Is schizophrenia the price we pay for an evolving brain?

Schizophrenia is pretty darned common, and it's a terrible disorder with clear inherited roots. So why is it so common?

Scientific American 9/6/07: It's No Delusion: Evolution May Favor Schizophrenia Genes

New research reveals that genes related to the debilitating disorder may also provide developmental advantages..

...Dorus co-authored a report, appearing in this week's Proceedings of the Royal Society B, about the evolution of genes linked to schizophrenia. After analyzing human DNA from several populations around the world and examining primate genomes dating back to the shared ancestor of both humans and chimpanzees, researchers reached a striking conclusion that several gene variants linked to schizophrenia were actually positively selected and remained largely unchanged over time, suggesting that there was some advantage to having them.

"Schizophrenia can be explained by a lot of individual alleles (variations of genes)," Dorus notes. "There are many different loci that impact the actual manifestation of the disease." Over the past decade, several dozen genes have been identified as potential culprits, and scientists believe that several genes cause disruptions in protein formations predisposing a person to schizophrenia.

...the team ... focused on 76 gene variations most strongly related to schizophrenia. By comparing these combinations with the evolution of other genes known to affect neuronal processes, the researchers determined that 28 of the schizophrenia-associated genes have been evolutionarily preferred in recent years by either Caucasian, Asian or African populations.

"Because it's a such a complex genetic trait … you actually expect there to be some variability from population to population, in terms of what genes are playing a role in the disorder," Dorus says. He notes that he was surprised that the study turned up a positive selection for some of the genes most closely associated to the disease, including DISC1 (disrupted in schizophrenia 1), which is involved in the transport of proteins along the relatively lengthy cell bodies of neurons, among them. "The most important thing is we don't really know what the basis of the selection has been," he says. "It could be due to an entire range of neurodevelopmental processes."

Co-author Crespi says that a number of theories have been floating around regarding the persistence of schizophrenia's genetic underpinnings. One holds that schizophrenia is a "disorder of language" and that the illness is an unfortunate consequence of the development of human speech, expression and creativity. "Whenever you get strong selection, it's like a big plus, and you can drag along a lot of minuses," he says. "You can think of schizophrenics as paying the price of all the cognitive and language skills that humans have—they have too many of the alleles that taken individually…might have positive effect, but together they are bad."

Dorus says the team will now home in on the 28 genes fingered in positive selection in the hope of finding new treatments for the mysterious disorder.

The explanation seems to be that it's very hard to construct a functioning human brain, and that the brain is still actively evolving. So in this case there's not necessarily an advantage to a schizophrenia gene, but rather that the diffuse set of disorders we label as "schizophrenia" arise because the human brain is very much a work in progress, one with a high defect rate ...

Update 7/2/2010: Structural variation in the human genome and its r... [Annu Rev Med. 2010]...

... The discovery of submicroscopic copy-number variations (CNVs) present in our genomes has changed dramatically our perspective on DNA structural variation and disease. ... CNVs, to a larger extent than SNPs, have been shown to be responsible for human evolution, genetic diversity between individuals, and a rapidly increasing number of traits or susceptibility to traits; such conditions have been referred to as genomic disorders. In addition to well-known sporadic chromosomal microdeletion syndromes and Mendelian diseases, many common complex traits including autism and schizophrenia can result from CNVs. Both recombination- and replication-based mechanisms for CNV formation have been described.

A picture to remember - Rangoon

TIME, September 27, 2007

Pictures of the Week - TIME

Photographer Kenji Nagai takes photographs after being shot by soldiers in Rangoon as the Burmese Army fired on the crowd. Kenji later died.

Send a letter to Rush

Army of Dude: The Real Deal is a post from a former Limbaugh listener, and veteran, who's opinions have changed. Apparently the latest right wing meme is to label any veteran who disagrees with them a "phony soldier". I'm sure someone will send it to Rush as a letter ...

Apple guilty of second degree iPhone murder?

We know there's a civil war brewing between Apple and an arguably critical part of their customer base -- the OS X geek community. If it turns out that Apple deliberately configured the latest OS X update to destroy hacked iPhones, the conflict will move up a notch. Glenn Fleishman of the venerable and respected Tidbits organization says Apple is not guilty of iphoneslaughter, but rather of murder in the second degree ...

