Let’s play “spot the flaw in that argument!

Today’s exciting game will be played with quotes from Softbank Robotics CEO Masayoshi Son given at the Mobile World Congress in Barcelona. A tech CEO? This will be a target-rich opportunity. You can expect a flurry of ambitious exaggerations from this one!

Players at home, you know what to do: get your buzzers ready, and slap that big red button and be prepared to give a succinct summary of what exactly was wrong with the statement. If you are chosen, you stand a chance to win fabulous prizes.

Are you ready? Brace yourselves, here it comes:

In 30 years, the singularity

Whoa! That was quick! The switchboard lit up like a Christmas tree with that one. Too easy?

OK, first answer is from Ronald in Ohio, who takes exception to the 30 year claim. No, I’m sorry, Ronald, you do not win a prize. That number is actually correct. As we all know, the singularity is always 30 years away.

Our next caller is Darlene in Seattle, who asks, “What the heck is a singularity?” and — judges, what is your call on that? — the judges say yes! That is a damn good question! Pierces right to the heart of the issues! It’s a quasi-mystical boojum that is invoked in place of the idea of “heaven”, which makes many technocrats uncomfortable because it is too unsciencey.

But poor Son, we didn’t even finish his quote. Here’s the rest:

will happen and artificial intelligence in all the smart devices and robots will exceed human intelligence.

Ouch! Our board lit up so bright that the room lights flickered and dimmed! Let’s take…caller #1274. Vonda in Florida, what’s your criticism?

“Thanks for taking my call, PZ. I’ve been trying to get through for years, and this is my first time on.”

Great, Vonda. And the flaw you spotted is…?

“Well, there’s a couple: one is that he can’t define ‘human intelligence’, and another is that he can’t possibly define it as a single scalar in a range on one axis that you could speak of something exceeding something else.”

Excellent, Vonda! Judges? Yes, the judges agree! Let’s move on with this juicy speech.

Just to give you a hint, Son is about to try to answer Vonda’s question:

Son says that by 2047, a single computer chip will have an IQ of 10,000 — far surpassing the most intelligent people in the world.

Yikes! The responses are pouring in —

Dmitri in Siberia: “…absurd reductionism. You can’t assign intelligence a single number…”

Kim in Korea: “…what kind of IQ test can generate scores that high…”

Jim in Manitoba: “…if you can measure the IQ of a computer, tell me what the IQ of a Dell Windows 10 machine is right now…”

Rudy in New South Wales: “…God won’t let a computer get that smart…”

Andrea in New York: “…IQ tests are designed to test human minds…”

OK! Except for Rudy, you all win!

I’m going to let Son complete his thought. Don’t buzz in on this one, gang, we’re just going to let him finish digging that hole already.

Where the greatest geniuses of the human race have had IQ’s of about 200, Son says, within 30 years, a single computer chip will have an IQ of 10,000. “What should we call it,” he asks. “Superintelligence. That is an intelligence beyond people’s imagination [no matter] how smart they are. But in 30 years I believe this is going to become a reality.”

I know. It’s embarrassing. The man is a CEO and he doesn’t understand what IQ is, and thinks that sticking a “super” prefix on something makes it clever or informative. Maybe he’s just hoping that if he lives another 30 years, he might learn something.

Let’s go on. This one is for scoring:

Son built this prediction by comparing the number of neurons in a brain to the number of transistors.

Uh-oh. The Big Board is on fire. Literally on fire. Hold those calls!

He builds the comparison by pointing out that both systems are binary, and work by turning on and off.

Oh, christ, we’ve got a thousand enraged neuroscientists trying to get through. Watch out! Those cables are shorting out! Get the studio audience out of here!

According to his predictions, the number of transistors in a computer chip will surpass the number of neurons in a human brain by 2018. He is using 30 billion as the number of neurons, which is lower than the 86 billion that is estimated right now, but Son says he isn’t worried about being exactly right on that number.

Oh god. He actually said he isn’t worried about being exactly right on the number? With this audience? Cut the power. Cut the power! Call emergency services!

