Bad medicine at the University of Maryland

Pseudoscience is insinuating itself into our medical schools across the nation, going by the name "Integrative Medicine." Integrative medicine is just the latest buzzword for a collection of superstitions, myths, and pseudoscience that has gone by various names over the years. First it was Holistic medicine, and once that fell out of favor, it became Alternative medicine, followed soon after by Complementary and Alternative medicine (CAM), and lately Integrative medicine. These names can't disguise the fact that many of the practices lumped together are bad medicine. What disturbs me particularly, as a professor, is that CAM is moving into the medical curriculum at respectable medical schools, including the University of Maryland.

Perhaps the best way to reverse this trend is to call attention to it. Academic freedom allows professors to proclaim all sorts of wild ideas, including nonsensical ones, but we don't have to allow them to teach courses with no basis in reality. That same academic freedom, incidentally, allows me to criticize bad science wherever I find it, including my own university.

So what's going on at Maryland's medical school? UMM is home to one of the nation's premier "integrative medicine" programs, which promotes a wide range of questionable practices. Its clinical services include:

• Acupuncture
• Homeopathy
• Reflexology
• Reiki
• Qi Gong

Although each of these has a different history, all of them are, well, nonsense. Let's take a closer look homeopathy, which is perhaps the most ridiculous pseudoscience on the list. Homeopathy is based on two ideas: that "like cures like", and that vanishingly small quantities of medicine are stronger than larger quantities. Both ideas were invented by Samuel Hahnemann in the late 1700s, back when most medicine was pretty bad for you. Unfortunately for Hahnemann, his ideas were no better.

The idea that "like cures like" is used to justify treating (for example) itchiness with extract of poison ivy. I'm not making this up: this is a standard homeopathic preparation, promoted on many homeopathic sites, even (sorry, cycling fans) on Lance Armstrong's Livestrong website.

The second idea is that you dilute these substances so much that instead of causing the symptom, they cure it. Alas, Hahnemann was unaware that when you dilute a substance to the degree that he recommended, you end up with nothing left. Typical dilutions used today go by the abbreviations 10C, 20C, or 30C. One "C" is a dilution of 1 in 100, and 20C means that you dilute the active ingredient 100-fold, and then repeat the process 20 times over. This is a dilution of 100 to the 20th power, a ridiculously large number. If you had a single molecule immersed on a sphere of water the size of the entire planet, it would still not be dilute enough.

That's right: homeopathic treatments are just water. Or rather, water dropped onto a sugar pill, and sold at stores such as Whole Foods, which has a section devoted to homeopathic remedies. And offered up as medicine by the University of Maryland's Center for Integrative Medicine through their clinical services. (Why isn't this malpractice? I haven't figured that out yet.)

The other treatments offered by the UMM Center are no better. Their Qi Gong brochure explains that

"sickness, pain or physical disorders are the result of qi blockage, or unbalanced qi in the body. Qigong practice helps to balance the qi system in the body and break the qi blockage(s) to recover health."

There's no scientific basis for qi - it is simply magical thinking. The brochure, though, claims that Qigong will give you "an increased resistance to illness through a stronger immune system." None of these claims have any good science to back them up.

But it gets worse. The Center for Integrative Medicine is offering lectures and courses in all four years of the medical school curriculum, and it boasts that the "integrative medicine elective has become a top choice for fourth year medical students." How unfortunate that this pseudoscience has infiltrated its way into the medical curriculum, and that the UMM Center is, in essence, mis-training medical students at one of the nation's oldest medical schools.

By providing a respectable home for these pseudoscientific practices, UM Medicine is undermining its own scientific and educational missions. But when the money is coming in, the administration seems quite happy to support it. Last August, the Dean of Medicine issued a glowing press release about the Center, after its Director published a very poor study (see my earlier blog about that one) arguing for the use of acupuncture. I don't know if the Dean believed that press release, but someone ought to tell him that Integrative Medicine has no place in a 21st century medical curriculum. I guess I just told him.

Note: why do I pick on U. Maryland? Primarily because it's my own institution (although I noted previously that UM Medicine is a separate campus from the main campus at College Park where I work). There are plenty of other Integrative Medicine programs at reputable medical schools, most of them just as deserving of criticism.

Pseudoscientific Chinese Medicine infiltrates scientific publishing

So it turns out that Chinese Medicine has its own journal, published by BioMed Central, a large scientific publisher. The Chinese Medicine journal promotes, according to its own mission statement, studies of "acupuncture, Tui-na, Qi-qong, Tai Chi Quan, energy research," and other nonsense. Tui na, for example, supposedly "affects the flow of energy by holding and pressing the body at acupressure points."

