Clinical Trials in Five Years – Interview by Laura Sanz Olacia

logo_bgLaura Sanz Olacia
Aubrey de Grey


Editor’s Note: In this interview originally published by our allies at the Life Extension Advocacy Foundation (LEAF), Laura Sanz Olacia discusses with Dr. Aubrey de Grey his anticipation that treatments aimed at reversing biological aging may enter clinical trials within five years. The U.S. Transhumanist Party is pleased to feature these insights from Dr. de Grey. 

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, December 18, 2018

 


In November, Dr. Aubrey de Grey, a graduate of the University of Cambridge, was in Spain to attend the Longevity World Forum in the city of Valencia, and he gave a press conference organized by his friend, MIT engineer José Luis Cordeiro.

Dr. Aubrey de Grey is the scientific director (CSO) and founder of the SENS Research Foundation. In Madrid and Valencia, Dr. de Grey reaffirmed for Tendencias21 one of his most striking statements of 2018: “In the future, there will be many different medicines to reverse aging. In five years, we will have many of them working in early clinical trials.”

The Longevity World Forum is a congress on longevity and genomics in Europe. It is heir to the first congress in Spain, the International Longevity and Cryopreservation Summit, which was held at the CSIC headquarters in Madrid in May 2017, and Dr. de Grey also participated in that event. In Valencia, his presentation was recieved with interest, and Dr. de Grey explained to this select audience that aging will be treated as a medical problem in the near future. Rather than treating its symptoms using the infectious disease model, the root causes of aging will themselves be treated.

It was published recently on longevityworldforum.com that a therapy to reverse aging will be a reality within five years. What will be its mechanism of action, roughly?

There will not be just one medicine; there will be a lot of different medicines, and they will all have different mechanisms of action. For example, some of them will be stem cells, where we put cells back into the body in order to replace cells that the body is not replacing on its own. Sometimes, they will be drugs that kill cells that we don’t want. Sometimes, they will be gene therapy treatments that give cells new capabilities to break down waste products, for example. Sometimes, they will be vaccines or other immune therapies to stimulate the immune system to eliminate certain substances. Many different things. In five years from now, we will probably have most of that working. I do not think that we will really have it perfect by then; probably, we will still be at the early stages of clinical trials in some of these things. Then, we will need to combine them, one by one, to make sure that they do not affect each other negatively. So, there will still be some way to go. But, yes, I think it’s quite likely that in five years from now, we will have everything, or almost everything, in clinical trials.

Then clinical trials for seven years until it’s perfected. Don’t clinical trials usually take a long time?

It depends. For example, in aging, because there is this progressive accumulation of damage, you could have therapies that slow down the rate at which damage accumulates, or you could have therapies that repair the damage that has already happened. The second type of therapy is what we think is going to be most effective and is going to be easiest to do, and you can see results from that very quickly, like in one or two years. Now, of course, you still want to know what happens later on, but the first thing is to determine whether this is working at all, and as soon as it starts to work, then you can start to make it available. Clinical trials are changing in that way. Historically, clinical trials had to be completed before anybody could get these drugs, but now we are getting new policies; there is a thing called adaptive licensing, which is becoming popular in the US and elsewhere, where the therapy becomes approved at an earlier stage, and then it’s monitored after that.

Beyond the humanitarian perspective of avoiding the pain and suffering that comes with old age, if increasing the years of healthy life in people will significantly reduce health care spending by governments, why don’t they promote research in this area?

You’re absolutely right. It’s quite strange that governments are so short-sighted. But, of course, the real problem is psychological: it’s not just governments that are short-sighted. Almost everybody in the world is short-sighted about this. The reason I believe why that’s true is people still can’t quite convince themselves that it’s going to happen. Since the beginning of civilization, we have known that there is this terrible thing called aging, and we have been desperate to do something about it, to get rid of it. And people have been coming along, ever since the beginning of civilization, saying, “Yes, here’s the solution, here’s the fountain of youth!” And they’ve always been wrong. So, when the next person comes along and says they think they know how to do it, of course, there is going to be some skepticism until they have really shown that it’s true. Of course, if you don’t think it’s going to work, then you’re not going to support the effort financially. It’s very short-sighted, but it’s understandable.

