Epigenetics and magical thinking

[updated to correct typos, clarify and add a link to the article I disagreed with]

Someone sent me a link to Dr. Mecola's website, in which he argues that because epigenetics exist, we are free from the Overlord of Determinism and can think our way out of cancer.  Or something.  I found the article to be carelessly written, misleading and just plain wrong about a lot of the science.  So I wrote a rebuttal and tried to post it in the comment section.  Have a look at the article - it's a short read.

The article reminds me of "The Princess Bride."  One of the characters keeps saying "inconceivable!"  to things that actually happened.  Another character says, real quiet, "You keep on using this word. I do not think it means what you think it means."  That's my initial reaction to this article.  It's interesting to see how people are trying to apply and misapply concepts like epigenetics.  It really speaks to how badly we as scientists convey the beautiful insights of the field effectively and accurately.

As a side note, the article seems to deeply confuse DNA sequence vs. DNA expression.

Here are my main responses.  Article quote appears first, then my response to it.

--"Epigenetics Shatters "The Central Dogma""
I have no idea what this statement means :-)  The central dogma hasn't been "shattered,"  nor would it be a bad thing if it were.  Scientists have made careers and even won Nobel prizes characterizing apparent exceptions to it (we have one of these here at UCSF).  In order for the central dogma to be "shattered," it would have to have been replaced with a theory that has better predictive power.  Epigenetics doesn't do that; it explains a set of apparent anomalies by tacking on an additional mechanism for transmitting information in the form of DNA "marks."  It's actually a pretty cool story.


--"The ramification of buying into the central dogma is that it leads to belief in absolute determinism, which leaves you utterly powerless to do anything about the health of your body; it's all driven by your genetic code, which you were born with."

Maybe for this guy, that statement is true.  And in fact I do think "determinism" is probably the most accurate description of what's happening here, at the end of the day.  But epigenetics is simply another causally-based mechanism to explain observations.  For instance, epigenetic modifications can happen for all kinds of reasons, both those reflecting conscious changes to lifestyle and those reflecting exposure to environmental factors of which one is completely unaware :-)

--"'Cairns took bacteria whose genes did not allow them to produce lactase, the enzyme needed to digest milk sugar, and placed them in petri dishes where the only food present was lactase [I think they mean lactose here]. Much to his astonishment, within a few days, all of the petri dishes had been colonized by the bacteria and they were eating lactose. The bacterial DNA had changed in response to its environment.This experiment has been replicated many times and they have not found a better explanation than this obvious fact – that even primitive organisms can evolve consciously.'"

The experiment demonstrates natural selection in action, a process that for 150 years or so has proven to be very good at predicting things like speciation.  Bacteria do have processes to acquire or reshuffle genes in times of extreme stress like starvation.  It's their version of sex, a process which most eukaryotes use to generate diversity in populations.  That some organisms "win" using this strategy demonstrates why it's been conserved in one form or another for billions of years: at the population level, diversity works.  So yes, in a sense you could call this "evolving consciously," meaning that an active process exists to generate diversity within populations, but I don't see how that "shatters" the central dogma, nor does it in itself imply consciousness (although I do believe in a kind of consciousness across all life), any more than being hungry and seeking food does.  These are evolved responses to stress, and they were selected because they worked.

--"What this all means is that you are not controlled by your genetic makeup. Instead, your genetic readout (which genes are turned "on" and which are turned "off") is primarily determined by your thoughts, attitudes, and perceptions"

This would be cool if true, but nothing in the previous text actually supports what he just said here.  It's also kind of ridiculous in a way surely the author didn't intend.  First of all, the entire question of whether "you" are being "controlled" by a genetic program seems deeply misleading.  Who are "you?" in this scenario and who are the nefarious "genes" seeking to control you?  But more seriously, of course you are "controlled" by your genes in the sense that the information you need to respond appropriately to the environment is encoded within them!  Africans have a set of gene encoding melanin production that protects them from solar radiation.  Are they "controlled by their genes" when they activate melanin production constitutively?  There's a well-defined genetic program that's required to accurately separate chromatids during meiosis.  are these genes "controlling you" when you activate them to make offspring?  This makes no sense.

--"Now here's where epigenetics comes in … certain foods, such as broccoli and other cruciferous vegetables, garlic, and onions contain substances that act as histone inhibitors, which essentially block the histone, allowing your tumor suppressor genes to activate and fight cancer. By regularly consuming these foods, you are naturally supporting your body's ability to fight tumors."

Surely the author realizes that all genomic DNA (in eukaryotes anyway) is packaged in histones.  Therefore eating foods that, if such activity resided in the food itself, "block the histone" would, in the logical extension, prevent any cell from accessing virtually all of its DNA.  Therefore what's being suggested is that food can promote the appropriate acetylation of histones, driving a packaging configuration that prevents transformation (making cancer cells).    While that may be true, and would be wonderful as preventative therapy, it's of course also true that the enzymes enacting this acetylation are responding to many cues.  Some are environmental (and we can change that!) while some are coming from the hundreds of other proteins encoded by the genome.  Shifting the emphasis entirely onto epigenetic modifications, as this article does, is just misleading.

"So the good news is that you are in control of your genes … You can alter them on a regular basis, depending on the foods you eat, the air you breathe, and the thoughts you think."