Wait, what’s that loud rumbling sound I’m hearing from the bowels of the building? The generators? GET OU…

technicaldifficulties

Another reason to be cranky

This week we worked out our teaching schedules for next year, and it has been determined that next Fall I will teach cell biology and a section of our writing course, and in the Spring I will teach…evolution (a new course for me) and neurobiology (a course I haven’t taught in over 5 years), which is going to be painfully intense, possibly worse than this semester. I think the anticipation of stress is contributing to my insomnia.

It will be an interesting time, at any rate. I have some of the same complaints about the current status of neuroscience that Ed Yong describes.

But you would never have been able to predict the latter from the former. No matter how thoroughly you understood the physics of feathers, you could never have predicted a murmuration of starlings without first seeing it happen. So it is with the brain. As British neuroscientist David Marr wrote in 1982, “trying to understand perception by understanding neurons is like trying to understand a bird’s flight by studying only feathers. It just cannot be done.”

Oh, man, Marr was amazing. I could just spend the whole semester trying to puzzle out his work on color perception, which is a perfect example of complex processing emerging out of simple subunits, all figured out with elegant experiments. I went through his vision book years ago, it was bewilderingly complex.

A landmark study, published last year, beautifully illustrated his point using, of all things, retro video games. Eric Jonas and Konrad Kording examined the MOS 6502 microchip, which ran classics like Donkey Kong and Space Invaders, in the style of neuroscientists. Using the approaches that are common to brain science, they wondered if they could rediscover what they already knew about the chip—how its transistors and logic gates process information, and how they run simple games. And they utterly failed.

Wait! That’s perfect! I once knew the 6502 inside and out, writing code in assembler and even eventually being able to read machine code directly. I still have some old manuals from the 1970s stashed away somewhere. I wonder if the students would appreciate signing up for a course on how brains work and then spending the semester trying to figure out how an antique 8-bit chip works by attaching an oscilloscope to pin leads?

Even when I last taught it, that was the struggle. It was easy to give them the basics of membrane biophysics — it’s all math and chemistry — but the step from that to behavior was huge. If I just teach it from top down, beginning with behavior, it’s a psychology course, which is a subject so vast that we’d never get down to the cellular level. There is no in-between yet.

I have a year to fret about it. Who needs sleep anyway?

The word for the day is “inured”

I think Larry Moran has just discovered Michio Kaku. All those years on talk.origins must have toughened his hide, because he seems really unperturbed about the idiocy and ignorance pouring out of Kaku’s mouth. The only thing worse than Kaku here is the stupidity in the YouTube comments…but that goes without saying.

Who needs knowledge when being sublimely confident is regarded as a perfectly acceptable substitute?

Juggling flies, fish, and students all week long

farsidevet

Time for another reflection on my mundane week of teaching. I know this is unexciting, but I’m trying to be self-aware about what I’m doing in the class.

I’ve already summarized some of what I did this week: we explored the meaning of “epigenetics”, and I made a big push to get them to think critically about the papers we’re reading. They’re supposed to be developing a topic they’ll explore independently, so I’ve had them doing library work to find a line of research they find interesting, and master the skill of extracting the key questions the work is trying to address. I’ve got a small stack of short papers that I’m going to read this weekend and we’ll see how well they can do that.

We also discussed symbiotic interactions in development, and next week the topic is other environmental effects. They are getting much, much better at opening up and talking at the miserable hour of 8am.

The other regular highlight of my week is FlyDay, when I have to scrub dead maggots and pupae out of fly bottles. I had to postpone FlyDay this week! Yesterday I was scheduled to meet with students and parents visiting the university to confirm their plans to attend, and I was all spiffed up in a nice suit, which isn’t the best thing to wear when one is flicking bits of chitin and gooey medium around. I went in early this morning to scrub bottles and get them cooking in the autoclave.

By the way, at that student meeting I was the official biology representative, and although biology is currently the largest major on campus, almost no one stopped by to talk to me. It might have been my terrifying glare, or my sciencey reek, but no: it was because there was a separate table for the pre-professional programs (pre-med, pre-vet, pre-dental, etc.). This is a minor peeve of mine: this is not 19th century England. You do not graduate from your public school education and go straight into medical school — no, here in 21st century America you get a broad-based undergraduate education first, and then you apply to med school. You should be thinking about your liberal arts education first, and in a couple of years we’ll start coaching you on how to get into those professional programs.

