Otto West: Apes don’t read [genomics]
Otto West: Apes don’t read philosophy.
Wanda: Yes they do, Otto. They just don’t understand it.
Some of you remember that last year we were treated to a strange case of DNA denialism that was making the rounds of the foodie community. Michael Pollan was all excited and aerated about it for some reason. Even Marion Nestle, who should know better, propagated this cherry-picked and non-peer-reviewed “study” that purported to show that DNA had no influence at all on common diseases.
There are some people who so fervently want to believe that you can dismiss DNA entirely and just live in harmony with the natural world with good, clean living–if we stop using chemical toxins and we all rode our bikes to work–that they have pushed a meme that Mary Carmichael deemed “Environmental Determinism”.
Latham was undaunted by the various upbraidings provided by people who actually understand genomics, and recently took his case to The Guardian with a missive entitled “The failure of the genome“. Once again he uses his flawed grasp of GWAS and twin studies to try to lead you to conclude that all of our disease problems would be solved if you just ate organic food. Let’s revisit what he said at HuffPo on this:
That means environment must be the entire cause of ill health, i.e. junk food, pollution, lack of exercise, etc. The reason we wrote an article about human genetics (when we are a food and agriculture website) is that we believe that if people live right, agriculture and therefore the planet will more or less fix itself. Because there is indeed only ‘one health’. Bravo!”
See, it’s so simple: the environment must be the entire cause of ill health! Live right, dammit! It’s so clear.
Nobody I’ve seen in biology anywhere presumes that the environment doesn’t influence gene expression, and we actually have a fairly decent understanding of why we have surface receptors on cells–because we get outside signals, both positive–like the food we take in, and negative–like infectious invaders. But your underlying genome contains variations that mean it can only react in certain ways to stimuli–and why I react to caffeine, or medications, or all sorts of things differently than you do. Why am I tone deaf and some people have perfect pitch–is it really because they had organic food as babies and I didn’t? Some people can resist HIV infections because of a mutation they have in a receptor gene–but not everyone can. (By the way, this may also be why some people can resist other infections.) Is this because they are in better harmony with the world than suffering AIDS patients?
Sometimes those wires get crossed though. For example, for most people peanuts are a nutritious food–sometimes life saving, in fact. For me, they could kill me. Why? Because my immune system genes over-react to a protein in peanuts. How did that happen to me? It’s entirely likely that happened because I have a broken filaggrin gene.
“Living right” with organic peanuts could kill me. And not because the peanuts are a bad environmental toxin on their own. Because of a predisposing filaggrin gene, and because of my immune system DNA response.
We know Latham has this agenda–to prove that living right solves all human ills, by declaring the genome invalid. He’s never explained why the GWAS data in dogs is so compelling. And I don’t know how he’d be able to resolve the fact that dog breeds are prone to specific medical issues. Do you really think doggie lifestyle is the only factor Jonathan? How do you explain that chocolate could kill my dog, but my Easter candy is ok for kids? Wouldn’t the toxin be the same? Could it be something in the doggie genes and how the doggie genome handles the metabolism?? Is there really “one health”?
Why isn’t the GWAS data in humans pleasing Latham? First, of course, because he doesn’t seem to understand them. And for some reason he seems to think this was the only technique that was supposed to yield all the answers. People actually in this field know better. Certainly there have been inflated claims and poorly-reported science news items that all make us roll our eyes. But that doesn’t mean the techniques and strategies aren’t valuable and providing real leads.
But the fact that sometimes we haven’t found the silver-bullet signals he wants is partly because human breeding is not so tidy as dog breeding. We are much more outbred–carrying lots of variations that have combined in everyone’s genome rather differently.
Some genomic issues are also going to be hard to tease out for technical reasons. That filaggrin gene that is an issue in my family–it’s a terribly nasty sequence with lots of repeats, and sequencing it was a major challenge. Because of this it may also not have been well represented in studies of SNPs. There are plenty of other genomic regions that may share this technical barrier–and mechanisms other than SNPs that cause problems and wouldn’t come out of a GWAS study. And other regions that have not be represented at all to date, which we are just starting to learn about through ongoing genomics projects.
Another reason is that human biology is actually quite robust. A paper I’ve been thinking about a lot reminded me of how good cells really are at solving assaults they face. Most cell divisions and processes of daily life in your body actually go pretty smoothly, if you really think about it. Why? Because we have a sort of redundancy of functions. On purpose:
Degeneracy, the ability of elements that are structurally different to perform the same function or yield the same output, is a well known characteristic of the genetic code and immune systems. Here, we point out that degeneracy is a ubiquitous biological property and argue that it is a feature of complexity at genetic, cellular, system, and population levels. Furthermore, it is both necessary for, and an inevitable outcome of, natural selection.
Complexity–including (but not limited to) redundancy and degeneracy–is a feature, not a bug.