Right. What is this doing in a scientific journal? Actually, there are plenty of garbage journals out there, and I'd ignore this one like I do the others, but BioMed Central (and their owner, Springer Science) is a respectable publisher. It's also one of the largest open-access publishers, which means they make all their articles from their 213 journals freely available. I support BMC and I'm on the Editorial Boards for three of their journals (BMC Biology, BMC Genomics and BMC Bioinformatics). But their corporate leaders seem to care more about expanding their stable than about maintaining the integrity of science. Chinese Medicine simply does not belong in the company of respectable scientific journals.

What is "Chinese Medicine" anyway? (Should we also have journals for Russian Medicine, or American Medicine, or Swedish Medicine?) Actually, the name refers to what is usually called Traditional Chinese Medicine, or TCM. TCM is a grab-bag of superstitious practices taken from Chinese history, most of which are ineffective or even harmful. The most common justification for studying TCM (and using it on patients) is something along the lines of "this is an ancient Chinese practice" as if anything old must be worthwhile (also known as the argument from antiquity, a logical fallacy). But using the term "medicine" to describe Qi-gong, acupuncture, and "energy research" is, to put it bluntly, nonsense.

And by the way, "energy research" in this context doesn't refer to methods for producing electricity. No, the energy research in this journal refers to mysterious energy fields in the body, stuff like the "deqi" in this article from the January 2011 issue of Chinese Medicine: "Perception of Deqi by Chinese and American acupuncturists: a pilot survey." It's a laughably bad study, but here's a link for those with a high tolerance for quackery.

Ancient medicine was almost always bad medicine. People died very, very early in those good old days, and ancient China didn't have any special secrets. 2000 years ago, if you were lucky enough to survive past childood, you might just make it to your 30's. Life expectancy has climbed dramatically in recent times, for the past 150 years or so, thanks to modern hygiene and medicine. So forming a scientific journal whose goal is to validate antiquated, unproven superstitions is simply not science, whatever the editors of Chinese Medicine claim. The journal's claim to be "evidence-based" (yes, they do claim that) is little more than a smoke screen.

BioMed Central publishes at least one other pseudoscience journal, BMC Complementary and Alternative Medicine. BMC should be embarrassed to be publishing journals that promote anti-scientific theories and otherwise muddy the literature. By supporting these journals, they undermine the credibility of many excellent BMC journals. They should cut these journals loose.

It's time to destroy our smallpox

The eradication of smallpox was possibly the greatest victory of science over disease in the history of mankind. Thanks to a determined, worldwide vaccination effort, led by the World Health Organization, the last known human smallpox case occurred over 30 years ago, in Somalia in 1977. The WHO declared smallpox eradicated in 1980.

But smallpox isn't completely gone. That's because two large government laboratories, one in the U.S. and one in Russia, insist on maintaining stocks of the smallpox virus (called variola). In the U.S., the smallpox virus is kept at the Centers for Disease Control in Atlanta. In Russia, it's at the Vector lab in Siberia.

Why keep this incredibly deadly virus around? The scientists at the CDC and in Russia give the same answer: more research is needed to develop better vaccines, to protect us from a bioterrorism attack. "We still have work to do to protect the public," said Ali Khan, a smallpox researcher at the CDC, quoted just last week in the Washington Post.

They've been making this argument for 30 years now, but they are wrong. The only thing they need to do is to destroy their stocks of smallpox, and wipe out this virus once and for all. This seems like an obvious thing to do, but it's obvious now that the scientists whose jobs depend on keeping the smallpox around will never agree to destroy it. Nor will their bosses at the CDC. Yet keeping the smallpox around dramatically increases the risk that a deranged person will get his hands on it and release it in the population.

A smallpox outbreak would indeed be a frightening scenario: smallpox has a mortality rate of 30-35%, and it has been called one of the most devastating diseases in the history of mankind. In the 18th century, it killed 400,000 Europeans each year, and in the 1950s it was still infecting 50 million people a year worldwide. Routine vaccination ended about 35 years ago, which would make an outbreak today truly devastating. But an outbreak cannot happen if we destroy the smallpox that the U.S. and Russia are still holding.

Back in 1999, the WHO set a deadline to destroy the remaining smallpox samples, but the U.S. and Russia have repeatedly delayed action. At the 2006 meeting of the World Health Assembly (WHA), virtually every country agreed, again, that the smallpox should be destroyed, but the U.S. and Russia objected, and no date was set to destroy the remaining stocks. The WHA will meet again this coming May, and smallpox will be on the agenda. Unless President Obama takes a firm stand, I expect that the U.S. will once again insist on keeping its smallpox stores.