Oh, well. They ignore me now, but I know that I’ll get my claws on most of them soon — they’ll want all those bio classes to prep them for the MCATs.

I should mention that I am teaching another course beyond ecological development — I’m teaching a lab course on transmission genetics. They’ve been doing crosses with flies all semester long, and we’re getting to an interesting point.

The first half semester we’re doing a mapping cross, using recombination to estimate the distances between a couple of genes on the X chromosome. We’re using flies that are mutant for eye color (white, w), wing length (miniature, m), and bristle morphology (forked, f), and I’ve also got a few groups mapping body color (yellow, y), wing veins (crossveinless, cv) and forked, f; the latter are doing a pilot test to see if I want to add that cross to our regular repertoire.

The way this works is that they are given wild type and triple mutant flies. I first have them raise a new generation of the purebred stock, simply to get a little practice in sexing flies and basic skills in growing them. So they first do these crosses:

♀w m f/w m f x ♂w m f/Y

which produces bottles full of homozygous white-eyed, miniature-winged, forked-bristled flies, and

♀w+ m+ f+/w+ m+ f+ x ♂w+ m+ f+/Y

which produces bottles full of homozygous wild type flies.

Then I have them do a reciprocal cross of flies from the two bottles. These are X-linked traits, so it matters which strain is the mother and which the father, and I want them to see that. That is, they cross wild type females to triple mutant males, like so:

♀w+ m+ f+/w+ m+ f+ x ♂w m f/Y,

which produces progeny that are all wild type, both male and female (they all inherit the dominant wild type allele at all loci from their mothers). After they’ve scored the flies from this cross, we dispose of them all and don’t think any further about them.

They also cross mutant females to wild type males, like this:

♀w m f/w m f x ♂w+ m+ f+/Y.

That has the useful result that all the sons inherit w m f from their mother and a Y chromosome from their father, so they all express the mutant phenotype. The daughters, however, are all heterozygous, inheriting the mutant alleles from their mother and a wild type chromosome from their father, so their genotype is:

♀w m f/w+ m+ f+

Now the fun begins. Meiotic recombination in those flies will rearrange the +’s and -‘s in those chromosomes with a frequency dependent on their distance from one another — you’ll get less recombination between genes that are close to one another.

This week, they completed the reciprocal cross and got their heterozygous females and mutant males. Yay! That worked. They are now setting up a test cross to assess recombination frequencies.

I just want to say that I think I planned everything perfectly. That test cross will be ready to score next week, which is the week before spring break, which means we’ll have the data for all the calculations before they leave, and when they get back, I’ll be able to lead them through all the theory. It also means I’ll be able to purge a lot of fly bottles and get them scrubbed up over the break (you can tell already that I have glamorous plans for my short vacation). Trust me, though, this is good — there have been semesters where, due to student error, the flies haven’t been ready, and then my spring break is spent maintaining 120 bottles of student flies.

It also means we can launch into the next experiment as soon as they get back: we’re going to do a complementation cross between two eye color mutants, brown eye (bw) and scarlet eye (st). If I’ve got this one all timed out correctly, we’ll be getting F2 results of crosses between heterozygotes for both loci a week before the end of classes.

Now you know. I choreograph fly sex for my convenience.

Next up, I have to choreograph my schedule. It turns out I have been summoned to Howard Hughes headquarters on 8 March and 18 April, which punch big holes in my planned lessons, and which I hadn’t accounted for in my syllabi. I’m going to have to juggle lectures and exams and rearrange the order of various things in a big way this coming week.

Historical zebrafish!

Way back in the dim, distant past, before YouTube and publicly accessible digital media, two of my friends, Don Kane, now at Western Michigan University, and Rolf Karlstrom, now at Amherst, made a video of zebrafish development. This was in 1992. It was on VHS tape. (If you don’t know what that is, ask your grandparents).

Then in 1996, a whole issue of Development was dedicated to zebrafish development and genetics, and they translated that tape into modern technology: a flip book. The top right corner of the issue featured one frame of the video, so you could flip through it and see a nice little timelapse. Like this:

Isn’t that quaint?