Why do you think that the pharmaceutical industry does not devote its research and development efforts to this area, which causes the death of 100,000 people every day?

Today, the pharmaceutical industry is geared toward keeping old people alive when they are sick. It makes its money that way. It’s not just the pharmaceutical industry, it’s the whole of the medical industry. And so, most people say that they are worried that maybe the pharmaceutical industry will be against these therapies when they do come along. I don’t think that’s true at all. I think they will be in favor because people will be in favor, but people are not really in favor yet. People don’t really trust preventive medicine. They think “Okay if I am not yet sick…” They don’t trust medicine in general; they know that this is experimental. So, when they are not yet sick, they think “Well, I’ll wait until I am sick,” but we can change that. Eventually, people will understand that it’s going to be much more effective to treat yourself before you get sick, and then the whole medical industry will just respond to that; they will make the medicines that people want to pay for.

So you don’t think that they will be against these therapies?

No. They will follow.

But now, they are not focusing their research into this field.

That’s right because they don’t need to. The big pharmaceutical companies don’t really do much of their own research in the first place. They just wait to see what happens, and then they buy small companies.

In the car analogy that you use, you say that a car is built to last 10 or 15 years, but with proper maintenance, it can last up to 100 years. Isn’t this expressing the idea that aging is programmed and that the life of a car is also programmed?

No, it’s not. All of you know that, a long time ago, Henry Ford invented a concept called planned obsolescence, which was a way of building a car so that you could predict pretty accurately how long it would last. But, of course, the only reason that the prediction works is because people are lazy, and they don’t mind replacing their cars, so they only do the minimum amount of maintenance that the law tells them to. The reason that some cars last 100 years is not because those cars were built differently, it’s because there are a few people out there who fall in love with their cars and they don’t want them to get old. So, it really is exactly the same. In the human body, we have aging, because there are certain types of damage that are not automatically repaired when they happen. Of course, many types of damage in the human body are repaired automatically when they happen, so we don’t need medicine for that, but some of them are not. So, if we can develop medicines that do fix those things, it’s exactly the same as with a car.

If aging is not programmed, why do different species have different lifespans?

Because they have different qualities of built-in repair machinery. When I talk about all these types of damage, they are the types of damage that accumulate in the body, and they accumulate because the body does not have ways to repair them. There are massive amounts of other types of damage that I don’t call damage, and the reason I don’t call them damage is because they don’t accumulate. The reason that they don’t accumulate is because we already have built-in machinery to repair them when they happen. So, long-lived species have more comprehensive automatic repair machinery built into them.

Do you think that first we can focus on just replacing organs and restoring their function, and eventually we can eliminate the root causes of aging? Once we reach longevity escape velocity, maybe we can focus on just eliminating it?

We will never be able to stop the body from creating this damage. The body is going to do that because it is intrinsic to metabolism, but the better we get at repairing the damage, the fewer problems we have.

What healthy habits do you follow now?

I don’t do healthy habits. I’m lucky, I don’t need to do anything; I can drink whatever I like and nothing happens. I don’t even do much exercise, and also I don’t get nearly enough sleep, which is probably shortening my life, but it is worth it because I am hastening the defeat of aging, so it is a net positive.

Which generation will live to be a thousand years old? Do you think it is born already?

I think it is very probably born already, yes. But, of course, we cannot know until we get the medicines.

Which country do you think is more aware, or the people is more aware that this is a problem that we need to fix?

I would say Russia.

Russia?

Yeah. Surprising, isn’t it? But when I go to Russia and I talk about all of this, it’s so wonderful; I don’t get any of the uninformed questions, and everyone seems to understand it.

They don’t ask you ethical questions?

