World Health Organization

Here is an example of what I think is a passable submission to Google's Project 10100, with a focus on mitochondrial science. I could probably run one up for LysoSENS-like work as well, but one thing at a time.

Bring Mitochondrial Repair to Phase 1 Trials

What one sentence best describes your idea? (maximum 150 characters):

Our mitochondria degrade over the years, contributing greatly to age-related disease and frailty - but medical technology can fix this problem.

Describe your idea in more depth. (maximum 300 words):

I propose that the most promising of nascent mitochondrial repair technologies be funded from their present early-stage standing to readiness for Phase I clinical trials in humans. As a condition of funding, methodologies will be published free of restriction for any group to further develop and bring to market. This will be accomplished with the aid of a non-profit research organization like the Methuselah Foundation, with a history of raising matching funds for large donations, so as to maximize the impact of the funding program.

Mitochondria are tiny power plants inside our cells, churning away to turn food into energy. They were once free-roaming bacteria and have retained their own mitochondrial DNA, distinct from our own nuclear DNA. As our mitochondria fail, however, so do we. The Mitochondrial Free Radical Theory of Aging points to progressive damage to our mitochondrial DNA as an important - and arguably the most important - root cause of age-related degeneration, disease, and frailty.

At present, a range of plausible technologies exist to repair mitochondrial DNA, replace mitochondrial DNA, or make damage to this DNA irrelevant. These technologies stand at varying points between ideation and animal trials: whole-body replacement of mitochondrial DNA was demonstrated in mice as early as 2005, for example, as has the process of allotopic expression: moving a single important mitochondrial gene into the cellular nucleus, such that the necessary proteins are still made, and a damaged mitochondrion continues to function.

These technologies are progressing very slowly and with a paucity of funding, partly because this is the nature of early research, partly because of perverse regulatory incentives. This is unacceptable when considered against a) the comparatively low cost of basic research in this age of biotechnology, and b) the vast potential benefits to humanity. Philanthropic funding can overcome these hurdles.

What problem or issue does your idea address? (maximum 150 words):

Consequences of damaged mitochondrial DNA include failing organs, clogged arteries, neurodegeneration, and much more. This is the Mitochondrial Free Radical Theory of Aging, well supported by decades of evidence. A working repair technology pushed into the clinical system has the potential to entirely remove this large contribution to disease and frailty. But first it must be finalized from the promising beginnings presently in the laboratory.

Regulatory bodies like the FDA restrict all application of medical science to specific, named diseases; this makes early stage research to produce a general repair technology for mitochondria unprofitable. It would be hard to license, as a developer would struggle to make money on that license. Yet it costs little to move established research to Phase I trial readiness - $1 million is a fortune for a single laboratory - and developers leap at license-free medical technology. This is where careful philanthropy can unjam the gridlocked system.

If your idea were to become a reality, who would benefit the most and how? (maximum 150 words):

A mitochondrial repair technology demonstrated to be ready for human trials, free of licensing cost, free from intellectual property restrictions, and unjammed from the system of perverse incentives in early-stage research stands to benefit everyone. It will be as universally beneficial a medicine as aspirin; the elderly will benefit immediately upon availability, we will benefit from it in decades to come, and our children will benefit when their bodies too start to run down.

Everyone has mitochondria, and mitochondrial degeneration is a universal condition, bringing myriad forms of suffering and pain. We got rid of tuberculosis and smallpox as soon as we could, so why not this? Repair of mitochondrial DNA damage is a very plausible near-future win for everyone, given where the science is today. We can make it happen.

What are the initial steps required to get this idea off the ground? (maximum 150 words):

I envisage the opening labor as follows: 1) Identify the existing non-profit research group and volunteer cadre to run this project - my vote is for the Methuselah Foundation, given their record and contacts within the research community, and the way their mission aligns with that of this project; 2) Identify the best groups and laboratories presently engaged in mitochondrial repair and related research; 3) Develop prospective work, milestone, and funding plans with researchers; 4) Start raising matching funds through existing channels; 5) Select the initial funding opportunities from the best of those produced, and get the researchers to work.

From there, I would like to see established a low-overhead but effective volunteer group of researchers and advocates to manage the cycle of grants, matching fundraising, and evaluation of progress and new research opportunities going forward.

Describe the optimal outcome should your idea be selected and successfully implemented. How would you measure it? (maximum 150 words):

The optimal outcome, after the completion of the project, is: a) for one or more different repair technologies to be successfully readied for Phase 1 human trials; b) protocols and methods to be fully detailed and published, free of restriction; c) multiple medical development concerns to be working on bringing applications to market in diverse regulatory regions; d) independently funded follow-on research taking place with the aim of improving upon the initial technology; e) matching fundraising to effectively continue even after the Google grant is complete.

Sample metrics for success include: a) the breadth and effectiveness of the technologies developed; b) the quality of the published material; c) range of developers working on applications; d) the range of independently funded lines of work spawned by this philanthropic funding; and, most crucially, e) the amount of matching funding and independent research and development funding drawn by this philanthropic project.

If you'd like to recommend a specific organization, or the ideal type of organization, to execute your plan, please do so here. (maximum 50 words):

The ideal organization is a research non-profit with existing connections to scientists already involved in mitochondrial repair research, a very low cost of operation for delivered funding, and a history of raising matching funds for large donations. The ideal example is the Methuselah Foundation, as you might have gathered.