Sadly, I have not been able to find a copy of the flip book transported to the convenient medium of youtube (maybe I can find my copy of the file and upload it, but that thing was over 20 freaking years ago, so it may take me a while to excavate it), but at least there’s a version available via facebook, as facebook reminded me today.

I routinely make better videos than that one now, but it’s because I’ve got hi-res digital video cameras and fancy software — just remember that historical flip book was made off of VHS tape and edited by hand frame by frame. It’s really a vast improvement over the prior version, which was chiseled on slabs of sandstone and mounted in a row, so you had to run past them very fast to get the animation effect.

Also, the subject didn’t get much reward or glory, and probably ended up going down a drain in Eugene, Oregon.

What the heckity-gosh-darn is epigenetics?

comfortable

Today in my class we talked for a while about epigenetics. I used it as an example of a term we’d encountered more than once in our ecological developmental biology course, but that has some complicated ambiguity and fuzziness that has led to all kinds of weird popular confusions about the subject. I was also using it as an example of critical analysis of a paper, as I discussed yesterday, and it was a lead-up to having the students discuss papers on relevant topics they were interested in — so we spent most of our time talking about other things.

But I’m going to talk now about just this one paper I read. You see, Larry Moran and I have been having this long-running disagreement about epigenetics — nothing hostile, just an occasional cocked eyebrow in each other’s direction — which you can see on display in this article by Larry on epigenetics, in which he disagrees with my definition of epigenetics, back in 2008. Here’s my definition:

Epigenetics is the study of heritable traits that are not dependent on the primary sequence of DNA.

And here’s the definition used in Gilbert’s text:

…molecular processes around DNA that regulate genome activity that are independent DNA sequence and are mitotically stable.

And here’s Larry’s objection:

Here’s the problem. If this is epigenetics then what’s the point? When I was growing up we had a perfectly good term for these phenomena—it was regulation of gene expression. Why is there a movement among animal developmental biologists to use “epigenetics” to refer to a well-understood phenomenon?

While I agree that “epigenetics” is a huge, broad, diverse category of phenomena, I think he’s overlooking a key point to claim it is synonymous with gene regulation. It is gene regulation that is heritable and mitotically stable. It’s still far too open-ended, but it’s not just any old example of gene regulation.

It’s also clear and consistent. Larry challenges us with eight instances of regulatory phenomena and asks which ones qualify as epigenetic. Easy. 1, 2, 6, 7, 8. Those are the ones where he specifically mentions multi-generational inheritance of a regulatory state. 3, 4, and 5 describe responses within a single cell in a single generation (5 is sneaky, though: Drosophila oocytes are having gene expression modified in ways that might be transmitted through multiple generations — it’s just that those cells are being loaded with bicoid RNA, not having their bicoid genes being set to a sex-specific state).

I am also comfortable with the idea that inheritance of the regulatory state of the lac operon is an example of epigenetics. It’s arguable whether that’s a useful category, but it does fit the definition.

So one approach that could be taken is to come up with a more specific or more practical definition.

Larry has a more recent article in which he agrees with a new paper by Deans and Maggert that tries to do exactly that. It also takes a much appreciated historical approach, giving the various definitions that have been wafting about since the 1930s. For instance, here’s Waddington’s ancient physiological definition:

the branch of biology that studies the causal interactions between genes and their products which bring the phenotype into being

Yes, I agree — that would simply be gene regulation nowadays. You can’t blame us wicked developmental biologists for promoting that one, though, because we don’t use it anymore.

Now we favor the Holliday definition:

the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail change in DNA sequence.

To me, “heritable” is the magic word that makes all the difference. This, however, is not enough for Deans and Maggert. They want to add more focus, often a good thing, and narrow the definition. I was not happy with their argument, and thought it poorly made, though. See if you can find what was objectionable in this section of their paper (I highlighted it to make it easy, an epigenetic modification that does not change the sequence of the letters in the text.)

