A little history of zebrafish research

I was amused to see this review of the history of zebrafish publications. It describes some of the trends in the research (read: lots of developmental biology), and plots the number of papers published. I started working with zebrafish in 1979, so I’ve marked where I began.

zfpapers

You know, when I started out as a grad student in this field, the literature search was pretty easy. Almost all the people who had published on this model system were right there in this one collection of labs at the University of Oregon, with a few other former students scattered elsewhere, so I could just turn to all of the primary authors and ask them directly about anything. There were a few older papers, but as I recall, almost all of them had to do with zebrafish as guinea pigs in environmental toxicology studies.

It’s a little bit different now.

(Of course, that didn’t mean I didn’t have lots to read — the questions were all focused on neurobiological and developmental topics in other organisms. Even now you shouldn’t center your reading on just one experimental animal!)

Higher order thinking

The one thing you must read today is David Dobbs’ Die, Selfish Gene, Die. It’s good to see genetic accommodation getting more attention, but I’m already seeing pushback from people who don’t quite get the concept, and think it’s some kind of Lamarckian heresy.

It’s maybe a bit much to ask that the gene-centric view of evolution die; it’s still useful. By comparison, for instance, it’s a bit like Mendel and modern genetics (I’ll avoid the overworked comparison of Newton and Einstein.) You need to understand simple Mendelian genetics — it gives you a foundation in the logic of inheritance, and teaches you a few basic rules. But once you start looking at real patterns of inheritance of most traits, you discover that it doesn’t work. Very few traits work as Mendel described, and one serious concern is that we tend to select for genes to study that behave in comprehensible ways.

And every geneticist knows this. Mendel was shown to have got some things wrong within a decade of his rediscovery: Mendel’s Law of Independent Assortment, for instance, simply does not hold for linked genes, and further, linkage turns out to hold important evolutionary implications. But I still teach about independent assortment in my genetics course. Why? Because you need to understand how to interpret deviations from the simple rules; it’s an “a-ha!” moment when you comprehend how Morgan and Sturtevant saw the significance of departures from Mendel’s laws.

Most of genetics seems to be about laying a foundation, and then breaking it to take a step beyond. Teaching it is a kind of torture, where you keep pushing the students to master some basic idea, and then once they’ve got it, you test them by showing them all the exceptions, and then announcing, “But hey! Here’s this cool explanation that tells you what you know is wrong, but there’s some really great and powerful ideas beyond that.”

That’s what’s fun about genetics: compounding a series of revelations until the students’ brains break, usually right around the end of the term. Over the years I’ve learned, too. Undergraduate genetics students usually collapse in defeat once I introduce epistatic interactions — the idea that the phenotype produced by an allele at one locus is dependent on the alleles present at other loci — but it’s always great to see the few students who fully grasp the idea and see how powerful it is (future developmental biologists identified!).

And that’s how I see the gene-centric view: absolutely essential. You must understand Mendel, and Fisher, and Wright, and Hamilton, and Williams, and once you’ve mastered that toolkit, you can start looking at the real world and seeing all the cases where it’s deficient, and develop new tools that let you see deeper. The new idea that Dobb’s describes, and that is actually fairly popular with many developmental biologists, is that phenotype comes first: that organisms are fairly plastic in response to the environment in ways that can’t be simplified to pure genetic determinism, and that the genes lag behind, acting to consolidate and make more robust adaptive responses.

I’ve written about genetic assimilation/accommodation before, and have given one lovely example of phenotypic change occurring faster than the generation of new mutants can explain. It’s always baffled me about the response to those ideas: most people resist, and try to reduce them to good old familiar genes. It’s a bit like watching students wrestle with epistatic modulation of gene expression when all they understand is Mendel, and rather than try to grasp a different way of looking at the problem, they instead invent clouds of simple Mendelian factors that bring in multi-step discrete variations. They can make the evidence fit the theory — just add more epicycles!

I’m seeing the same responses to Dobbs’ article — it’s still all just genes at the bottom of it, ain’t it? Oh, sure, but the interesting parts are the interactions, not the subunits. We need to take the next step and build tools to study networks of genes, rather than reducing everything to the genes themselves.

Now you too can pretend you were at Skepticon this year

Here’s my talk on the Cambrian from Skepticon 6.

