‘Social Life of Genes’: David Dobbs’ My Dinner with Andre

gene-expression

(ILLUSTRATION: JEREMY DIMMOCK) From Dobbs, Social Life of Genes

David Dobbs’ Social Life of Genes was racing past 6000 words when it screeched to a halt with an exhortation from Steve Cole. The quote could have come right out of a positive psychology motivational talk:

“Your experiences today will influence the molecular composition of your body for the next two to three months,” he tells his audience, “or, perhaps, for the rest of your life. Plan your day accordingly.”

The message is that we had better be careful how we think, feel, and act because irreversible, life-altering change could result from the next move we make.

Of course, there is a potential self-contradiction or two here hiding in plain sight. If today is so important, so is tomorrow, which might be able to reverse anything that happens today. If genomic expression is so mutable, maybe it can be changed back. But that is not the point that Cole is going after. He wants to emphasize that “our social lives can change our gene expression with a rapidity, breadth, and depth previously overlooked.”

Readers who have been following Steve Cole’s work may recognize the connection to his recent article in Proceedings of the National Academy of Sciences (PNAS). His co-authors included Barbara Fredrickson, a psychologist professor, but also known as a rising positive psychology coach and author of the pop psychology advice book, Love 2.0.

The PNAS article had the immodest goal of providing “an objective approach to moral philosophy.” It tackled a question posed by ancient philosophers: whether people should just pursue happiness (hedonic well being) or go after meaning (eudaimonic well-being).  The article claimed identification of “distinct gene regulatory programs” associated with pursuing these different pathways in the past week. Eudaimonic striving won, they concluded. So there, question answered.

Unfortunately, as I showed in a recent blog post, these claims are based on psychometric malpractice and voodoo statistics. These authors started with an off-the-shelf psychological measure. They  ignored its scoring and factor analyses in picking items that they hoped would measure distinct strivings. They did not check how the items actually performed before mounting the study. They then popped their data into inappropriate multivariate analyses that were guaranteed to produce a particular pattern of results.

Measures of these supposedly distinct strivings were essentially tapping statistically indistinguishable characteristics. The authors’ not able to identify distinctive strivings, and so  they were prevented   from identifying distinctive profiles in genomic expression that go with them.

Dobbs presents dramatic, even if highly selective examples of changes in gene expression from studies of the birds and the bees and fish.

He then describes meeting with Steve Cole for sushi. I tried to imagine the frenetic waving of chopsticks and splattering wasabi and soy sauce in the rapid fire conversation.  I conjured up scenes from the 70s cult classic My Dinner with Andre.my dinner with andre

The three hour movie stars Andre Gregory and Wallace Shawn, and involves the two discussing aesthetics, the meaning of life, postmodernism, science versus the supernatural, and Halloween on Long Island. The film has been described as one which many wish to have seen, but few wish to see.

I actually sat through it twice, but fell asleep both times.  If you want to pass for knowledgeable, but not have to see it, you can view the 9 minute clip here.

Steve Cole’s conversation with Dobbs is rambling, but much more interesting than My Dinner with Andre. Ultimately, though, the talk is oppressive in ways that movie is not.

The article falls into some familiar traps with repeated attempts to enlist what are portrayed as scientific findings to strengthen messages from positive psychology. Namely, all of us need to assume a heightened sense of personal responsibility for how our circumstances affect us and for our health. If we do, we can triumph over adversity.

If applicable anywhere, the message is much more appropriate for rich people. Their wealth affords them better circumstances and better chances for health and longevity.  The message of positive psychology gives the socially advantaged the smug reassurance that it is not their circumstances, but what they make of their circumstances that accounts for their superiority.

David Dobbs and his sushi eating companion preach a reductionistic genomic expression ueber alles. They neglect the rich context of linked biopsychosocial signaling systems in which gene expression occurs. There are lots of complex, reciprocal feedback loops within which gene expression can be dampened or amplified, bypassed, or turned on or off by other processes.

