Update on the unfinished count of the human genome

I'm a big fan of Bill Clinton, but he did have a talent for useful hokum. It often served a greater cause, but it did have the disadvantage of being a bit ummm untrue. The Y2K "human genome sequenced" story was a bit like that. The real timeline of the project seems suspiciously close to how long the grumpy old skeptics thought it would take. We're still slogging away. Carl Zimmer brings us up to date. The original article has a fascinating link to "PANTHER", an academic project for assigning genes to functional categories. Don't miss Zimmer's ending sentence ...

The Loom : You Don't Miss Those 8,000 Genes, Do You?

... When Craig Venter and his colleagues published their rough draft of the human genome in 2001 they identified 26,588 human genes. They then broke those genes down by their functions. Some were involved in building DNA, some in relaying signals, and so on. Remarkably, though, they classified 12809 genes--almost half--as "molecular function unknown."

... There are web sites where you can observe works in progress, such as the human genome. One of those sites is called PANTHER. I contacted the top scientist behind it, Paul D. Thomas, with my question, and he sent me a link. When I clicked on the link, I got the pie chart I've posted here (click on the image to go to the original page if it's hard to read).

The pie shows that we're now down to just 18,308 genes. That's over 8,000 genes fewer than six years ago. Many sequences that once looked like full-fledged genes, capable of generating a protein, now don't make the grade. Some genes turned out to be pseudogenes--vestiges of genes that once worked but have been since wrecked by mutations. In other cases, DNA segments that appeared to be parts of separate genes have turned out to be part of the same gene.

Today scientists still don't know the function of 5898 genes in the human genome...For all the work that has poured into the genome, for all the grand announcements, we still don't know have the faintest idea of what about a third of our genes are for.

... few human genes have experimental evidence for their function in humans. In one study of 35329 proteins, scientists estimated that only 2784 met this gold standard.

... And then there's the whole matter of all the other DNA that doesn't encode proteins (98.5% of the genome all told). A lot of it is most likely a mishmash of broken genes and viral DNA. It's possible to cut huge swaths of it out of a mouse's genome with no apparent ill effect. But there are also a lot of important players hiding in that wilderness--switches that proteins can use to turn genes on and off, sequences that do not give rise to proteins but rather RNA molecules that create their own control system for a cell. In all of these complications, scientists will probably find the answer to the question, "How do roughly the same number of genes encode such different kinds of animals?" Complexity isn't purely a matter of the number of genes you have. It's also how you use them.

...few human genes have experimental evidence for their function in humans. In one study of 35329 proteins, scientists estimated that only 2784 met this gold standard...

... I would not have been able to have created this pie chart without Thomas's help. Perhaps some science writers will become more like investigative political reporters who know how to sift through Federal election databases for the real news...

I recall from Dickson's 1970s "Dorsai" cycle that much research in that "space opera" consisted of mining "the encyclopedia" (re: the web) for knowledge. Zimmer is quietly predicting "knowledge mining" will become a bit part of science description -- not just writing, but also doing science. In fact, I'm not sure there's a clear difference between knowledge mining and classic science, though I confess knowledge mining seems to have some resemblance to the medieval scholasticism.

We're now in the story of the 'incredibly shrinking genome'. Meanwhile we learn elsewhere in Zimmer (I think it was there) that humans and chimpanzees are much less alike than we'd thought. There are many ways to encode complexity, and evolved organisms have a rather baroque approach to solving such problems.

Update: If we extrapolate a bit, it would not be surprising to discover that we have about 16,000 genes that code for 35,000 proteins. So there's a 2:1 compression ratio from gene to expression, which is comparable to best lossless compression algorithms run against highly complex data. The 2:1 ratio presumably must have some implications for how natural selection can proceed. It's easy to imagine that a mutation in a gene that "improves" the function of one protein product might disable another protein coded by the same gene. So evolution would typically proceed "two steps forward and one step backwards", or at best with peculiar side-effects on a secondary protein arising from changes to the primary protein.

Elizabeth and John Edwards

The NYT interviewed the Edwards about their decision to continue John's presidential campaign despite Elizabeth's metastatic breast cancer:

Facing a New Battle, Mrs. Edwards Set Campaign’s Fate - New York Times:

...Mrs. Edwards — whose decision to push her husband to run for president in spite of her life-threatening illness provoked an intense discussion across the country about illness, ambition, child-rearing and death — said her husband’s candidacy was not only about his needs and desires, but also her own life and her wish to be something other than a woman best known for her life-threatening illness.