TidBITS iPod & iPhone: Staff Roundtable: Apple Should Do No Harm to iPhones

... Apple has changed that equation with the iPhone's latest firmware and operating system upgrade. The iPhone is a powerful little computer controlled by powerful interests. Like almost all electronics sold today, includes a variety of kinds of firmware, or the software that controls the hardware. The firmware may be stored in different places, too, with radio cards and separate modules have their own internal firmware. Part of the firmware handles the boot procedure that allows the device to load the operating system; other parts handle upgrading and installing new firmware. Because the iPhone uses non-volatile, electrically erasable memory, there should be no problem with restoring a phone that has had every manner of change applied to it, as long as the boot routines aren't affected.

The hacks that unlock an iPhone to work with other carriers write special instructions to the firmware that controls the cellular network association to allow the use of any SIM - the authentication module used on worldwide GSM cellular networks - and not just AT&T's. This shouldn't affect the bootstrapping or firmware and operating system restore process one bit.

Gizmodo posted an interview with the iPhone Dev Team, a community effort that resulted in unlocking software. In the interview, the Dev Team makes it clear that Apple could very simply have included in the update a way to check whether the code related to the lock has been modified, and rewrite it. The team says that Apple could also fairly easily restore a default state and then more securely lock the phone down. (The team is also positive they can restore iPhones to a factory default state that have been "bricked," or turned into an unusable hunk of electronics.)

Has Apple lost its collective mind?

Bicycling and Skating: Urban variations?

Minneapolis is a great bicycling city, and Saint Paul is not far behind. On the other hand, we don't have as many inline skaters as one might expect. We invented the darned sport (ignore the cheese heads in the corner please), but our Friday Night Skates occur only twice a month, and we rarely get more than twenty skaters. Our inline skate club is a great group, but we're a bit on the ... experienced side of 40 (I'm going to sign up my 10 yo to drop our average age).

So why do many of these cities have pretty active night skates, not to mention Amsterdam and especially Paris?

... It takes place every Friday night, except when it rains, and can attract as many as 20,000 skaters. Group skates have been around awhile in the United States and Europe, especially since the advent of in-line skates, which provide speed and maneuverability not possible with quad roller skates. But, in scale and longevity, nothing matches the festive Parisian skates, which began in a small way in 1994 and quickly grew to a point where, in 1997, the police decided to become involved for the safety of everyone concerned -- skaters, motorists, and onlookers. Today, the police not only block off roads and provide an escort for the skaters, but about 20 officers on skates join the rolling ranks during the weekly "rando," derived from the French word "randonée," or tour...

Ok, so Paris is bigger and has lots of tourists. Still, you think we'd be able to muster a few hundred!

One theory I've heard is that the bicycling and skating populations are very similar people. In Minneapolis that population bicycles, but in other cities the bicycle routes aren't nearly as appealing -- so skating is more common. Of course that doesn't explain Amsterdam ...

Curious. I do think we ought to try a weekly skate, but since I get free to join 'em only about twice a year I'll have to wait for someone else to make that happen.

Helmets: good for inline, not so good for bicycling?

Inline skaters should wear a helmet. But what about bicyclists? I wear a bike helmet, and so do my children. It seems to make sense anyone riding on a bicycle path, but today I read that it may not work for anyone riding with cars.

The problem, alas, is the car driver.

Cars are not much of a factor in head injuries occurring during inline skating; inline skaters rarely mingle with cars. Bicycles, however, do. Most bike fatalities and injuries are automobile related.

It turns out that automobile drivers, on average, give more space to bicyclists not wearing a helmet. If you wear a helmet, there's a 23% increase in automobiles passing within the 1 meter danger zone [1]

I suspect that this is doubly true for motorcyclists, though the researchers did not study that topic. So much for all my disparaging remarks about bare headed motorcyclists; if my guess is right than the decreased risk of automotive impact will far outweigh the decrease in head protection. Aging boomers -- let your residual hair flow free ...

Maybe.

So what do we do while researchers sort this out? If you're not riding in traffic the evidence strongly favors riding a bicycle helmet. If you ride in traffic, however, things are trickier than I'd once believed. There's a case for putting the helmet on the bike rack when entering traffic, and donning it for the bike trail...

I won't change what I do. For one thing surprising results require confirmation, for another I need to reinforce the children's behavior. For them the helmet is an unadulterated good.

In the meantime, let's find out what other things we can do to get more space from cars. How about a horizontal flag that extends one foot left? Professor Walker, please retest with the flag. Let's see what we can do to get those drivers outside the 3 foot limit. Maybe a flag and a helmet together will provide both head protection and a lower impact risk.

[1] Scientfic American Fact or Fiction, October 2007. Walker et al, Accident Analysis and Prevention, March 2007. The summary didn't mention gender variation. My experience is that women drivers give much less room than men drivers, perhaps because of a greater reluctance to cross the solid center line.

