Public sector


Welcome to the tenth edition of Hourglass, our blog carnival about the biology of aging. This month, the carnival has returned home to Ouroboros. In this issue, we have submissions from six bloggers, including a nice mix of veterans and new participants. Several of the posts are united by common themes: we have heavy representation from the neuroscience community, and multiple discussions of the clinical and social payoffs that are likely to result from progress in lifespan extension.

At psique (which hosted Hourglass IX), Laura Kilarski describes an important, evolving online tool for biogerontologists: the Human Aging Genomics Resources:

As I was reading a paper earlier about chromosomal region 11.5p and its putative association with aging (Lescai et al, 2009) I came across an interesting sounding url, namely http://genomics.senescence.info. Turns out that the website is home to HAGR, an interdisciplinary project devoted to the genetic study of aging … GenAge constitutes a major part of the site, and is a manually curated database of genes which could possibly be associated with human aging, largely based on studies done on the usual suspects: Mr. Mouse, Drosophila, C. elegans, and yeast. … The AnAge database on the other hand contains entries for over 4000 animals and some basic life-span-related facts. … And then there’s the ‘Δ Project’, the aim of which is to figure out transcriptional differences between young and old organisms.

Laura describes HAGR in depth and also provides some of her own analysis of the available resources.

On another age-related subject, neurodegeneration, Laura discusses the potential value of regular brain scans for early ascertainment of diseases such as Parkinson’s. Free brain scans for all! It’s a moving piece, which underscores the human cost of neurodegenerative illness and describes the author’s personal reactions on the subject, while also addressing important clinical and scientific issues.

As we age, we all suffer from some level of neurodegeneration, though in most cases this falls below the threshold of a clinical pathology. Slow chronic change isn’t the only form of age-related brain damage: let’s not forget about strokes, which can wipe out otherwise healthy neurons in macroscopic regions of the brain. While the risk factors for stroke and neurodegeneration are distinct, therapies might ultimately be quite similar — since in both cases, the goal is to regrow neurons to replace those that have been lost. At Brain Stimulant, Mike tell us about a clinical trial that will use stem cells to treat stroke:

The company Reneuron has just recently gotten the go ahead to commence a new trial that will use stem cells to treat patients with stroke damage. The trial will use stem cells to replace missing brain matter in those who have had stroke brain trauma. They are injecting doses of approximately 20 million stem cells into the stroke patients brain. Interestingly these ReN001 stem cells will not require a patient to have immunosuppression therapy.

He goes on to discuss the future challenges posed by the prospect for brain engineering: precise cell delivery, control of axon sprouting and pathfinding, and the possibility of using non-invasive methods to encourage the growth of new cells.

Also coming from a neuroscience perspective, Christopher Harris of Best Before Yesterday writes about What we need to accelerate biomedical research and fight aging.

A few hundred years ago I could not have been born. I was massive – 5.5kg – and the birth eventually turned caesarean and took many long hours. I owe my life to medical science. One day, 11 years later, I was out biking and realized for the first time that the annihilation following my death would be infinite. Now, 25 years after my complicated birth, I think a lot about whether medical science, rejuvenation research of the SENS variety in particular, will save me a second time.

What do we need? According to Harris: (1) Safe and inexpensive brain surgery (to install devices that can manipulate the reward circuitry of the brain); (2) Widespread use of enhanced motivation through deep brain stimulation (specifically to encourage exercise and healthy living); and (3) Rewarding brain stimulation for research centers (to accelerate scientific progress).

One of my favorite new sites, the Science of Aging Timeline, has a new entry about the Sinclair lab’s discovery of sirtuin-activating compounds:

Working off a model of calorie restriction via sirtuins David Sinclair et al. worked to find molecules which could modulate sitruins activity, and thus longevity.

