The End of Europe as We Know It?

gnxp's Razib Khan links to this article about Greek protests and comments:

Wow. Every news story makes me wonder if it’s the end of Europe as we know it.

It may be, but not because of the riots.

Riots are as Greek as olive and feta pie (look at 2008), while France has a proud tradition of civil disobedience. The UK also has a good history of protest, although in recent years we've refrained from violence. So the student protests were a shock, although the level of bloodshed was nowhere near that seen in say Greece: rocks were thrown, but no petrol bombs. The police beat some people, and dragged a guy out of his wheelchair for no apparant reason, but there were no water cannons or teargas.

If anything, the level of disorder in Europe has been remarkably low. Compared to some of the reasons why people rioted in Europe during the 20th century, the current austerity measures are far more serious. If this was happening 20 years ago, we would have seen governments brought down by strikes and disorder by now. That hasn't happened because the European left isn't what it used to be.

Europeans (outside Germany and Scandinavia whose economies are strong as always) are basically being faced with a future structured on centre-right lines, after spending the past 60 years building nice centre-left welfare states. And it's not their fault, it's "the bankers", or at least that's what everyone believes. Europeans are angry and you can see why. But not angry enough to stop it.

So in a sense this is the end: the end of Europe as the land of tax-and-spend (which has never been a dirty phrase over here). At the moment the model is tax-and-don't-spend, which is obviously unpopular. But when the budgets are balanced again, in say 5 years, governments may find it easier to just cut taxes rather than trying to rebuild the welfare and social programs they dismantled.

The End of Europe as We Know It?

gnxp's Razib Khan links to this article about Greek protests and comments:

Wow. Every news story makes me wonder if it’s the end of Europe as we know it.

It may be, but not because of the riots.

Riots are as Greek as olive and feta pie (look at 2008), while France has a proud tradition of civil disobedience. The UK also has a good history of protest, although in recent years we've refrained from violence. So the student protests were a shock, although the level of bloodshed was nowhere near that seen in say Greece: rocks were thrown, but no petrol bombs. The police beat some people, and dragged a guy out of his wheelchair for no apparant reason, but there were no water cannons or teargas.

If anything, the level of disorder in Europe has been remarkably low. Compared to some of the reasons why people rioted in Europe during the 20th century, the current austerity measures are far more serious. If this was happening 20 years ago, we would have seen governments brought down by strikes and disorder by now. That hasn't happened because the European left isn't what it used to be.

Europeans (outside Germany and Scandinavia whose economies are strong as always) are basically being faced with a future structured on centre-right lines, after spending the past 60 years building nice centre-left welfare states. And it's not their fault, it's "the bankers", or at least that's what everyone believes. Europeans are angry and you can see why. But not angry enough to stop it.

So in a sense this is the end: the end of Europe as the land of tax-and-spend (which has never been a dirty phrase over here). At the moment the model is tax-and-don't-spend, which is obviously unpopular. But when the budgets are balanced again, in say 5 years, governments may find it easier to just cut taxes rather than trying to rebuild the welfare and social programs they dismantled.

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XMRV - Innocent on All Counts?

A bombshell has just gone off in the continuing debate over XMRV, the virus that may or may not cause chronic fatigue syndrome. Actually, 4 bombshells.

A set of papers out today in Retrovirology (1,2,3,4) claim that many previous studies claiming to have found the virus haven't actually been detecting XMRV at all.

Here's the rub. XMRV is a retrovirus, a class of bugs that includes HIV. Retroviruses are composed of RNA, but they can insert themselves into the genetic material of host cells as DNA. This is how they reproduce: once their DNA is part of the host cell's chromosomes, that cell is ends up making more copies of the virus.

But there are lots of retroviruses out there, and there used to be yet others that are now extinct. So bits of retroviral DNA are scattered throughout the genome of animals. These are called endogenonous retro-viruses (ERVs).

