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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

« Consciousness and the culture wars, part 2 | Main | Multi-Dimensional Mangling »

October 26, 2003

Stalking the Perfect Tree

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Posted by Carl Zimmer

When Charles Darwin was thrashing out his theory of evolution, he would doodle sometimes in his notebooks. To explain how new species came into existence, he wrote down letters on a page and then connected them with branches. In the process, he created a simple tree. Across the top of the page, he wrote, "I think."

That single tree has given rise to the thousands of trees that are published in scientific journals these days. A particular tree may show that humans are more closely related to chimpanzees than gorillas. It might show how the SARS virus in humans descends from viruses in other animals.

When you look at the picture of a tree in a scientific paper, it is easy to take it as an illustration of an unadorned fact. That is not, however, how science works. A tree represent a hypothesis that offers the best explanation of the data at hand. It shows the most likely pattern by which new species might have branched off one another, taking on new traits along the way, and giving rise to the range of species a scientist is studying.

These hypotheses are not simple to come by. Large-scale studies of phylogeny only became possible when computers began turning up the desks of biologists. You need that computing power because even in a simple comparison of a dozen species, there are so many alternative trees to test. Say you have 3 species, A, B, and C. A and B might be more closely related, or maybe A and C, or B and C. Three choices. But as you add more species, the possibilities explode to millions and more. Sifting through those possibilities takes both gigaflops and smart statistics.

From life's long reign, we have relatively few pieces of information to figure out the shape of its tree. The first evolutionary biologists to draw trees could only compare features that they could see through a microscope or on a fossilized skeleton. These days, most trees are based on genes. Once scientists could sequence genes, they tapped into a far richer lode of information than previous generations could reach. What's more, genes offer a much crisper picture of the evolutionary process than, say, a horn or a petal. After all, mutations to genes lead to inherited changes in how the body develops. Whereas the change to the body may be hard to tease out, the mutation may be as simple as snipping out a few nucelotides in a gene sequence.

But gene trees are not unadorned facts, either. Some genes have evolved relatively quickly, so that if you compare them in different species that took millions and millions of years to diverge, it may offer a distorted picture of how they are related. On the other hand, a gene that evolves too slowly may not be able to distinguish the fine details of a recent explosion (like the cichlids of Africa that I wrote about recently). In bacteria and other single-celled organisms, the picture gets even more fuzzy when you consider the fact that they can trade genes with one another, rather than just inheriting them from ancestors. In some regions, the tree of life is more like a mangrove, with branches grafting together rather than splitting apart.

One convenient thing about building evolutionary trees is that you can get an idea of how much confidence you can have in it. One way is to pick out a random subset of your data to base a new tree on. In some cases, the switch may produce a tree with a different shape. Perhaps just one section of it changes. Or perhaps the tree barely changes at all. By repeatedly testing the evidence in different combinations, it's possible to estimate how likely each branch point is authentic.

Gene trees have shed a lot of light on the history of life. Just to pick one case among many, several different studies have strongly supported the notion that hippos are the closest relatives to whales on land. But these studies are like telescopes for looking back in evolutionary time, and they are only as precise as their design allows. Studying one gene in all animals may give you a different picture of animal evolution than studying a different one. It's not as if one gene will point to snapdragons as the closest relative of fish, or link mushrooms and monkeys. But it can get hard to determine whether comb jellies are more closely related to jellyfish or to crustaceans, vertebrates, and other more complex animals. This is may sound esoteric, but it's not really. If comb jellies are closer to us, scientists could find some important clues in them about our own evolution. If they're out on a more distant branch, they aren't so important to our own evolutionary story.

In recent years, some scientists have argued that the best way to bring the evolutionary telescope into tighter focus is to study a bunch of genes at once. Fortunately, in this age of genomics, we're swimming in genes. Scientists have just started running studies in which they compare dozens of genes in various species. The results have been promising. But until now, no one had looked systematically at how much help multiple genes could offer to unsolved mysteries in phylogeny.

All of this is a very long preamble to a fascinating study in Nature this week from Sean Carroll at the University of Wisconsin and some of his current and former students. They looked at seven species of yeast, all of whose genomes have been fully sequenced in recent years. They picked out 106 genes in all seven species, choosing them because they clearly show signs of being variations of each other, descended from a common ancestral gene that duplicated many times Then they used each gene to come up with a tree showing how the yeast are related. Many of the genes produced different trees. Not surprising. What was surprising was what happened when they analyzed all 106 genes together. Suddenly, a single tree emerged as the most likely. And no matter how they tested the tree, they found 100% confidence at every node. As the authors note, this certainty is unprecedented, and they argue that they have established the evolutionary history of these seven species.

It seems that the annoying disagreements from individual genes fade away when a computer can crunch down on a lot of them. Carroll and his co-authors realized that they may have been indulging in overkill by using 106 genes, and so they narrowed down their data set to see how few genes they needed to get the same sort of overpowering results. They could get down to just 20 genes and still produce the same tree.

Carroll et al haven't found the guaranteed method to figure out every evolutionary tree. Each group of species will have its own peculiarities to take into account. But their astonishing results offer a very sunny forecast for phylogenies in the next few years. The days of "I think" may be over.

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