They accomplished this by screening a number of small molecule libraries, which included analogues of epsilon-acetyl lysine, NAD+, NAD+ precursors, nucleotides and purinergic ligands. Results from the screening where assayed against human SIRT1 to identify potential inhibitors, and the following molecules where found: Resveratrol, Butein, Piceatannol, Isoliquiritigenin, Fisetin, and Quercetin. Of all of these, resveratrol proved to be the most potent …

In the copious spare time left when he’s not working on the comprehensive history of biogerontology, timeline curator Paul House has started another ambitious project: a catalog of all the labs working on aging. It’s early days yet, and only a few labs are listed, but I’ve already seen Paul take one great idea (the timeline) from seed to oak, so I have every confidence that this page will grow substantially in the weeks and months to come. Those who are interested in having their labs listed on the page can send Paul an email.

Over at Fight Aging!, Reason continues excellent coverage of recent papers in biogerontology; I daresay that the detail of coverage on primary scientific literature has improved even further in the past month or so, concomitant with the site’s participation in the ResearchBlogging tracking system for blog posts about journal articles. For this edition of Hourglass, Reason has submitted two excellent analyses of recent papers, and a third piece of a more philosophical bent:

It is from the last piece that I’ve chosen an excerpt:

Wouldn’t it be nice to wake up and find that we were all immortal? That would save a whole lot of work, uncertainty, and existential angst – and we humans are nothing if not motivated to do less work. The best of us toil endlessly in search of saving a few minutes here and a few minutes there. So it happens that there exist a range of metaphysical lines of thought – outside the bounds of theology – that suggest we humans are immortal. We should cast a suspicious eye upon any line of philosophy that would be extraordinarily convenient if true, human nature being what it is.

Moving on from a philosophical post written by a scientifically minded life-extension advocate, our next posts are scientific posts written about life extension from a political philosopher. Colin Farrelly of In Search of Enlightenment has submitted two long, thoughtful articles, the first about the clinical and social importance of tackling aging, the second about the cognitive biases that affect the way we think about risk and the significance of aging as a cause of mortality:

The “availability heuristic” was a new one on me. Here’s an operational definition as it applies to our thinking about aging:

In a rational world, aging research would be at the forefront of a global collaborative initiative to improve the health and economic prospects of today’s aging populations (and all future generations).

But humans are not rational. We suffer many cognitive biases. One prominent bias is the availability heuristic. Risks that are easily brought to mind are given a higher probability; and conversely, the less vivid a risk, the more likely we are to underestimate the probability of their occurring.

The two tests above reveal how prominent this heuristic is in your own comprehension of the risks facing yourself, your loved ones and humanity. Because death by aging is not something that is vivid is most people’s minds (though it is in the minds of the scientists who study the biology of aging and thus know all too well how it affects a species functional capacities), odds are you probably underestimated it as a risk of mortality.

The benefits of lifespan extension, both with regard to human health and society as a whole is sometimes called the Longevity Dividend. Alvaro Fernandez from SharpBrains sent in a long piece about the Longevity Dividend (written by a contributor from the Kronos Longevity Research Institute). Ever heard of the Longevity Dividend? Perhaps Gray is the New Gold:

The Longevity Dividend is a theory that says we hope to intervene scientifically to slow the aging process, which will also delay the onset of age-related diseases. Delaying aging just seven years would slash rates of conditions like cancer, diabetes, Alzheimer’s disease and heart disease in half. That’s the longevity part. … The dividend comes from the social, economic, and health bonuses that would then be available to spend on schools, energy, jobs, infrastructure—trillions of dollars that today we spend on healthcare services. In fact, at the rate we’re going, by the year 2020 one out of every $5 spent in this country will be spent on healthcare. Obviously, something has to change.

Alvaro, the editor of SharpBrains and founder of the parent website, has recently published a book, The SharpBrains Guide to Brain Fitness, which is the subject of this recent (and quite favoriable) review. If you’re interested in learning more, here’s list of cognitive fitness references, based on the authors’ research for the book.

That’s all for now. If you’d like to host a future installation of Hourglass, please email me.

Advertisements

UCSC, the institution that brought you the industry-standard genome browser, has now launched the UCSC Cancer Genomics Browser:

The browser is a suite of web-based tools to integrate, visualize and analyze cancer genomics and clinical data. This browser displays a whole-genome and pathway-oriented view of genome-wide experimental measurements for individual and sets of samples alongside their associated clinical information.

