Writing the Future Revisited

I went to see Daniel Suarez and Andy Weir read at an SF in SF event at the Emerald Tablet in North Beach last night.  Suarez is one of my favorite authors and has a new novel out called Influx that deals with the authoritarian control of innovation.  Andy Weir is a new author whose book, The Martian, has attracted a lot of attention.  It’s about an astronaut stranded on Mars and is notable for its adherence to scientific accuracy.  Weir, like Suarez, started out self-published, but sold enough copies independently to get picked up by a publisher.

influx-daniel-suarez I am halfway through Influx now and in some ways it continues a central theme found in Suarez’s work.  He is is concerned about the way technology can concentrate power into fewer and fewer hands as it progresses.  His novel deals with the stagnation of innovation idea by suggesting that innovation has actually occurred, but that it is continually harvested and hidden by a secret government organization that is intent on maintaining social order.  He also suggests that an attempt to create superhuman AI capable of innovative insights, but lacking in free will, is an abomination.  It represents for him a sort of cybernetic slavery that could put unthinkable power into the hands of a single person.

the-martian-andy-weir-smallI haven’t read Andy Weir’s book, The Martian, but his reading was very compelling.  He tells the story of an astronaut stranded on Mars in the form of smart-assed entries into a mission log.  Weir is a computer programmer and was obsessed with getting all of the technical details correct in order to make the story scientifically feasible.  He credits this adherence to scientific accuracy for providing him with many unexpected plot twists as he thought through the scenario one step at a time.  His book has received a good amount of positive press and I look forward to reading it.

During the question and answer period, I brought up Neal Stephenson’s Hieroglyph Project, which is encouraging SF writers to write stories that can inspire the next generation of scientists and engineers to create innovative technical breakthroughs.  Suarez was ambivalent about the idea and Weir was frankly opposed to it.  In Weir’s view, entertainment should be entertaining and not aspire to social benefit.  I found his position interesting because The Martian seems that it would fit quite nicely into the Hieroglyph Project.  It appears to be a positive story that highlights the ability of humans to overcome difficult obstacles and also shows the feasibility of humans traveling to and surviving on Mars.

For my own part, I was previously much more skeptical of the impact that science fiction can have on the future of innovation, but I have become more amenable to the idea over time.  Technological progress is a story that involves science in a complex dance with economics, politics, and other cultural forces.  Even in this scientific era, the stories we share shape how we conceive of reality.  Great stories of positive and plausible future outcomes have inspired not just engineers, but also politicians and business people.  Utopian stories are justly criticized by Pinker and others, but we do need a common narrative to move in a coherent direction as a society.  It may be that storytellers do have an important role to play and need to take up this difficult responsibility.

So much can go wrong in the  future and many paths must be avoided, but what directions SHOULD we go in?  Our stories can point the way.  I haven’t finished Influx yet, so I can’t say in what direction Suarez would point us.  Weir offers his own succinct answer:  We should go to Mars.

Harnessing the Hustlers to Address Global Megatrends

I recently attended the 2014 Foresight conference, which is a nanotechnology conference that was held in Palo Alto.  They have a strict media policy, so I can’t write about the presentations per se, but a lot of the scientists have already published related work, so I will focus on those ideas.  I would like to address the gap between basic research and commercialization here in the US, and how that fits into global trends for the future.

Banning Garrett of the Atlantic Council gave a presentation on the Global Trends 2030 report by the National Intelligence Council.  I look forward to reading that in full and writing a separate summary, but the gist is that the world population will become more urban and the global middle class will be growing dramatically:

“Demand for food, water, and energy will grow by approximately 35, 40, and 50 percent respectively, owing to an increase in the global population and the consumption patterns of an expanding middle class.”

The report also asks a crucial question:

“Will technological breakthroughs be developed in time to boost economic productivity and solve the problems caused by a growing world population, rapid urbanization, and climate change?”

Timothy Persons of the GAO gave a presentation on nanomanufacturing.  One key point was that there is a funding and investment gap between basic research in the labs and commercialization by the private sector.

Persons mentioned the industrial commons being built by SUNY Albany and UT Austin to help transfer technology developed at those schools into the private sector and bridge that gap.  Although the US leads the world in scientific research, technology developed here is often commercialized overseas.

One barrier (highlighted in the media recently) to commercializing scientific research in the US stems from problems with reproducibility.  A recent Bayer study showed that many cancer studies were not reproducible.  I had previously focused on problems with incentives in academia that reward showy, positive results, while downplaying reproducibility and research with a lower media impact.  But another issue came to light during discussions with various scientists at Foresight.  The scientists were asserting that the reproducibility problem is based on not recognizing the “control parameters” of the experiments in question.  There are some crucial parts of experiments that grad students or lab techs are taking for granted, or not noticing, and then not recording properly.  So there are some opportunities there to capture and document these processes better.

Many schools already have technology transfer offices, and startups are created all of the time, but a lot of good ideas languish for lack of funding.  Scientists tend not to be business people, so they often just shrug their shoulders and move on to the next interesting research topic.  I am reminded of the hipster/hustler/hacker paradigm.  Startups need a hipster (or designer) to make a product cool, a hacker or engineer to make a product work, and a hustler to make a product sell (i.e. ensure the product is satisfying a demand in the market).  But scientists are fairly removed from this triad of personalities.  Scientists are not engineers, let alone designers or MBAs.  So who is going to capitalize on all this great technology?

The NIC is showing us that the world faces huge challenges in generating enough energy, food, and clean water for everyone.  Not to mention the environmental pressure from the increased consumption that will occur as billions more enter the global middle class.  Technology will be absolutely essential to facilitate favorable outcomes for humanity.  It makes sense for us all to focus on this key gap in the technology development process that occurs between basic research and the manufacturing of products for the market.

2013 in Review: CRISPR Gene Editing, Deep Learning AI, and Massive Government Surveillance

Edward Snowden’s revelations call to mind George Orwell’s 1984.

When I was planning do a futurist review of 2013, I initially thought that I would just talk about some of the cool developments in technology and imagine how great things would be if they all panned out.  But this techno-optimism only tells part of the story.  Ramez Naam gave a great talk at Humanity+ 2012 criticizing bad futurism for ignoring economics and glossing over the downsides.  Benjamin Bratton recently gave a TED talk criticizing TED, in which he pointed out that culture dictates how technology plays out in the real world.  So as I review the year, I am going to try to address both the positives and negatives of some key economic, cultural, and technological developments of 2013.

One positive cultural narrative that caught my attention recently was presented by Stephen Pinker in his book, The Better Angels of Our Nature.  Pinker makes a convincing case that humans have become less and less violent over the years.  Even the bloody 20th century had fewer war deaths per capita than previous eras.  However, one big idea in Pinker’s theory (which he borrowed from Hobbes) is that as states rise, violence decreases, because the state assumes a monopoly on the use of force.  This discourages individuals from hurting others for their own gain.  The problem is that the power of the state can grow too much.  As Edward Snowden has revealed, the US government has almost omniscient powers of surveillance.  We effectively live in a panopticon of constant surveillance.  We may be on a path toward a world with absolutely no crime, but where your every move is monitored by Big Brother and the PreCrime Police come and take you away before you are able to commit a crime.

