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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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July 05, 2005

Return of Mad Cow Memories

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Posted by Carl Zimmer

How long can an idea stay tantalizing?

Back in 2003, I blogged about an experiment that suggested, incredibly enough, that our long-term memories are encoded by prions— the misfolded proteins that are generally accepted to be the cause of mad cow disease. The evidence came from studies of a protein (known as CPEB) that plays a key role in laying down memories in neurons. Scientists found that it had a structure much like prions. When a normal protein misfolds and becomes a prion, it acquires the ability to lock onto other proteins and force them to misfold in the same way. The misfolding can spread until it has devastating results—as in the case of mad cow disease, in which prions from cow brains get into our own brains. But the discovery of prion-like memory proteins hinted that maybe they could play a beneficial role as well.

Not long after I blogged on this research, I ran into a neuroscientist I know (and who shall remain nameless). He sneered at the prion paper, pointing out that the authors of the paper didn't show that the protein acts like a prion in neurons. Instead, they had only shown that it acts like a prion when it is inserted into yeast. They took this peculiar step because yeast have prions, and they had the tools to study prion behavior in yeast. It is far harder to experiment with prions in neurons. But this neuroscientist I spoke to thought they shouldn't have gone public until they had taken this last, hard step.

I've been waiting ever since. And in the June issue of Nature Review Genetics I came across a paper entitled "Prions as adaptive conduits of memory and inheritance." One of the co-authors is Susan Lindquist of MIT, one of the scientists who made the memory-prion connection back in 2003. Eager for an update, I read on. And what do I find? There's a lot of new research on the role of prions in yeast, where they may play an important role in evolution. But as for prions and memory, there's nothing beyond what Lindquist had to offer in 2003.

My patience has probably been irreparably damaged by today's minute-by-minute news cycle, but I have to wonder why we're still in prion-memory limbo. Is the next experiment too hard to do? Does it take years to finish? Or is the link between memories and prions just not there?

Just as I'm tempted to give up hope, out comes another paper. It may not seal the deal, but at least keeps me eager for more. Psychiatrists in Switzerland were inspired by the original prion-memory experiments to look for evidence in people's genes. Some studies have suggested that the strength of people's memories is at least partly the result of genetic variation. But no one knew which genes were involved. So the psychiatrists took a look at the prion protein gene (PRNP), which causes mad-cow disease when it misfolds. (No one is sure what it does for us in its normal shape.) People have different versions of PRNP, some of which are more prone to misfolding than others. The scientists genotyped 354 subjects to see which version they carried and then gave them a memory test.

In a paper in press at Human Molecular Genetics, they report that people with one or two copies of the misfolding version recalled 17% more information than those without a copy. It's a puzzling result for many reasons, not the least of which is the fact that the link originally proposed between prions and memory did not involve PRNP but CBEP. But it's enough to keep me wanting more.

Comments (6) + TrackBacks (0) | Category: Brains


COMMENTS

1. mccm on July 5, 2005 11:08 PM writes...

Surely that second study looking for PrP polymorphisms wasn't suggesting that when the protein goes into prion-mode it encodes a memory, which is what Lindquist and Kandel were arguing in 2003 for CPEB. We already know what happens when PrP goes into prion-mode and it is not good for memory. The CPEB story is quite intriguing, but its also interesting to keep in mind that there are plenty of mechanisms for making a protein permanently different outside of the sensational prion mechanism (i.e. post-translational modifications, degradation of regulatory subunits, or even regulation and processing that alters the initial structure of new copies of that protein). I suggest you look up PKMzeta or CaMKII autophosphorylation for examples. I don't want to sound too suspicious, but the lab that put out that initial prion story already has the media's ear in a major way and that may be why they were able to get a less than perfect story out so quickly. BTW, the acronym is misspelled in the last paragraph :).

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2. Ben Hyde on July 5, 2005 11:22 PM writes...

Oh dear, it's the a scifi plot: the memory that makes you go mad.

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3. Henry Astley on July 6, 2005 09:03 AM writes...

Oh dear, it's the a scifi plot: the memory that makes you go mad.

Or an H.P. Lovecraft novel. Can we re-name the gene "Cthulhu"?

-----

What I'm wondering is, if this is true, how would it work? How would sensory input or synaptic plasticity interact with this protien?

And can't we do knockout studies in mice? It won't be conclusive, but it might tell us *something*.

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4. wolff on July 6, 2005 09:39 AM writes...

I am confused about your statement of, "When a normal protein misfolds and becomes a prion...." Are you saying that other proteins can become a prion protein? I thought prion was the term given to the protein itself, not a class of proteins that behave like the prion protein. I was under the impression that there is only one "prion" protein, regardless of its folding. The prion protein (i.e. the protein in BSE) has two forms. The normal form is typically termed PrPC for "cellular." The misfolded form is termed PrPSc for "scrapie."

On a second note, knockout studies on PRNP have already been done. Strangely there is little affect on the mice (it did affect circadian rythms), leading some to conclude that whatever the prion protein does, there must be redundancy in the cell. These studies are under question now because knockout of the PRNP gene caused upregulation of a protein downsteam known as Doppel, which has some structural characteristics of the prion protein. And the saga continues.....

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5. Torbjorn Larsson on July 6, 2005 01:56 PM writes...

"the memory that makes you go mad."

Even worse - it's also the memory that you will keep in the grave.

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6. Ann on July 9, 2005 06:23 PM writes...

Given that it took 20+ years for the prion hypothesis to be accepted in the first place, and given that it was only indisputably demonstrated recently that prions - without nucleic acids - act as infectious agents, I think a more patience is warranted. Two years is the blink of an eye in a molecular biology lab.

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