Oh, hey, I just realized I could post the content of that text-heavy slide I flashed, showing the sources I used. So here you go:

Web reviews from Donald Prothero, Nick Matzke, Larry Moran.

Briggs, D.E.G.; Fortey, R.A. (1989). The early radiation and relationships of the major arthropod groups. Science, 246(4927), 241-243.
Budd, G. E., and S. Jensen. 2000. “A critical reappraisal of the fossil record of the bilaterian phyla.” Biological Reviews 75:253-295.
Erwin D and Valentine J (2013). The Cambrian explosion : the construction of animal biodiversity. Greenwood Village, CO, Roberts and Company Publishers.
Marshall, Charles R. (2006). “Explaining the Cambrian ‘explosion’ of animals.” Annual Review of Earth and Planetary Sciences. 34: 355-384.
Smith MP, Harper DAT (2013) Causes of the Cambrian Explosion. Science 341:1355.
Long M, Betran E, Thornton K, Wang W (2003) The origin of new genes: glimpses from the young and old. Nature Rev Genet 4:865.
Knoll AH, Carroll SB (199) Early Animal Evolution: Emerging Views from Comparative Biology and Geology. Science 284:2129.
Erwin DH, Laflamme M, Tweedt SM, Sperling EA, Pisani D, Peterson KJ (2011) The Cambrian conundrum: early divergence and later ecological success in the early history of animals. Science. 334(6059):1091.
Peterson KJ, Dietrich MR, McPeek MA (2009) MicroRNAs and metazoan macroevolution: insights into canalization, complexity, and the Cambrian explosion. Bioessays. 31(7):736.

Amazon’s next attempt at world domination

They’re going to be doing deliveries by drone.

I don’t think I’ll live close enough to a distribution center for these to come buzzing by my house, so I’m not going to worry about them yet. I’m am remembering that in my younger days I was a deadly shot with a slingshot…I may have to start practicing.

I might change my pessimism about fleets of drones flitting about overhead, if they’re actually shown to represent an energy savings.

Friday Cephalopod: Black Friday

Vampyroteuthis would like you to know that it is forgivable that you visit Walmart or any of the other greedy big box stores today in search of bargains; however, the retailers who exploit their workers and gin up scarcity and treat the desperate poor as targets are going to someday find themselves dying cold, dark, hypoxic deaths, and the grim clammy bleak squid of their conscience will rise up to drag them down into oblivion. Live humanely while you can. They wait.

Casual reductionism and genetic determinism

Finally, a tiny voice of caution speaks out against the genetic testing hype.

The Food and Drug Administration has ordered DNA testing company 23andMe to stop marketing its over-the-counter genetic test, saying it’s being sold illegally to diagnose diseases, and with no proof it actually works.

The heavily marketed test includes a kit for sampling saliva, and the company promises to offer specific health advice. “Based on your DNA, we’ll provide specific health recommendations for you,” the company says on its website. "Get personalized recommendations."

In an unusually scathing letter dated Friday, the FDA says it’s been trying to work with the company to get some sort of evidence that the test can do that with any accuracy.

I had no idea that 23andMe was making any health claims, and that’s deplorable. You can’t do that. That’s naive billiard-ball-biology, and it’s never going to be as simple as testing a few markers and then declaring that you understand physiology.

I prefer the approach of the National Genographic project, where the results are used to infer relationships rather than leaping to biomedical conclusions. We have far more accurate tools for determining your medical condition — it’s direct and involves examining your health, rather than indirectly looking at genes that have a remote connection to your health.

Which brings me to an essay that had me gawping in disbelief. A neuroscientist, James Fallon, noticed the results of a PET scan of his own brain.

“I got to the bottom of the stack, and saw this scan that was obviously pathological,” he says, noting that it showed low activity in certain areas of the frontal and temporal lobes linked to empathy, morality and self-control. Knowing that it belonged to a member of his family, Fallon checked his lab’s PET machine for an error (it was working perfectly fine) and then decided he simply had to break the blinding that prevented him from knowing whose brain was pictured. When he looked up the code, he was greeted by an unsettling revelation: the psychopathic brain pictured in the scan was his own.

OK. If this happened to me, I’d place the most importance on my personal experience — if I were a successful professional with no history of unethical behavior, I’d say “uh-oh…maybe these scans aren’t such a reliable indicator of personality after all.” I would not say, “uh-oh, I must be a psychopath.”

