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Japan Liberalizes Gene Therapy and Regenerative Medicine – Article by Alex Tabarrok

Japan Liberalizes Gene Therapy and Regenerative Medicine – Article by Alex Tabarrok

The New Renaissance HatAlex Tabarrok
September 17, 2015

Japan is liberalizing its approval process for regenerative medicine:

Regenerative medicines in Japan can now get conditional marketing approval based on results from mid-stage, or Phase II, human trials that demonstrate safety and probable efficacy.

Once lagging behind the United States and the European Union on approval times, there is now an approximately three-year trajectory for approvals, according to Frost’s Kumar. That compares with seven to 10 years before. …

Around the world, companies have also faced setbacks while pushing such treatments. In the U.S., Geron Corp., which started the first nation-approved trial of human embryonic stem cells, ended the program in 2011, citing research costs and regulatory complexities. …

While scientists globally have worked for years in this field, treatments have been slow to come to market. But there is hope in Japan that without the political red tape, promising therapies will emerge faster and there will be speedier rewards.

Japan is liberalizing because with their aging population treatments for diseases like Alzheimer’s and Parkinson’s disease are in high demand.

Under the new system, a firm with a gene or regenerative therapy (e.g. stem cells) can get conditional approval with a small trial. Conditional approval means that the firm will be able to sell its procedure while continuing to gather data on efficacy for a period of up to seven years. At the end of the seven-year period, the firm must either apply for final marketing approval or withdraw the product.

The system is thus similar to what Bart Madden proposed for pharmaceuticals in Free to Choose Medicine.*

Due to its size and lack of price controls, the US pharmaceutical market is the most lucrative pharmaceutical market in the world.

Unfortunately, this also means that the US FDA has an outsize influence on total world investment. The Japanese market is large enough, however, that a liberalized approval process if combined with a liberalized payment model could increase total world R&D.

Breakthroughs made in Japan will be available for the entire world so we should all applaud this important liberalization.

This post first appeared at Marginal Revolution.

* Editor’s note from the Foundation for Economic Education: There may well by a direct connection here. According to Madden, an early version of his proposal in Free to Choose Medicine was published in a booklet by the Heartland Institute, which was then translated and distributed in Japan by a Japanese free-market think tank.

For more on free markets in medicine, see Bart Madden’s article “The Pathway to Faster Cures” in the autumn print edition of the Freeman and on The Rational Argumentator.

Alex Tabarrok is a professor of economics at George Mason University. He blogs at Marginal Revolution with Tyler Cowen. 

A Simpler Path to Creating Pluripotent Stem Cells – Article by Reason

A Simpler Path to Creating Pluripotent Stem Cells – Article by Reason

The New Renaissance Hat
January 31, 2014

An improvement on current methods of creating pluripotent stem cells has been in the news the past few days. It involves stressing cells with simple mechanisms, and is straightforward enough that I hear numerous laboratories and individual researchers have started in on trying it out immediately, as well as revisiting other variants of stressing cells to see what the outcome might be. The methodology is something that DIYbio enthusiasts could carry out as a weekend project with minimal cost and equipment, which is a great improvement over prior standard methods involving delivery of genes or similar operations.

As with all such potential infrastructure improvements, one pillar of importance is the reduction in cost and difficulty of research. When someone figures out a much cheaper way of achieving any particular goal, all further work that builds on that goal moves more rapidly: existing groups can do more, and new groups that previously couldn’t afford to join in now start work. Cell pluripotency is near the base of regenerative medicine and tissue engineering: ways to better achieve it accelerate the whole field.

As you can see, there are also other ramifications, however, such as for persistent reports of pluripotent stem cells isolated from adult tissues – VSELs and others – and the debate over difficulties in replicating that research.


In 2006, Japanese researchers reported a technique for creating cells that have the embryonic ability to turn into almost any cell type in the mammalian body – the now-famous induced pluripotent stem (iPS) cells. In papers published this week, another Japanese team says that it has come up with a surprisingly simple method – exposure to stress, including a low pH – that can make cells that are even more malleable than iPS cells, and do it faster and more efficiently.

“It’s amazing. I would have never thought external stress could have this effect,” says Yoshiki Sasai. It took Haruko Obokata, a young stem-cell biologist at the same centre, five years to develop the method and persuade Sasai and others that it works. “Everyone said it was an artefact – there were some really hard days.”