DI - Lake Peigneur

It's only 27 years ago, you'd think I'd remember this ...

Damn Interesting » Lake Peigneur: The Swirling Vortex of Doom

...Within two days, what had previously been an eleven-foot-deep freshwater body was replaced with a 1,300-foot-deep saltwater lake....

Turns out there's a good reason I don't remember this. The NYT story from 11/21/1980 is a brief, understated, summary within the "In the Nation" column.

There's a interesting gap between the miniscule national attention given the story in 1980 and what had really happened. Today it would be on FOX and CNN around the clock.

The evolutionary biology of Giardia - no mitochondria

Giardiasis is an annoying and fairly common infection, but we don't think it's not a big deal for a healthy adult. Turns out that the Giardiasis bug, Giardia, has some very interesting biology ....

The Loom : Carrying Ancient History In The Gut

... Giardia, many researchers suspected, was one of those early-branching eukaryotes. This suspicion was generated at first by simply eyeballing the creatures. They are quite weird. Their teardrop-shaped bodies have eight tails for swimming and a suction pad to clamp onto the wall of the intestines. They also carry two nuclei, each with its own DNA. How Giardia manages to keep all those genes coordinated--and why it even has two nuclei--remain mysteries. Bizarre single-celled eukaryotes are pretty easy to find. What set Giardia apart from most other eukaryotes was what it lacked. Scientists could not find a lot of those compartments in which the business of most eukaryote cells takes place.

Most significantly, it was missing mitochondria. Lots of things take place inside these sausage-shaped structures, most importantly the generation of ATP, the energy-bearing molecule found in all living things. Mitochondria started out as free-living bacteria and later evolved into permanent symbionts inside the eukaryote cell. (Mitochondria still carry some DNA of their own, which bears a strong resemblance to one group of free-living bacteria.) The fact that Giardia seemed to be missing mitochondria hinted that it was a transitional eukaryote...

Alas, the story is more complex than this, so you do need to and read Carl Zimmer's essay. Fascinating stuff.

I probably invited this bug onboard during a particularly rough college train trip through Mexico. I didn't realize I was carrying a possible echo of biology's "big bang".

Incidentally, speaking of parallels to cosmology, there's apparently a suspicion among some biologists that there's a kind of "dark matter" component to biology. They're looking for terrestrial life forms so bizarre that we don't even recognize them as "living" ...

Apple is at war with its own uber geeks

When Apple last returned from the grave, for the second or third time, geeks were important. OS X is a respectable piece of software, and geeks made it work. In several domains, particularly in communications and knowledge management, OS X now has a better range of solutions than XP.

Today, however, Apple is at war with its uber-geeks -- because of the iPhone. Saul Hansell describes the mood in the NYT, though he's confusing the unlockers with those who want the best possible iPhone on AT&T...

Steve Jobs Girds for the Long iPhone War - Bits - Technology - New York Times Blog

... This afternoon, Apple did release the update. And the gadget blogs confirm that it does indeed wreak havoc on modified iPhones. Some phones have indeed been “bricked.” In others, unofficial applications have been disabled. And there are worries that hacking the updated phone will be harder.

The result: Serious hackers will keep find new ways to break in. Less technically inclined may well find themselves chastened into technological submission, assuming they can get their pricey toys to work at all. Will Apple really refuse to help people with iBricks?

Speaking in London last week, Steve Jobs, Apple’s chief executive, said the company is in a “cat and mouse” game with hackers.

“People will try to break in, and it’s our job to stop them breaking in,” he said.

There is something futile about the way Apple appears to be fighting some of its most ardent fans, those who want to use the full capabilities of the iPhone...

... Since the iPhone is a very sleek, capable handheld computer, people are going to want to run programs on it. They are going to want to hack and see what they can build. It’s a law of nature. And Apple might as well be fighting gravity.

Many other cell phones are locked down, of course. But few other phones capture the imagination of programmers the way the iPhone does.

There are two loosely allied groups of Apple geeks now at war with Apple. The unlockers want to use the phone with other providers; but most of Apple's geeks are willing to respect Apple's deal with Satan -- especially if the iTouch is improved. Everyone, however, is now united for at least a partly open iPhone and iTouch native development platform.

Geeks don't trust Apple to put the solutions we need on the iPhone. Apple's aiming at the mass market, and we're not mass market. We understand Apple can't justify investing in the solutions we need, but that's ok. There are lots of small, low overhead, high quality OS X development shops that will be able to make a very good living off the markets Apple doesn't want. Would it really kill Apple to have a 3rd party bluetooth keyboard added to the iPhone? How about the PIM/Outlook solutions Apple won't build? FileMaker Mobile? The list is long.