“I expect to live a long time,” Mrs. Edwards said. “I expect us to have lots and lots of years together. I do believe that. But if that’s not the case, I don’t want my legacy to be that I pulled somebody who ought to be president out of the race. It’s not fair to me, in a sense.”

Saying she hoped to be “heavily involved” in her husband’s campaign, she said: “My feeling is, if we gave up what we have committed to as our life’s work, wouldn’t I be getting ready to die? That’s what I’d be doing. This cause is not just John’s cause, it’s my cause.”...

The Edwards' know a bit about hard times. What I think is irrelevant, but in fact I'd have "approved" (like that matters!) whatever they decided. Bad things happen to even the luckiest of us mortals, we can't fall over every time tragedy whacks us -- though some tragedies will put most anyone down for a while. An early death of a parent and partner is a bad thing, but they've lived through worse.

Anyway, the odds are decent that Elizabeth will live a through at least part of a second term, and she knows how badly we need the leadership John and his team can deliver. This is her legacy. I hope we are wise enough to justify her gift.

In the absence of Al, I've been leaning towards John. I'm glad I'll have the opportunity to learn more about him.

A review of the pet food industry

Aside from globalization, factory food, homeland security, and personal tragedies, the aminopterin poisoning of 2007 has shed some light on the pet food industry. Emphases mine. I admit, I was surprised to learn that pet food is less rigorously regulated than cow feed -- because we don't eat pets ...

Pet Food - Pets - Menu Foods - Poisonings - Dogs - Cats - New York Times

.... Q. What’s in pet food then? Is it regulated?

A. Pet food is regulated by the F.D.A. through the same state agencies that regulate food for farm animals. But product excluded from animal feed can go into pet food — meat and bone meal, nervous system tissue — parts of animals not allowed for anything else. There were cases of mad-cow disease in cats in England. The opportunity for cheap byproducts is much greater in pet foods. The assumption is that better brands don’t do that, but it’s not verified.

Q. If a few companies are making many of the brands, are pet foods all the same then?

A. Nutritionally, they have to meet the same industry standards, though they’re priced very differently. You read the labels and they all look alike — corn is the first ingredient in a lot of dry food.

Q. Why are some brands more expensive?

A. The quality of the ingredients. Are you using human-grade food or food that humans wouldn’t care to eat? It doesn’t matter to animals but it matters to the people who own them.

Q. What about health claims?

A. When you see food claims on breakfast cereal — for instance, that it lowers cholesterol — there has to be some scientific substantiation behind them. Pet foods have claims on them, that they support a healthy immune system, reduce risk of whatever, but they don’t have to be supported by large amounts of science. They’re worded in such a way that doesn’t violate the F.D.A.’s labeling rules. I think the F.D.A. will have to take a much closer look at pet foods — this is the second recall in a short time.

Q. What do cats and dogs enjoy eating?

A. Cats don’t have a taste for sugar; they don’t taste sweet things. They have a particular taste for what is referred to in the industry as “animal extract” — God knows what’s in it. Dogs can taste sweet, but, dogs will eat anything. Cats are very fussy, as any cat owner will tell you. The one thing that’s never been studied is to find out how long it would take for a cat to eat something it doesn’t like — owners never wait it out. People are very attached to their pets, and it’s painful to watch a cat not eat.

Q. Should owners prepare their own food for pets or feed them table scraps?

A. There’s evidence that dogs can be fed table scraps and do quite well, provided they’re healthy table scraps — meat, dairy, vegetables, fruit. The problem is a lot of humans don’t eat that way.

A mixture of expensive "organic" pet food and healthy table scraps sounds good and perhaps relatively cost-effective. It's impressive how little we know about whether our "premium" pet food is really very premium at all.

Six "top 10" lists for software people

Coding Horror: Top 6 List of Programming Top 10 Lists is excellent. Read and study them all. I've copied the entire post to a "note" in my Palm [1] so I can periodically refer to them. So far they all feel familiar, but I love this kind of review. Nice job assembling them CH!

