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.

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 #11: Aging – Death by Damage vs. Death by Design

Sorry for the provocative title,  let me start by clarifying that  I in no way subscribe to intelligent design.  I am just trying to contrast the viewpoints of the two speakers that I saw at Health Extension Salon #11 last week: Cythia Kenyon and Justin Rebo.  More on that later.

The Health Extension Salon was held at Runway SF this month, and it was outstanding as usual.  I haven’t been getting out enough lately, so it was great to chat with interesting people and hear about amazing science.  Runway SF, as you may know, is an incubator/co-work sort of thing in the Twitter building on Market Street in San Francisco.  I guess it’s by invitation only.  They have an igloo, and I saw some quadra-copters laying around and whatnot.  So  you know, it’s pretty cool.

I bumped into Hank Pellissier, who I first met years ago at my East Bay Futurist Meetup, and he told me a bit more about his new book, Brighter Brains.  Hank has compiled a huge list of factors that affect intelligence from environmental factors to inbreeding.  It seems like an interesting survey.

Then I listened in to a conversation with some blindingly smart people, R.J. and J.Y. among others, and wisely kept my mouth shut.  J.Y. suggested that programmed death might be an adaptive trait that increases a species’ evolvability.  More on that later as well.  He also blew my mind by wondering aloud if the lunar cycles of women were a throwback to our ancient ancestors that dwelled in tidal pools.  He pointed out that many illnesses varied in intensity of symptoms based on the time period during a woman’s menstrual cycle, but that the medical profession failed to take this into account when prescribing dosages of medicine.  Thus, many women find themselves overdosed for half the month and underdosed for the other half.  He suggested that there is a vast potential to exploit this to improve women’s health.  I hope some bio-hackers look into this further.

J.Y. also suggested that anaphylaxis (like from a severe nut allergy) might be the result of a sort of epinephrine (adrenaline) regulation problem.  This was an idea his young child apparently suggested upon learning that an epinephrine injection was the only reliable treatment.  From the mouth of babes.  I got the impression that J.Y. was brimming with ideas for potential medical breakthroughs.

Before introducing the speakers, the charismatic and charming Dinelle Lucchesi challenged the crowd to call out potential roadblocks standing in the way of progress in anti-aging research.  There was some disagreement about whether the fact that aging is not designated as an illness by the FDA is an issue.  Justin Rebo thought this was unimportant since any effective anti-aging treatment would be sure to combat any number of illnesses.  It was also suggested that aging is difficult to measure with bio-markers.  But my favorite roadblock was that “biology is hard.”  Yep, that sums it up.

Health Extension founder and awesome person, Joe Betts-LaCroix, then took to the stage to reiterate the fact that aging research is underfunded:

  1. Most healthcare money treats age-related diseases.

  2. Aging is the single biggest risk factor for these diseases.

  3. But funding to address the biochemical processes of aging is <0.01% of healthcare spending!

Typical shortsighted narrow-mindedness prevents us from exploring preventative medicine to the degree that we should.  But I was also excited to hear that Health Extension has commissioned a study by students from Moscow’s Skolkovo Management School* to make a quantitative case for more funding in aging research.  I guess Joe will be heading off to Washington with this in hand to beat Congressmen over the head with it or something.  I wish him the best of luck, but he might be better off packing a suitcase full of money.

The first guest presenter of the evening was Justin Rebo, CEO of Open Biotechnology.  In 2009, working with SENS, he built a device to filter out senescent immune cells from the blood.  This mechanism was interesting in that he attached metallic particles to antibodies which selectively bound to defective T cells, and then was able to pull them from the blood using a magnet.  There is something brutal and almost mechanical about this approach.  I like it.  I guess it might help with the ineffectiveness of flu vaccines for the old.  This blood scrubber seems to be something like a dialysis machine in that it filters all the blood of an animal and replaces it.  This work focuses on bioremediation of the blood, which reminds me of the work being done around rejuvenation of old mice using blood from young mice.  Rebo is now working on a new version of this device, which will add positive factors in addition to removing the negative ones.  He sees great promise in getting the blood compounds of older creatures to match the levels found in young animals.

So Rebo’s approach seems well aligned with the SENS model, in that it both treats aging as an accumulation of damage and toxins and seeks to remediate the damage.  This looks to be a sensible short-term solution (Well, except for this whole move the mitochondrial DNA into the nucleus business, that seems crazy.  But what do I know?).  The next speaker of the evening seemed to suggest a deeper cause of aging: it’s programmed by our genes.