This site hosts the public UCSC Cancer Genomics Browser. The public site contains a rapidly growing body of publicly available cancer genomic data, including 12 published studies, datasets from the TCGA consortium, and others.

We encourage you to explore these data with our tools. The browser enables investigators to order, filter, aggregate, classify and display data interactively based on any given feature set including clinical features, annotated biological pathways, and user-edited collections of genes. Standard statistical tools are integrated to provide quantitative analysis of whole genomic data or any of its subsets.

I suspect that the Cancer Genomics Browser will provide an indispensable tool for biogerontologists who are seeking to explore the mechanistic connections between aging and cancer. I’m currently trying to think up an interesting way to use the service (and publicly available data) in my own work: e.g., tumors all have to undergo cellular senescence; would it be possible to find some fingerprint of senescence bypass mechanisms by looking at expression data from large numbers of tumors?

Bush administration science policy was a mini-Dark Age for American science. Religious dogma superseded evidence and there was very little room for scientists in the halls of power. As that era recedes into the past, there’s cause for optimism — President Obama began his term with a pledge to “restore science to its rightful place” in government, and he has demonstrated a willingness to seriously consider the advice of scientific experts in formulating policy. Most exciting from the biogerontologist’s perspective, he has taken steps to do so by reversing George Bush’s ill-advised and religiously motivated ban on the use of federal funds in embryonic stem cell research.

An article in Seed magazine makes the excellent point that the new administration are not motivated (nor should they be) by a love of all things scientific. Rather, freedom of inquiry and a prominent role for evidence-based methods in policymaking are corollaries of the moral values that underlie a functional democracy — per the subtitle of the piece, “the sound conduct of science and the sound conduct of democracy both depend on the same shared values.”

The Essential Parallel Between Science and Democracy

Many have interpreted these moves as welcome signs of Washington’s renewed respect for science, and they are right to do so. But if understanding stops there, then we’re in trouble. For the restorative steps Obama has taken vis-à-vis science are praiseworthy not so much because they respect science as because they respect the grand institutions of democracy. This is no accident, because the very virtues that make democracy work are also those that make science work: a commitment to reason and transparency, an openness to critical scrutiny, a skepticism toward claims that too neatly support reigning values, a willingness to listen to countervailing opinions, a readiness to admit uncertainty and ignorance, and a respect for evidence gathered according to the sanctioned best practices of the moment.

The article continues with a warning against technocracy (ceding of authority to scientists without continuing to rigorous embrace of scientific modes of thought) and a reminder that scientists should always be enthusiastic about speaking truth to power — i.e., even if the establishment accepts us, we shouldn’t turn that acceptance in an opportunity to make ourselves into a priesthood that plays by special rules.

A nice piece about the systemic challenges facing academic biologists appeared in Olivia Judson’s blog, The Wild Side. The post, entitled Letting Scientists Off the Leash, was written by Stephen Quake, an HHMI investigator currently working at Stanford University. Rather than excerpt the item itself, I’ll reproduce the commentary of our friend and former contributor Lev Osherovich, at his blog William Butler Yeast:

Steve Quake has a totally spot-on op-ed piece in the NY Times Science blog about the medieval economics of academic science. In brief, competition for scarce funding together with the role of university bureaucracies as intellectual slumlords traps researchers in an endless grant-writing cycle that demands conformity and quashes creativity. One of the commentators correctly points out that this state of affairs is a consequence of massive overproduction of Ph.D. scientists.

I’m not in complete agreement with everything Quake says. In particular, I think he massively understates the extent to which private foundations are subject to the same conservatism as government agencies. Granted, the Howard Hughes Medical Institute does allow its investigators a lot of freedom, but one can only get an HHMI grant after succeeding for a decade or more at the plodding drudgery of NIH grant-writing. This generates a sort of Peter Principle effect: a professor is rewarded for long-term success at inside-the-box thinking by finally being let outside of the box and told that they can do whatever they want. Sadly, a dog that has been chained in the same spot for a long time will tend to stay in that spot long after they’re let “off the leash.”

Also, he has a weird understanding of what a “market” is, which makes for some strange reading in the middle of the piece.

