Christine Kenneally’s Rich, Rompy Read on Genes


Illo by Eric Nyquist, via NY Times.

Of Christine Kenneally’s father’s father — a man neither Kenneally nor her father ever knew, a man who did the deed requisite to reproduction and promptly vanished — she asks, “Did he leave anything more significant than the loud bang of a door shut down the generations?” Of course he did. He left his DNA and a granddaughter determined to draw from modern genetics and hard-won family history a coherent account of her roots.

So opens my appreciation on the cover of this week’s New York Times Sunday Book Review of  The Invisible History of the Human Race, Kenneally’s “smart, splendid, highly entertaining look at how DNA, increasingly visible to us since we first sequenced the human genome in 2000, can ‘open up tracts of human history that had been entirely obscure.'” The book itself opens up huge tracts of pleasure, curiosity, astonishment — and admiration at what Kenneally has done.

As I note in the review, the book could stand on its weird and delightful factoids alone, but hardly need do so. Its main argument is that DNA provides great insight into human and personal ancestry — if combined with other, broader perspectives, such as anthropology, economics, history, linguistics, and genealogy. to the prosaic work of mining archives for genealogy.

While DNA may now be visible, … it remains more hint than history. Kenneally, a journalist and linguist, shows that just as a gene usually delivers its genetic message only in conversation with an incoming chemical messenger, so our DNA tells its tales most fully only in light of the history of the people who carry and interrogate it. It takes all those threads to get the whole story. And Kenneally wants it all.

“If everyone had his DNA analyzed,” she writes, “and that information were linked to everyone’s historical information, it would be the nearest thing to the book of humanity.” She backs up this claim beautifully, showing how genetic analysis can be combined with skillful mining of historical, social and cultural information to solve fascinating riddles of ancestry.

It’s a splendid book. Do take in the full review at the Times, for more about its riches, as well as a Willie Nelson line I’ve been dying to deploy for such an occasion. Then treat yourself to Kenneally’s book (Powell’s, IndieAmazon. B&N). It’s been a good while since I’ve read such a rich, fun, engrossing book about genetics — or about any science.

How trolls work, from one who’s seen it up close

This comes to us, sadly, as part of what seems a goodbye from writer and coder Kathy Sierra, who was driven off the internet once before and returned a year ago.

I think this’ll ring true for anyone who’s had even a taste of getting trolled, or watched with attention as it happens.

The trolls aren’t stupid. The most damaging troll/haters are some of the most powerful people (though they self-describe as outcasts). Typically, the hacker trolls are technically-talented, super smart white men. They’re not just hackers. They are social engineers. They understand behavioral psych. They know their Kahneman. They “get” memes. They exploit a vulnerability in the brains of your current and potential listeners.

How? By unleashing a mind virus guaranteed to push emotional buttons for your real, NOT-troll audience. In my specific case, it was my alleged threat to a free and open internet. “She issued DMCA takedowns for sites that criticized her.” Yes, that one even made it’s way into a GQ magazine article not long ago, when the writer Sanjiv Bhattacharya interviewed weev and asked about — get this — the “ethics” of doxxing me. Weev’s explanation was just one more leveling up in my discredit/disinfo program: DMCA takedowns. I had, apparently, issued DMCA takedowns.

If you are in the tech world, issuing a DMCA takedown is worse than kicking puppies off a pier. But what I did? It was (according to the meme) much much worse. I did it (apparently) to stifle criticism. If a DMCA takedown is kicking puppies, doing it to “stifle criticism” is like single-handedly causing the extinction of puppies, kittens, and the constitution. Behold my awesome and terrible power. Go me.

But here’s the thing. I never did that.

via Trouble at the Koolaid Point — Serious Pony. H/t Steve Silberman

Tall tales about tall genes, revised edition.


How do genes generate traits? A prime answer emerging from the ever-increasing power of genetic studies is that genes create traits through accidental teamwork. That is, as far as our still-early tools and techniques can tell, many and perhaps most traits for which we can find any genetic contributions are influenced by many genes of small effect.

Another consistent trend is that as our genetic tools grow more powerful and we are able to feed them the genomes of larger numbers of people, we tend to finder more and more genes contributing to any given trait or disease. For schizophrenia, for instance, the most recent study upped the number of contributing genes from about a couple dozen to about 80. This was hailed as a huge, even decisive step forward. The next study to go bigger will likely find more.

Same thing is happening with genes for height. Over the last few years, height has become a  example of how a highly obvious trait is actually shaped by many genes. At first the contributing number was thought to be a dozen; then several dozen; then maybe hundreds. Now a new study has muddied up this  relatively clean picture by finding that perhaps half of all human genes shape height — or, depending on how you count it, may all human genes. Or maybe, sort of, even more than all.