 The negative story of the economic decline of the US has also figured prominently in 2013.  Wages are stagnant, unemployment is high, and wealth inequality is reaching medieval proportions.  Yet, worldwide poverty seems to be at an all time low (if the World Bank numbers are to be believed).  So I wonder if we rich Americans are biased in our view of economic decline.  Maybe it’s a good thing for Americans to get marginally poorer if the rest of the world gets richer.  But an even brighter vision is of economic growth where everyone can benefit as more human potential is tapped.  As millions of people in places like China and Africa rise from abject poverty and are freed from disease, they will be able to learn, reach their full potential, and participate in the world economy.

Since I do love science and technology, let me indulge in some bright and dark notes from this year.  On a downbeat, we are seeing more and more problems come to light with the current state of science.  The bottom line is that many scientific papers are rubbish and cannot be reproduced.  This may be due to bad incentives; scientists are rewarded more for flashy positive results than mundane or negative results.  But a study that reveals a hypothesis to be flawed increases human knowledge more than a paper which falsely overstates a significant breakthrough,

Nonetheless, there were some technological developments worthy of note.  Consider the CRISPR gene editing technique, which can very precisely modify genes using an immune strategy from bacteria.  Conventional virus based therapies can add good genes, but cannot repair problem genes the way CRISPR can.  George Church discussed this at the 2013 Foresight conference, and further studies have shown its potential to modify genes in mammals.  Unlike many science stories that cause a big stir initially, but are never heard of again, this one seems like the real deal. This breakthrough may give the GMO industry an incredible new tool to customize organisms, possibly even humans.  If it works in humans, many congenital diseases could be conquered.  People may even be able to get modifications that make them more resistant to diabetes or Alzheimer’s.  The dark pessimist in me worries that we may see humans modified without their knowledge or consent by overreaching governments.  Or we may see the rise of a new elite that can outcompete the have-nots.


A deep learning AIs concept of faces and cats.

In the artificial intelligence world, we are seeing big breakthroughs in “deep learning.”  This is a machine learning algorithm that somewhat mimics the neural networks found in brains.  Google has used it to analyze videos and identify human faces and, of course, cats.  This past year, AI researcher Andrew Ng built a much cheaper deep learning system using graphics processors (GPUs), so Google’s $1 million deep learning computer cluster could be matched by a $20,000 system.  The fact that Facebook is jumping on board by snapping up their own deep learning guru makes me suspect that this is not a flash in the pan.  Also, my favorite Bay Area AI researcher, Monica Anderson, seems to approve of this general approach to machine learning.   This could be an incredibly powerful AI.  The big downside of AI getting too powerful has been well explored from Frankenstein to The Terminator, so I won’t belabor this point; there are folks who are thinking deeply about how to prevent those scenarios.  But one big upside of AI could be to help us sort through this overwhelming firehose of information that is growing all the time, so that we can make sense of this world and find solutions to problems.

In conclusion, 2013 had both positive and negative developments.  Technologically, there were some amazing advancements, including the CRISPR gene editing technique and deep learning AI.  Economically, there emerged a complex story of economic stagnation in developed nations, paired with a reduction in poverty in the developing world.  Politically, we saw some chilling examples of government overreach in surveillance.  My hope is that futurists will expand their horizons beyond the technological, to think about the best role for our government going forward, and the best paths toward greater economic inclusion.  The optimists among us should take heed of the pessimists’ warnings.  For their part, the pessimists should take a moment to pause in their dire predictions and ask themselves, “Yes, this could all go terribly awry, but what do I think should happen?”  At the end of the day, if we take into account all the competing forces that define what is possible, I do believe we can chart a course toward progress.

[UPDATE 2/10/2014]

I actually wrote up a presentation for the first Transhuman Visions conference on this topic and those notes are here: http://bit.ly/tv-oak

I attended Foresight this year and some scientists were asserting that the reproducibility problem is based on not recognizing the “control parameters” of the experiments in question.  There are some crucial parts of the experiment that the grad students or lab techs are taking for granted or not noticing and then not recording properly.

Also, I am taking Pinker’s modern murder decline numbers with a grain of salt after Annissimov pointed out that modern medicine might be masking the violence of modern times by saving victims that would have otherwise died.  Of course, modern guns make it easier to attack others, so that should be taken into account, not to mention that attempted murders have probably gone down, but nonetheless, there are valid questions around Pinker’s trends.

Anarchists to Googlers: Get Out of Oakland!

google-bus-protest

As you may have heard, Oakland protesters recently smashed the window of a Google bus in protest of gentrification.  I am of many minds on this issue.  Of course it’s always fun to smash windows because … punk rock.  Then the rationalist in me pipes up and questions whether Google employees are really the cause of this gentrification, but it doesn’t really matter.  Smashing stuff makes the news and generates discussion.  The realpolitiker in me scoffs at the idea that generating some idle conversations will have any impact on housing policy.  Occupy supposedly changed the national discourse on the topic of wealth inequality, but clearly the Tea Party approach has had more policy impact.  Of course Occupy wouldn’t have attracted the sort of cash that the Koch brothers et al. dumped into the Tea Party, but still.

I was at a party with some rationalists recently, and it was readily agreed that the real solution to rents being driven up by Silicon Valley engineers is to create more housing, which should drive prices down again.  And at first this seemed to make sense, but then again, surely there is still plenty of cheap housing down by the coliseum here in Oakland.  What is this gentrification thing we speak of?  There is probably plenty of cheap housing all down the East Bay from San Leandro to Fremont.  The engineers are flocking to Oakland because it’s hip.  Oakland is awesome, by the way.  Then I spoke with my frequent sparring partner, Robin, and he mentioned another point worth considering.  These office drones getting crushed by the high pressure 9-5 grind at these world class tech companies have little to offer the culture of Oakland other than their cash and bottled up tension.

The problem of gentrification for the poor is that it pushes them out of familiar areas, close to their work, where they have social connections.  It’s more of a hardship for them to find new housing than it would be for the engineers.  The flip side to this is that these engineers do bring cash along with them.  A fellow at Cro cafe in Temescal Alley commented that he was doing good business selling doors and doing carpentry for these well-heeled folks coming to town.  The answer clearly isn’t for Googlers to get the fuck out of Oakland; the money they bring will boost the economy.  As far as the poor are concerned, there just needs to be more low income housing available for them.  Possibly the Bay Area counties could form a new meta-association to help address this issue.

But then again, gentrification is a problem for the gentrifiers as well.  Presumably they are choosing Oakland over San Leandro for its culture and proximity to SF.  What happens when the stressed out engineers force out all of the anarchists, artists, and other hipsters?  They will be left with a sterile strip mall of a city that used to be cool.  You may think SF is cool, but SF’s First Friday can’t hold a candle to Oakland’s First Friday.  As a matter of fact, I have often remarked that the low rent down in pre-Katrina New Orleans lent that city far more gnarl per capita than SF has today.  Even my downtrodden hometown of Buffalo in the 90s seemed to have many more music and art venues than one should expect from a rust belt city of its size.  The fact is that when rent is low, people can follow their hearts.  They can do art or even just be like The Dude in The Big Lebowski and simply abide without having to crumple up their souls into their tightly balled fists and march into a cube farm every weekday morning.