Only by imposing artificial punctuation, can a sentence begin “Gene expression causes…” The endless, uninterrupted flow of the sequence is more accurately “…and then something prompts gene expression, the results of which can in turn be further amplified or dampened by…. and provisional  outcomes can be temporarily or permanently undone by…”

Many readers come to the article with limited examples and a distorted understanding of genomic expression. They are inclined to focus on gene expression as producing blue eyes. Dobbs and Cole want to shock and confront them with evidence that maybe social experiences can change blue eyes into brown. Dobbs sets the reader with a description of an altered genomic expression in the African cichlid Astatotilapia burtoni fish:Astatotilapia burtoni

The fish underwent massive surges in gene expression that immediately blinged up his pewter coloring with lurid red and blue streaks and, in a matter of hours, caused him to grow some 20 percent. It was as if Jason Schwartzman, coming to work one day to learn the big office stud had quit, morphed into Arnold Schwarzenegger by close of business.

Jason Schwartzman

Jason Schwartzman

I haven’t bothered to check Google Scholar about African cichlids

Arnold Schwarzenegger

Arnold Schwarzenegger

and their displays of color, but I am quite sure that Jason Schwartzman won’t be confused with Arnold Schwarzenegger anytime soon.

My expertise is more in social and behavioral sciences, epidemiology, and methodology.  But I have enough tools to identify in the Dobbs-Cole conversation lots of hyperbole, good science being given distorted interpretation, and mediocre or small-scale, preliminary science being given exaggerated importance.

Let’s jump to what Coles says through Dobbs in a blazing blue-lettered sidebar:

“If you actually measure stress, using our best available instruments, they can’t hold a candle to social isolation. Social isolation is the best-established, most robust social or psychological risk factor for disease out there. Nothing can compete.”

This is a weird boast from a social epidemiological perspective. It borders on nonsense when it is put to use in the many correlates of social isolation to a matter of specific genomic or immunological mechanisms.

A nerdy epidemiologist might have yawned: “Sure, so your measurement of social isolation is more confounded than my measure of stress. Too bad. And we cannot really neatly separate stress from social isolation neat and cleanly, anyway.  So what?”

Community surveys of correlates of social isolation are observational studies, not experimental manipulations, and so any causal inference always involves some speculation. Social isolation is correlated with a lot of background characteristics that have identifiable associations with health themselves. In turn, health problems result in social isolation.

Being socially isolated is associated with stress and deprivation, poverty, unemployment, recent losses such as divorce or bereavement, poorer adherence, restrictions in function due to health, delay in help seeking for acute and chronic health problems, etc. etc. Being sick is associated with socially isolation and can cause it.

Technically speaking, problems await anyone trying to make sweeping statements about the power of social isolation versus stress:  reverse causality, confounding variables; unidentified, poorly measured, or incompletely controlled confounds; residual confounding, spurious associations, and a host of mechanisms relating social isolation, as well as competing explanatory variables like stress to health outcomes.

Bottom line: causal inference in epidemiological studies is complex and depends on imperfect efforts to rule out a variety of alternative interpretations.. You just cannot validly make sweeping statements like Cole does here and expect to remain credible.

A 1988 Science article by Jim House, Kevin Landis, and Deb Umberson has been cited over 4000 times as showing that the evidence linking low social support and social isolation was as strong as the evidence that had first linked smoking to lung cancer. Yet, just a few years earlier, Jim House had  been unable to demonstrate the importance of social relationships for mortality among women in a large prospective community study. Epidemiological studies can be frustrating that way.

One of the more reasonable things that Cole admits to Dobbs: “Epidemiology won’t exactly lie to you. But it’s hard to get it to tell you the whole story.”

Cole led into his declaration by citing an earlier study in which he says showed that closeted HIV men succumbed to the virus much more readily. He claimed to have found

that HIV-positive men who were lonely also got sicker sooner, regardless of whether they were closeted. Then he showed that closeted men without HIV got cancer and various infectious diseases at higher rates than openly gay men did.

