Wednesday, April 11, 2012

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!

11 comments:

Allen Henderson said...

It seems I misunderstood one of his points. He says: "substances that act as histone inhibitors, which essentially block the histone, allowing your tumor suppressor genes to activate and fight cancer."

What I think he's asserting is that some foods can drive histone acetylation, thus making DNA less tightly bound to histones and able to activate gene transcription. It still doesn't make sense, and for the same reason: hat's called for is *differential* regulation, not blanket changes across the genome. But I do want to accurately represent his argument.

Allen Henderson said...

In response, a Twitter friend sends me this article, showing how exercise changes DNA methylation in muscles: http://www.cell.com/cell-metabolism/abstract/S1550-4131%2812%2900005-8#Introduction

MaryAnnH said...
This comment has been removed by the author.
MaryAnnH said...

Thanks for posting your response to Dr. Mercola's article. I, too, thought it was too simplistic. In fact, because it IS simplistic I thought it was a disservice to the general public.

My family has a hereditary gene mutation that predisposes us to certain types of cancer. Our mutation is SDHB, and our family gets paraganglioma and pheochromocytoma. We inherited this mutation from Mother (who is still alive). All 4 of her children have this mutation. Of the four, I am the only one who has not presented with cancer (yet).

Mom didn't have a tumor until she was 79. Eldest child had first tumor at 9 mos of age and died at age 28. Gene mutation was known at the time of her death, and there were no tissue samples to test. However, researchers are certain she also had the mutation. Second child had first tumor at age 56. I am child #3. Child #4 got tumor at 52, but was not symptomatic. His tumor was found only because the genetics researchers said we should get screened yearly for these tumors. This was after we all had our DNA run to look for the SDHB mutation that Child #2 had. Her DNA was run first to see what the mutation was. The rest of the family was tested (including 2 of her children) after her DNA came back with the SDHB mutation.

I tell you this lengthy story to say this...Child #2 is the most health conscious person in the whole family. She eats properly, exercises, and lives a positive life. Her tumors grew unchecked until the pain in her cervical spine reached an unbearable point, and chiropractic wasn't helping. The tumors on the spine were metastases of a tumor very near the pancreas--which was found by CT scan AFTER the MRI revealed the cervical problems. Truly, if it were possible to control your genes by healthy living, Child #2 should never have had any expression of the gene mutation, right? And I, who am the least health conscious sibling, should have lots of tumors, right?

It angers me a little when people take such a simplistic approach to such a complicated problem.

Allen Henderson said...

Thanks for the story. I'm sorry to hear about your sister's pain and hope she's able to find some relief.

While it's true that simplifying things can lead to insight, in terms of science education I think it's a terrible disservice to everyone. What's worse is that in this country we have a terrible history both of destructive charlatanism and self-delusion. I'm not in any way saying that Dr. Mecola's site engages in that, but rather pointing out that these kinds of narratives can be used in support of far more destructive applications. In this case, getting it as right as you can really does matter.

I looked up SDHB (http://en.wikipedia.org/wiki/SDHB). In case others want to check it out, looks like the disease is due to a mutation in the nuclear-encoded gene for succinate dehydrogenase that acts in mitochondria. It turns out that a connection between energy metabolism and malignancy was noted long ago (http://en.wikipedia.org/wiki/Warburg_effect) and that treating misregulation of this metabolic pathway is an active area of research (http://cancerres.aacrjournals.org/content/65/2/613.abstract).

I hope there will be better treatments for your family in the future :-)

MaryAnnH said...

Hey, thanks for replying. I'm always looking for more information on SDHB and its components.

My sister (Child #2) had the abdominal tumor removed at Mayo Clinic in Rochester, MN. This was followed by radiation therapy on her cervical spine here at home (which I'll not identify for obvious reasons, lol).

My brother's tumor (Child #4) is still there, located quite close to his thoracic spine. We're still trying to find a neurosurgeon talented enough to remove the tumor.

Persistence is the key in our case. There seems to be no rhyme or reason as to how the mutation presents itself. Both of Mom's sisters obviously had the mutation, because my cousins also have the mutation.