So my advice to the engineers is this: the next time a brick lands in your lap during your morning commute, don’t get mad.  The unwashed anarchists just need you to help them out.  They are generally too stoned and self-righteous to actually roll up their sleeves and do the hard work required to change the housing policies here the Bay Area.  So set aside a few cycles of your world class engineering brains and dedicate them to solving this problem.  The policies in place got there somehow or other.  If you can debug a kernel dump, you can figure this mess out.  When you are enjoying the rich and vibrant culture of Oakland with housing for all, you will be glad you did.

UPDATE:  Here is an interesting draft paper on Bay Area housing.  The Association of Bay Area Governments (ABAG) and the Metropolitan Transportation Commission (MTC) recently adopted the Plan Bay Area to address these growth issues as well.

Health Extension at Mithril

Yoga instructor Bette Calman, 83

Yoga instructor Bette Calman, 83

Health Extension Salon held a fundraising dinner at Mithril Capital in the Presidio this week.  This is definitely my favorite monthly meeting these days.  Mithril is an investment firm that funds growth companies tackling tough problems.  They seem to be putting cash into later rounds of funding, as opposed to initial startups.  This is a Peter Thiel fund, so I was particularly interested in this venue.  I find Thiel’s arguments on the stagnation of innovation to be fairly compelling, and I am eager to see if he can use his mountains of cash to trigger innovation in areas where it is most needed.  Thiel’s former PayPal partner, Elon Musk, has grabbed the space and automotive industries by their throats and is giving them the vigorous pummeling they both so sorely deserve.  I wonder what further tricks Thiel has up his own sleeve.

As is his wont, Health Extension founder Joe Betts-LaCroix opened the evening with an update on current events.  This was a dinner talk, so Joe gave his updates while the attendees clanked their plates and silverware together noisily.  But far be it from me to criticize the table manners of the other primates gentlefolk in attendance.  Anyway, Joe brought up an encouraging piece of science in a recent study by Hannum and Guinney et al. that uses methylation profiles as a way to measure aging.  This might be a big deal since there aren’t very good ways to measure aging at a biological level right now.  Joe often points out how useful a metric like blood pressure has been as a proxy for cardiovascular health.  A drug that targets blood pressure can now be approved by the FDA as a treatment for your heart.  If a similar metric can be found for aging, a drug that targets that metric could theoretically be approved by the FDA as a treatment for aging.  (Assuming aging is even acknowledged as a disease by the FDA, that is.)  So Hannum and Guinney’s work is a big step in the right direction if the findings hold up.

Their goal is to compile a database of longevity compounds…  Databases of this sort are very important because there is such a vast amount of research out there that much of it is overlooked by the researchers who can best use this information.

Joe went on to announce that the Longevity Variants database that was created by interns as a Health Extension project is being submitted to a new journal.  This is a meta-study that analyzed a bunch of studies on genetics and aging and created the most comprehensive database of genetic variants associated with longevity in humans.  So this should be a really useful tool for researchers if they can just get it into a journal to spread the news properly.  On a related note, Health Extension is embarking on a similar project in conjunction with the Buck Institute.  Their goal is to compile a database of longevity compounds that will be comprised of all the studies they can find on how various compounds impact longevity.  Databases of this sort are very important because there is such a vast amount of research out there that much of it is overlooked by the researchers who can best use this information.  Proper curation should help solve that problem by reducing the effort researchers must expend to locate information.  It’s cool to see the Health Extension folks rolling up their sleeves and making this happen.  Curation rules.

Joe then discussed an event called the Bay Area Aging Meeting, which is a biennial research conference.  The organizers were trying to get younger researchers more involved by having them submit research posters, but they had trouble generating excitement.  Then they decided to offer a modest $1,000 poster prize with the stipulation that two of the winners would need to present research that was relevant to humans.  This prize idea was immensely successful and created a buzz.  Many more young people submitted posters, and there was much more interest in them as folks went around trying to guess who would win.  Prizes do seem to be an economical way to encourage much more effort than could be purchased directly with the same sum.  Joe solicited some additional funds for this worthy effort, and several generous folks stepped up and offered to contribute toward a poster prize for the next Bay Area Aging Meeting.  It’s important to support young people who show interest in longevity research, before they get sucked into big pharma and end up squandering their talents to develop erectile dysfunction medicines.

The first speaker was Brian Kennedy, CEO and president of the Buck Institute, which does research on aging.  Brian is not only the president, but he is also a principal investigator, who heads a lab and does research.  He started out by showing a chart of the average lifespan over the past 10,000 years, to highlight the fact that humans have only enjoyed our current, relatively long lifespans for a very short period of time, historically speaking.  So in one sense, the problems of aging that we see today are a new phenomenon, rarely experienced by ancient humans.  He also pointed out that evolution optimizes for reproduction, and that aging only happens when selective pressure breaks down (i.e. humans stop getting eaten by saber-toothed tigers or starving to death during the winter).  Yet, some animals like naked mole rats or clams live much longer than we might expect, so nature does have some tricks up its sleeve to extend lifespans if needed.

Kennedy outlined three major theories of aging: damage accumulation, loss of homeostasis, and antagonist pleiotropy.

Kennedy outlined three major theories of aging:

1. Damage accumulation – This seems fairly straightforward.  Everything breaks down in this world.  Entropy rules.  Yet clearly, living things oppose this tendency by building themselves and self-organizing.   It seems to me that there must be more to this story than parts getting worn down.

2. Loss of homeostasis – This is the balance between the various systems of the body breaking down.  I can’t help but think of traditional Chinese medicine with its idea of yin and yang when I hear of homeostasis.  I am interested to see what grain of truth the empirical testing of traditional cultural wisdom will be able to reveal.  But that’s a different discussion.

3. Antagonist pleiotropy – Err, huh?  I guess this is the idea that some processes which are beneficial earlier in life become detrimental later on.  An example of this is testosterone levels in men.  Higher levels of testosterone are favorable early in life, but they increase the risk for prostate cancer later on.

Kennedy went on to discuss some ways to possibly extend your healthspan.  He brought up calorie restriction and suggested that it has been shown to extend the lifespan of primates.  I need to look this up more because I thought that it had NOT been shown to do this in primates.  I understood that it only works for simpler species.  He also reiterated the importance of exercise for health.  Of course everyone knows this already, but it bears endless repeating for those of us who may not get enough exercise.  Where is my HIIT app?

Kennedy then described the overall architecture of biology research.  He pointed out that the reduced cost of experiments on lower life forms (like yeast or flies) allows for the broad testing of an unbiased hypothesis.  These simpler organisms basically enable a shotgun approach in which scientists can test any ideas they can think of, no matter how unlikely.  Once the results of those studies are in, they point out likely candidates for more expensive research on higher animals like mice or even humans.  This is possible because a surprising number of gene functions are conserved across species.  Yeast has a similar insulin pathway to humans.

Rapamycin, which is normally used as an immunosuppressant for organ transplants, has also been shown to extend the lifespan of mice.