This is false.  Your body does have ways to modulate the expression of your genes - true.  "You" are not able to "alter them on a regular basis" in the sense implied here.  The primary known ways that gene sequences are altered "on a regular basis" is in the immune system, where B and T cells induce hypervariability in antibody regions to create the ability to bind antigens (a cool story), during meiosis, when chromosomal arms cross over to generate diversity in offspring (also a cool story!) or for instance due to repair after oxidative damage to DNA.

Probably there are other ways that human cells change their own DNA sequence and expression, and it will be great to discover them!  But framing the effect of epigenetics as a "little guy beats back mean old determinism" and blandly telling people they can think away their cancers, if only they just think the right thought! - is badly misinformed and borderline irresponsible.  What if every reader took that as their new reality?  They go off, change their thoughts, eat broccoli and decide what the hell do I need checkups for?  I'm thinking fine and eating miracle epigenetic diets!

Climbing: Yosemite and Sonora, April 2012

My buddy Kyle and I travelled to Yosemite to inaugurate this year's climbing season.  Getting there wasn't pretty.  I had stayed up until 5AM the night before to prepare my lab data presentation, a wholly avoidable tragedy created by my unwillingness to stop collecting data and start making a presentation.  I mention this because the sleep deprivation caused me to miss several turns on the way to Yosemite, and we were therefore unable to crash until well after 1AM Friday night.

Kyle volunteers with Bay Area Mountain Rescue Unit.  One his buddies who volunteers for the NPS, Blake, was already set up at Camp 4 and kindly let us split the site with him.  So we were able to roll in late and get our tents set up without too much trouble.  I slept very well!

Saturday morning I roll out of the tent, slap on some shoes and take care of the only thing that matters: COFFEE.  We then hook up with several other NPS friends of Blake's (Sebastian, Val and ...?), then all head out to Reed's pinnacle.  The more experienced climbers are looking to get some trad crack climbing in there, so Kyle and I bail out to Five and Dime for easy 5.8 warmup sport leads.  Here's me trying to do justice to the view from the top of that wall.

After that we headed over to Pat and Jack's to meet up with Blake and friends.  Kyle and I tackled the first pitch of this 5.9 - at least I think that was the route:

That's Kyle at the top.  Beyond him is a technically beautiful - I mean really stunning - trad 5.10b that I got to climb with a top belay, following Sebastian after those guys arrived.  Surprising moves, everything you needed but none of it obvious.  Really nice climb.

When Sebastian led the route we had just done, he took two 9.8-ish mm ropes with him in order to top-belay me.  Once I was up there, he set up a rappel and went to take off.  I stopped him, looking at the "excuse-me-is-that-a-granny-knot?" overhand knot he had used to tether the ropes to one another.

Me: "uh...so, yeah.  How sure are you that this knot is safe?"

Him, in thick German accent: "I am glad you asked! Never take anything for granted! It is an overhand knot that will not capsize [come undone under tension] under loads up to (...5?) kN!  Also, look how its asymmetry makes it roll over rocks.  This knot won't get stuck when you pull rope, and that is what ["vat"] makes it so useful!"

He was very enthusiastic about his knot.  I, on the other hand, was enthusiastic about letting him be the first to rap down on his knot.  Ultimately it worked fine for us both.

Once down, Blake and Kyle kept referring to this knot as an EDK.  This, Sebastian discovered, is short for European Death Knot.  He laughed and laughed at this, bending himself over in giggles the whole hike back every time he said "EDK."

We got back and were invited to a potluck with some of the NPS/BAMRU folks.  That was great fun until the last two days came down on me like a sandbag.  Kyle and I hiked back to our tents.  It was a full moon so I stopped to admire El Capitan and the frozen-but-moving ghostliness of Bridalveil Falls in the half light.  And then I slept.  And slept.

Lucky for us on the way to Yosemite, one of the wrong turns I took led us near signs for Sonora.  Sonora!  That was where I first climbed outdoors, under the guidance of many of my then climbing buddies/mentors: Brian and Nick (who went on to climb El Cap together the next year), Joel ("It's a video") Tornatore and Annika before she abandoned us all for New Zealand.  There's a secret-feeling place there called The Grotto, at the end of a rocky and pastoral approach, and it is truly gorgeous.

Once there, we hooked up with a sarcastic and fun group of climbers - and, alas, engineers - from the Bay Area.  Kyle and I warmed up on a juggy 5.9.  Here's Kyle doing what turned out to be his most skilled activity that day - hangdogging:

After playing belay monkey and smack talking some more, the alas-engineers were nice enough to let us toprope some of their sport- and trad-led routes.  Here's me working on another excellent, technical 5.10 (c?) with a super-fun crux about 2/3 of the way up.  Everyone else went left to a side pull, then back over.  I tried to, and eventually managed to, go straight up after learning how to trust my feet on all that smeary goodness.  The crux is just below the small outcropping directly above my head in this shot:

 And here's me waving from the top:

After that we exchanged emails with the alas-engineers, talked about future climbing adventures together and then Kyle and I hiked back out.  Traffic was light and before I knew it, I was happily back home with wife and cat.

As usual, I couldn't wait to get back into lab :-)