If Apple keeps the iPhone closed they'll alienate their uber geeks -- not just from the iPhone, but from the entire OS X platform. Maybe they're ready to run that risk, but I don't think the gain outweighs the likely costs. Keeping the iPhone virus free is a good reason to have a software certification program and a signed secure installation package, but it's not sufficient justification to close the platform.

Apple doesn't need to open the iPhone today, but they need to provide a roadmap in the weeks to come. Otherwise the Apple blogs are going to turn mean ...

Update 9/28/07: Wired has a brilliant summary of what Apple is failing to do -- the iPhone pre and post bricking. Some Apple employee ought to paste the Wired graphic to Steve Jobs door.

My double rainbow

Wikipedia's picture of a double rainbox (left, credit) is lovely, but mine was even better. The secondary rainbow was better defined, and I think I counted nine distinct bands in the primary. It arced, like this picture, from ground to ground.

I wasn't in a beautiful Alaskan national park, I was leaving my office in Roseville, Minnesota. There'd been a downpour, but the rain was now steady but widely spaced, an odd pattern I don't see much. The sun was at about 25 degrees above the horizon, and the western sky had cleared, so the light was completely unobstructed.

I stood and watched in amazement. It lasted only about four to five minutes, then the secondary began to fade. I phoned home when I saw it, but it couldn't be seen even 15 miles south of me. It was a private show.

I don't think I've ever seen a rainbow like that, and perhaps I never will again. It was just one of those odd, unexpected gifts, like a letter from an old friend.

Cringely runs the shark over

My favorite tech commentator has not merely jumped the proverbial shark, he's run it over. Cringely is going to launch a rocket to the moon and drive a rover around. The man needs a vacation.

I'll have to donate some money of course. Lunacy of this sort must be encouraged.

BBC IOT - Theories of Everything With Brian Greene

Even In Our Time has its limits. I wrote last April that Lord Bragg was struggling with the Poincare Conjecture, and compared it to my physics reading then ...

... Which brings me to my recent readings in physics. I'm reading Gribbins on Quantum Mechanics (1994) and Brian Greene with another cosmology/string theory overview, the Gribbins book is my personal favorite, but it's a bit dated now. Together though, they make it hard to overlook that physics seems to be getting harder and harder. We have more physicists than ever, and I'd wager there's a Feynman or two in the bunch, but we've been stuck for decades now...

I've been savoring Greene's The Fabric of the Cosmos ever since, reading a few pages every day. It's rich stuff! I'll have a post on the book soon, but I confess I'd underestimated the progress of the 90s; quantum speckles on the microwave echoes of Higgs driven inflation is darned impressive.

Which brings me to the podcast I'm listening to now -- Theories of Everything, feature none other than ...

Brian Greene, Professor of Physics and Mathematics at Columbia University and author of The Fabric of the Cosmos (Allen Lane, 2004)

John Barrow, Professor of Mathematical Sciences at the University of Cambridge and author of The Constants of Nature (Vintage, 2003)

Dr Val Gibson, particle physicist from the Cavendish Laboratory and Fellow of Trinity College, Cambridge

Further reading
The Elegant Universe by Brian Greene (Vintage, 2000)
[jf: odd choice, they should have recommended The Fabric of the Cosmos, his current book]
Theories of Everything by John Barrow (Vintage, 1992)

Now that's ambitious. Alas, Bragg is weakest when he ventures into math and physics, and his guests seemed to be struggling as well. At one point Gibson and Green talk about the relationship of extra dimensions to string theory, but they just miss making the key point -- that while finding extra dimensions won't prove string theory, not finding them will severely weaken string theory.

I was also left with the impression that the "string" metaphor is overdone. Maybe it would work better if Green were to say something like "we've developed very fancy maths that allow us to model both the jittery quantum world and the continuous world of cosmology", and one way to imagine the mathematics is to think that it's describing wee little bits of strings ...

Full points to IOT for courage, but Lord Bragg was traveling in alien territory ...

Update 9/30/07: I wrote this post pretty quickly -- like all my posts. Melvynn stayed lost, but his guests warmed up around the half way mark, so it did turn into a strong episode.