That’s right, yeah. They understand that this is a medical problem, it needs to be fixed, and it can be fixed.

Kriorus [the first and only cryonics company in Eurasia] is there right?

Yeah, I know Kriorus, I know the people very well.

Alcor [the world leader in cryonics located in Arizona] is the most expensive.

It gives the best service. I mean, it makes sense to have a very expensive, high-quality service and also less expensive and lower quality service. That is normal.

Where are you currently living?

I live in the United States, but I go everywhere when I am invited to speak and so on.

Laura Sanz Olacia, has a degree in Pharmacy from the Complutense University of Madrid (2015). Between 2016 and 2017 she worked for nine months in different pharmacies in London. She also worked in a pharmacy laboratory compounding medicines and cosmetics in Madrid. More recently she worked in IQVIA as Data Management Analyst. She is very interested in research and, in particular, in the area of ​aging. During her stay in London, she participated in the organization of the Antiaging Conference London 2016, and back in Madrid, she collaborated closely with the organizing committee of the International Longevity and Cryopreservation Summit 2017. She wants to devote her career to doing research in this field.

The Rise of Oisin Biotechnologies – Interview with Gary Hudson, CEO of Oisin Biotechnologies, by Ariel VA Feinerman

The Rise of Oisin Biotechnologies – Interview with Gary Hudson, CEO of Oisin Biotechnologies, by Ariel VA Feinerman

Ariel VA Feinerman
Gary Hudson


Gary Hudson

Preface

What is ageing? We can define ageing as a process of accumulation of the damage which is just a side-effect of normal metabolism. While researchers still poorly understand how metabolic processes cause damage accumulation, and how accumulated damage cause pathology, the damage itself — the structural difference between old tissue and young tissue — is categorized and understood pretty well. By repairing damage and restoring the previous undamaged — young — state of an organism, we can really rejuvenate it! Sounds very promising, and so it is. And for some types of damage (for example, for senescent cells) it is already proved to work!

Today in our virtual studio somewhere between cold rainy Saint-Petersburg and warm rainy Seattle, we meet Gary Hudson!

He has been involved in private space flight development for over 40 years. Hudson is best known as the founder of Rotary Rocket Company, which in spending ~$30 Million attempted to build a unique single stage to orbit launch vehicle known as the Roton. He helped found Transformational Space T/Space in 2004 and AirLaunch LLC which was awarded the DARPA/USAF FALCON project in 2003.

Previous projects included designs of the Phoenix SSTO, the Percheron, and other rockets, founder of Pacific American Launch Systems, and various consulting projects. Currently, he is the President and CEO of the Space Studies Institute.

Now Hudson brings his excellent engineering skills into rejuvenation biotechnology! He is a founding partner of Oisin Biotechnologies, who are developing a liposomally delivered DNA therapy for the removal of senescent cells from the body. Hudson provided an initial seed donation to help fund the creation of the Methuselah Foundation and SENS Research Foundation.

Interview

Feinerman: Hello, Mr Gary Hudson!

Hudson: Thanks for inviting us to this interview!

Feinerman: You have recently visited an amazing Undoing Aging 2018 conference, which took place in Berlin, 15–17 March, where your colleague, Matthew Scholz, was a speaker. What is your impression?

Hudson: It was a great conference with several important presentations. It put me in mind of the early SENS conferences in Cambridge, UK, which I helped to sponsor. I understand it will now become an annual event. Our CSO Dr. John Lewis also gave an important summary of our work to date.

Feinerman: Will Oisin’s presentations from conference be available for general public?

Hudson: I believe that the SENS Foundation will be posting them but I don’t have details about the timing.

FeinermanYour last interview was in July 2017, more than half a year ago. What has been accomplished?

Hudson: We have conducted many pre-clinical mouse experiments on both cancer and senescent cell removal. All have been successful and produce very remarkable results. We’ve also conducted a pilot toxicity and safety trial on non-human primates. The results of that trial were also successful and encourage us to proceed to human safety trials as soon as regulatory authorities approve them. We have also spun-out a cancer-focused company, Oisin Oncology, and raised a seed round for that venture.