Brian Kennedy went on to talk about this drug rapamycin, which is normally used as an immunosuppressant for organ transplants, but has also been shown to extend the lifespan of mice.  This mechanism has something to do with the TOR pathway.  (Fun fact – TOR actually stands for Target Of Rapamycin.)  Now there are many caveats with rapamycin that should discourage folks from running out and shooting the stuff into their veins.  Extended administration of rapamycin leads to problems with insulin resistance.  But Kennedy was upbeat since there are really two TORs – mTORC1 and mTORC2.  If only mTORC1 is inhibited, the problems with insulin resistance don’t materialize, and Kennedy thinks the Buck Institute has found just the compound to do that.  Further discussion revealed that mTORC1 suppression might interfere with wound healing, but Kennedy maintained that the compound could be discontinued in the event of injury or just used intermittently.  He didn’t share what that compound might be, which might be a good thing since I would be sorely tempted to run out and try it myself.

Kennedy then described a Buck study of longevity compounds.  Four different labs were tapped to suggest a candidate for this longevity study in which they will minutely test the mice to see how aging is affected.  Kennedy was quite proud of their ability to measure functional levels, such as devices that provide microscopic bone cross sections of living mice, and cages that can measure mouse respiration.  They are not finished with the study yet, but one of the compounds is outperforming rapamycin already.  The candidates are all small molecules, one is novel, one is off patent.  I look forward to seeing the results of this.

Where aging research shines is with increasing healthspan, and pharma mostly doesn’t address this. Kennedy argues that this is exactly the type of thinking we need to shift toward.

Kennedy closed with a diagram that contrasted aging research with current pharmacological interventions.  Aging research isn’t effective at treating disease, but that is the entire focus of pharma.  Aging research and pharma can both contribute somewhat to disease prevention.  But where aging research shines is with increasing healthspan, and pharma mostly doesn’t address this.  Treating healthy people to keep them healthy is not in the current pharma mindset.  Kennedy argues that this is exactly the type of thinking we need to shift toward, and I couldn’t agree more.

The final speaker of the evening was Berkeley researcher, Professor Andrew Dillin.  He began his talk by warning the audience that he didn’t give many talks because he really preferred to hide in his lab, but he was an engaging speaker who demonstrated an acerbic wit.  Dillin outlined three main areas of exploration: Alzheimer’s, pain, and obesity.  He began by considering the oldest known human, Jean Calment.  Though he didn’t have access to her medical records, he posited that she seemed to have had no cancer nor any dementia, though she lived to the age of 122 years.  Thus, her body was able to maintain both her genome (which would prevent cancer) and her proteome (which would prevent Alzheimer’s).

Speaking of Alzheimer’s, Dillin referred to a study he led, which showed that mice with slowed aging were protected from Alzheimer’s.  They slowed the aging process by lowering the activity of the IGF-1 pathway, which is sort of like encouraging insulin resistance, and seems that it would induce something like diabetes in humans.  Yet some long-lived people show similar mutations in the genes that regulate this insulin/IGF-1 pathway, so I don’t really understand this mechanism.  Anyway, another finding of the study was that non-Alzheimer’s mice had a similar amount of beta amyloid plaques as Alzheimer’s mice, but that the plaques were more densely packed in the non-Alzheimer’s mice.  This adds evidence that beta amyloid plaques are not the villains they have been portrayed as to date, and might even be protective.  Remember to take every scientific model with a grain of salt, my friends.  This too will pass.

Apparently, reported pain increases with age, so naturally Dillin wondered if the reduction of pain would reduce aging.

Dillin next directed our attention to the connection between pain and aging.  Apparently, reported pain increases with age, so naturally Dillin wondered if the reduction of pain would reduce aging.  What if pain is somehow triggering aging?  Mice with a specific pain receptor called capsaicin knocked out lived longer.  (I was unable to locate this study, but I will keep looking.)  Dillin said it was important that the neurons which connect to the pancreas had that pain receptor knocked out, as they regulate metabolism.  Also, the surprisingly long-lived naked mole rats have no capsaicin receptors.  My notes say that there was some suggestion of CGRP inhibitors (which I guess are being explored for migraines) being relevant to this, but somehow if the neurons that regulate metabolism are feeling no pain, then it may extend lifespans?  Sounds good.  It’s painful enough to exercise and eat properly.  We deserve a break now and then.

The dividends of a successful investment in health extension research will tower far above all of the toys our billionaires might briefly amuse themselves with during their short stint on earth.

As usual, Health Extension delivered a potent dose of exciting longevity science.  Aging is complex, but there are many brilliant researchers attacking this problem.  More money is needed to push this research forward, especially since Larry Ellison from Oracle has withdrawn from the game.  Frankly, I am amazed that more billionaires aren’t rushing to fund this research.  Diminishing marginal utility dictates that the third yacht simply can’t be as satisfying as the first.  Yet, the dividends of a successful investment in health extension research will tower far above all of the toys our billionaires might briefly amuse themselves with during their short stint on earth.  I can only hope that more of these plutocrats will take a look at the science and see that aging is a solvable problem.  Thiel himself seems to have figured this out.  We all stand to benefit if they do.

GMO Study Discredited?

gmo-mouse-tumors

The genetically modified organism (GMO) debate flared up again this week.  Last year, a French study led by Gilles-Eric Séralini claimed that Roundup and corn modified to be resistant to Roundup was toxic.  Roundup is a very common weed killer and some crops are genetically modified to withstand it.  Rats in the study developed grotesque tumors.  There was a big outcry of criticism in response to this study, and the journal that published it is now threatening to retract the study.  I don’t know if the study is junk or not.  Séralini’s response to critics seems fairly reasonable.  But if it is a poorly designed study, then I wonder why there aren’t properly designed long-term studies of Roundup safety that would settle this matter more definitively.

Just to clarify my position, I remain skeptical of GMOs and of the safety of consuming Roundup in particular, but I in no way intend to advocate for GMOs to be banned.  GMOs clearly hold huge promise for solving world hunger problems.  I just don’t like the way this debate is being framed.  GMO skeptics are painted as being anti-science.  This might largely be true, but some of the blanket statements issued by scientific organizations to assert the scientific consensus of GMO safety seem… well, unscientific.  Consider this statement on GMO safety by the National Academy of Science:

All evidence evaluated to date indicates that unexpected and unintended compositional changes arise with all forms of genetic modification, including genetic engineering. Whether such compositional changes result in unintended health effects is dependent upon the nature of the substances altered and the biological consequences of the compounds. To date, no adverse health effects attributed to genetic engineering have been documented in the human population.

Ok, so that means that someone ran GMOs through the gold standard of scientific evaluation and performed a large-scale, double-blind study to prove the safety of GMOs on humans then, right?  Umm, no.  In fact, it appears that not many long-term studies of GMO safety have even been performed on mammals, let alone humans.  So I wonder how the NAS confidently arrived at the conclusion that GMOs are safe.  Well, to be fair, they do hedge their bets with that statement, but consider the final sentence:

To date, no adverse health effects attributed to genetic engineering have been documented in the human population.

