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Corante Blogs examine, through the eyes of leading observers, analysts, thinkers, and doers, critical themes and memes in technology, business, law, science, and culture.

The Press Will Be Outsourced Before Stopped

Vin Crosbie, on the challenges, financial and otherwise, that newspaper publishers are facing: "The real problem, Mr. Newspaperman, isn't that your content isn't online or isn't online with multimedia. It's your content. Specifically, it's what you report, which stories you publish, and how you publish them to people, who, by the way, have very different individual interests. The problem is the content you're giving them, stupid; not the platform its on."
by Vin Crosbie in Rebuilding Media

Travels In Numerica Deserta

There's a problem in the drug industry that people have recognized for some years, but we're not that much closer to dealing with it than we were then. We keep coming up with these technologies and techniques which seem as if they might be able to help us with some of our nastiest problems - I'm talking about genomics in all its guises, and metabolic profiling, and naturally the various high-throughput screening platforms, and others. But whether these are helping or not (and opinions sure do vary), one thing that they all have in common is that they generate enormous heaps of data.
by Derek Lowe in In the Pipeline

Disrobing the Emperor: The online “user experience” isn't much of one

Now that the Web labor market is saturated and Web design a static profession, it's not surprising that 'user experience' designers and researchers who've spent their careers online are looking for new worlds to conquer. Some are returning to the “old media” as directors and producers. More are now doing offline consulting (service experience design, social policy design, exhibition design, and so on) under the 'user experience' aegis. They argue that the lessons they've learned on the Web can be applied to phenomena in the physical and social worlds. But there are enormous differences...
by Bob Jacobson in Total Experience

Second Life: What are the real numbers?

Clay Shirky, in deconstructing Second Life hype: "Second Life is heading towards two million users. Except it isn’t, really... I suspect Second Life is largely a 'Try Me' virus, where reports of a strange and wonderful new thing draw the masses to log in and try it, but whose ability to retain anything but a fraction of those users is limited. The pattern of a Try Me virus is a rapid spread of first time users, most of whom drop out quickly, with most of the dropouts becoming immune to later use."
by Clay Shirky in Many-to-Many

The democratisation of everything

Over the last few years we've seen old barriers to creativity coming down, one after the other. New technologies and services makes it trivial to publish text, whether by blog or by print-on-demand. Digital photography has democratised a previously expensive hobby. And we're seeing the barriers to movie-making crumble, with affordable high-quality cameras and video hosting provided by YouTube or Google Video and their ilk... Music making has long been easy for anyone to engage in, but technology has made high-quality recording possible without specialised equipment, and the internet has revolutionised distribution, drastically disintermediating the music industry... What's left? Software maybe? Or maybe not."
by Suw Charman in Strange Attractor

RNA Interference: Film at Eleven

Derek Lowe on the news that the Nobel Prize for medicine has gone to Craig Mello and Andrew Fire for their breakthrough work: "RNA interference is probably going to have a long climb before it starts curing many diseases, because many of those problems are even tougher than usual in its case. That doesn't take away from the discovery, though, any more than the complications of off-target effects take away from it when you talk about RNAi's research uses in cell culture. The fact that RNA interference is trickier than it first looked, in vivo or in vitro, is only to be expected. What breakthrough isn't?"
by Derek Lowe in In the Pipeline

PVP and the Honorable Enemy

Andrew Phelps: "Recently my WoW guild has been having a bit of a debate on the merits of Player-vs.-Player (PvP) within Azeroth. My personal opinion on this is that PvP has its merits, and can be incredible fun, but the system within WoW is horridly, horribly broken. It takes into account the concept of the battle, but battle without consequence, without emotive context, and most importantly, without honor..."

From later in the piece: "When I talk about this with people (thus far anyway) I typically get one of two responses, either 'yeah, right on!' or 'hey, it’s war, and war isn’t honorable – grow the hell up'. There is a lot to be said for that argument – but the problem is that war in the real historical world has very different constraints that are utterly absent from fantasized worlds..."
by Andrew Phelps in Got Game

Rats Rule, Right?