XMRV is extremely similar to certain ERVs found in the DNA of mice. And mice are the most popular laboratory mammals in the world. So you can see the potential problem: laboratories all over the world are full of mice, but mouse DNA might show up as "XMRV" DNA on PCR tests.

Wary virologists take precautions against this by checking specifically for mouse DNA. But most mouse-contamination tests are targeted at mouse mitochondrial DNA (mtDNA). In theory, a test for mouse mtDNA is all you need, because mtDNA is found in all mouse cells. In theory.

Now the four papers (or are they the Four Horsemen?) argue, in a nutshell, that mouse DNA shows up as "XMRV" on most of the popular tests that have been used in the past, that mouse contamination is very common - even some of the test kits are affected! - and that tests for mouse mtDNA are not good enough to detect the problem.

• Hue et al say that "Taqman PCR primers previously described as XMRV-specific can amplify common murine ERV sequences from mouse suggesting that mouse DNA can contaminate patient samples and confound specific XMRV detection." They go on to show that some human samples previously reported as infected with XMRV, are actually infected with a hybrid of XMRV and a mouse ERV which we know can't infect humans.
• Sato et al report that PCR testing kits from Invitrogen, a leading biotech company, are contaminated with mouse genes including an ERV almost identical to XMRV, and that this shows up as a false positive using commonly used PCR primers "specific to XMRV".
• Oakes et al say that in 112 CFS patients and 36 healthy control, they detected "XMRV" in some samples but all of these samples were likely contaminated with mouse DNA because "all samples that tested positive for XMRV and/or MLV DNA were also positive for the highly abundant IAP long terminal repeat [found only in mice] and most were positive for murine mitochondrial cytochrome oxidase sequences [found only in mice]"
• Robinson et al agree with Oakes et al: they found "XMRV" in some human samples, in this case prostate cancer cells, but they then found that all of the "infected" samples were contaminated with mouse DNA. They recommend that in future, samples should be tested for mouse genes such as the IAP long terminal repeat or cytochrome oxidase, and that researchers should not rely on tests for mouse mtDNA.

They're all open-access so everyone can take a peek. For another overview see this summary published alongside them in Retrovirology.

I lack the technical knowledge to evaluate these claims, no doubt plenty of people will be rushing to do that before long. (Update: The excellent virologyblog has a more technical discussion of these studies.) But there are a couple of things to bear in mind.

Firstly, these papers cast doubt on tests using PCR to detect XMRV DNA. However, they don't have anything to say about studies which have looked for antibodies against XMRV in human blood, at least not directly. There haven't been many of these, but the paper which started the whole story, Lombardi et al (2009), did look for, and found, anti-XMRV immunity, and also used various other methods to support the idea that XMRV is present in humans. So this isn't an "instant knock-out" of the XMRV theory, although it's certainly a serious blow.

Secondly, if the 'mouse theory' is true, it has serious implications for the idea that XMRV causes chronic fatigue syndrome and also for the older idea that it's linked to prostate cancer. But it still leaves a mystery: why were the samples from CFS or prostate cancer patients more likely to be contaminated with mouse DNA than the samples from healthy controls?

Robert A Smith (2010). Contamination of clinical specimens with MLV-encoding nucleic acids: implications for XMRV and other candidate human retroviruses Retrovirology : 10.1186/1742-4690-7-112

XMRV - Innocent on All Counts?

A bombshell has just gone off in the continuing debate over XMRV, the virus that may or may not cause chronic fatigue syndrome. Actually, 4 bombshells.

A set of papers out today in Retrovirology (1,2,3,4) claim that many previous studies claiming to have found the virus haven't actually been detecting XMRV at all.

Here's the rub. XMRV is a retrovirus, a class of bugs that includes HIV. Retroviruses are composed of RNA, but they can insert themselves into the genetic material of host cells as DNA. This is how they reproduce: once their DNA is part of the host cell's chromosomes, that cell is ends up making more copies of the virus.