See, the problem with this statement is that there have been no studies of GMO health effects on humans to produce this documentation of harm.  There is no control group to compare GMO eaters to.  Some estimate that 60 to 70 percent of the processed food in the US contains GMOs.  You need a population that isn’t eating GMOs to compare the rest of us to.  One can’t just say that cancer rates have been flat, so there has been no cancer impact from GMOs.  What if cancer rates would have gone down if GMOs weren’t being eaten?  The Amish might be people to study, except for the GMO cross contamination problem and the fact that their lifestyle is so radically different that it would introduce many confounding factors (i.e. Maybe the Amish are healthier because of being closer to the land.).

Another problem is that it will be very hard to document the harm from GMOs if it doesn’t happen immediately.  Who can say what caused health problems that occur after years of GMO consumption?  How could it be shown that GMOs caused harm as opposed to the water that was consumed or other potentially toxic exposures?  The NAS’s final sentence is a bit like saying, “To date, the general public has not documented the existence of the Higgs Boson.”  The public doesn’t have the tools to show which substances might cause long-term harm.  We need scientists to do that for us.

Agribusiness clearly has the cash and political clout to influence legislation.  It’s not realistic to expect any regulation that requires GMOs to be tested for safety the same way that say, drugs are tested.  But it’s not unscientific to question GMO safety given the scarcity of mammalian studies.  Yes, GMOs look good on paper, but show me the empirical data.  Salmon and chickens don’t seem to be hurt by GMOs, but human biology is more complicated.  I would feel much more confident if someone would just run a proper long-term human clinical study and be done with it.  The money spent to prevent GMO labeling in California could have funded plenty of research.  

I would feel much more confident if someone would just run a proper long-term human clinical study and be done with it.  The money spent to prevent GMO labeling in California could have funded plenty of research.

Of course, it’s hard to control what people eat long-term.  But it seems that low security prison populations might provide good candidates.  (They could be given some incentive to participate, not be forced.  The test group would not be any worse off than the general population, after all.)  Their diet is largely controlled already, and I assume that low security convicts stab each other less frequently than high security prisoners, so that would be one less thing to control for when computing mortality rates I guess.

My friend Razib criticized my squeamishness and said that there are plenty of other substances and activities that are probably worse for human health than GMOs.  It’s certainly rational for starving folks in the developing world to risk potential health problems at some time in the future in order to eat Vitamin A enhanced GMO rice today, for example.  But I don’t live in the Global South, and I personally already avoid a lot of the things that more obviously cause harm, so I am a crybaby and I don’t want to touch this GMO stuff until they can show me some REAL scientific evidence of safety.

I know, I know.  I just wrote a post last week examining why many of the scientists I know dismiss dietary interventions to improve health.  Perhaps I am not updating my beliefs properly here?  Give me time, self-optimization is a difficult habit to break, especially since I am more of a fox than a hedgehog.  As Anatoly pointed out recently, generalist “foxes” might be more inclined to self-optimization.  In the final analysis, the world will probably be better off with GMOs than without them.  They provide the potential to feed far more people with less land and fewer resources than organic farming.  Far be it from me to stand in the way of progress.  Pour me a shot of Roundup.

Gratitude Journal for Thanksgiving

thank-you

It’s wonderful to have a holiday like Thanksgiving devoted to gratitude.  Taking the time to feel grateful might help us shift a negative outlook by forcing us to contemplate the good things in life.  Seligman would have us keep regular gratitude journals to improve our sense of well-being.  My own partner and I always try to talk about three things we are grateful for each day.  But I am generally terrible at this, so I need help.

pat-snlLuckily, I heard a “Giving Thanks” show on NPR featuring actress Julia Sweeney, who created the androgynous character Pat on Saturday Night Live.  She talked about some of the things she was grateful for.  My favorite offering by Sweeney was that she was thankful for the margin for error that her life allowed her.  I can relate to that.  I am truly grateful that I have been able to make mistakes in my own life and have still been able to flourish.  So many folks in the Global South live on the knife’s edge, where mistakes are impossible to recover from.   Another great point Sweeney made was that she was grateful for a stable community.  Consider all the folks who live in war zones from Afghanistan to Somalia.  Even here in Oakland, many folks must feel they are in a war zone with all the murders going on.

Now let me get back to futurism.  It may be that we need to develop meaningful happiness by cultivating gratitude in order to update our negative filters and recognize the path toward a future with better outcomes, to regain that optimism America had back in the 60s, but lacks now.  So let’s all recognize what we have to be grateful for.  Our future may depend on it.

Why Do Scientists Disdain Supplements?

I’ve been taking supplements for a long time now. Gretchen, my partner of many years, gave me a niacin flush back when we were in our 20s. I can’t say that I recommend it. Imagine taking enough niacin to turn bright red all over and feel as though your entire body was being pricked by needles for a couple of hours. Also, I just learned that the fact that I flushed at all is evidence that I probably wasn’t schizophrenic in the first place, which may come as a surprise to my friends from that time. I was even fed Flintstone’s chewable vitamins as a child, so I feel as though I grew up in a culture of supplementation. Why do I take them? To be healthier? More productive? To live longer? Take your pick.

So when I read Fantastic Voyage by Ray Kurzweil, it was right up my alley. I happily went out and bought the top twenty supplements that Ray & Terry were suggesting right away. My friend John warned me about this. He had initially tried the same strategy, but stopped in favor of eating whole foods. We haven’t learned enough about biology yet to know what will be effective, he said. But John had the discipline to sit and eat an entire tub of organic lettuce while chatting at my Futurist Meetup, and I doubted that I had his same level of resolve. So I reduced my confidence in supplements, but I figured they might help offset my shoddy diet.

As the years go by, more and more studies about supplements have shown a lack of efficacy or even detrimental effects. Of course I was quick to defend my beliefs and look for flaws in the studies, blissfully ignoring my own confirmation bias. Sure, the science is flawed in some cases. Maybe big pharma actually works to game the results since naturally occurring substances that can’t be patented could pose competition to its products if proven effective. But as irrational as I may be in defense of my pet concepts, my confidence in supplements erodes further and further over time.

But as irrational as I may be in defense of my pet concepts, my confidence in supplements erodes further and further over time.

In this Bay Area futurist scene, it isn’t hard to find plenty of folks looking for hacks to optimize their personal performance. Rationalists seem particularly fond of nootropics, etc. So my faith in supplements was bolstered somewhat by various things I learned. I might say, oh sure, maybe even mixed tocopherol vitamin E isn’t very effective, but surely this acetyl-glutathione will do the trick. You just need to find the right pill to pop.

As I got involved in Quantified Self, where everyone does self experimentation, I realized how utterly foolish I was being by not monitoring my biomarkers more frequently. Ray Kurzweil might choke down 200 pills a day, but he’s constantly getting blood work done and poring over the results. So my approach of performing a single liver test once a year wasn’t looking too responsible, especially when other QS’ers were monitoring their blood sugar in real time for kicks.

I also had jarring experiences trying to talk about supplementation with actual scientists. Several smart biologists mocked my supplement regimen. Recently, I was at a party and asked Joe Betts-LaCroix and some other science people if anyone followed the paleo diet or did supplements, and I was a bit surprised to find general disdain. Should we return to a paleo era life expectancy? Perhaps we should forego vaccines and sanitation as well? Joe referred me to his brief blog post on this topic, the gist of which being that although there are billions of people with a broad range of diets, no one population is extraordinarily long lived. Thus, we can assume that diet doesn’t contribute much to longevity.