[1] The Palm OS Note or Memo is the simplest possible application. The Microsoft Outlook Note is barely more sophisticated (it has categories, but no scroll bar, so maybe they're even). The two sync almost perfectly (category problem). Thanks to full text search (Lookout for Outlook, native to the Palm) they are very powerful tools. Nobody uses them. Rock solid. Simple. Useful. Puzzling ....

Are you an engineer? (and a joke)

CH quotes from The Inmates Are Running the Aslum who quotes an old joke. Here's the joke:

Coding Horror: The Rise and Fall of Homo Logicus:

Three people are scheduled for execution: a priest, an attorney, and an engineer. First, the priest steps up to the gallows. The executioner pulls the lever to drop the hatch, but nothing happens. The priest claims divine intervention and demands his release, so he is set free. Next, the attorney takes a stand at the gallows. The executioner pulls the lever, but again nothing happens. The attorney claims another attempt would be double jeopardy and demands release, so he is set free. Finally, the engineer steps up to the gallows, and begins a careful examination of the scaffold. Before the executioner can pull the lever, he looks up and declares, 'Aha, here's your problem.

Yeah, I might do something like that. It's a good test to see if you're an engineer-type. The rest of the post is worth reading too, it's really a rant that "engineers" need to realize that their customers are usually not like them. That's very true, but it's not just engineers who fall into this trap. The single most important thing I was taught about product management was never to assume that I resembled the customer in any significant way. I had to be taught this, I didn't figure it out on my own -- but once I heard it I knew it was true.

My (few) readers may think that it's obvious that I don't resemble many people, but, to be honest, at some unconscious level, I thought I was pretty typical. I think this is a common misapprehension among engineering types -- it's probably related to having a touch of autism. My guess is that there are some neural configurations that are prone to this self/other error, and some aren't.

Border crossings: searching random laptops for porn

It seems some custom officials feel obliged to search some laptops for pornography. It's not clear if this is a work mandate or a personal mission. They may or may not have a "profile" to search; it seems that carrying a personal versus corporate laptop may be a red flag. Tom Kyte (via Schneier) tells the story:

The Tom Kyte Blog: Crossing the border...

... The person doing the search - they were afraid of the computer. They did not use one. They did not know what they were looking for. They did not know how to look for it. I felt like giving him POINTERS as we were going through this. I had to bite my tongue and refrain from giving him tips. The reason - the last person on the planet you want to annoy - the customs people at a border crossing. They can really ruin your day if they want to...

Customs officials have unlimited power in their domain, Kyte knows better than to annoy them in any way. I wonder what they do if they find a picture of the 3 yo standing in the tub. Probably seize the laptop at the least.

I suspect they're following some idiotic mandate arising from some incompetent legislative action from the past (GOP) congress. It will take a long time to undo the mountain of stupidity congress belched up between 2000 and 2006.

Cats, Canaries and Homeland security

Legend has it miners of old brought canaries with them. If the canary died the air was tainted. Homeland security must be having a lot of late nights now ... (emphases mine)

Rat Poison Found in Tainted Pet Food | World Latest | Guardian Unlimited

... The substance in the food was identified as aminopterin, a cancer drug that once was used to induce abortions in the United States and is still used to kill rats in some other countries, state Agriculture Commissioner Patrick Hooker said.

The federal government prohibits using aminopterin for killing rodents in the U.S. State officials would not speculate on how the poison got into the pet food, but said no criminal investigations had been launched...

... The Food and Drug Administration has said the investigation into the pet deaths was focused on wheat gluten in the food. The gluten itself would not cause kidney failure, but it could have been contaminated, the FDA said.

Paul Henderson, chief executive of Menu Foods, confirmed Friday that the wheat gluten was purchased from China.

Bob Rosenberg, senior vice president of government affairs for the National Pest Management Association, said it would be unusual for the wheat to be tainted.

``It would make no sense to spray a crop itself with rodenticide,'' Rosenberg said, adding that grain shippers typically put bait stations around the perimeter of their storage facilities.

Scientists at the New York State Animal Health Diagnostic Center at Cornell University and at the New York State Food Laboratory tested three cat food samples provided by the manufacturer and found aminopterin in two of them. The two labs are part of a network created after the Sept. 11 terrorist attacks to keep the nation's animals and food supply safe.