The results could fuel a long-running debate. For years, various groups of scientists have reported finding pluripotent cells in the mammalian body. But others have had difficulty reproducing such findings. Obokata started the current project by looking at cells thought to be pluripotent cells isolated from the body. But her results suggested a different explanation: that pluripotent cells are created when the body’s cells endure physical stress.

Obokata has already reprogrammed a dozen cell types, including those from the brain, skin, lung and liver, hinting that the method will work with most, if not all, cell types. On average, she says, 25% of the cells survive the stress and 30% of those convert to pluripotent cells – already a higher proportion than the roughly 1% conversion rate of iPS cells.


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

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

A Speculative Order of Arrival for Important Rejuvenation Therapies – Article by Reason

A Speculative Order of Arrival for Important Rejuvenation Therapies – Article by Reason

The New Renaissance Hat
October 6, 2012

A toolkit for producing true rejuvenation in humans will require a range of different therapies, each of which can repair or reverse one of the varied root causes of degenerative aging. Research is underway for all of these classes of therapy, but very slowly and with very little funding in some cases. The funding situation spans the gamut from that of the stem cell research community, where researchers are afloat in money and interest, to the search for ways to break down advanced glycation endproducts (AGEs), which is a funding desert by comparison, little known or appreciated outside the small scientific community that works in that field.

While bearing in mind that progress in projects with little funding is unpredictable in comparison to that of well-funded projects, I think that we can still take a stab at a likely order of arrival for various important therapies needed to reverse aging. Thus an incomplete list follows, running from the earliest to the latest arrival, with the caveat that it is based on the present funding and publicity situation. If any one of the weakly funded and unappreciated lines of research suddenly became popular and awash with resources, it would probably move up in the ordering:

1) Destruction of Senescent Cells

Destroying specific cells without harming surrounding cells is a well-funded line of research thanks to the cancer community, and the technology platforms under development can be adapted to target any type of cell once it is understood how to target its distinctive features.

The research community has already demonstrated benefits from senescent cell destruction, and there are research groups working on this problem from a number of angles. A method of targeting senescent cells for destruction was recently published, and we can expect to see more diverse attempts at this in the next few years. As soon as one of these can be shown to produce benefits in mice that are similar to the early demonstrations, then senescent cell clearance becomes a going concern: something to be lifted from the deadlocked US regulatory process and hopefully developed quickly into a therapy in Asia, accessed via medical tourism.

2) Selective Pruning and Support of the Immune System

One of the reasons for immune system decline is crowding out of useful immune cells by memory immune cells that serve little useful purpose. Here, targeted cell destruction can also produce benefits, and early technology demonstrations support this view. Again, the vital component is the array of mechanisms needed to target the various forms of immune cell that must be pruned. I expect the same rising tide of technology and knowledge that enables senescent cell targeting will lead to the arrival of immune cell targeting on much the same schedule.

Culling the immune system will likely have to be supported with some form of repopulation of cells. It is already possible to repopulate a patient’s immune system with immune cells cultivated from their own tissues, as demonstrated by the limited number of full immune system reboots carried out to cure autoimmune disorders. Alternatives to this process include some form of tissue engineering to recreate the dynamic, youthful thymus as a source of immune cells – or more adventurous processes such as cultivating thymic cells in a patient’s lymph nodes.

3) Mitochondrial Repair

Our mitochondria sabotage us. There’s a flaw in their structure and operation that causes a small but steadily increasing fraction of our cells to descend into a malfunctioning state that is destructive to bodily tissues and systems.

There are any number of proposed methods for dealing with this component of the aging process – either repairing or making it irrelevant – and a couple are in that precarious state of being just a little more solidity and work away from the point at which they could begin clinical development. The diversity of potential approaches in increasing too. Practical methods are now showing up for ways to put new mitochondria into cells, or target arbitrary therapies to the interior or mitochondria. It all looks very promising.

Further, the study of mitochondria is very broad and energetic, and has a strong presence in many areas of medicine and life science research. While few groups in the field are currently engaged in work on mitochondrial repair, there is an enormous reservoir of potential funding and workers awaiting any method of repair shown to produce solid results.