Say what?

As one person observed on Twitter, the idea that pretty much every single one of our genes helps to shape height comes close to meaningless. Now, in an essay titled “The height of folly”, veteran geneticist and sometime troublemaker (in the best sense of that word) Ken Weiss picks that up and runs with it. It’s a fun, smart, learned, and deliciously mischievous romp.

Weiss opens by commenting on a quote about height from famed geneticist Thomas Henry Morgan, whose fruit fly work laid the foundation for tracing traits to genes.

In 1926, geneticist Thomas Henry Morgan wrote this about stature:

A man may be tall because he has long legs, or because he has a long body, or both. Some of the genes may affect all parts, but other genes may affect one region more than another. The result is that the genetic situation is complex and, as yet, not unraveled. Added to this is the probability that the environment may also to some extent affect the end-product.
> (TH Morgan, The Theory of the Gene, p 294, 1926):

His point, of course, was not about stature per se but about the difficulty of identifying genes ‘for’ traits because there are many pathways to a trait, and they aren’t all genetic. This was understood eighty-eight years ago, and yet we have had study after study, ever larger, merging smaller studies, and all sorts of fancy statistics to account for various internal complications in genome sampling, and still the results pour forth as if we haven’t learned what we need to know about this and many traits like it.

Then Weiss considers the height paper’s assertion that even though the genetic factors contributing to height may seem incalculable, they are not:

The authors rather glibly come to what they seem to feel (did they take a poll?) is the comforting conclusion that while number of causally contributing genes is huge, it isn’t ‘infinite’. But that is at most technically true and in fact is farther from the real truth than the authors intended, or perhaps even realized.

Finally Weiss argues, half for fun (and he’s having a lot of fun) but mostly for real, that the proper number to consider, for both practical and conceptual purposes, actually is infinity.

We’re not just playing word games here. The number of causes, even just the genetic causes, of stature variation is truly infinite. It is misleading of the authors to try to reassure readers that at least the number is finite. That is in essence a tactic, perhaps inadvertent, that justifies the enumeration-approach form of business as usual.… If the science is to advance beyond a pretense of causal enumerability, what we need to do is develop some new, quantitative rather than enumerative causal concepts. How we should do that is unknown, unclear, debatable,…. and in our business-as-usual environment, probably unfundable.

Weiss, if I read him right, is posing a highly disruptive argument: That in a time when the effects of genes on traits appear more uncertain, unpredictable, vague, and circumstantial by the day, with seemingly every study finding more genes but fewer answers, the hunt for Yet More Genes threatens to turn into a chase that does more to justify itself than it does to show us anything new.

By saying the number of causes of stature variation is finite they essentially mean that they are enumerable and that there is an end to the counting, by which time all causes of stature will have been accounted for. That is simply false.

It’s not that genes are meaningless; it’s that perhaps they don’t mean what we think they do — and that we’re so locked into seeing genes as playing a sort of directorial role, and so convinced that if we count them properly we’ll gain some fundamental new insight, that we keep asking the same questions even though the answers are increasingly meaningless. Accordingly, we need to ask different questions.

The wise TH Morgan realized these issues in early 20th century form without needing to have all the expensive and extensive data that we are amassing. But his statement was generic and one might say it called for confirmation. We have had many other sorts of confirmation for similar traits, but perhaps what’s been reported for stature closes the book on the basic question.

So now, if the science is to advance beyond a pretense of causal enumerability, what we need to do is develop some new, quantitative rather than enumerative causal concepts. How we should do that is unknown, unclear, debatable,…. and in our business-as-usual environment, probably unfundable.

Get the whole romp at The Mermaid’s Tale.

Today’s Nobel was about how the brain navigates space. Here’s what happens when it can’t.

Today’s Nobel Prize in Medicine and Physiology went to a trio of researchers who figured out the basis of how the brain tracks and manages space, a task that is closely tied to memory.

This ability to remember and manage space — to navigate your way through life — is vital. Here, in a brief story I told at a Story Collider evening in Brooklyn,  is what happened when I realized I seemed to have lost that ability. That is, I was standing on my front steps one morning preparing to drive my two youngest children to preschool, which I’d done hundreds of times, and realized I had no idea how to get there. Keys in hand. Kids already in the car.

My first decision was whether to b) go back inside and tell my wife I had no idea how to drive to the preschool or b) go ahead and drive anyway.

Story starts at 1 minute. Tap that first little notch in the timeline below to get there, or just  just push the arrow and get the intro.

Schizophrenia is a thing we all carry a bit of.