Both of Mom's sisters have also had cancers, though not paras and pheos. Mom's oldest sister died of brain cancer metastasized from the lung. The next oldest sister had breast cancer, but still lives. I've had two cousins in their 50s who died from paraganglioma.

It is believed that my Mom and her siblings received the mutation from their dad, my Grandpa. His side of the family has several deaths from cancer, although Grandpa never had cancer. He obviously passed the mutation on, though.

The field of genetic mutations is still abuzz with research and new findings. Hopefully, like you said, we will figure out how to turn off the nefarious activity. :) I'm just a layman, but I've researched lots. I'm quite a bit more healthy in lifestyle now than I was before. :)

JP Glutting said...

I'm having broccoli for lunch today, Allen. Don't harsh my buzz.

JP Glutting said...

And "Unknown" is me - JP Glutting. Google asked me to sign in, but then ignored who I am. Feels familiar.

Lillyth ~ Fairly Rabid said...

I think, Allen, you are misunderstanding him. I don't think Dr. Mercola is saying to abandon treatment and go think away your cancer.

If you do any kind of research into the matter, you will find scientific proof that your thoughts and emotions affect your body. For example, there was a research study done at your very own UCSF. They gave chemo pills to one set of cancer patients, and to the other set they gave sugar pills. ONE-THIRD of people who took the sugar pills had their hair fall out SIMPLY BECAUSE THEY BELIEVED IT WOULD. This was a double-blind study. If our thoughts can affect our bodies in a negative way like this, why not in a positive one?

There was another study done (also at UCSF, also a double blind study) where heart surgery patients were split into two groups. One group was prayed for by a local prayer group, and the other was not. No one in the study was aware of the prayers. Even the doctors did not know which patients were being prayed for. The group that was prayed for recovered faster, healed better, and had less (I even want to say ZERO?) fatalities post-surgery than the group that was not prayed for. Thus proving that not only can our own thoughts and emotions affect our physical bodies, other people's can as well.

As you and I discussed on my birthday, Celiac disease is a gene carried by 40% of the population. The percentage of people expressing that gene is considerably lower, but any "trauma" has to potential to turn the gene on. Child birth, car accidents, and surgery being the biggest three causes of trauma. I find the term "trauma" to be very telling. My last surgery, for endometriosis, was in NO way a trauma for me. It was a joyful experience. I have a very positive relationship to surgery as a result. So much so I am GIDDY thinking about my upcoming disc replacement. Therefore, (forget for a minute that my Celiac gene is already turned on) my upcoming surgery would not be likely to turn it on, since I would not relate to it as a trauma. I have a friend however, who, upon having a surgery, triggered PTSD from being a medic in the Viet Nam war. It is not so much what happens to us, as our reaction to it that constitutes trauma. So I find it very telling that even according to the experts in the field, is it negative emotions ("trauma") which turn on the Celiac gene.

If trauma can cause negative genes to express themselves, might not positive feelings have the opposite effect?

Lillyth ~ Fairly Rabid said...

I forgot to click the email follow up button, so I am adding another comment to do that. Doh!

Allen Henderson said...

I don't think I misunderstood him - he is saying you can think away your cancer. The title of his post is "Falling for This Myth Could Give You Cancer " and the second topic sentence is "According to some scientists, changing your health may be as "simple" as changing your thoughts and beliefs." If this were the only instance of Mercola's website being dangerously misleading, I'd give it a pass. His entire website is based on misrepresenting science. I assume it's to drive ad traffic and move product by promising miracles.

If his website was the source of merely 10% of the claimed miracle cures, why isn't it the most visited on the web? Mercola drives traffic using tribal identity, selective misrepresentation/demonization of science and sold victimhood in a classic huckster pitch. Every reader is a falsely victimized member of a select few who are in-the-know. That's what he sells, and he's doing well enough to keep it up for years.

As for the effects you mentioned, no one, myself included, disputes the reality of placebo effects. Why it happens is fascinating and tragically under-explored. What has the Mercola website done to advance our understanding of this promising phenomenon?