Something about feeling stressed or alone was gumming up the immune system—sometimes fatally.

Note the shift from social isolation to stress and loneliness. I imagine his voice suddenly booming his next statement, startling anyone else eating along the sushi bar into drop their chopsticks.

“You’re besieged by a virus that’s going to kill you,” says Cole, “but the fact that you’re socially stressed and isolated seems to shut down your viral defenses. What’s going on there?”

Robert Gross, an infectious disease expert at University of Pennsylvania enlisted me as co-investigator in a clinical trial in which we would utilize psychological interventions to reduce viral load in HIV/AIDS patients. I would have had to flee the meeting in embarrassment if I have proposed harnessing  any of the mechanisms claimed by Cole. Whatever their theoretical interest, they do not have demonstrated clinical significance.

We instead developed a problem-solving intervention to improve adherence to HIV-medication. Comparing the intervention to routine care in a randomized trial, we found that we had succeeded in actually reducing viral loads.

The nice thing about adherence was that we could establish its importance in observational and quas- experimental studies, quantify the likely effect size, and then manipulate adherence in a clinical trial. Not as sexy as genomic expression or psychoneuroimmunological mechanisms, perhaps, but at least testable and in a way that our hypothesis could be disconfirmed.

At another point, Dobbs describes Cole’s work with John Cacioppo in which they picked from 153 healthy people

the eight most socially secure people and the six loneliest and drew blood samples from them. (The socially insecure half-dozen were lonely indeed; they reported having felt distant from others for the previous four years.) Then Cole extracted genetic material from the blood’s leukocytes (a key immune-system player) and looked at what their DNA was up to.

He found a broad, weird, strongly patterned gene-expression response that would become mighty familiar over the next few years. Of roughly 22,000 genes in the human genome, the lonely and not-lonely groups showed sharply different gene-expression responses in 209.

This passage conjures up Andrew Kaufman’s My Breakfast with Bassie, a spoof of My my breakfast with blassieDinner with Andre. The film is a lot more watchable, because it is not as pompous and pretentious. In the film, Kaufman who in real life mostly wrestled women,  goes to breakfast with Freddie Blassie, who is a  professional wrestler and now self-proclaimed King of Men.

Andy and Freddie say outrageous things, which eventually draw in some other people who challenge them. If I were at the sushi bar, I might have felt compelled to intervene here with Cole:

What?!! You did a Genome-Wide Association Study (GWAS) with 14 subjects and claim that you isolated a pattern involving 209/22,000 genes? Ever think about having capitalized on chance as an explanation? Don’t you know that a GWAS requires hundreds more participants in order to obtain a robust, replicable findings? And that most GWAS findings don’t replicate?  Maybe you got away with the study back when you published it, but surely would not expect to publish it today! Why are you still bragging about it?

I’m glad I wasn’t there, because then he went on to discuss a study he did with my friends Greg Miller and Edith Chen, who are now at Northwestern University. I would have disputed his interpretation of their work. Cole reports selecting 16 poor and 15 well-off children who had asthma from a larger sample and running genomic expression analysis. Not surprisingly, the poorer children had poorer functioning immune systems.

Forget the problems of trying to compare such small samples and the need to ignore the many other ways in which these groups of children differ. Cole is on his way to making a stream of points:

The poorer kids perceived more threat; the well-off perceived less…..

To an extent that immunologists and psychologists rarely appreciate, we are architects of our own experience. Your subjective experience carries more power than your objective situation. If you feel like you’re alone even when you’re in a room filled with the people closest to you, you’re going to have problems. If you feel like you’re well supported even though there’s nobody else in sight; if you carry relationships in your head; if you come at the world with a sense that people care about you, that you’re valuable, that you’re okay; then your body is going to act as if you’re okay—even if you’re wrong about all that.”

Cole was channeling John Milton: “The mind is its own place, and in itself can make a heaven of hell, a hell of heaven.”