Amazon MP3 Store: great news for Apple customers

Amazon's MP3 store is a smash hit among OS X gurus like Gruber:

Daring Fireball: The Amazon MP3 Store and Amazon MP3 Downloader

...The songs sound great and come with high-resolution album art. Singles cost $.89 or $.99, and album prices start as low as $4.99 — i.e. they’ve introduced variable pricing to sell music for less, not more, than the iTunes Store. When you search for songs from an artist whose entire catalog is not available through their MP3 store, Amazon provides a direct link to the artist’s catalog in their CD store. Two million total songs is far less than the six million Apple offers at the iTunes Store, but it’s a pretty good start, and all of Amazon MP3’s songs are DRM-free. I’m not sure how many DRM-free iTunes Plus tracks Apple offers, but it certainly seems like far fewer than one-in-three, and thus far fewer than two million. So while Amazon can’t claim to offer the most songs, they might be able to claim the most DRM-free songs. In just a few minutes of shopping, I found plenty of songs at Amazon that are only available from the iTunes Store with DRM. Given the Amazon MP3 Store’s audio quality, prices, and user experience, I can’t see why anyone would buy DRM-restricted music from iTunes that’s available from Amazon. And given that Amazon is quite a bit cheaper than iTunes Plus, you might as well check Amazon first. I plan to...

Hallelujah. Amazon's not messing about, they launched this for OS X and Windows simultaneously. At last, Apple has very serious competition.

Of course since Amazon's tunes work perfectly with iPods, it's not going to hurt Apple's revenue stream all that much. I wouldn't be surprised to see Apple's share price fall a bit then recover as investors realize Amazon's play is poison for Microsoft's strategy.

The joy of it is that it will make Apple work harder to keep its customers happy, and it will strengthen the anti-DRM solution.

Now, just wait until Gruber realizes that Amazon has embedded a unique identifier in each song that they can connect back to his credit card* ....

* How do I know this? I don't. I'd bet on it though. I'm sure Apple does the same sort of thing with their non-DRMd tunes, I even expect that an AAC you burn from a CD using iTunes contains some sort of embedded identifier.

Update 9/26/07: I'm 99% sure John Gruber doesn't read this obscure blog, but shortly after I worte of the "Amazon unique identifier" he told us that while Apple embeds an identifier (which happens to resemble an email address but is tied to credit card identification) in their DRM-free downloads Amazon, in the NYT, says they don't (!). Well, gee, I was wrong. That's never happened before :-). Gruber has an essay on the broader implications too.

Error types in software and fort construction

CH pointed me to this one. A programming guru classifies errors in a family constsruction project, and relates them to software development. Emphases mine, number 4 is my fave.

Building a Fort: Lessons in Software Estimation - 10x Software Development

1. Numerous unplanned problems collectively added up...

2. Underestimation of unfamiliar tasks. My estimates weren't too far off for a lot of the work that I'd done before. But some things, like mapping out the site for the footing holes, I assumed would be 15-30 minute task ended up taking several hours.

3. Not decomposing big tasks into smaller subtasks. I'd planned out my project in whole days. At a birds eye view nothing seems obviously wrong with planning "frame the fort in one day." But when you break it down ... you start thinking, can I really do a whole wall in 2 hours? If the answer's even close to "no," then you start to realize that the whole estimate for that big task is probably wrong.

3. Using overly round time units. Using round units like "1 day" contributes to not thinking hard enough about decomposing large tasks into smaller tasks.

4. Substituting a target for an estimate. I had 7 days to do the project, and my estimate turned out to be 7 days. That's a little suspicious, and I should have known better than to make that particular mistake!

5. Sweeping numerous little tasks under the estimation rug....

6. Never creating a real estimate. The fact of the matter is that I carried around a rough plan in my head for weeks, but I never actually committed a schedule to paper...

7. All's Well That Ends Well. My kids love their fort, and I had a great time building it. "All's well that ends well" is one reason that companies don't improve their software practices more often than they do. If people like the software that the team produced, and the software is successful, then that reduces the incentive to try to do better next time.

Broadband speed trickery: couldn't happen here

In the UK broadband firms advertise speeds using the words "up to". Shockingly, the reality is typically less than 50% of the "up to" number...

BBC NEWS | Technology | Broadband speeds under scrutiny

Broadband speeds in the UK are much slower than advertised by internet service providers, a study by Computeractive magazine has found. Some 3,000 readers took part in speed tests and 62% found they routinely got less than half of the top speed advertised by their provider. It is the latest in a series of questions over the way net firms advertise broadband services...

Scandalous. It would never happen here of course.

Seriously, the interesting bit here is that a trade magazine actually did something useful. There was never much life in the trade journals (except for BYTE) to begin with, and I'd thought the web had completely killed them.