Michael O’Donovan and Kenneth Kendler, eminences in psychiatric genetics for good reason, look at the implications of recent (early) progress in identifying the dispersed genetic roots of schizophrenia. For ease of reading, I’ve inserted a few paragraph breaks in their long paragraph, which is the last of 9 points they make about recent findings. The money quote’s in the last graf.

Throughout much of its history, modern psychiatry has sought to ground its categorical diagnostic approaches in basic biological findings. One such effort was to locate the “gene for” schizophrenia. It is now widely agreed that no such gene exists. Rather, the genetic vulnerability to this tragic disease is widely distributed across the genome in a way that resembles the multifactorial threshold models so popular for years in statistical genetics.

This has 2 noteworthy implications.

First, the old divisions between psychiatric genetic epidemiologists (who studied families, twins, and adoptions) and molecular geneticists—where the former did “just statistics” and the latter studied “real genes”—should crumble. Indeed, the twin researchers, using multifactorial threshold models, probably had a more accurate genetic model of psychiatric illness than molecular researchers doing linkage and candidate gene association analysis, who typically assumed single-locus models of relatively large effect. Statistical and molecular tools will need to be fully integrated in the years ahead.

Second, and more profoundly, while there is surely a discrete phenomenological state of psychosis that clinicians can agree about reliably, there is no such dichotomy at the level of genetic risk. All of us carry schizophrenia risk variants, and the vast majority of us carry quite a lot of them. With respect to genetic risk, there is no “them” and “us,” only subtle shades of gray.

The paper, published online in JAMA Psychiatry, is behind a paywall. Most lay readers will find it a bit technical paper. But the motivated who do not mind PDFs may download one at this link, where someone uploaded a copy for distribution for collegial scholarly sharing.


Photo by David Dobbs

Our Ebola response shows our true colors. Ain’t pretty.

I am very much of Helen Branswell’s mind that the world’s effort on Ebola, including that of the United States, should be focused on West Africa. That’s the fire; the U.S. patient is a spark. To stop sparks, snuff the fire.

In the meantime, however, the U.S. response to the appearance in Dallas of what is essentially our Patient Zero is, to put it charitably, not encouraging.

First, this yesterday from Delay in Dallas Ebola Cleanup as Workers Balk at Task, by Kevin Sack and Manny Fernandez at the NY Times. NB: There are four people living in that apartment, ordered to stay there so as not to spread infection. This is also after the hospital failed to admit the patient and sent him back to the apartment when he first went in.

More than a week after a Liberian man fell ill with Ebola and four days after he was placed in isolation at a hospital in Dallas, the apartment where he was staying with four other people had not been cleaned and the sheets and dirty towels he used while sick remained in the home, health officials acknowledged on Thursday afternoon.

And from the Guardian, US Ebola patient’s friends quarantined under armed guard:

At midday on Thursday, a child peeked out from behind a red diamond-pattered curtain in one of the apartments while at ground level a team of three contractors – none wearing any sort of protective clothing – power-washed the front porch. A stroller stood at the bottom of a staircase.

Earlier, a representative of one of the agencies who issued the control order said that arranging clean bedding was the responsibility of the family – despite the ban on them leaving their home. “The individuals, it’s up to them … to care for the household,” Erikka Neroes of Dallas County health and human services told the Guardian. “… Dallas County has not been involved in a disinfection process.”

So the richest country on earth has no team to contain the first appearance of one of the most deadly viruses we’ve ever known. Instead, apparently untrained contractors without protective clothing show up four days late and use not bleach and buckets to kill and contain the presumed hazard, but a power sprayer to blast them around.* The family this patient was staying with, meanwhile, is left to its own devices, isolated from the world. They’re left to deal with the sheets and towels themselves. The fate of these linens, uninspected but possibly the most infectious single item associated with Patient Zero, is left to chance.

This response is what you get when a country essentially has no sense of what public health is about. It’s a crystallized expression of an abiding feature of our so-called healthcare system: Health is something you do in a hospital or a doctor’s office. Generally you must pay to get it. Reach one of those places and maybe we can help you — an event more likely if you show ability to pay, and pay big. (Would the hospital have so quickly sent home a patient who had insurance? Statistically less likely.) Outside the paywalled environs of hospitals and offices, though, you’re on your own.

This is no way to treat fellow human beings. This is no way to stop an epidemic.


*At least one reader feared I was spreading panic here, and noted that any virus on the porch, depending on what it was in (surface v liquid, etc.), might (or might not) have died by the time the power-spraing occurred. Apparently there was TV and web coverage last night that made much of the power-washing and speculated heavily on how it might spread things.