If I go for sushi, I had better make sure that David Dobbs and Steve Cole are not there. Otherwise, I would risk having to hear them talking this insensitive, classist positive psychology trash.  I might feel compelled to ruin the dining experience for all three of us by calling them out about their trying to pass off their ideology as science.

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3 Responses to ‘Social Life of Genes’: David Dobbs’ My Dinner with Andre

  1. Pingback: ‘Social Life of Genes’: David Dobbs’ My Dinner with Andre | Science News, Research Articles, Papers, Dissertations, Journals

  2. David Dobbs says:

    I’m the author of the article under discussion. I find it discouraging that a post ranting about bias, alleged cherrypicking, mirepresentation, and distortion should indulge in so much bias, cherrypicking, mirepresentation, and distortion.

    Coyne’s bias was clear from his first tweets about my story, in which, based (by his report) only on some quotes from the article he saw on Twitter, he decided I had “gone goofy” (see https://twitter.com/CoyneoftheRealm/status/378120771270213632) over … a paper and idea I had not written a word about. When I pointed this out to him, he first insisted that I had “written about it without mentioning it,” even though I hadn’t read the paper in question until after I wrote my story. When I pointed that out, he switched from blaming me for pimping papers I’d never read to blaming me for other things I’d never done.

    I don’t mean to engage in extended debate with someone so willing to distort — for more distortions are sure to follow — but thought readers should know of the following distortions in Coyne’s post above. I suggest they read my article (http://www.psmag.com/health/the-social-life-of-genes-64616/) and draw their own conclusions.

    So much for his bias. I don’t expect everyone to read my article or follow all this. But it’s only fair that readers here know of the following cherrypicking and distortions in Coyne’s post above:

    * From Coyne’s first paragraph he sets up a complaint about a ‘contradiction,’ presumably overlooked by me, about something that I acknowledge in the article. He’s speaking of a supposed contradiction residing in the fact that gene expression that changes you might actually change you back — as if I’m hiding the latter, or that Cole or I had suggested that such change is a one-way, irreversible process. He says this supposed contradiction is “hiding in plain sight,” when in fact I have called it out.

    To make his point, he draws on a quote from Cole at the very end of my article — one that I think most readers will take as partially tongue-in-cheek — to insist that Cole wants us to believe gene expression changes you forever. Coyne fails to state that that quote comes only a few short paragraphs after a passage in which I note that Cole doesn’t see gene-expression changes as deterministic, but rather as reversible, and then quote Cole as saying just that. The contradiction exists only in Coyne’s mind, and in his insistence on misreading and misrepresenting the text he criticizes.

    * He says my argument is classist, a gift to the privileged, and all about positive psychology. He manages to omit that much of the literature discussed is about people in extreme circumstances, ranging from people dying of AIDs to children in abusive homes and people living in poverty. I think the findings relevant to both the struggling and the fortunate, and I hope that comes through clearly in the article, if not in Coyne’s read of it.

    As to positive psychology, that’s not what my article is about; my article is about a role played by gene expression which, yes, of *course*, is complicated and involves other pathways, but which is important and utterly novel to most lay readers. The responses to the article on Twitter made it clear that many in this article saw for the first time something that Coyne complained was old hat: that gene expression is fluid, and that the genome is important not just as an architecture plan, but as an ongoing remodeling project. I consider this a worthwhile advance in the public’s understanding of genetics.

    * Coyne centers most of his complaints on comments that Cole is quoted making in a short section at the end of my article. He fails to acknowledge that in the midst of that section — the sushi dinner that Coyne finds so dyspeptic — I explicitly state that the conversation quoted has turned away from the proven and perhaps even from the testable, and that we’re not in arenas usually discussed in philosophy. I write, in fact, in its own paragraph, so hopefully the point won’t be lost: “We were obviously moving away from what he could prove at this point, perhaps from what is testable. We were in fact skirting the rabbit hole that is the free-will debate. Yet he wanted to make it clear he does not see us as slaves to either environment or genes.”