4) Reversing Stem Cell Aging

The stem cell research field is on a collision course with the issue of stem cell aging. Most of the medical conditions that are best suited to regenerative medicine, tissue engineering, and similar cell based therapies are age-related, and thus most of the patients are old. In order for therapies to work well, there must be ways to work around the issues caused by the aged biochemistry of the patient. To achieve this end, the research community will essentially have to enumerate the mechanisms by which stem cell populations decline and fail with age, and then reverse their effects.

Where stem cells themselves are damaged by age, stem cell populations will have to be replaced. This is already possible for many different types of stem cell, but there are potentially hundreds of different types of adult stem cell – and it is too much to expect for the processes and biochemistry to be very similar in all cases. A great deal of work will remain to be accomplished here even after the first triumphs involving hearts, livers, and kidneys.

Much of the problem, however, is not the stem cells but rather the environment they operate within. This is the bigger challenge: picking out all the threads of signalling, epigenetic change, and cause and effect that leads to quieted and diminished stem cell populations – and the resulting frailty as tissues are increasingly poorly supported. This is a fair sized task, and little more than inroads have been made to date – a few demonstrations in which one stem cell type has been coerced into acting with youthful vigor, and a range of research on possible processes and mechanisms to explain how an aging metabolism causes stem cells to slow down and stop their work.

The stem cell research community is, however, one of the largest in the world, and very well funded. This is a problem that they have to solve on the way to their declared goals. What I would expect to see here is for a range of intermediary stopgap solutions to emerge in the laboratory and early trials over the next decade. These will be limited ways to invigorate a few aged stem cell populations, intended to be used to boost the effectiveness of stem cell therapies for diseases of aging.

Any more complete or comprehensive solution for stem cell aging seems like a longer-term prospect, given that it involves many different stem cell populations with very different characteristics.

5) Clearing Advanced Glycation Endproducts (AGEs)

AGEs cause inflammation and other sorts of mischief through their presence, and this builds up with age. Unfortunately, research on breaking down AGEs to remove their contribution to degenerative aging has been a very thin thread indeed over the past few decades: next to no-one works on it, despite its importance, and very little funding is devoted to this research.

Now on the one hand it seems to be the case that one particular type of AGE – glucosepane – makes up 90% or more the AGEs in human tissues. On the other hand, efforts to find a safe way to break it down haven’t made any progress in the past decade, though a new initiative was launched comparatively recently. This is an excellent example of how minimally funded research can be frustrating: a field can hover just that one, single advance away from largely solving a major problem for years on end. All it takes is the one breakthrough, but the chances of that occurring depend heavily on the resources put into the problem: how many parallel lines of investigation can be followed, how many researchers are working away at it.

This is an excellent candidate for a line of research that could move upward in the order of arrival if either a large source of funding emerged or a plausible compound was demonstrated to safely and aggressively break down glucospane in cell cultures. There is far less work to be done here than to reverse stem cell aging, for example.

6) Clearing Aggregates and Lysomal Garbage

All sorts of aggregates build up within and around cells as a result of normal metabolic processes, causing harm as they grow, and the sheer variety of these waste byproducts is the real challenge. They range from the amyloid that features prominently in Alzheimer’s disease through to the many constituents of lipofuscin that clog up lysosomes and degrade cellular housekeeping processes. At this point in the advance of biotechnology it remains the case that dealing with each of the many forms of harmful aggregate must be its own project, and so there is a great deal of work involved in moving from where we stand today to a situation in which even a majority of the aggregates that build up with age can be removed.

The most promising lines of research to remove aggregates are immunotherapy, in which the immune system is trained or given the tools to to consume and destroy a particular aggregate, and medical bioremediation, which is the search for bacterial enzymes that can be repurposed as drugs to break down aggregates within cells. Immunotherapy to attack amyloid as a treatment for Alzheimer’s is a going concern, for example. Biomedical remediation is a younger and far less funded endeavor, however.

My expectation here is that some viable therapies for some forms of unwanted and harmful metabolic byproducts will emerge in the laboratory over the next decade, but that will prove to be just the start on a long road indeed. From here it’s hard for me to guess at where the 80/20 point might be in clearing aggregates: successfully clearing the five most common different compounds? Or the ten most common? Or twenty? Lipofuscin alone has dozens of different constituent chemicals and proteins, never mind the various other forms of aggregate involved in specific diseases such as Alzheimer’s.