I see my critic’s point about the danger of spreading panic (and the fuzzyness of whether the spray-washing was a real hazard). I still suspect that no matter what the hazard at that point, power-washing is unlikely to be best practice, since it spreads stuff rather than gathers it. But I want to make it clear I pointed this out not because I consider the practice in this case a huge threat and that we should freak out because OMG We’re All Gonna Die, but because power-washing by unprotected contractors 4 days late is another indicator of a weak, uncoordinated, and tardy response at an important site.

Paleo-tourist puts a bug up his ass. John Hawks calls BS.

From Hawks:

Jeff Leach, at the “Human Food Project”, has written pungently about a bout of microbiome self-experimentation: “(Re)Becoming Human: what happened the day I replaced 99% of the genes in my body with that of a hunter-gatherer”.

AS THE SUN set over Lake Eyasi in Tanzania, nearly thirty minutes had passed since I had inserted a turkey baster into my bum and injected the feces of a Hadza man – a member of one of the last remaining hunter-gatherers tribes in the world – into the nether regions of my distal colon. I struggled to keep my legs in the air with my toes pointing towards what I thought was the faint outline of the Southern Cross rising in the evening sky. With my hands under my hips – and butt perched against a large rock for support – I peddled an imaginary upside down bicycle in the air to pass the time as I struggled to make sure my new gut ecosystem stayed put inside me.

I have to say, this is just wrong.… There seems to be a lot of quackery here — almost a New Age belief in the power of a guy unspoiled by burgers and fries.

“Just wrong” is dead right. Call it colonialist colonic tourism. As Hawks notes,

The Hadza have their own long evolutionary history. Their diet is merely one representative of the marked dietary diversity of recent hunter-gatherers. Other foraging groups, for example, the Ache of Paraguay, have a very different dietary composition. The study of these microbiomes is scientifically very interesting, and we may discover commonalities among them. But the idea that the microbiome of any Hadza person represents an “ancestral” or “healthy” human population is nonsense. They have their own distinctive set of challenges affecting their microbiomes, including the aforementioned parasites. A microbial community that has formed within a Hadza gut might work equally well anywhere else, but there’s really no reason to expect that it will.

Also, as Ed Yong describes here in Nature, microbes in hosts with different genetic backgrounds (as in, two different people of different cultures, environments, and dietary legacies) can have very different effects. Some strains of a bug called H. pylori, for example, are “more likely to cause tumors when they did not co-evolve with their hosts.”

In other words, this stuff is complicated. Mr. Leach seems to think it’s simple, and that he can pick up paleo power as readily as one can put on a fedora to go noir.

I suppose Mr. Leach might answer that it’s his body, so he’s free to subject himself to such experimentation. Which he is. But his gleeful presentation of this stunt as sensible experiment, eco-adventure tourism, and a sort of wonderful carefree lark is irresponsible — to say nothing of the revolting and mindless colonialist aspects of him reducing the Hazda culture to a source of stool. The layers of yuck here are deep enough to drown in.

Are we at peak paleo yet? Lord I hope so.




Michael Lewis: “The Ray Rice video for the financial sector has arrived.”


Goldman Sachs Tower, NYC. Photo by Ludovic Bertron via creative commons.

Our financial regulatory system is obviously dysfunctional. But because the subject is so tedious, and the details so complicated, the public doesnt pay it much attention.

That may very well change today, for today — Friday, Sept. 26 — the radio program “This American Life” will air a jaw-dropping story about Wall Street regulation, and the public will have no trouble at all understanding it.

The reporter, Jake Bernstein, has obtained 47½ hours of tape recordings, made secretly by a Federal Reserve employee, of conversations within the Fed, and between the Fed and Goldman Sachs. The Ray Rice video for the financial sector has arrived.

From The Secret Goldman Sachs Tapes – Bloomberg View.

Photo by Ludovic Bertron via Flickr, creative commons license. 

The best healthcare system in the world.

Waiting for healthcare in coal country. Photo Lucian Perkins, via Politico.

It is 5:30 a.m. on Saturday—the second day of the Wise County RAM clinic—when Brock begins allowing people into the clinic’s makeshift tents. Hundreds of people—many of them with their children in tow—have spent the entire night waiting outside or in their cars to get treatment, and they push forward and crowd the entrance.

First, Brock lets in people with wrist bands who were seen the day before and need to have more dental, eye or medical work done. The remaining 1,500 people to be seen on Saturday, who started receiving their admission tickets at 2 a.m. that morning, are then called in order. Those who did not receive tickets will have to repeat the entire process the following day. Many others will have to return in September.…

Gardner, executive director of the clinic that hosted RAM, recalls attending the funeral of an uninsured 28-year-old woman who had died of cervical cancer. A decade earlier, she’d had abnormal pap smears. By the time she was able to see a doctor about her pelvic pain, the undiagnosed cancer in her cervix had metastasized to all her organs.

When the Doctor Comes to Coal Country, at Politico.