Feinerman: Great to hear! However, when can we see some papers? People usually trust papers more than mere interviews or press releases. Of course, papers need many efforts not related to research but they will allow you attract more attention from general public, researchers, and investors.

Hudson: Papers are being prepared now for submission to major journals, but that process takes time, especially the peer review. For the moment, most of our data is only available to investors and partners in pharma and the biotech industry.

Feinerman: You planned human clinical trials, have you carried them out?

Hudson: It takes quite some time to organize a human trial and to get it approved. Before one can be conducted, we have to set up so-called “GMP (Good Manufacturing Practice) manufacture of our therapeutic, and then we have to conduct “GLP (Good Laboratory Practice) Tox” studies in two different species. Once that is all completed later this year, then we can begin a human safety trial, or a “Phase 1” trial. All this takes time, but we hope that first safety trials in oncology indications might begin this year, or in early 2019.

Feinerman: Does that mean we have a race between Unity Biotechnology and Oisin and you have all chances to win the race?

Hudson: I don’t see it as a race or a competition. I believe that future anti-aging treatment will require multiple complimentary approaches.

Feinerman: When we can expect your therapy available in the clinic?

Hudson: It’s very difficult to predict. I believe that our cancer treatment will make it to the clinic first, and that could happen in less than five years. Since the FDA doesn’t regard ageing as an indication, it may take longer for our SENSOlytic™ treatment to reach the public, since the regulatory environment will need to change.

Feinerman: As Michael Rae has said, we need not to wait when ageing will be recognised as a disease. You can mark your senolytics as a therapy for specific ageing pathology like fibrosis or chronic inflammation in the same way as Unity does.

Hudson: This is certainly true and is part of our strategy, but many of those endpoints are more difficult to ascertain than oncology endpoints. Additionally, going after oncology approvals can be faster and easier to get to clinic. But we will push forward on several fronts as funding permits.

Feinerman: In your previous interview you have said that you make some tweaks to both the promoter side and the effector side of the constructs that will provide even more interesting and useful extensions to the basic capability, but you can’t discuss those for IP reasons. Can you now say about them?

Hudson: I still can’t say too much about them, but we have conducted animal trials on some of these “tweaks” and they work quite well. The downside to the matter is that every “tweak” requires new trials, and our goal is to get something to the clinic as soon as possible, so many of the improvements will have to wait. Progress is limited based on available funds and personnel resources, of course, but we will move as quickly as we can.

Feinerman: Do you use any CAD software to design your constructs? Are you going to make them public so independent engineers will be able to help you identify new useful pairs of promoters and effectors? Your technology is so powerful that Open Source approach would be very helpful!

Hudson: No, the design of the current constructs are very straightforward and simple. As our patents are issued, their design will become public. If people wish to design their own constructs for particular applications they may contact us for collaboration, though we do have several collaborations active at the moment so we may already be working on similar ideas.

Feinerman: What do you think on targeting your machinery on cells with abnormal telomerase activity to kill cancer? Can you use several conditions — like in programming — several promoters to be more specific?

Hudson: If we targeted telomerase we’d also kill stem cells, just like the side effects of much of conventional chemotherapy. That’s probably not a good idea. But multiple promoters, or synthetic promoters, might be used to achieve the aims of killing only cancer cells. Our initial therapeutic will likely just employ p53 promoter targeting, since we have good data that works.

Feinerman: Yeah, the same issue as when we remove or break telomerase gene: there would be nice to do this only in compromised tissue, but as researchers say it is very difficult to make the removal selective. However, it is not a problem with ALT genes, which cause 15–20% of cancers. Are you going to collaborate with the OncoSENS lab? Also killing cells actively expressing telomerase will be very useful in WILT implementation.