Although there are billions of people with a broad range of diets, no one population is extraordinarily long lived. Thus, we can assume that diet doesn’t contribute much to longevity.

Now some might argue that this speaks to longevity, but not to performance. Maybe it can be shown that diet and supplements can improve performance. At one time I would have been more open to that idea, but I am starting to grow skeptical. Joe’s point is that folks should stop wasting large amounts of effort for small or nonexistent personal gains and should focus instead on the basic research needed to unlock the deep complexity in the foundations of our biology. Of course, not all of us are cut out to do that research.

Dan Millman actually touched on this point at Ted X Berkeley this year. Millman ponders the question of whether it is better to focus energy on improving the world or on improving ourselves. He concluded that self improvement gives us the leverage to change the world more effectively. I am no great fan of Millman’s productized philosophy. He’s like some of these other “gurus” who package up ideas as products and sell them in a way that seems as though they have never heard punk rock or read post-modernism. But I think I can agree with that point – self improvement lends leverage to our endeavors. The question then becomes a cost/benefit analysis. At what point does self improvement offer diminishing returns?

Joe is an interesting person to listen to in this regard. No one can accuse him of not working on himself. He was a big QS’er from the beginning and did calorie restriction for years. He does HIIT, and he even broke out and tried living a 28 hour day. He has also been working fervently to improve the world for years, from his work at the ill fated Halcyon Molecular to his current Health Extension Salon project to combat aging. Yet, here he is admonishing folks to stop piddling around with diet and supplements and get to work on the real problems of this world.

Then there is this other fellow I happen to know named Walter Funk. A friend shared an article about a TA-65 alternative supplement that can supposedly increase your telomeres and roll back aging. This seemed at first to be utter quackery, yet there in the references, low and behold, was a paper by the venerable Dr. Walter Funk. So I said, Walter, tell me, what is this nonsense? He said that the basis of TA-65 is astragalus and that it modestly but reproducibly increases telomerase activity (i.e. protects telemeres which keep your DNA from unraveling, sort of like the plastic on the tips of shoelaces). He pointed out that astragalus is just an herb and regulation of herbs is becoming lax, but that other organic compounds that are purported to increase telomere activity would require clinical trials for FDA approval.

Then I found this article which seemed to suggest that telomerase might contribute to the immortality of tumor cells. But Dr. Funk assured me that reasonable animal data suggested that telomerase might actually prevent cancer. The telomerase activation associated with tumors occurred at a later stage after a bunch of other damage had occurred. So I said, well, that sounds OK then. Do you take TA-65, Walter?  But I got a sardonic reply about him relying on good women and the kindness of strangers. He also offered to forward me a summary of all the NIH supplement studies that showed no benefit or some detriment.

Furthermore, when Cynthia Kenyon spoke at the Health Extension Salon in July 2013, she mentioned a study which showed that antioxidants prevent the increase of insulin sensitivity following physical exercise. In other words, exercise causes stress which normally triggers your body to repair the damage, however, antioxidants seem to prevent your body from recognizing the damage that has occurred. So antioxidants fix some of the damage, but prevent your body from providing a more robust response. This goes hand in hand with recent research, which calls into question the long held belief that aging is caused by oxidative stress (or free radical damage). There’s something else going on here.

Recent research calls into question the long held belief that aging is caused by oxidative stress (or free radical damage).

Part of me wonders if there is something in the personalities of scientists that makes them disdain diet and supplementation. Gretchen suggested that they may all be absent minded professors forgetting that their brains are attached to bodies that need nutrients. The performance hackers seem like a more charismatic and risk tolerant crowd, almost thrill seeking, though I must say they seem to have fewer papers to their credit. At the end of the day, I suspect that scientists disdain diets and supplements because they hold assertions of efficacy to higher standards than many of us do. I strongly suggest that my fellow supplementers listen more closely to what the science is trying to tell us. I will attempt to do the same, although it sure isn’t easy to give up your imagined silver bullet.

Additional references:
Walter sent me these additional references for those of you who are still clinging to your vitamin bottles. (I probably need to read these myself in order to let go.)

Here’s the big flop of one of the most touted supplements, omega-3 for heart disease has absolutely no effect on normal individuals.
http://www.medpagetoday.com/Cardiology/Prevention/38969

No one, especially males, should take vitamin E (tocopherol).
http://www.cancer.gov/newscenter/newsfromnci/2011/SELECTupdateJAMAOct2011

Antioxidants have been shown to not help with cancer.
http://www.cancer.gov/cancertopics/factsheet/prevention/antioxidants

An attack on the low carb crowd from a microbiome investigator.
http://humanfoodproject.com/sorry-low-carbers-your-microbiome-is-just-not-that-into-you

Health Extension Salon #14: Greg Fahy Regrew His Thymus

Greg Fahy and Joe Betts-LaCroix at Health Extension Salon #14.  Photo courtesy of Traci Parker.

Greg Fahy and Joe Betts-LaCroix at Health Extension Salon #14. Photo courtesy of Traci Parker.

Health Extension Salon yet again lit up my life with wonderment at Hacker Dojo in Mountain View.  As usual, there was a great crowd of lively and brilliant attendees.  I got to chat with some old acquaintances and some new folks as well.   I met techno optimist Kevin Russell, whose website Serious Wonder is worth consideration.   Being the hip traveller that he is, he just got back from the Singularity University’s FutureMed conference down in San Diego.  He promised that he would be writing it up soon.  When pressed for a highlight, he mentioned something about laser surgery at the nucleus level, which sounds fascinating.  So I will be looking forward to his write-up.  He also pointed out that Craig Ventner has a new book on synthetic life called Life at the Speed of Light.   Russell mentioned the CRISPR technique that allows for precise gene editing, which is back in the news these days. George Church was excited about CRISPR back in January at Foresight this year.   So it looks like CRISPR may not be another one of these flash in the pan science blurbs that go nowhere.  Let’s keep an eye on it.

Health Extension Salon founder Joe Betts-Lacroix always gives an introductory talk during which he highlights the goal of the Health Extension Salon, “to accelerate efforts toward therapies to prevent age-related diseases.”  He makes a strong case that aging research needs more funding given the huge cost of age-related diseases.  Joe mentioned a recent geroscience summit at the NIH to further this cause.  The NIH is a vast source of research funding, but aging research only represents a tiny fraction of that pie.  This summit gave the geroscience community within the NIH a chance to share some of their findings with their peers at the NIH who work in other fields.  The goal was to raise interest and possibly funding for basic research into the biology of aging.

Joe also mentioned Google’s new health extension company, Calico, headed by Art Levinson of Genentech and Apple.  I guess Joe was impressed when he saw Levinson at this aging research conference scribbling madly away, taking notes.  Not many CEO’s do this sort of thing, so it may bode well for Calico.  I had previously heard that Levinson has a vast network of connections, and now it seems that he is immersing himself in the field to learn what directions to explore firsthand.  Very promising indeed.

The next Health Extension Salon will be a fundraiser held at Mithril Capital.  Check healthextension.co for details.  Mithril is Thiel’s vehicle for investing in middle range companies that fall between the initial startup phase and the pre-IPO.  Nonetheless, it wouldn’t be a bad idea for bright young founders in need of funding to show up and rub elbows with the well heeled hosts.  Just saying.