Let’s look a one human gene, calmodulin. It appears to be involved in lots of cell communication. Did you know there are 3 calmodulins in your genome–with remarkable genomic sequence identity? To illustrate their protein similarity, let me show you an alignment of the 3 different calmodulin proteins which reside on different chromosomes: CALM1, CALM2, and CALM3. From RefSeq I get the proteins: CALM1, CALM2, and CALM3. I aligned them with Clustalw at UniProt (click for the full view):
Look at the identity at the protein level among these 3 distinct genes. Now, you don’t even need to know much biology to make some guesses about what might happen if one of your calmodulins was broken. There may be regulatory region differences that cause one of them to be more expressed in some tissues than others, or respond to different stimuli, etc. But there are lots of cases in the human genome where other genes could compensate for damage in complex disease situations well enough that it’s hard to tease out the subtleties. But we may find that in some cases, at some times, in some tissues, in some populations, a calmodulin problem may affect disease states. But it’s complicated. And protein modifications or other interactors or pathway members, may be able to upregulate or downregulate to compensate too.
It’s weird to me that Latham doesn’t get this. I’ve seen him argue in the past that teeny changes in plant genes may raise all sorts of havoc. One time he tried to argue to the Advisory Committee on Novel Foods and Processes that genetic modification of plants could have horrible consequences (PDF). What the plant scientists tried to tell him to calm him down:
The Committee is unaware of any evidence that random genetic changes in food plants are likely to be a hazard to the health of consumers; indeed, if there were such evidence, it would call into question the safety of all the current methods of plant breeding and the food we currently eat. For example, non-GM plant varieties carrying induced mutations have been widely grown and consumed for several decades and natural mutants are included in conventional breeding programmes. The Committee would therefore not agree with the assumption in your review that any unintended change to plant DNA equates to a risk.
Some other plant biologists also tried to set Latham and Wilson straight here: Are Mutations in Genetically Modified Plants Dangerous? I can’t figure out how he’s gone from the huge risk of small changes in plants, to DNA not mattering at all in humans.
I have no idea if we’ll ever really understand Latham’s motives for this misrepresentation he’s propagating. I do know that he’s being used as a useful idiot by people who have environmental agendas that they need to raise money for, and these same ideas are also being spread by peddlers of woo who want you to buy their detox teas, diet products and other “wellness” solutions, like Mark Hyman.
I know some people want simpler and quicker answers to some of the medical situations we face. And some people really just can’t grasp the level of complexity. And others want to sell you stuff. Others will simply refuse to believe that their DNA may have contributed to their child’s issues–because that is a burden of guilt to carry. But the fact that we don’t have all the answers yet–that doesn’t permit you to dissemble.
Some of the deception is probably harmless. But I’ve seen the public health consequences of these strategies around the vaccines and autism debates by people who pretend vaccines have no value. I’ve seen anti-GMO activists use these kinds of misrepresentations to block aid to Africa. Deceptions about the genome could eventually have public health consequences, just like those other ones have. And that would be shameful.
See these dueling Guardian pieces for the background:
The Human Genome Project was just the starting point [oops, fixed link]
And the rebuttal from the Genomes Unzipped team: The genome hasn’t failed and Jonathan Latham came by in the comments.
And letters from Guardian readers: How the genome affects our health
Why we get sick—debating the genetic vs. environmental causes of diseases: Here’s an interesting audio debate where Latham assures the interviewer that they (The Bioresource Project) have proved genes don’t cause disease–and offers some numbers–claiming fewer that 10 genes have been found. And just like anti-vaxxers, he says this information has been suppressed. But he has the proof. He claims we’ve looked at everything and haven’t found it. And guess what! He includes autism in the list of things that he claims to know are caused by junk food and lack of playgrounds for kids. And Congress could fix these instantly if they wanted–but they don’t want to. Kids have autism because of Congress. Srsly. And when directly questioned on whether there might be some genetic and some environment features combined, he says the data does not support that. Stanley Nelson tries to bring the sanity, but is largely cut off and limited by the interviewer. It was interesting to hear Latham talk though, and any of us that wind up in audio debates with him should be aware of this interview. It would be a bit like debating creationists, climate deniers, and anti-vaxxers.
Edelman, GM., & Gally, JA. (2001). Degeneracy and complexity in biological systems Proceedings of the National Academy of Sciences, 98 (24), 13763-13768 DOI: 10.1073/pnas.231499798
Berchtold, M., Egli, R., Rhyner, JA., Hameister, H., & Strehler, EE. (1993). Localization of the Human Bona Fide Calmodulin Genes CALM1, CALM2, and CALM3 to Chromosomes 14q24-q31, 2p21.1-p21.3, and 19q13.2-q13.3 Genomics, 16 (2), 461-465 DOI: 10.1006/geno.1993.1211
Schouten, H., & Jacobsen, E. (2007). Are Mutations in Genetically Modified Plants Dangerous? Journal of Biomedicine and Biotechnology, 2007, 1-3 DOI: 10.1155/2007/82612
Shorter Jonathan Latham: Apes don’t read genomics.
Shorter Genomes Unzipped and OpenHelix: Yes they do, Jonathan. They just don’t understand it.