    If Coyne wants to argue that scientists can’t discuss such things and that writers can’t quote them discussing such things, fine. But he shouldn’t’ make it sound as if I’m presenting Cole’s musings here as proven science rather than speculation.

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    • I am honored by David Dobbs’ stopping by to comment on my blog post, and would be disappointed if he chose not to stay to elaborate upon what he considered my “distortions.”

      Let me say that I have always followed the work of Steven Cole with great respect and interest, even where we have disagreed. However, first there was the serious distortion and bad science displayed in the Proceedings of the National Academy Of Sciences (PNAS), which I dissected elsewhere.

      I was prepared to dismiss the problems I saw with this PNAS paper to Cole’s reliance on his co-authors for expertise concerning psychometrics. We can’t be experts on all things and I presumed that his contribution of this paper was in the area of genomic expression. As I continue to look carefully at this not always transparently reported paper, I saw that there were additional problems in capitalization on chance in the analyses of genomic expression that he should have caught.

      Then I stumbled upon David Dobbs’ Social Life of Genes and saw some of the same problems from work that Cole cited that did not involve collaboration with Barbara Fredrickson. However, I don’t know where else the quote from Steve Cole with which Dobbs ends his long read the article could have come. It is a sentiment that expresses well the theme of Cole’s paper with Fredrickson and her pop psychology writings and workshop descriptions as well.
      Dobbs further indicates that Cole “often” ends talks with this quote. Dobbs notably did not indicate the specific source of this or many of the instances in which Cole invokes his own work. Overall, I think my assumption that it is tied to the PNAS paper is fair, but I would welcome a correction of from just where it comes.

      Dobbs and Cole do indeed cite work with HIV AIDS patients and children with asthma living in adverse circumstances. But that makes all the more patronizing the subsequent references to such people being “architects of their own experience” with no mention of their being as in so many ways victims of their circumstances.

      And it is Dobbs who adds the statement:
      Cole was channeling John Milton: “the mind is its own place, and in itself can make a heaven of hell, a hell of heaven.”

      This is the kind of ultra subjectivism and anti-materialist thought that so saturates positive psychology and its unrealistic proposal for social change that poor people need to build their characters and think more positively. Nowhere in the Dobbs-Cole conversation do I see appropriate references to how social environments can “fix” people who try to transcend their immediate adversity by changing their thinking. Sure, genomic expression is part of an interlocking system, but so is ideology, stigmatization, and punishment and suppression of deviant thought.

      In the weeks before and after Dobbs’ discussion of his sushi dinner with Cole, a number of scientific articles, news articles and blog posts appeared that attempt to explain parts of the complex self perpetuation of poverty. These sources can at least in part provide an antidote to the classist insensitivity portrayed by Dobbs report of the discussions with Cole. Namely

      How Being Poor Makes You Poor
      New research shows how poverty can often be a self-perpetuating trap.
      http://www.psmag.com/business-economics/poor-makes-poor-66414/

      One in five Scottish children living in ‘persistent poverty’
      ONE in five children in Scotland is still living in extreme poverty, seriously jeopardising health, happiness and education
      http://www.scotsman.com/news/one-in-five-scottish-children-living-in-persistent-poverty-1-802124

      Opinion: ‘Chemical brain drain’ endangers generations of children
      Grandjean “calls this threat “chemical brain drain.” “It is insidious and silent, as it is usually not linked to any medical diagnosis, and it is serious, as the combined deficits are affecting the brains of a whole generation of children, upon whom our future relies,” Grandjean writes. “Our knee-jerk demand for proof leaves the brainpower of the next generation in harm’s way.”
      http://www.environmentalhealthnews.org/ehs/news/2013/opinion-chemical-brain-drain

      As for other readers and me apparently missing the transition to tongue-in-cheek efforts at humor, just where did Dobbs and Cole shift gears from HIV/AIDS, poverty, and social deprivation to the laugh track?

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