Derek Lowe: "So, you're developing a drug candidate. You've settled on what looks like a good compound - it has the activity you want in your mouse model of the disease, it's not too hard to make, and it's not toxic. Everything looks fine. Except. . .one slight problem. Although the compound has good blood levels in the mouse and in the dog, in rats it's terrible. For some reason, it just doesn't get up there. Probably some foul metabolic pathway peculiar to rats (whose innards are adapted, after all, for dealing with every kind of garbage that comes along). So, is this a problem?.."
by Derek Lowe in In the Pipeline

Really BAD customer experience at Albertsons Market

Bob Jacobson, on shopping at his local Albertsons supermarket where he had "one of the worst customer experiences" of his life: "Say what you will about the Safeway chain or the Birkenstock billionaires who charge through the roof for Whole Foods' organic fare, they know how to create shopping environments that create a more pleasurable experience, at its best (as at Whole Foods) quite enjoyable. Even the warehouses like Costco and its smaller counterpart, Smart & Final, do just fine: they have no pretentions, but neither do they dump virtual garbage on the consumer merely to create another trivial revenue stream, all for the sake of promotions in the marketing department..."
by Strange Attractor in Total Experience

The Guardian's "Comment is Free"

Kevin Anderson: "First off, I want to say that I really admire the ambition of the Guardian Unlimited’s Comment is Free. It is one of the boldest statements made by any media company that participation needs to be central to a radical revamp of traditional content strategies... It is, therfore, not hugely surprising to find that Comment is Free is having a few teething troubles..."
by Kevin Anderson in strange
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

The Loom

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November 28, 2005

The Mosquito and the Bottle

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Posted by Carl Zimmer

Natural selection is not natural perfection. Time and again, biologists have discovered traits that are both beneficial and harmful. Perhaps the most famous example is the devastating disorder known as sickle-cell anemia. To get sickle-cell anemia, you have to inherit two faulty copies of a gene that helps build hemoglobin, the molecule that traps oxygen in red blood cells. In this condition, hemoglobin can't hold its shape if it's not clamped around oxygen. Without it, the defective hemoglobin collapses into needle-shaped clumps, which then turn the cell itself into a sickle shape. The sickle cells snag in small capillaries, and the blood can no longer supply as much oxygen to the body. People who inherit only one copy of this defective gene can get by on the hemoglobin made by the remaining normal copy. But people who get two copies of the bad gene make nothing but defective hemoglobin, and they're usually dead by the time they're thirty. A person who dies of sickle cell anemia is less likely to pass on the defective gene, and that means that the disease should be exceedingly rare. But it's not--one in 400 American blacks has sickle cell anemia, and one in ten carries a single copy of the defective gene.

In the 1940s, scientists discovered what keeps sickle-cell anemia so common: the defective gene provides protection from malaria. Carrying a single copy of the gene reduces a person's chance of getting severe malaria by a factor of ten. Malaria is caused by a single-celled parasite called Plasmoidum carried by mosquitoes. Normally it feeds on hemoglobin, but a red blood cell deformed by the sickle-cell gene somehow becomes a miserable home for the parasite. The needle-shaped clumps of hemoglobin may be able to spear the parasites, or the deformed cells may not be able to pump in potassium, an element essential to Plasmodium. It's also possible that it is easier for the immune system to recognize infected blood cells when they are deformed by sickle cell anemia.

Malaria wreaks colossal damage in many parts of the world. Today it kills over a million people a year, mostly children, and it has been plaguing our species for thousands of years. Carrying a single copy of the sickle-cell gene boosts the odds that people can have children in malaria-prone regions. Unfortunately, when two people who carry the gene have children together, there's a one-in-four chance that each child will get both copies of the gene. Over many generations, the advantage of having one copy of the gene outweighs the disadvantage of having two—at least in populations that have endured centuries of malaria.

In the decades since the discovery of the sickle-cell trade-off, scientists have discovered that several other defenses to malaria have evolved where the disease is a high risk—in Africa, the Mediterranean, Southeast Asia, and New Guinea. And many of these adaptations come with drawbacks of their own. Now a new study offers evidence of yet another mixed blessing: one defense against malaria may make people prone to alcoholism.

The discovery of this defense sprang up in an unexpected place: on the tongue. In recent years scientists have deciphering the molecular biology of how we taste. They have pinpointed several of the genes that produce receptors on taste bud cells. They've also reconstructed the structure of the receptors, and have even discovered some of the molecules that locked onto them. And scientists have also been reconstructing the evolution of those taste receptors. It turns out that they're the product of a complicated history. Taste receptor genes can get accidentally duplicated, and mutations to the new copies can cause them to grab different molecules. This growing diversity of receptors can let animals perceive a growing diversity of tastes—in some cases tastes of dangerous toxins in foods.