``Any amount of this product is too much in food,'' Hooker said.

Aminopterin is highly toxic in high doses. It inhibits the growth of malignant cells and suppresses the immune system. In dogs and cats, the amount of aminopterin found - 40 parts per million - can cause kidney failure, according to Bruce Akey, director of Cornell's diagnostic center.

``It's there in substantial amounts,'' Akey said.

Donald Smith, dean of Cornell's veterinary school, said he expected the number of pet deaths to increase. ``Based on what we've heard the last couple days, 16 is a low number,'' Smith said.

Aminopterin is no longer marketed as a cancer drug, but is still used in research, said Andre Rosowsky, a chemist with the Dana Farber Cancer Institute in Boston.

Rosowsky speculated that the substance would not show up in pet food ``unless somebody put it there.''

Henderson said Menu Foods does not believe the food was tampered with because the recalled food came from two different plants, one in Kansas, one in New Jersey. Menu continues to produce food at the two plants.

I'm reading varying reports of how much of Menu Food's gluten is imported from China. Reports range from "some" to "all". Aminopterin is used in China, but not in North America. Another report says that Menu Foods has been looking for a toxin since February, but reference labs couldn't find anything. Even the U of Minnesota vet lab has been consulted, though I don't know when.

When Menu Foods says the "the food" was not tampered with, they mean the poison was introduced by a common ingredient supplier before it reached them.

If this was an industrial accident, then those cats and dogs in dying may yet save thousands and millions of lives by awakening our dysfunctional government. Now that the GOP no longer rules Congress, there's yet a chance the legislature will enact long delayed reforms. If this was a deliberate poisoning ...

Poisoned pets: Chinese gluten, rat poison and lessons for trade and regulation

[The original post was accidentally deleted during a blogging tool test. This is a repost]



The latest hypothesis is that a rat poison got into Chinese gluten:

Menu Foods president says as a pet owner he's angry over poisoned food

... New York state officials had found a toxic chemical used to kill rats and treat cancer in recalled dog and cat food produced by the company.

Traces of aminopterin were found in tests of food suspected of causing kidney failure in cats and dogs, the officials said...

...The U.S. Food and Drug Administration has said the investigation into the pet deaths focused on wheat gluten imported from China. Wheat gluten itself would not cause kidney failure, but a common ingredient could have been contaminated, the FDA said.

These search results are interesting: China aminopterin.



It could be intentional (a form of industrial sabotage, a disgruntled worker, etc) or accidental. Either way, it reminds me of lead contamination in Chinese manufactured holiday lights, and the use of living animal fur in "fake fur" products. It also reminds me of the 1989 contaminated L-tryptophan induced eosinophila-myalgia syndrome "epidemic", thought to have been due to contamination with an industrial product during manufacture of a dietary supplement/alternative medicine.



The common thread in all these cases, and possibly in this one, are the risks of going outside the regulatory and judicial frameworks we are accustomed to. Another theme, of course, is the risk of industrial food -- and what could be more industrial than importing massive amounts of gluten from China? Wouldn't you like to know how the gluten is transported?



In the meantime I haven't been able to switch our mongrel completely off commercial dog food (Eukanaba gluten-free dry - Kateva has canine gluten enteropahthy). Our vet, for example, was quite unenthusiastic. It seems the standards for canine nutrition are hard to meet at the grocery store.



Assuming this is traced to poisoned Chinese gluten, what lessons can we draw? I think it starts with restoring the regulatory framework that, I am reasonably certain, Cheney et al have trashed. We need to take a very hard look at industrialized food for pets and humans alike. Our family now eats "organic" meats and largely "organic" produce, we need to do the same for our dog.



Outside of food, economists need to recognize that "regulatory compliance" and "judicial accountability" is not only a protectionist anti-globalization tactic, it's a legitimate social and public health concern.



Update 3/24/07: Rat Poison Found in Pet Food Linked to 14 Deaths: NY authorities don't know if the aminopterin is really in the gluten, and only some of the gluten was imported from China. They are now explicity saying they haven't ruled out "sabotage". The CDC has been notified. Nobody is talking yet about the all-nighters at the Department of Homeland Security ... (note: I'm just guessing about the Homeland Security part. If I were running it there would be some late nights now.)