Experts such as D.A. Henderson, who led the effort to eradicate smallpox, have pointed out that we can develop new vaccines without the virus. The genome has been sequenced several times over, and we have the technology to synthesize parts of the virus if we really need it for vaccine design. Despite these facts, the old guard at the CDC will never agree to destroy their smallpox willingly.

President Obama: here is an opportunity to do the right thing. You can order the CDC to destroy their stocks of smallpox, and eliminate this unnecessary risk from the planet. The United States can and should take the moral lead on this public health threat, rather than stonewalling once again at the next World Health Assembly. Destroy the smallpox, and wipe out this scourge once and for all.

Supreme Court saves the vaccine system

Unbeknownst to most people, the Supreme Court heard a case last week that, had they ruled differently, might have destroyed the vaccine system in the United States. On February 22, the court ruled 6-2 to keep the special Vaccine Court system intact. In particular, they ruled against Russell and Robalee Bruesewitz, who were suing for damages on behalf of their daughter Hannah. But even though the system is saved for now, the two judges who voted in the minority demonstrated a frightening disregard for possible consequences, and encouraged those who would like to take us all back to an era when millions of children died each year from diseases like measles, polio, and whooping cough.

Hannah Bruesewitz's case is heartbreaking: she suffered a seizure in April 1992, within a day of receiving the vaccine for diphtheria, pertussis, and tetanus (DPT), and she had many more seizures in the following months. She was eventually diagnosed with with “residual seizure disorder” and “developmental delay" which she still has today. Her parents blamed the vaccine, and in 1995 they sued in Vaccine Court. They lost, although the Special Master of that court awarded them $126,800 for lawyer's fees and other costs. The Bruesewitzes rejected the award and sued in a state court in Pennsylvania.

The case last week wasn't about whether Hannah's disability was caused by the DTP vaccine. It was only about whether her parents could sue in state court after losing their case in vaccine court. The Supreme Court said no. Had they allowed the case, state courts across the country would have been flooded with thousands of vaccine lawsuits, and it is entirely likely that vaccine makers would simply stop selling vaccines in the United States. The ensuing loss of vaccines would be a public health disaster of enormous magnitude, leading to tens of thousands of deaths from diseases that we now have largely defeated in this county.

This sounds awfully dire. Why do I claim it could happen? Because it almost did, some 25 years ago.

Back in the 1980s, largely due to one incredibly irresponsible, inaccurate television documentary called DPT: Vaccine Roulette "started a firestorm" of panic, as Paul Offit explains in his latest book (1). It also caused an avalanche of lawsuits, and juries were soon making multi-million dollar awards. As Dr. Offit documents, jury awards in vaccine cases increased from $25 million in 1981 to $3.2 billion in 1985. Two of the three companies making the DPT vaccine stopped distributing it, leaving only one company, Lederle (now owned by Wyeth) supplying it.

It wasn't just DPT. Companies making measles and polio vaccines also dropped out of the U.S. market, leaving just one company for each. We were very close to a situation where we simply wouldn't have childhood vaccines in this country.

Then, remarkably, the federal government passed the National Childhood Vaccine Injury Act of 1986. This set up a special fund to compensate anyone damaged by vaccines, covered by a tax on all vaccines. It also created a special Vaccine Court to hear cases, and required that vaccine cases go through this court. The standard of evidence for the court was lower than regular courts: for some conditions, the parents merely have to show that their child suffered the condition soon after getting a vaccine, regardless of whether the vaccine was the cause.

The law also took juries and state courts out of the equation. Vaccine makers were protected, and the childhood vaccination system was saved. The Vaccine Court functions remarkably well, using Special Masters who become far more educated about vaccines and possible side effects than any regular judges can be. There is a very small but real risk of harm from vaccines, and the Vaccine Court has made thousands of awards to compensate victims. Meanwhile, millions of severe illnesses and countless thousands of deaths have been prevented by vaccines.

So I was very dismayed that two justices, Sandra Sotomayor and Ruth Bader Ginsburg, voted against the majority. I usually agree with these two, but their reasoning in this case was wildly off. Sotomayor's dissent shows her to be misinformed, confused, or just plain naive:

"Trial courts, moreover, have considerable experience in efficiently handling and disposing of meritless products liability claims, and decades of tort litigation (including for design defect) in the prescription-drug context have not led to shortages in prescription drugs. Despite the doomsday predictions of respondent and the various amici cited by the concurrence ... the possibility of a torrent of meritless lawsuits bankrupting manufacturers and causing vaccine shortages seems remote at best."