Compared to other primates, humans and chimpanzees have a relatively bad sense of taste—perhaps because we eat meat and fruits, as opposed to leaves and other plant material that's loaded with dangerous foods. But scientists have identified a couple taste receptors that have experienced a significant amount of natural selection in the human lineage. This summer a team of scientists reported the discovery of one of these highly evolved genes, known as TAS2R16. The evidence indicates that the receptor causes a feeling of bitterness in response to compounds called beta-glucopyranosides, which plants and insects produce to protect themselves against predators. If these compounds get into a person's intestines, they produce cyanide as they are broken down. Avoiding beta-glucopyranosides thanks to a bitter taste may keep people healthy, and thus be favored by natural selection. The researchers found that an ancestral version of the receptor was replaced by newer versions on many occasions, beginning over 80,000 years ago. The newer versions produce a nastier taste to the beta-glucopyranosides.

But the researchers discovered a peculiar exception to this rule. Some populations in Africa had unusually high levels of the ancestral version of the gene. These populations also turn out to be at very high risk of malaria.

Why would malaria favor a weaker sense of bitterness? One possibility is that beta-glucopyranosides can fight the parasite that causes the disease. Cyanide isn't just bad for people, but for Plasmodium as well. It can even trigger a sickle-cell-like condition in red blood cells. When malaria poses a major risk, the danger of eating poisons may be offset by their protection against the disease.

TAS2R16's intriguing history prompted scientists to look for other conditions with which it might be associated. Previous research had found a genetic disposition towards alcoholism, although the scientists could only link the diseases to a large chunk of chromosome seven. In a new study in press at the American Journal of Human Genetics, researchers now report that this region contains TAS2R16. The scientists zeroed in on the taste receptor gene, comparing the versions carried by alcoholics and their relatives (2310 people were studied all told).

The researchers discovered that people who carried the low-bitterness version of the gene were at a significantly increased risk of alcoholism. They also found that this gene was rare in European-Americans in their study, but 45% of the African-Americans carried it. Based on these results, the scientists suggest that a weak sense of bitterness not only provided protection against malaria, but also changes the taste of alcohol. Other versions of TAS2R16 may give alcoholic drinks a nasty taste. When these drinks don't taste as bad, it may be easier for people to develop alcoholism. This study by no means slight the complexity of alcoholism--genes probably only account for half of the variation in people's risk, and those genes probably all have their own complex evolutionary history. But it's further evidence of the many evolutionary trade-offs that have shaped our genomes, and our lives.

Comments (5) + TrackBacks (0) | Category: Evolution


1. djlactin on November 28, 2005 09:40 AM writes...

clearly, none of this qualifies as "intelligent" design!

if it were the deity, i'd...

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2. Bzimmer on November 28, 2005 11:47 AM writes...

A couple of quibbles: any genetic defect only prevents its own propagation if it kills before the host reaches sexual maturity. Since sickle cell patients would live into late teens or early twenties, even under primitive conditions, there is nothing to prevent a homozygote (both bad genes) from passing them along. The alternative is to die in infancy from cerebral malaria.

The mechanism of sickling is related to oxygen content of the red blood cell. Oxygenated hemoglobin S has a normal configuration; unoxygenated S deforms. In the normal course of events, when an unoxygenated sickled cell passes through the spleen, that organ performs its assigned physiologic function (snarf up damaged red blood cells) and removes them from the circulation. Incidentally, it takes the parasite with it and destroys it along with the cell. That's how sickle cell protects the host from malaria.

By the way, with modern treatment, a homozygote sickle cell patient can expect to live a normal life span.

Keep the good stuff coming!

Barry Zimmerman

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3. David Harmon on November 28, 2005 12:10 PM writes...

Don't forget that Asian allele which knocks out ethanol metabolism altogether! ("Victims" don't get drunk at all, they just flush and feel sick.)

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4. luca on December 1, 2005 03:18 AM writes...

Great read.

I hope youn won't mind me using your incipit "Natural selection is not natural perfection" in my PhD thesis. It was just what i was looking for to express the concept of less-than-optimal solutions to a problem (I work with Genetic Algorithms)

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5. Anonymous on February 1, 2006 11:13 AM writes...

Yes.. I agree ..8

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