Hudson: We’ve had conversations with the SENS Foundation about OncoSENS and cooperated in a preliminary fashion, but I don’t believe it is currently a research priority for them. We already have enough projects to keep us busy for some time, too!

Feinerman: Now you use only suicide gene as an effector, do you plan to use other genes? For example to enhance the cells, give them ability to produce new enzymes, or temporarily shut down telomerase to help anti-cancer therapy to be more effective.

Hudson: We believe we can express any gene under the control of any promoter we wish to use, so the possibilities are almost endless.

Feinerman: Now we know that epigenetic changes (shift) play a huge role in ageing. Even though there is no consensus among researchers whether they are a cause or a consequence of ageing, experiments show that temporal expression of OSKM transcription factors may have some health benefits by restoring “young” epigenetic profiles. You can remember the Belmonte work, for example. However, the problem in their work is that they used transgenic mice and express OSKM in every their cell. If you temporarily express OSKM in an “old” cell, that is OK, you can “rejuvenate” such a cell. While if you express OSKM in a stem cell which is already biologically “young”, you can force the cell into iPSC, which is a way to cancer. Using your machinery we can target only cells which have “old” expression profiles, and involving normal mice! Such a work will be much “cleaner” and safer than Belmonte’s work.

Hudson: With respect to your comments about reprogramming, Oisin is currently working with a university group on exactly this approach, but I can’t say more at this time. We also believe that first you have to clear existing senescent cells, then you can reprogram successfully.

Feinerman: How many resources, finances, and personnel do you need to move as quickly as possible? Do you have open positions? Maybe, some of our readers have enough finances or experience.

Hudson: We could effectively spend tens of millions or dollar or more, very easily, but it isn’t realistic to assume we could raise that amount — and if we did, we’d lose control of Oisin’s ageing focus, since investors would most likely want us to aim at quick returns. We are always interested in talking with “mission minded” investors, however. As for hiring, we have to do that slowly and judiciously, since labour is one of the biggest costs to a start-up company, and over-hiring can sink a project quickly. We already have more potential hires than we can bring on-board.

Feinerman: Now cryptocurrencies and blockchain technologies allow completely new and efficient ways for investments. We can see this as various no-name companies easily rise tens of millions dollars via ICOs for clearly doubtful projects. Would you like to make an ICO? Oisin shows real progress and can easily rise big sums! People say that they will be glad to buy your tokens if you issue them. You have said that you prefer to work with “mission minded” investors. There are thousands people out there who can invest from $1,000 to $100,000 in cryptocurrencies and who believe that radical extension of healthy life is possible!

If you are worried about legal issues, you can use various cryptocurrency investment funds who act like proxies between holders of cryptocurrencies and companies.

Hudson: We have investigated several of these financing options, but we are not expert in this area, so we have been reluctant to move too quickly. But we continue to have conversations with relevant parties. There is a lot of regulatory uncertainty surrounding ICOs, however, so we must move cautiously.

Feinerman: Now we know enough about ageing to defeat our main enemy. Do you agree that first comprehensive rejuvenation panel is not a scientific problem and even not an engineering problem, but a problem of engineering management?

Hudson: I wouldn’t say that there is no science left to do, but as an engineer myself I naturally agree that proper engineering management and program management skills must be brought to bear on the problem of ageing.

Feinerman: One person has said, we get what we ask for. Can we now aim high and publicly claim that our main goal is not additional five years of life but LEV — Longevity Escape Velocity and finally unlimited healthy life?

Hudson: This is a difficult “public relations” problem. Most investors, the scientific community, and the public are not yet ready to embrace the notion of longevity escape velocity. Thus at Oisin we do pitch health span as a primary goal. But personally I don’t believe that you can obtain health span improvements without making significant progress towards LEV. So in the end, I think we get LEV by targeting health span, and we reduce the controversy by doing so.

Feinerman: Some people ask me how to buy your stocks or invest in Oisin. What can you say?