Joe introduced Greg Fahy by playing a clip from a recent episode of Nova that features Fahy’s work in the cryopreservation of organs.  Apparently Fahy was able to find an antifreeze (M22) that is nontoxic to mammals and allowed him to freeze and rethaw a functional rabbit kidney.  This research could lead to organ banks in which human organs could be safely stored long-term.  It seems that Alcor switched to M22 in 2005 for freezing heads, but I am not sure if they still use it.  But that was just a glimpse into the polymathic Fahy’s varied work.

When Fahy took the mic, he outlined the goal of his new company, Intervene Immune, to  combat immunosenescence (the crapping out of your immune system over time) by rejuvenating the thymus.  The thymus is this organ behind your breastbone that is sort of a university for white blood cells.  Apparently it degrades severely as you age until it basically dries up by the time you are 65. (Am I the only one who didn’t even know this about the thymus?)  The immune system incompetence that results from the aged thymus shriveling up results in a lot of flu deaths.  Fahy said that some think this thymus degradation is an adaptive trait since the thymus must discard most of the T-cells it educates and thus is highly energy intensive.  Though he seemed to agree with Cynthia Kenyon that aging may be a programmed process.

Fahy was inspired by the work of Dr. Laura Napolitano, who showed that human growth hormone could reverse this thymic involution (shrinking of thymus with age) in AIDS patients.  Now given that AIDS kills T-cells, but a regenerated thymus makes more and better T-cells, that’s a really good thing. Go Dr. Napolitano, go!  Though we westerners have pills to fight AIDS pretty effectively, it’s still a huge problem in the global south, and this thymus regeneration approach might be a better solution there.

So Fahy decided to regrow his own thymus using growth hormone and DHEA.  Yep.  He just performed an N=1 experiment by himself, on himself.  It was very difficult and expensive though.   First of all, HGH (human growth hormone) blocks insulin function.  So that’s a problem.  Fahy figured out that DHEA counteracts this effect.  He speculated that the high HGH levels in young people didn’t impact their insulin function due to high levels of DHEA.  DHEA has a plethora of other beneficial side effects, so that was a win win situation.  Another problem is that HGH works by stimulating IGF-1, but IGF-1 can cause cancer at high levels.  So the HGH dosage must be carefully controlled to keep IGF-1 levels in range.  But he figured it all out and he estimates that he was able to basically roll back the clock 25 years in terms of this thymus function.   He physically regrew the organ as evidenced by MRI scans.  He also showed that his level of good “naive” T-cells increased.  That’s a good thing.  Look it up.

Now Fahy is a super scientist who vitrifies rabbit organs by day and unlocks thymic magic by night, so definitely don’t try this at home.  Sign up for his human trial instead.  Intervene Immune is kicking off a Thymus Regeneration, Immunorestoration, and Insulin Mitigation Trial (TRIIM).  This study is for men only, between 50-65 years old, in good health, with low cancer risk, who have not used HGH before.  Contact Fahy [at] interveneimmune.com for information on how to join.  If I was a little bit older, I would definitely check it out.  Fahy has worked out a very rigorous protocol in which he improves upon previous protocols by Napolitano, et al.  He also looks amazingly good for his age, and I have to wonder if that thymus rejuvenation hasn’t helped preserve his appearance as well.

But as amazing and exciting as the real prospect of immunorestoration is, that’s not all Fahy has in store.  Killer T-Cells attack invaders. The thymus trains these T-cells to differentiate between invaders and native tissues.  In autoimmune disorders such as Type-1 diabetes, this process goes astray.   I guess animal studies have succeeded in taking small sections of the affected tissue, putting them into the thymus, and retraining the T-cells not to attack that tissue.  (Still looking for references.)  Fahy said that the same thing has been done with organ transplants in animals.  So you could transplant organs without needing to knockout the immune system.  Just trick the thymus into treating the transplanted organ tissue as native.  This is really mind-blowing stuff.  Thymic magic.

I have to extend my thanks and admiration to Joe and the Health Extension Salon team for putting on yet another inspiring and mind-expanding event.  It’s really exciting to see the amazing talent being applied to these tough problems of aging.  Even my persistent pessimism is disarmed by the audacity and vision of people like Greg Fahy.  Aging really is a problem that can be conquered. Human suffering can be vastly reduced.  Get on board people!  Let’s make it happen.

Health Extension Salon #13

The only events I can seem to attend these days are Health Extension Salons.  But I also attended the 2013 Quantified Self Conference in San Francisco, so I was exposed to plenty of new ideas there as well, which I will be sharing soon.  Health Extension Salon #13 was held at Runway SF, which is a cross between a co-working space and an incubator.  At the beginning of the talks, the operations person from Runway said that their uniquely high percentage of shared public space supercharged the startups based there as the teams intermingled and ideas were cross-pollinated.  Apparently they have have a good number of successful exits, which for an incubator must mean getting funding or something.  It’s an amazing space, but they are still pretty stealthy.  They don’t even have a website that I could locate.

For those who don’t know:

The Health Extension community is committed to collaborative action to extend healthy and happy human life spans to 123 years and beyond. Our members are scientists, entrepreneurs, and social influencers dedicated to fixing the degenerative cellular processes that cause deadly human diseases.

Health Extension was founded and is executively directed by scientist/entrepreneur Joe Betts-LaCroix.  Joe gave his standard presentation pointing out how absurdly underfunded aging related research is.  Basic research into the biochemical processes behind aging represent a tiny fraction of healthcare spending, while aging related diseases account for the vast majority of healthcare costs.  So obviously there is a disconnect somewhere.

The field of aging research it clearly underfunded, so Google’s new Calico project seems very encouraging.  Aubrey De Grey is certainly in favor of it.  Google clearly has cash to throw at the problem, but some folks question whether they can find the right talent.  However, accomplished biotech scientists have assured me that Calico’s CEO Arthur Levinson has an extraordinary contact list and can get the talent he wants.  So the hunt is on in earnest with the data wizards over at Google on the case.

Joe highlighted some very interesting findings by researchers at the University of Pittsburgh School of Medicine.  They looked at lymph nodes and reconsidered why cancers often begin their deadly migration of metastasis there.  Lymph nodes provide direct access to nutrients, growth factors, and signaling proteins that aid in cell recruitment.  Then they turned this idea on its head and asked – “Hey, why don’t we see if we can grow little mini-organs there in the lymph nodes?”  And so they did.  They injected mouse lymph nodes with liver cells, and the little masses of liver cells that grew in the lymph nodes were functional enough to save the mouse from liver failure.  Then they performed the same trick with thymus cells and pancreatic cells.  So yeah, that sort of blew my mind.

When you stop to think about it, you can imagine ways to make all organs fault tolerant by overloading lymph nodes with little micro-organs distributed throughout the body.  This almost reminds me of highly-available computer clusters.  Of course, evolution probably arrived at a centralized liver for a reason.  It may be that a single large mass of liver tissue can more quickly transfer bigger doses of important factors like glycogen to other vital organs.  Messing with any complex system like this will surely lead to a bunch of broken functions.  But if I were faced with the choice of that or liver failure, I might take the chance.  There aren’t enough donor livers to go around.