Surprise: AAC to CD to AAC produces awful results

I've never done much with Apple's iTunes store, but recently I realized the time had come to stop entirely. What should I do, however, with the 20 or so DRMd tunes that the children or I had collected over the years?



I figured I'd just burn them to a CD and then recode them as AAC. iTunes even creates a "Text CD", which passes the critical metadata to the CD. It took a few minutes, but I did all twenty. Then, as I was cleaning up, I decided to compare the orginal AAC (128 bit) to recycled new AAC (160 bit VBR).



The copy was bloody awful. It was the difference between a CD (or at least a good tape) and AM radio. I don't have any musical talent or abilities whatsoever -- this was not subtle. I knew there'd be some loss of quality, but I didn't expect it to be this bad. I deleted the bunch.



So now I have to choose between buying the CD for the music I own, or looking for pirated copies of key tunes that I've paid for. Hmmm.



One thing is for sure. I have to tell the relatives not to send any more iTunes gift certificates!

Evil

Egregious Moderation: Sahar: The Number

A friend of mine called me to tell me the bad news. Her brother had been kidnapped, and the ransom set at $100,000...

Another terrible story.

Gopher lives

I was at some family medicine computer playground, back when email was still slightly novel and we were teaching our colleagues to use Grateful Med* to retrieve articles. (PubMed still isn't as good.) I think it was around 1991 or 1992, maybe in San Francisco. Paul Kleeberg, an old friend even then, showed me something called "Gopher" from his home state of Minnesota. We browsed the meeting minutes of some Australian city council meeting.

I was stunned. I felt the tidal wave of history crashing down. It made me think differently about the University of Minnesota. Gopher probably has something to do with why I did a health informatics fellowship at the U in 1994 -- though by then Mosaic (on NeXTstep boxes) was on the rise. I'm still in Minnesota, and I even teach at the U a bit. All thanks, in part, to Gopher.

I thought Gopher was completely gone, though a few years back I was giving away a PowerBook 165 and I fired up the Gopher client. I found a few old sites. I figured it would be a great way for hackers and bad guys to communicate -- who would ever know? Gopher, after all, was dead.

Only it wasn't quite ...

TidBITS: Down the Gopher Hole

... Back in 1991, Gopher sprang out of a University of Minnesota campus information service project aimed at building a 'friendly' method of accessing university documents and services. (The University of Minnesota's sports teams are the Golden Gophers.) In those days, most campuses and corporations maintained their own walled-garden services and access policies, and almost all of them operated in unique and sometimes wildly different manners.

In contrast, Gopher provided a unified, consistent hierarchical interface to access everything. The approach translated well to both text and graphical interfaces, and better still, it offered an easy way to connect a varied set of hosts using simple links. This beat the stuffing out of getting files via FTP, which usually required using a command line. Gopher's method was a large improvement over interacting with library and campus directory systems via Telnet and trying to remember how to compose searches from system to system. Thanks to Gopher, the public resources other servers offered weren't merely accessible - they were usable...

The article mentions GopherVR (remember any VR? I barely remember that one), but not HyperGopher (German I think). Turns out the protocol is kept alive by some contrarian hobbyists, including the author -- a country doctor and part-time hacker. It's a great read for geezer netizens.

* Damn, Grateful Med deserves a Wikipedia entry. I may have to author it if nobody else does!

Kashmir - tourists again

When I was a callow youth (vs. a callow gomer), I wandered not far from Kashmir. I thought in a few years I'd visit the famed lakes, and sleep on a house boat.



Then tourists began losing heads, and that was the end of sane tourism in Kashmir. Now, it's back, though these tourists are quite mad. Maybe I'll get there before I konk...

Spam with real addresses: another revolting development

Blacklists usually have limited value because spammers use bots, fake domains, etc. Lately, however, much of my spam has been coming from real companies and organizations with persistent email addresses. The good news is this spam is trivially easy to blacklist.



On the one tentatcle the legitimization of spam feels like another bit of bad news for our ailing email, but on the other tentacle ever since I figured out how I was making Gmail hate me I've been pleased with its spam filtering. Email is still alive, for now ...