I’m willing to give him a lot of latitude, however, since he’s so compelling on his main theme of institutional barriers to creativity in extramurally funded research. He even suggests a fairly straightfoward solution: rather than forcing scientists to support their own wages and their lab funding from the same grant-derived pot, simply guarantee their salary and let them apply for grants for resources beyond that minimum amount. That way, scientists won’t be gambling their ability to pay the mortgage on each grant proposal, and they’ll be more likely to take genuine risks.

(It’s worth mentioning that Quake is a recipient of the prestigious HHMI investigator award. If he thinks the situation is bad, then it’s bad.)

In universities across the USA today, we are breathing a collective sigh of relief — the long national nightmare of an anti-science administration will soon come to a close.

We knew that the Bush administration’s days were numbered, of course, but I’m pleased that our next chief executive does not come from a party whose scientific judgment is dictated by the “moral” strictures of its religious fringe.

As a biogerontologist, here’s what I’m most interested to know: How soon after his inauguration President Obama will overturn GWB’s executive order banning the use of federal funds in embryonic stem cell research?

As I mentioned, I spent most of last week and weekend attending two unconferences, BioBarCamp and Scifoo.

By their very nature, unconferences tend not to converge on a single topic; over the past week, I paricipated in discussions whose topics ranged from the importance of database annotation to how mushrooms could save the world to the current technical considerations involved in settling Mars. Nonetheless, even in the anarchic environs of an unconference, self-reinforcing trends arise over the course of the discussions, and themes do emerge (though each participant might perceive different patterns and come away with a completely different report of an event’s most important themes).

For me, the most powerful and important theme emerging from the week was the idea of “open science.” This term refers not to any one initiative or project, but the cloud of concepts that includes open access publication, use of open source solutions (especially for protocols and software), commons-based licensing, and full publication of all raw data (including “failed” experiments). It also incorporates more radical ideas like opening one’s notebook in real time, prepublishing unreviewed results, replacing current models of peer review with annotation and user ratings, and redesigning (or ditching) impact factors. The world implied by these concepts is one of radical sharing, in which credit still goes where credit is due but by dramatically different mechanisms.

Open science isn’t so much “pay it forward” (though there is a bit of that) as an effort to create a (scientific) world in which no one is paying at all, a world in which there’s no incentive to withhold or protect ownership of data. The science fiction writer Iain M. Banks once wrote that “money implies poverty” — indeed, many of the current models of data ownership and publication, and their accompanying “currencies” of proprietorship, prestige and closed-access publication, imply a world in which data is scarce and must be hoarded. But data is not scarce anymore.

Given a suitable set of one-to-one and one-to-many agreements between the stakeholders, then, the benefits of sharing could come to outweigh any conceivable advantage derived from secrecy. Perhaps “open science” could be defined (for the moment) as the quest to design and optimize such agreements, along with the quest to design the best tools and licenses to empower scientists as they move from the status quo into the next system — because (and this is very important) if it is to ever succeed, open science has to work not because of governmental fiat or because a large number of people suddenly start marching in lockstep to an unnatural tune, but because it works better than competing models. Proof of that particular pudding will be entirely in the eating.

During the meetings, I met quite a few people involved in this mission, and I want to mention their organizations and projects here:

  • OpenWetWare, “an effort to promote the sharing of information, know-how, and wisdom among researchers and groups who are working in biology & biological engineering” – including tools for protocol sharing and open notebooks;
  • Epernicus, a social networking site for scientists that automatically connects peers based on institution, history, skills and research focus;
  • JournalFire, “a centralized location for you to share, discuss, and evaluate published journal articles” (still in beta);
  • Science Commons, the scientific wing of the Creative Commons, which “designs strategies and tools for faster, more efficient web-enabled scientific research. We identify unnecessary barriers to research, craft policy guidelines and legal agreements to lower those barriers, and develop technology to make research data and materials easier to find and use.”;
  • Nature Precedings, “a free online service launched in 2007 enabling researchers in the life sciences to rapidly share, discuss and cite preliminary (unpublished) findings”; and
  • UnPubDatabase, a discussion of ways for scientists to rapidly and efficiently publish “negative” results, both to allow re-analysis of data and to prevent the scientific community from following the same blind alley more than once.