But there are lots of retroviruses out there, and there used to be yet others that are now extinct. So bits of retroviral DNA are scattered throughout the genome of animals. These are called endogenonous retro-viruses (ERVs).

XMRV is extremely similar to certain ERVs found in the DNA of mice. And mice are the most popular laboratory mammals in the world. So you can see the potential problem: laboratories all over the world are full of mice, but mouse DNA might show up as "XMRV" DNA on PCR tests.

Wary virologists take precautions against this by checking specifically for mouse DNA. But most mouse-contamination tests are targeted at mouse mitochondrial DNA (mtDNA). In theory, a test for mouse mtDNA is all you need, because mtDNA is found in all mouse cells. In theory.

Now the four papers (or are they the Four Horsemen?) argue, in a nutshell, that mouse DNA shows up as "XMRV" on most of the popular tests that have been used in the past, that mouse contamination is very common - even some of the test kits are affected! - and that tests for mouse mtDNA are not good enough to detect the problem.

• Hue et al say that "Taqman PCR primers previously described as XMRV-specific can amplify common murine ERV sequences from mouse suggesting that mouse DNA can contaminate patient samples and confound specific XMRV detection." They go on to show that some human samples previously reported as infected with XMRV, are actually infected with a hybrid of XMRV and a mouse ERV which we know can't infect humans.
• Sato et al report that PCR testing kits from Invitrogen, a leading biotech company, are contaminated with mouse genes including an ERV almost identical to XMRV, and that this shows up as a false positive using commonly used PCR primers "specific to XMRV".
• Oakes et al say that in 112 CFS patients and 36 healthy control, they detected "XMRV" in some samples but all of these samples were likely contaminated with mouse DNA because "all samples that tested positive for XMRV and/or MLV DNA were also positive for the highly abundant IAP long terminal repeat [found only in mice] and most were positive for murine mitochondrial cytochrome oxidase sequences [found only in mice]"
• Robinson et al agree with Oakes et al: they found "XMRV" in some human samples, in this case prostate cancer cells, but they then found that all of the "infected" samples were contaminated with mouse DNA. They recommend that in future, samples should be tested for mouse genes such as the IAP long terminal repeat or cytochrome oxidase, and that researchers should not rely on tests for mouse mtDNA.

They're all open-access so everyone can take a peek. For another overview see this summary published alongside them in Retrovirology.

I lack the technical knowledge to evaluate these claims, no doubt plenty of people will be rushing to do that before long. (Update: The excellent virologyblog has a more technical discussion of these studies.) But there are a couple of things to bear in mind.

Firstly, these papers cast doubt on tests using PCR to detect XMRV DNA. However, they don't have anything to say about studies which have looked for antibodies against XMRV in human blood, at least not directly. There haven't been many of these, but the paper which started the whole story, Lombardi et al (2009), did look for, and found, anti-XMRV immunity, and also used various other methods to support the idea that XMRV is present in humans. So this isn't an "instant knock-out" of the XMRV theory, although it's certainly a serious blow.

Secondly, if the 'mouse theory' is true, it has serious implications for the idea that XMRV causes chronic fatigue syndrome and also for the older idea that it's linked to prostate cancer. But it still leaves a mystery: why were the samples from CFS or prostate cancer patients more likely to be contaminated with mouse DNA than the samples from healthy controls?

Robert A Smith (2010). Contamination of clinical specimens with MLV-encoding nucleic acids: implications for XMRV and other candidate human retroviruses Retrovirology : 10.1186/1742-4690-7-112

Winner!

The winner of my giveaway is #71, Alice. Please send me an email so I can mail you your prize. A big Thank you to everyone that entered! I hope to do another giveaway really soon. :) C

The Almond of Horror

Remember the 90s, when No Fear stuff was cool, and when people still said "cool"?