The robotic ape: Morality and the ventromedial prefrontal cortex

Persons with damage to the ventromedial prefrontal cortext behave more like Mills and less like Kant (emphases mine):

Study Finds Brain Injury Changes Moral Judgment - New York Times

... findings, published online by the journal Nature, confirm the central role of the damaged region — the ventromedial prefrontal cortex, which is thought to generate social emotions, like compassion.

Previous studies showed that this region was active during moral decision-making, and that damage to it and neighboring areas from severe dementia affected moral judgments. The new study seals the case by demonstrating that a very specific kind of emotion-based judgment is altered when the region is offline. In extreme circumstances, people with the injury will even endorse suffocating an infant if that would save more lives.

“I think it’s very convincing now that there are at least two systems working when we make moral judgments,” said Joshua Greene, a psychologist at Harvard who was not involved in the study. “There’s an emotional system that depends on this specific part of the brain, and another system that performs more utilitarian cost-benefit analyses which in these people is clearly intact.”...

...The new study focused on six patients who had suffered very specific damage to the ventromedial area from an aneurysm or a tumor. ...The area in adults is about the size of a child’s fist.

People with this injury can be lucid, easygoing, talkative and intelligent, but blind to subtle social cues, making them socially awkward. They also have some of the same moral instincts that others do.

... All three groups also strongly rejected doing harm to others in situations that were not a matter of trading one certain death for another. They would not send a daughter to work in the pornography industry to fend off crushing poverty, or kill an infant they felt they could not care for.

But a large difference in the participants’ decisions emerged when there was no switch to flip — when they had to choose between taking direct action to kill or harm someone (pushing him in front of the runaway boxcar, for example) and serving a greater good.

Those with ventromedial injuries were about twice as likely as the other participants to say they would push someone in front of the train (if that was the only option), or to poison someone with AIDS who was bent on infecting others, or suffocate a baby whose crying would reveal to enemy soldiers where the subject and family and friends were hiding...

...The ventromedial area is a primitive part of the cortex that appears to have evolved to help humans and other mammals navigate social interactions. The area has connections to deeper, unconscious regions like the brain stem, which transmit physical sensations of attraction or discomfort; and the amygdala, a gumdrop of neural tissue that registers threats, social and otherwise. The ventromedial area integrates these signals with others from the cortex, including emotional memories, to help generate familiar social reactions.

... This tension between cost-benefit calculations and instinctive emotion in part reflects the brain’s continuing adjustment to the vast social changes that have occurred since the ventromedial area first took shape. The ventromedial area most likely adapted to assist the brain in making snap moral decisions in small kin groups— to spare a valuable group member’s life after a fight, for instance. As human communities became larger and increasingly complex, so did the cortical structures involved in parsing ethical dilemmas. But the more primitive ventromedial area continued to anchor it with emotional insistence an ancient principle: respect for the life of another human being.

It's hard not to wonder what a similar study would find find on adult genetic relatives of children with autism. The study is too small to be persuasive on its own, but it's just another in a flurry of recent research that hammers home the reality that we are our brains, and that we have more in common with science fiction robots than we once fancied. Pull out our emotion chip and we switch to a relatively "cold-blooded" judgment system. Disable that, and you probably get a sociopath. I would wager that a successful sniper has a relatively inactive VPC.

Eventually we'll discard the illogical concept of 'individual responsibility'. I wonder if I'll live long enough to see what will replace it ...

Science and faith in the senate

Emphases mine.

BBC NEWS | Americas | Al Gore makes global warming plea:

...Representative Joe Barton, the leading Republican on the House Energy and Commerce Committee, challenged global warming science as "uneven and evolving".

"You're not just off a little, you're totally wrong," he said of Mr Gore's conclusions that carbon dioxide emissions contribute to global warming....

My understanding is that there's probably a 1/15-1/20 chance that we'll eventually discover that carbon dioxide emissions have been a relatively small contributor to global climate change to date. Even if the 20:1 odds paid off, Mr. Barton, of course, would still be operating on faith, not reason. There is nothing in the data to support his confidence, ergo it must arise from some sort of faith.

Had history played out a little differently, he would be chairman of the House Energy and Commerce Committee. Chairman. The thought chills the soul.

How can any reasoning person vote for the modern GOP? The party needs to be rebuilt from top to bottom.