But work is work: it can be surmounted. Pertinently, and again, the dominant issue in timing here is the lack of funding and support for biomedical remediation and similar approaches to clearing aggregates.

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

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

Update to Resources on Indefinite Life Extension – July 10, 2012

Update to Resources on Indefinite Life Extension – July 10, 2012

TRA’s Resources on Indefinite Life Extension page has been enhanced over the past two months with links to numerous fascinating articles and videos.


– “Scientists turn skin cells into beating heart muscle” – Kate Kelland – Reuters – May 22, 2012

– “Is Amyloidosis the Limiting Factor for Human Lifespan?” – Lyle J. Dennis, M.D. – Extreme Longevity – May 22, 2012

– “Israeli scientists create beating heart tissue from skin cells” – The Telegraph – May 23, 2012

– “Paralyzed rats walk again in Swiss lab study” – Chris Wickham – – May 31, 2012

– “New Cancer Drugs Use Body’s Own Defenses” – Ron Winslow – Wall Street Journal – June 1, 2012

– “Bristol immune drug shows promise in three cancers” – Julie Steenhuysen – Reuters – June 2, 2012

– “Prostate cancer drug so effective trial stopped” – Victoria Colliver – San Francisco Chronicle – June 2, 2012

– “New ‘smart bomb’ drug attacks breast cancer, doctors say” – Associated Press – June 3, 2012

– “Alzheimer’s vaccine trial a success” – Karolinska Institutet – June 6, 2012

– “Man Cured of AIDS: ‘I Feel Good’” – Carrie Gann – ABC News – June 8, 2012

– “Artificial Lifeforms Promise Cleaner World, Healthier Humans” – Dick Pelletier – Positive Futurist – June 9, 2012

– “Secret of ageing found: Japanese scientists pave way to everlasting life” – RT – June 9, 2012

– “How aging normal cells fuel tumor growth and metastasis” – Thomas Jefferson University – June 14, 2012

– “People Who Justify Aging are Profoundly Wrong – Aging is Abhorrent” – Maria Konovalenko – Institute for Ethics & Emerging Technologies – June 14, 2012

– “Scientists tie DNA repair to key cell signaling network” – University of Texas Medical Branch at Galveston – June 15, 2012

– “Deciding How We Age as We Age” – Seth Cochran – h+ Magazine – June 19, 2012

– “How we die (in one chart)” – Sarah Kliff – Washington Post – June 22, 2012

– “Modified humans: the most cost-efficient way to colonize space” – Dick Pelletier – Positive Futurist – June 2012

– “Japanese Scientists Grow Human Liver From Stem Cells” – Reuters and Singularity Weblog – June 2012

– “Why Do Naked Mole Rats Live So Long? Do they hold the key to human life extension?” – Maria Konovalenko – Institute for Ethics & Emerging Technologies – June 29, 2012

– “Scientists Develop Alternative to Gene Therapy” – ScienceDaily – Scripps Research Institute – July 1, 2012

– “How to live beyond 100” – Lucy Wallis – BBC News – July 2, 2012

– “Earth 2050-2100: longer lives; new energy; FTL travel; global village” – Dick Pelletier – Positive Futurist – July 3, 2012

– “Scientists discover bees can ‘turn back time,’ reverse brain aging” – – Arizona State University – July 3, 2012

– “Secret formula may be key to reverse aging” – Mike Holfeld – Click Orlando – July 4, 2012

– “Is there a biological limit to longevity?” – Aubrey de Grey – KurzweilAI – July 5, 2012

– “Demystifying the immortality of cancer cells” – Medical Xpress – July 5, 2012

– “Suggesting a Test of Rapamycin and Metformin Together” – Reason – – July 5, 2012

– “Earth 2050-2100: Longer Lives; New Energy; FTL Travel; Global Village” – Dick Pelletier – Positive Futurist – July 7, 2012


Aubrey de Grey

Aubrey de Grey – Aging & Suffering – Interview with Adam Ford – May 31, 2012

Nikola Danaylov (Socrates)

Anders Sandberg on Singularity 1 on 1: We Are All Amazingly Stupid, But We Can Get Better – May 27, 2012

Hugo de Garis on Singularity 1 on 1: Are We Building Gods or Terminators? – June 2012