Apparently Sotomayor is unaware of the actual "torrent of meritless lawsuits" from the 1980s that forced Congress to create the Vaccine Court in the first place, although I cannot understand how she could fail to know this history. I am also disappointed by her naive faith in trial courts to quickly dispose of "meritless product liability claims." Perhaps in an ideal world, yes. But a smart lawyer, a sympathetic victim, and a complex medical case can easily confuse both judge and jury, leading to enormous jury awards regardless of what the scientific evidence shows.

Apparently Sotomayor can't bear to limit the ability of plaintiffs to sue wherever they choose. The Vaccine Court, although imperfect, is a much better model for handling complex medical claims than the roulette of a jury trial. We should all breathe a sigh of relief that the Supreme Court kept this system intact.

Of course, the anti-vaccination movement has been quick to attack the decision. Age of Autism, one of the biggest anti-vax sites, posted an article titled "Supreme Court Ruling Abandons Vaccine-Injured Children, Threatens Vaccine Safety" in which they call the decision "a crushing blow to the rights of every U.S. citizen." A coalition of anti-vax organizations including Generation Rescue issued a press release calling the decision "misguided" and making a number of incorrect claims about vaccine safety. But scientists and doctors, notably the American Academy of Pediatrics, applauded the decision.

Reference

1. Paul A. Offit, M.D. Deadly Choices: How the Anti-Vaccine Movement Threatens Us All. Basic Books (2011). See especially pages 2-12.

Get football out of our universities

(In which I take on the football-industrial complex, and get myself in trouble)

The Super Bowl is over, finally. The college football^* season is over too. Now we can be spared the breathless, hyperbolic stories about football for a few months, at least until next season. The culture of football in American universities is completely out of control. It is undermining our education system and hurting our competitiveness in technology, science, and engineering. If we keep it up, the U.S. will eventually be little more than the big, dumb jock on the world stage - good for entertainment on the weekend, but not taken seriously otherwise.

Too harsh? I don't think so. I think we need to eliminate football entirely from our universities if we want to maintain our pre-eminent position as the world's scientific and technological leader.

Why do we need to get football out of our universities? I've watched over the years as football has taken an ever-more prominent role in our high schools and colleges, as football coaches have been paid ever-higher salaries, and as football staffs and stadiums have been super-sized. All of this effort goes to the care and feeding of a very small number of (exclusively) male students, most of whom get a poor education and almost none of whom succeed as professional players. Our universities are providing a free training ground for the super-wealthy owners of professional football teams, while getting little in return.

This has got to stop. The core mission of our universities is to educate our students, not to entertain them with big-time sports events. Our political leaders, and all too often our university presidents, seem to have lost sight of this fact.

So I was very pleasantly surprised when President Obama, in his State of the Union speech on January 25, put in a plea for science over football:

"We need to teach our kids that it’s not just the winner of the Super Bowl who deserves to be celebrated, but the winner of the science fair."

Wow, not bad! Of course, as a politician he has to support football, so he argues only that the science fair deserves equal footing with football. (Even that is pretty radical for a politician.) I'll go a big step further: the winner of the science fair deserves far more praise and celebration than any winner of any football game. If football disappeared, we could get our entertainment from another sport, as we do every year after the football season ends. But if we stop producing scientists, other countries will make the discoveries that solve the technological, medical, and engineering problems of the future, and that form the basis for great civilizations.

Now that I've gotten myself in trouble with football fans (and there are many of them), let me get myself in even more trouble, with an example from my own university.

At the University of Maryland last year, the football coach fell out of favor with the athletic director, who wanted to replace him. (This despite the fact that the coach was very successful, with an overall winning record.) The problem was, he had one more year to go in his contract, and the university would have to pay him a cool $2 million if they fired him. U. Maryland doesn't exactly have money to burn: for three years running, it has imposed furloughs on all employees and prohibited all raises, including cost-of-living increases. So you'd think that blowing $2 million to pay a coach to sit on the sidelines, and paying who-knows-how-much to hire a new coach, would be out of the question.

Nope. The brand-new President of the university, in office just one month, announced the hiring of a new coach, along with a $2 million payout to the old coach.

What a bad move. That $2 million should have been spent on, well, how about educating the students? (And don't get me started on football coaches' salaries - they often make 3-5 times more than their own presidents.)

Do we want our universities to be known for their football teams? Or do we want them to be known as educational powerhouses? Apparently, the U. Maryland administration is more interested in building a better football team. Not surprisingly, many of the professors disagree. I can only hope that the students would side with the professors, but I honestly don't know.