Hudson: We do have a number of private investors (angel investors) who are “mission minded” or “mission focused” and we welcome discussions with qualified investors and firms who share our vision for dealing with ageing and cancer. Accredited investor candidates may contact us at info@oisinbio.com

Feinerman: David Gobel claims that “By advancing tissue engineering and regenerative medicine, we want to create a world where 90-year olds can be as healthy as 50-year olds by 2030.” And I secretly hope that 40 will become new 30 or even 20 by 2030! Can we achieve that — in principle?

Hudson: I certainly hope so! In 2030 I’ll be 80, so I’m looking forward to feeling like I’m 40…

Feinerman: Thank you very much for your amazing answers! That was a real pleasure to talk with such a great man like you. I hope we all will succeed in our goal and will have hundreds, thousands, and — who knows? — maybe even millions years of healthy life!

Hudson: It is kind of you to say so, but I only consider myself fortunate to be working with the really great men and women in the anti-aging community who are doing the real work. I’m only trying to facilitate their efforts and get treatments to the clinic as fast as possible. I don’t know what will be possible in the long term, but anything will be better than letting nature run its course, producing sickness and declining functional health.

Ariel VA Feinerman is a researcher, author, and photographer, who believes that people should not die from diseases and ageing, and whose main goal is to improve human health and achieve immortality.

Message from Ariel VA Feinerman: If you like my work, any help will be appreciated!

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New FDA Regenerative Medicine Framework is Win-Win for Gene Therapies – Article by Keith Comito and Elena Milova

New FDA Regenerative Medicine Framework is Win-Win for Gene Therapies – Article by Keith Comito and Elena Milova

Elena Milova
Keith Comito


Editor’s Note: In this article, Keith Comito and Elena Milova positively discuss new a FDA regulatory framework on RMAT (regenerative medicine advanced therapies) and on how it benefits the healthy-life-extension community. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, March 3, 2018

Back in November 2017, the FDA announced a comprehensive policy framework for the development and oversight of regenerative medicine products, including novel cellular therapies. Both draft guidance documents had 90-day comment periods, and we at LEAF joined forces with the Niskanen Center to submit comments to the FDA to ensure that the voice of the community for healthy life extension was heard. These new regulations could have considerable implications for the therapies and technologies being developed as part of the biomedical gerontology field.

The first draft guidance addresses how the FDA intends to optimize its regulatory requirements for devices used in the recovery, isolation, and delivery of RMATs (regenerative medicine advanced therapies), including combination products.

The second document explains what expedited programs may be available to sponsors of regenerative medicine therapies and describes what therapies may be eligible for RMAT designation.

According to new FDA regulations, a drug is eligible for designation as an RMAT if:

  • The drug is a regenerative medicine therapy, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except for those regulated solely under Section 361 of the Public Health Service Act and part 1271 of Title 21, Code of Federal Regulations;
  • The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and
  • Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition

We hope that this joint project will support the improvement of US regulations that concern these innovative treatments and will make the overall regulatory landscape more friendly. Below, we cite the most important notes from our resulting paper.

Last week, the Niskanen Center joined with the Life Extension Advocacy Foundation in filing comments to the Food and Drug Administration (FDA), offering our support for the agency’s new regenerative medicine advanced therapy (RMAT) designation draft guidance for industry.

Although there are opportunities for marginal improvements to the guidance, and FDA approval processes more generally, we are happy to see that the agency chose to include gene therapies in its interpretation of what qualifies as a regenerative medicine therapy.

Under section 3033 of the 21st Century Cures Act, the FDA was tasked with developing an accelerated approval process for regenerative advanced therapies. Such therapies would qualify for expedited review and approval so long as the drug (a) met the definition of a regenerative medicine therapy, (b) was “intended to treat, modify, reverse, or cure a serious condition,” and (c) “has the potential to address unmet medical needs” for a serious disease or condition. Unfortunately, the bill’s definition of a regenerative medicine advanced therapy was unclear on whether gene therapies, in particular, would qualify. Luckily, the FDA clarified this point. As the RMAT guidance document notes:

gene therapies, including genetically modified cells, that lead to a durable modification of cells or tissues may meet the definition of a regenerative medicine therapy. Additionally, a combination product (biologic-device, biologic-drug, or biologic-device-drug) can be eligible for RMAT designation when the biological product component provides the greatest contribution to the overall intended therapeutic effects of the combination product.