Cynthia Kenyon is a distinguished scientist based at UCSF:

In 1993, Kenyon and colleagues’ discovery that a single gene mutation could double the lifespan of C. elegans sparked an intensive study of the molecular biology of aging. These findings have now led to the discovery that an evolutionarily conserved hormone signaling system controls aging in other organisms as well, including mammals.

– from her Biosketch

She gave a presentation similar to her 2011 TED Talk, which is definitely worth watching.  Kenyon’s sparkling wit is a pleasure to experience.  The upshot of her presentation was that this longevity mutation she found in C. elegans (Daf-2) somewhat impaired the worms ability to bind to insulin and IGF-1, and this caused another gene called Daf-16 (if it was in the nucleus) to trigger all sorts of protective pathways and thus extend life **.  Sugar impairs this process, which is why Kenyon reluctantly admits that she eats a low glycemic diet.  This was a big topic of interest among the folks that thronged her with questions after her talk.  But Kenyon is a real scientist and cautiously avoided advocating for this diet since she says it hasn’t been proven to extend life.

As I mulled the two presentations over preparing to write this post, it occurred to me that there was some tension between the two talks.  Rebo and SENS are boldly striding ahead assuming that aging is a process of damage and that we can combat it by repairing damage.  But Kenyon seems to suggest a deeper, perhaps longer-term strategy of activating the body’s built in protective pathways to extend life.  She prefers small molecules for this, since they are easier to test.  Also, this modulation requires some finesse.  You can’t just go knocking genes out entirely.  If you couldn’t bind insulin at all, that would be a problem.

Kenyon’s work also suggests that aging might be a process that is controlled by genetic timers.  “How does the body know when menopause should occur?” she mused.  Perhaps the entire aging process is carefully timed by genetic pathways.  Maybe age-related death is an adaptive trait.  Wait, what?  Yep.  Think back to what J.Y. said earlier.  Death improves evolvability.  You would expect that an organism that died on a timer to evolve more.  Consider an environment that can support 100 organisms.  The more frequently those creatures die (assuming they can still reproduce), the greater the genetic diversity.  Uh, maybe I better stop here and go ask Razib.

For the sake of argument, let’s just say that aging and death are programmed, and that this does improve evolvability.  Well that suggests that the “repair the damage” guys are missing the boat somewhat.  After all, the body seems to have these protective pathways waiting to be activated.  That’s sort of how calorie restriction might work.  It tricks the body into activating protective genetic pathways.  Because a timed death is fine as long as you get to reproduce, but during time of stress, such as famine, our genes have a special bag of tricks that can help us survive.

But there is a further twist.  Kenyon mentioned that deactivating sensory input extends life in fruit flies.   They can’t sense their food and thus live longer.  I guess it has been shown that insulin rises more if you smell food.  So you calorie restriction people are best off skipping dinner with non-CR friends entirely.  It’s not just the food itself, but the signal of the food, that works it’s way into your genetic expression somehow.

But now we are getting into hormesis territory.  Someone get Seth Roberts on the phone.  A little bit of toxin triggers the body’s natural defenses.  Kenyon pointed out that mildly inhibited respiration was associated with extended lifespans and wondered if the resulting increase in toxins such as ROS were the cause.   Get my homeopathist on the phone.  So are the small amounts of herbicide on that non-organic food I disdain actually helpful?  Oh brother, now I have to rethink everything.  Maybe the SENS people should too, given that some of the supposedly damaging toxins like amyloid plaques might turn out to be protective mechanisms.  I guess this goes back to my favorite quote of the evening, “Biology is hard.”

Overall, I was impressed by both speakers.  Both the pragmatic Rebo and the deeply insightful Kenyon are striving to extend human health spans.  I don’t want to lose sight of this when I drill down into the details.  At the end of the day, successful anti-aging treatments will reduce suffering and increase health and happiness.  Imagine an 80-year-old as vibrant and healthy as a 20-year-old.  Even if I dropped dead right at 81, I would take that sort of old age in a heartbeat.  It’s a real shame that these aging researchers are so bereft of funding.  If anyone reading this knows any good policy wonks or lobbyists who care about longevity, you should direct them to the next Health Extension Salon so they can get involved.  Hey, I’m doing my part.  I’m getting the word out.

* Skolkovo might be the world’s coolest looking school by the way.

** It’s worth noting that at least some of Kenyon’s insulin/IGF mutants had normal reproduction. http://rstb.royalsocietypublishing.org/content/366/1561/9.full Thus there doesn’t seem to be a tradeoff between fertility and longevity.