Well, a new paper has brought No Fear back, by reporting on a woman who has no fear - due to brain damage. The article, The Human Amygdala and the Induction and Experience of Fear, is brought to you by a list of neuroscientists including big names such as Antonio Damasio (of Phineas Gage fame).

The basic story is nice and simple. There's a woman, SM, who lacks a part of the brain called the amygdala. They found that she can't feel fear. Therefore, it's reasonable to assume that the amygdala's required for fear. But there's a bit more to it than that...

The amygdala is a small nugget of the brain nestled in the medial temporal lobe. The name comes from the Greek for "almond" because apparently it looks like one, though I can't say I've noticed the resemblance myself.

What does it do? Good question. There are two main schools of thought. Some think that the amygdala is responsible for the emotion of fear, while others argue that its role is much broader and that it's responsible for measuring the "salience" or importance of stimuli, which covers fear but also much else.

That's where this new paper comes in, with the patient SM. She's not a new patient: she's been studied for years, and many papers have been published about her. I wonder if her acronym doesn't stand for "Scientific Motherlode"?

She's one of the very few living cases of Urbach-Wiethe disease, an extremely rare genetic disorder which causes selective degeneration of the amygdala as well as other symptoms such as skin problems.

Previous studies on SM mostly focussed on specific aspects of her neurological function e.g. memory, perception and so on. However there have been a few studies of her "everyday" experiences and personality. Thus we learned that:

Two experienced clinical psychologists conducted "blind" interviews of SM (the psychologists were not provided any background information)... Both reached the conclusion that SM expressed a normal range of affect and emotion... However, they both noted that SM was remarkably dispassionate when relating highly emotional and traumatic life experiences... To the psychologists, SM came across as a "survivor", as being "resilient" and even "heroic".

These observations were based on interviews under normal conditions; what would happen if you actually went out of your way to try and scare her? So they did.

First, they took her to an exotic pet store and got her to meet various snakes and spiders. She was perfectly happy picking up the various critters and had to be prevented from getting too closely acquainted with the more dangerous ones.

What's fascinating is that before she went to the store, she claimed to hate snakes and spiders! Why? Before she developed Urbach-Wiethe disease, she had a normal childhood up to about the age of 10. Presumably she used to be afraid of them, and just never updated this belief, a great example of how our own narratives about our feelings can clash with our real feelings.

They subsequently confirmed that SM was fearless by taking her to a "haunted asylum" (check it out, even the website is scary) and showing her various horror movie clips, as well as through interviews with herself and her son. They also describe an incredible incident from several years ago: SM was walking home late at night when she saw

A man, whom SM described as looking “drugged-out.” As she walked past the park, the man called out and motioned for her to come over. SM made her way to the park bench. As she got within arm’s reach of the man, he suddenly stood up, pulled her down to the bench by her shirt, stuck a knife to her throat, and exclaimed, “I’m going to cut you, bitch!”

SM claims that she remained calm, did not panic, and did not feel afraid. In the distance she could hear the church choir singing. She looked at the man and confidently replied, “If you’re going to kill me, you’re gonna have to go through my God’s angels first.” The man suddenly let her go. SM reports “walking” back to her home. On the following day, she walked past the same park again. There were no signs of avoidance behavior and no feelings of fear.

All this suggests that the amygdala has a key role in the experience of fear, as opposed to other emotions: there is no evidence to suggest that SM lacks the ability to experience happiness or sadness in the same way.

So this is an interesting contribution to the debate on the role of the amygdala, although we really need someone to do equally detailed studies on other Urbach-Wiethe patients to make sure that it's not just that SM happens to be unusually brave for some other reason. What's doubly interesting, though, is that Ralph Adolphs, one of the authors, has previously argued against the view of the amygdala as a "fear center".

Links: I've previously written about the psychology of horror movies and I've reviewed quite a lot of them too.

Justin S. Feinstein, Ralph Adolphs, Antonio Damasio,, & and Daniel Tranel (2010). The Human Amygdala and the Induction and Experience of Fear Current Biology