This is an excellent development and one that portends immense benefits for future gene therapy applications submitted for FDA approval. According to the guidance, the new RMAT designation, unlike other fast-track approval and review processes, “does not require evidence to indicate that the drug may offer a substantial improvement over available therapies.” Liberalizing the threshold standards of evidence for RMAT designation ensures that future gene therapies will encounter fewer unnecessary roadblocks in delivering more effective and innovative treatments for individuals suffering from debilitating diseases.

As we note in our concluding remarks:

Overall, we consider the RMAT guidance to be a stellar improvement over other expedited programs, especially in its qualifying criteria. However, greater clarity is needed in order to capture the benefits of more advanced cell therapies that can help contribute to the healthy aging and well-being of American citizens. As FDA Commissioner Scott Gottlieb recently noted: “The benefits of [gene therapy] science—and the products that become available—are likely to accelerate. How we define the modern framework for safely advancing these opportunities will determine whether we’re able to fully realize the benefits that these new technologies can offer.”

We agree wholeheartedly. Developing a regulatory framework that accommodates safety and innovation will be a key determinant of how quickly the benefits of regenerative medicine, gene therapy, and anti-aging research revolutionize the lives of Americans. This guidance is an important and promising step in the right direction. With the right modifications, it can help usher in a new age of healthcare improvement for individuals from all walks of life.

Read the full comments submitted to the FDA here.

Source: Niskanen Center

About Elena Milova

As a devoted advocate of rejuvenation technologies since 2013, Elena is providing the community with a systemic vision how aging is affecting our society. Her research interests include global and local policies on aging, demographic changes, public perception of the application of rejuvenation technologies to prevent age-related diseases and extend life, and related public concerns. Elena is a co-author of the book “Aging prevention for all” (in Russian, 2015) and the organizer of multiple educational events helping the general public adopt the idea of eventually bringing aging under medical control.

About Keith Comito

Keith Comito is President of LEAF / Lifespan.io and a long-time advocate of longevity research. He is also a computer programmer, mathematician, musician, lover of life and perhaps a man with too many hobbies. He earned a B.S. in Mathematics, B.S. in Computer science, and M.S. in Applied Mathematics at Hofstra University, where his work included analysis of the LMNA protein.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Alzheimer’s Drug Turns Back the Clock in Mitochondria – Article by Steve Hill

Alzheimer’s Drug Turns Back the Clock in Mitochondria – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill discusses an experimental drug, J147, for treating Alzheimer’s disease and also how Alzheimer’s disease is closely linked to aging.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 26, 2018

J147 is an experimental drug that has been shown to treat Alzheimer’s disease, and it also appears to reverse some aspects of aging. It is also poised to enter human clinical trials in the near future, although how it works has been somewhat of a puzzle.

A new study  published in the journal Aging Cell has changed all that, and the results are quite intriguing [1]. Researchers at the Salk Institute have solved the mystery of how J147 works and why it makes old flies, mice, and cells more youthful.

Rejuvenating mitochondria

The drug apparently works because it binds to a protein found in mitochondria, the powerhouses of cells; this, in turn, causes cells to function in a more youthful manner. Mitochondrial dysfunction is one of the hallmarks of aging and is thought to be a key reason why we age and develop age-related diseases [2]. This drug appears, at least partially, to address some of that dysfunction.

Finding the target of J147 was the key to revealing the link between Alzheimer’s disease and the aging process. It was the critical information the researchers needed and was holding the drug back from clinical trials.