But guess what interpretation Fallon put on it? He got genetic tests.

But when he underwent a series of genetic tests, he got more bad news. “I had all these high-risk alleles for aggression, violence and low empathy,” he says, such as a variant of the MAO-A gene that has been linked with aggressive behavior. Eventually, based on further neurological and behavioral research into psychopathy, he decided he was indeed a psychopath—just a relatively good kind, what he and others call a “pro-social psychopath,” someone who has difficulty feeling true empathy for others but still keeps his behavior roughly within socially-acceptable bounds.

Wow. And then he starts self-rationalizing. He’s aggressive when he plays games, therefore his diagnosis must be true. He admits that maybe this isn’t as clear-cut as he thinks.

But the fact that a person with the genes and brain of a psychopath could end up a non-violent, stable and successful scientist made Fallon reconsider the ambiguity of the term. Psychopathy, after all, doesn’t appear as a formal diagnosis in the Diagnostic and Statistical Manual of Mental Disorders in part because it encompasses such a wide range of symptoms. Not all psychopaths kill; some, like Fallon, exhibit other sorts of psychopathic behavior.

But one thing he doesn’t consider? That maybe PET scans and genetic tests aren’t as robust and interpretable as he thinks. What I find personally chilling is that he so blithely considers a scan or a gene so definitive that he will defend a diagnosis of psychopathy in himself; does he also judge the subjects of his research on the basis of these abstractions rather than on their behavior?

A rather remarkable deficiency

There’s a much ballyhooed article from Science going around that promotes the surprising conclusion that dogs were first domesticated in Europe. Dan Graur points out that there is one little problem with the data:

The take home message of the Thalmann et al. paper is simple: Dogs were not domesticated in the Middle East or China as previously claimed; they were domesticated in Europe. Let me repeat the main result of this paper: Dogs were domesticated in Europe; previous claims on the domestication of dogs in the Middle East or China are wrong and have been refuted.

Interestingly, on page 873, it is written:

“Notably, our ancient panel does not contain specimens from the Middle East or China, two proposed centers of origin (5, 6).”

So, the origin of dogs was moved from the Middle East or China to Europe by the simple expedient of omitting any sample from the Middle East or China.

Well, the paper does have the primary prerequisites for getting published in Science: superficially sexy data sets, involving a familiar large and photogenic animal, an unexpected result, with a high probability of drawing the attention of the mass media. That’s what we mean by “significant research,” right?

Say, isn’t that also the formula for a TED talk?

Time for the professional societies to take a stand on Burzynski

The 4th Quadrennial Meeting of the World Federation of Neuro-Oncology is meeting right now in San Francisco, and guess who is presenting there? There are four papers being presented by those criminal frauds of the Burzynski Clinic.

They sure can talk the science talk, can’t they? And they go through all the motions of attending and presenting at meetings of the Society for Neuro-Oncology, which I’m sure looks formidable to the rubes, but when you look at the results of recent reviews of their facilities and protocols (or read the summary in USA Today), they don’t walk the science walk. Read about the patients, or the story of the Burzynski scam. For over thirty years, he has been skating at the edge of credibility by carrying out the rituals of science without going the next step and actually testing his claims, getting rich off desperate people and killing them with bad therapies and sloppy protocols.

I know what these meetings are like. They will be full of professionals in nice dresses and conservative ties, and they will be talking shop and taking notes on the interesting presentations, and I know exactly how they will respond to Burzynskiites: they are beneath them, they will roll their eyes as they skip their talks, and they might grumble a bit at the bar afterwards. And that’s about it. I’ve seen it when creationists get their work into poster sessions at non-peer-reviewed science meetings.

But these guys are worse than creationists. These are con artists giving false hope to dangerously ill patients, using organizations like the SNO as a façade to bilk people out of hundreds of thousands of dollars, and skirting on the proper protocols to give the illusion that they’re doing legitimate science.

It is a huge ethical problem for these societies to provide cover for quacks. I would hope that, at the very least, attendees take time to read the facts about Burzynski and give these con artists a hard time in public; but more significantly, I think the only appropriate thing for the Society for Neuro-Oncology to do is to kick the bastards out. Don’t let them take shelter under your wing any more.