We don’t feel that it is possible to reconcile Waddington’s focus on gene regulation with Holliday’s more specific criteria within one field and still maintain the level of clarity needed to produce a useful definition. The efforts to preserve a relationship between these two conceptualizations have been impaired by the fact that there are just too many phenomena, with too few mechanistic connections, to categorize into one field. Also, among the definitions that do maintain the requirement of heritability, we feel that many lack the detail to be functionally useful in directing the testing of specific hypotheses, particularly as it relates to the location or site (cytoplasm or nucleus) of epigenetic phenomena. To mitigate these shortcomings, we advocate defining epigenetics as “the study of phenomena and mechanisms that cause chromosome-bound, heritable changes to gene expression that are not dependent on changes to DNA sequence.”

We feel that this definition makes a strong distinction between gene regulation (Waddington’s definition) and epigenetic inheritance (Holliday’s definition), and also emphasizes that epigenetic phenomena must deal exclusively with chromosome-bound changes. By making these distinctions, we have efficiently separated expressional changes caused by cytoplasmic compounds, which are more closely tied to gene regulation, from those which occur on, or in close association to, the chromosome. Doing so makes the focus of the field much clearer and identifies epigenetic mechanisms more explicitly.

We feel that this definition touches on several important elements not encompassed by other definitions, yet commonly implied in most uses. To further explain the reasoning behind our definition, as well as its utility for improving epigenetic research, we would like to offer a clarification and a test.

Yeesh. I don’t feel that your personall feelings are a strong argument, and I cringed when I hit that page. At least edit it to remove the emphasis on your personal discomfort; just say that the old definitions lack detail, rather than that you feel they lack detail.

So let’s pull out their shiny new definition.

the study of phenomena and mechanisms that cause chromosome-bound, heritable changes to gene expression that are not dependent on changes to DNA sequence

Well. All this fuss for a single change, the addition of the phrase chromosome-bound. That’s it. I agree, it does narrow the topic, but it’s still covering an awful lot of territory. I’m not feelin’ it. I have the impression that the primary virtue of the new definition is that it reduces a class of phenomena to a subset that many people are comfortable studying already, and in part reinforces a gene-centered perspective on cellular behavior.

It also leaves me wondering…what about the inheritance of cytoplasmic or membrane-bound factors that induce consistent changes in gene expression in daughter cells? The gene regulation aspect may be mundane, but it’s the inheritance that is interesting. Under the Deans and Maggert definition, this is no longer under the umbrella of epigenetics — it’s something different for which we have no general name now.

It makes Larry happier, though.

I think this is a useful definition. Nobody cares if dividing E. coli cells inherit molecules of lac repressor and continue to repress the lac operon. That’s a trivial form of epigenetics that never posed a threat to our understanding of evolution.

That’s odd. I do care that the lac repressor is cytoplasmically inherited, but then my primary interests, in the most general form, would be in the patterns of stability and change in cellular properties, rather than the metabolism of sugar. Telling me that I should only pay attention to inherited proteins or methylation states that are directly bound to DNA seems arbitrary.

I also don’t consider “poses a threat to our understanding of evolution” to be a relevant criterion. I agree that lac repressors don’t challenge evolutionary theory, but neither do heritable histone modifications or methylation. I’m one of those people who think epigenetics (even under the old definition!) is important and interesting, but doesn’t affect evolutionary theory much at all.

Larry and I agree.

Methylation is trivial.

Well then, if inheritance of the lac operon is such a trivial form of epigenetics that it should be excluded from the definition, then we apparently need yet another definition that excludes the triviality of methylation.

Or, really, we should recognize that “trivial” is not a good reason to exclude something.

I will still second Larry’s argument that none of this stuff overthrows modern evolutionary theory in any way. It would require extremely persistent inheritance of an epigenetic state over many generations to have those kinds of repercussions.

(The Gilbert text does mention one significant effect: the toadflax plant, Linaria vulgaris, has a radically different flower morph, Peloria, that Linnaeus himself classified as a different species. As it turns out, they only differ in the methylation state of the cycloidea gene, but the DNA sequence is identical. This is a case of an epigenetic change persisting for hundreds of generations. It’s a rare case, though, and also…would still definitely fall under the Deans and Maggert definition.)