Chris Patil of Ouroboros is blogging this year's Cold Spring Harbor Labs conference on the molecular genetics of aging. You might recall his coverage of the 2006 meeting as well. This time round:

The first conference post is up:

A lot of interesting detail follows, so take a look.

Today I thought I'd share a readable overview of presently discovered longevity genes: how they fit into a small number of broad categories, and are surprisingly similar across a range of different organisms. It's an open access paper, so don't miss the PDF link underneath the abstract.

Longevity Genes: Insights from Calorie Restriction and Genetic Longevity Models

Surprisingly, there are very few longevity models to evaluate the enhanced anti-oxidative mechanism, while there is substantial evidence supporting the oxidative stress and damage theory of aging. Either increased or reduced mitochondrial function may extend the lifespan. The role of Redox regulation and mitochondrial function in CR remains to be elucidated.

It is my impression from watching this all develop for some few years that mitochondrial research is where the big payoff is in the mainstream of aging research - those researchers who are not yet thinking along the lines of damage repair strategies, but are instead moving ahead with a slower approach. Half the field is working on a range of interconnected metabolic control mechanisms, which I can't see producing anywhere near as dramatic results as quickly as a full-court press towards repairing mitochondrial damage. Even somewhat slowing oxidative damage to mitochondria produces gains in life span in mice that are on the same order as that of calorie restriction - imagine what we could do with one of the more comprehensive mitochondrial repair technologies presently under development.

There are two papers out on science and medical blogging. The first is concerned with medical blogging, and I vaguely remember filling in the questionnaire some time ago. It is also reported on the blog of one of the authors, who also makes good use of lecture slides. There’s some interesting findings although the relatively small numbers, due to a response rate of 42% may make these results atypical. Ironically, given the media track record in science reporting, this is from a section entitled Journalistic Activities.

More than half of the responding medical bloggers have published a scientific paper (43/80, 54%), 35 (44%) bloggers have published a book or a chapter in a book, and 32 (41%) have published a newspaper article. Highly educated bloggers were more likely to have published a book or a chapter in a book (50% vs 14%, 21= 6.19, P= .01) and a scientific paper (62% vs 21%, 21= 7.57, P= .08) than those with lower levels of education. When it comes to best practices associated with journalism, the participants most frequently reported including links to original source of material and spending extra time verifying facts, while they rarely tried to obtain permission to post copyrighted material.

Female medical bloggers were found to get permission for posting copyrighted material more often than male bloggers (U= 386, n1= 25, n2= 44, P= .03). Bloggers who have published a scientific paper were more likely to quote directly other people or media than those who never published such a paper (U= 506.5, n1= 41, n2= 35, P= .016). Blog writers who were blogging under their real name were more inclined to include links to original sources than those writing under a pseudonym (U= 446.5, n1= 58, n2= 19, P= .01).

Kovic I, Lulic I, Brumini G
Examining the Medical Blogosphere: An Online Survey of Medical Bloggers
J Med Internet Res 2008;10(3):e28
http://www.jmir.org/2008/3/e28/

The second paper is about the role of blogs in academic science, and is effectively a call for institutions to engage with blogs as a new communication medium, although there are potential problems with the natural tendency of institutions wishing to control their public image, and the perhaps inhibitory consequences of blogging becoming part of a job, rather than a personal altruistic outpouring. I fully agree with this statement:

Scholarly journal articles are not intellectually accessible to most of the population, and are often behind an expensive pay-wall. Conversely, science blogs are freely accessible, interactive, and are generally written for a lay audience. Although only a small percentage of the 38% of 12- to 17-year-olds who read blogs may be reading science blogs, blogs clearly have the potential to reach an age group where excitement about a future career in science could be ignited. An excellent example of an educational, fun, and accessible science blog is The Panda’s Thumb, where evolutionary biologists tackle questions about evolution in easy-to-understand ways, and science teachers are an important part of their audience (http://www.pandasthumb.org/).

Batts SA, Anthis NJ, Smith TC (2008) Advancing Science through Conversations: Bridging the Gap between Blogs and the Academy. PLoS Biol 6(9): e240 doi:10.1371/journal.pbio.0060240

Researcher Joo Pedro de Magalhes - author of the excellent senescence.info website - is now set up with his own lab at Liverpool University across the pond. He'll be forming up the The Integrative Genomics of Aging Group and getting to work on what is clearly his passion. From the research introduction:

Because longevity evolved in the human lineage, we are particularly interested in employing modern computational methods in primates to study the evolution, structure, and function of genes associated with ageing, which may shed light on the genetic changes that contributed to the evolution of human longevity. Ultimately, our goal is to understand why we are different from each other and from other species and what is the role of each DNA base in the genome in determining these differences, in particular in the context of ageing and age-related diseases.

This is all fresh from the presses, and there are possibilities for undergraduates and postgraduates to help with this work. Take a look if you're at that stage in a life science career, and haven't already been spirited away by the Methuselah Foundation's Undergraduate Research Initiative.

For my part, I'm pleased to see that the goal of intervening in aging is ceasing to be the dreaded third rail of grantsmanship that must not be mentioned. As more labs around the world are founded with the explicitly stated agenda of treating aging to improve the human condition, the tide of public support and understanding will continue to turn. It's that tide, the broad sentiment of support for longevity science, that will sustain much needed growth in the research community over the long haul.