Next, Joe went on to relate that HE’s Aging Variant Database Project was rejected by the Nucleic Acid Research journal.  Apparently an editor fell victim to the halo effect bias.   They decided that the database must be tainted because it was hosted on a site that also hosted links to life extension topics and the mere mention of life extension is disreputable.  This database is a meta-analysis of existing studies meant to identify genetic variants related to aging.  This certainly isn’t quackery or pseudo-science and most of the reviewers realized that.  But Nucleic Acid Research is a prestigious journal.  And prestige is something that must be jealously guarded.  So the Health Extension researchers will be submitting the Aging Variant Database to another journal, possibly the modern, open-source PLOS One.

One thing I like about Health Extension is all the interesting people you can meet during the social periods.  I bumped into biotech entrepreneur and fellow Oaklander Ryan Bethencourt, who co-founded Sudo Room, Counter Culture Labs, and BerkeleyBiolabs.   He told me a bit about this “hackubator” Berkley Biolabs is setting up, which is biotech space for scientists with promising ideas to work out proofs of concept.   I guess there is this new crowdfunding site, Wefunder.com, that will be involved somehow. He then introduced me to Andre Watson, who won my admiration first by having seen every Star Trek episode, and secondly by telling me a bit about his work on nanotechnology for genome editing.  At Foresight this year, I had heard George Church mention the CRISPR gene editing technique that is a biomimicry of a bacterial proto-immune system.  So accurate human gene editing therapies might be coming down the pipe at some point.

As much I do love Star Trek (Picard not Kirk), I have this dark side that is contrary to the Gene Roddenberry optimism of Star Trek.  I am picturing governments editing the genes of their citizenry to make them more pliable.  Imagine the marketing potential there!  I asked Andre if he thought gene editing would be used for good or evil, and he sensibly replied “both.”  Which is, of course, the fate of all technology.  But a world where genes can be altered at will or against your will is very strange to imagine.  Will genetic traits be taken up and discarded like fashion statements?  Will we accidentally break all manner of delicately balanced genetic network interactions and wreak untold havoc?  It’s hard to say.

I then went on to talk to another scientist that I admire, JR, to hear what he was up to.  I had been wondering why SENS didn’t seem to be pursuing a strategy to activate protective pathways that prevent aging, similar to what Cynthia Kenyon found in her long-lived nematode mutants.  JR pointed out that since calorie restriction doesn’t even seem to increase longevity in mice, let alone primates, it would be difficult to exploit those pathways that Kenyon discovered.  He framed the question thus: would it be easier to tweak metabolism to prevent damage or to repair damage once it occurred?  He considered the latter to be simpler.  And this seems consistent with the SENS approach.  Repair damage as it occurs.  And that is perfectly reasonable, but I find myself a bit disappointed.  Kenyon seemed to point toward hidden capabilities just waiting to be unlocked.  Like a biological equivalent of the software Easter egg.  But practical people are pointing to something more like automobile maintenance.  Not that I would turn down longevity via that method.  I just want to believe I can fly.

Err, yeah. So then JR clued me into the immense potential of bone marrow transplants.  These have been found to “cure” AIDS.  It’s not clear how this applies to his own work, but he does like to work with blood because it’s easier to manipulate than organs or solid tissues.  See, this is why I like JR so much.  His approach appeals to my pragmatic side.  I look forward to seeing what practical human rejuvenation techniques he will develop.

Again, this is why I love Health Extension Salons.  I have already been inundated with exciting ideas and the main speaker hasn’t even presented yet.  The main speaker was Sean Mooney, Director of Bioinformatics at the Buck Institute for Research on Aging.  He started out by encouraging biotech startups to consider government SBIR and STTR grants to access non-dilutive capital.  He, like many academics, sits on various “study sections” that review these grants and said that he often doesn’t see enough projects worth funding.   I had never heard of these study sections, but I guess the recent government shutdown really threw a wrench into the works and some think that this threatens the US position as the worldwide leader in scientific research.  Of course my libertarian friends would have something to say in rebuttal, I’m sure.

Mooney then asked the room how many people had their entire genome sequenced. I initially raised my hand, foolishly thinking that my paltry 23andMe SNPs qualified.  But Mooney repeated the phrase “entire genome.”  And only one person raised their hand.  Apparently they had participated in a study through Personalis.  Mooney was impressed and said that he had asked that question at many conferences but rarely had anyone raise their hand.  He predicted that the entire genome sequencing would become very common as soon as the price plummets.  And the price is plummeting exponentially in a way that would warm Ray Kurtzweil’s heart.

<insert logarithmic graph here>

Mooney talked a bit about his work in translational research, which aims to bridge the gap between basic and applied research to move findings from research labs into medical clinics and move empirical data from the clinics back into the research labs.  This is a fascinating topic that certainly warrants further examination, but then Mooney went on to an even more interesting topic.  He brought up the CAGI challenge, which invited researchers to predict clinical medical outcomes based on genomic data using George Church’s Personal Genomes Project.  Currently, 23andMe gives you some estimates of that sort of thing for many diseases, but apparently their stuff doesn’t cut the mustard in the clinical world.  So this was a pretty tough challenge and actually none of the teams were able to accurately match more than a small minority of the genomes to medical outcomes.  I found this surprising.  I would have expected better results.  It’s not clear if this poor showing was the result of insufficient data, or if nurture really does trump nature in medical outcomes.  I understand that throwing methylation information into the mix would help improve the predictive power.  One biologist I related these finding to quipped that he wasn’t surprised by the results since DNA can’t tell you whether a person is alive or dead.

So what does this mean?  It seems to mean that scientists don’t yet have good models to predict what the real effect of genes are on phenotypes.  Yeah, so what good is this genetic data then?  Best take those 23andMe predictions with a grain of salt.  Mooney was quick to point out that he obviously wasn’t bearish on genomics being a bioinformatics person.  While genetic data might not be ready for clinical prime time, he had little doubt that doctors will be using genetic data in the near future.

One challenge to reaching this goal is that gene expression differs from tissue to tissue.  It was speculated during discussion after the talk that these differences in gene expression could pose unforeseen risks to Induced Pluripotent Stem Cell treatments.  Consider a cheek cell which expressed a mutation that increased the chance of liver disease.  This would be harmless since the cheek cell isn’t in the liver, but if that cell were scraped and converted into a stem cell to regrow liver tissue… well, that would be a problem.  At first, I naively thought that IPS stem cells would be better for medicine since the immune system wouldn’t need to be suppressed to avoid rejection.  But several scientists I spoke with pointed out that the complexity of modifying IPS posed more risks than naturally pluripotent embryonic stem cells, though having your own cord blood would be optimal.  Anyone have parents forward thinking enough to bank that stuff?  No?  Too bad.

Health Extension continues to provide an amazing forum to learn about real science from serious scientists who are pushing the field of aging research forward.  The more I learn about this stuff, the more daunting the problems seem sometimes.  But there are other ideas that seem so much closer to implementation, such as Justin Rebo’s blood scrubber, or even the idea of blood infusions from young to old to provide regeneration.  Health Extension is a real thing that can happen if the right resources are focused upon it, and that’s an exciting future to consider.