Academic scientists aren’t the only ones to potentially benefit, by the way — pharmaceutical companies routinely run the same experiments as one another and often find that expensive trials could be avoided if they’d only had access to data mouldering in a competitor’s vault — so open science can benefit the profit sector as well, and there are already plans underway to make that possible.

I’m enthusiastic about bringing open science into my own project and my own laboratory — indeed, in a fit of post-conference ecstasy I basically put myself on record promising to do so. For reasons that have everything to do with available energy levels, I suspect that full-blown openness is probably easier to accomplish when it’s present from the beginning of a project, so I’m especially eager to put these ideas to the test in a large-scale collaboration that is just getting underway. I have no idea how it will go — I expect to meet resistance, especially to the more radical ideas like open notebooks — but it’s nonetheless an exciting time. Will I be able to convince my collaborators to try out open science approaches? Once implemented, will they work? I don’t know, but I am convinced that it’s a hypothesis worth testing.

With this provocative title, linguist Steven Pinker begins his provocative article deconstructing the concept of “human dignity” as currently employed by the religious right in America. The piece is aimed primarily at refuting a document called Human Dignity and Bioethics, released recently by President Bush’s Council on Bioethics — a body made infamous by its politically motivated sacking of prominent biochemist Elizabeth Blackburn.

Among other things, the theoconservative movement cites considerations of “dignity” in cautioning against broad classes of biological research, including stem cell therapeutics and — more recently, as the idea becomes more thinkable — life extension technologies. (As Reason at Longevity Meme put it, and quite rightly: “‘human dignity’ is a keyphrase used by conservative bioethicists to justify relinquishing progress in longevity science.”)

Thus, in the process of enumerating the shortcomings of dignity as a desideratum, Pinker incidentally engages in a brief but cogent defense of life extension technologies, as we can see in the following passage. (The “Kass” he refers to is this hack; one of Pinker’s main points throughout the article is the manner in which the President’s Council on Bioethics lacks relevant expertise and seems to have only one qualification for membership, namely lockstep adherence to the precepts of conservative Christianity.):

In an essay with the revealing title “L’Chaim and Its Limits, ” Kass voiced his frustration that the rabbis he spoke with just couldn’t see what was so terrible about technologies that would extend life, health, and fertility. “The desire to prolong youthfulness,” he wrote in reply, is “an expression of a childish and narcissistic wish incompatible with devotion to posterity.” The years that would be added to other people’s lives, he judged, were not worth living: “Would professional tennis players really enjoy playing 25 percent more games of tennis?” And, as empirical evidence that “mortality makes life matter,” he notes that the Greek gods lived “shallow and frivolous lives”–an example of his disconcerting habit of treating fiction as fact. (Kass cites Brave New World five times in his Dignity essay.)

Kass has a problem not just with longevity and health but with the modern conception of freedom. There is a “mortal danger,” he writes, in the notion “that a person has a right over his body, a right that allows him to do whatever he wants to do with it.”

Pinker argues that as a moral value, autonomy is in every way superior to dignity, which he criticizes as a slippery and potentially harmful concept. I mostly agree, though with two qualifications: First, autonomy itself can be over-valued — specifically, when one neglects to apply veil-of-ignorance logic to social contracts and thereby ends up forced to ignore those situations in which “freedom” is merely “privilege extended”. Second (and more relevant to biogerontology), I believe that dignity does have a place in the discussion, in the following sense: There is nothing dignified about pain, senility, incontinence, or frailty; therefore, one of the primary justifications for studying the processes of aging in human beings is that we might hope to someday prevent the scourges of late-life disease and thereby increase dignity for all.

Ultimately, it sounds like Steven Pinker would agree:

Even if progress were delayed a mere decade by moratoria, red tape, and funding taboos (to say nothing of the threat of criminal prosecution), millions of people with degenerative diseases and failing organs would needlessly suffer and die. And that would be the biggest affront to human dignity of all.

(Hat tips to Longevity Meme and EvolutionBlog.)

Next Page »