Dave Schubert, head of Salk’s Cellular Neurobiology Laboratory, and his team originally developed the J147 drug in 2011. The team screened numerous plant-sourced compounds with the potential to reverse the cellular and molecular signs of aging in the brain. The drug was developed as a modified version of a molecule found in the spice curcumin, a common ingredient in Asian foods such as curry.

Since then, the researchers have shown that J147 can reverse memory deficits, increases the production of brain cells, and slows the progression of Alzheimer’s in mice [3]. However, at that point, they did not understand how J147 worked.

Finding the target

During the new study lead by Dave Schubert and Salk Research Associate Josh Goldberg, the researchers used a number of approaches to find out how J147 worked. They eventually identified that the target of J147 was the mitochondrial protein known as ATP synthase, specifically ATP5A, a subunit of that protein. ATP synthase is involved in the mitochondrial generation of ATP, which cells use for energy.

The researchers demonstrated that by reducing the activity of ATP synthase, they were able to protect neuronal cells from a number of toxicities associated with the aging of the brain. One reason for this neuroprotective effect is thought to be the role of excitotoxicity in neuronal cell damage.

Excitotoxicity is the pathological process by which neurons are damaged and killed by the overactivation of receptors for the excitatory neurotransmitter glutamate. Think of it being a bit like a light switch being turned on and off so rapidly that it ends up causing the light bulb to blow.

Recently, the role of ATP synthase inhibition for neuroprotection against excitotoxic damage was demonstrated in a mouse study [4]. The second study showed that mouse models expressing the human form of mutant ATPase inhibitory factor 1 (hIF1), which causes a sustained inhibition of ATP synthase, were more resilient to neuronal death after excitotoxic damage. This data is consistent with this new J147 study, in which an increase in IF1 in the mice reduced the activity of ATP synthase (specifically ATP5A) and was neuroprotective.

ATP synthase is implicated in aging

ATP synthase has previously been shown to influence aging in C. elegans worms and flies. Given that aging is the greatest risk factor for developing Alzheimer’s disease, it is no surprise that the target of the drug is also involved in the aging process.

The team also revealed that by modulating the activity of ATP synthase, they could influence the levels of ATP and other molecules and were able to encourage healthier, more stable mitochondria during aging. Mice given the compound showed profound changes, appearing to look younger at a cellular and molecular level.

The researchers believe that these results are not only encouraging for the treatment of Alzheimer’s, they suggest that J147 may also be useful in treating other age-related diseases.

“People have always thought that you need separate drugs for Alzheimer’s, Parkinson’s and stroke,” said Dave Schubert. “But it may be that by targeting aging we can treat or slow down many pathological conditions that are old-age-associated.”

With J147 having just completed the FDA required toxicology testing in animals, the next step is phase 1 human clinical trials, and the road to approval begins.

Conclusion

It is very heartening to hear important researchers suggesting that in order to treat age-related diseases, one needs to treat the aging processes themselves. This is the exactly what Dr. Aubrey de Grey and others have been saying for many years. It is good to hear more voices joining the call to tackle age-related diseases at their root: the hallmarks and damages where they all begin.

The process of age-related disease begins long before the familiar signs and diagnoses are made; by targeting the early processes that are not given specific disease names, we might yet defeat horrific diseases, such as Alzheimer’s, which rob us of who we are.

Literature

[1] Joshua Goldberg et al. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging Cell, 2018 DOI: 10.1111/acel.12715
[2] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
[3] Prior, M., Dargusch, R., Ehren, J. L., Chiruta, C., & Schubert, D. (2013). The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer’s disease mice. Alzheimer’s research & therapy, 5(3), 25.
[4] Formentini, L., Pereira, M. P., Sánchez‐Cenizo, L., Santacatterina, F., Lucas, J. J., Navarro, C., … & Cuezva, J. M. (2014). In vivo inhibition of the mitochondrial H+‐ATP synthase in neurons promotes metabolic preconditioning. The EMBO journal, 33(7), 762-778.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies Steve has provided the community with multiple educational articles, interviews and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.