Yes, I know the arguments on the other side. "Football makes a profit," some claim. To that I would say, so what? Universities could make a profit running a casino too - should they do that? If football is so profitable, then spin off the teams as private corporations, and let them pay the university a licensing fee to use the university logo. But let's stop pretending they have anything to do with education.

Don't get me wrong. I love sports - I've played them all my life - and I think students should participate in them. It's healthy and fun, and it's part of the college experience. But universities don't need big-time, pseudo-professional athletic teams with outsized coaching staffs. Look at the Ivy League, which comprises 8 of the best universities in the country. They play sports against each other, they don't award athletic scholarships, and their academic programs are the envy of the rest of the world.

The football-industrial complex has too much power over our universities. Nothing else can explain how we spend so much money and time on football, which contributes almost nothing to students' education, while academic departments are cutting faculty and staff. The culture of football worship has gotten so out of control that I think the only solution is to get rid of it entirely.

I don't expect any university to take my advice. But I'll end with another excerpt from President Obama's State of the Union speech, which we should take as a warning:

"Meanwhile, nations like China and India realized that with some changes of their own, they could compete in this new world. And so they started educating their children earlier and longer, with greater emphasis on math and science. They’re investing in research and new technologies. Just recently, China became the home to the world’s largest private solar research facility, and the world’s fastest computer.

So, yes, the world has changed. The competition for jobs is real. But this shouldn’t discourage us. It should challenge us. .... We’re the home to the world’s best colleges and universities, where more students come to study than any place on Earth."

President Obama is right: students do come from all over the world to study in our universities. But they don't come because of the football teams.

^*Note to my friends in other countries: by "football" I mean American football, that game with the peculiar oblong-shaped ball - not the wonderful game of soccer, which almost all other countries call "football."

ADDENDUM: I've done two radio interviews about this blog post, which you can listen to at the following links: 670 The Score, a Chicago sports radio program, and 1560 The Game, a Houston sports radio show.

Should we all be on statins?

Well, probably not.

But a new review published earlier this month in the Cochrane Reviews looked at 14 different trials, with a total of 34,272 patients, in an attempt to answer this question, and came out with conflicting results. Scientific and medical experts looked at the review and have already reached diametrically opposed conclusions, reported in their blogs and in commentaries in several leading journals.

Everyone has heard of statins: they are a class of cholesterol-lowering drugs that offer clear benefits in people who already have suffered heart attacks or other serious cardiovascular problems. But what about the rest of us? If you have slightly elevated cholesterol, or even normal cholesterol, should you take statins? Drug companies would certainly like you too, and they have been pushing statins (such as Levacor, Zocor, Pravachol, Lipitor, and Crestor) for years in the U.S., through ad campaigns in print and on television. I wrote about a study of Crestor back in 2008, and I found serious problems with the study's design and conclusions.

First, what did this large-scale review find? All of the studies ran for at least a year, and all were randomized controlled trials, the most rigorous type of study. Overall risk of death was reduced by 17%, and the risk of a heart attack was reduced by 28%, which seem to be very positive results. None of the patients had previous history of cardiovascular disease, although most of the studies recruited patients with other risk factors such as high cholesterol, diabetes, or high blood pressure.

But - and this is a big but - the authors of the Cochrane review had big problems with the way these studies were run. They wrote in their conclusion that

"there was evidence of selective reporting of outcomes, failure to report adverse events and inclusion of people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk."

So the review authors were not convinced that people without previous heart disease should all go on statins, even though their own numbers showed a decreased risk. I think their skepticism is justified, because the benefits they observed were very small. This means that subtle biases such as including people who did have cardiovascular disease, could create the appearance of a benefit even if there wasn't one. And 9 of the 14 studies were funded by pharmaceutical companies, which hints at possible bias.

Writing in the journal BMJ, Susan Mayor highlighted the skeptical interpretation. She quoted one of the study's authors, Shah Ibrahim, who said "Absolute benefits were small, and evidence of selective reporting of outcomes makes the evidence less robust.”

Over at Science-Based Medicine, neurologist and skeptic Steven Novella has a more positive interpretation. He concluded that

"there is solid evidence that statins have a real benefit for primary prevention. This benefit is small, which is exactly what I would predict for a preventive measure in a low-risk population. The data also show that statins are safe. ... For interventions that prevent death – that lower mortality – I think even small benefits are worthwhile."

However, he goes on to say that "it is still unclear where to draw the line in terms of which patients should receive statins."

I would love to believe that statins will reduce everyone's risk of heart disease, but I couldn't ignore one statistic: the "number needed to treat." Based on the new study's findings, you'd have to treat 1000 low-risk patients for one year to prevent one death. To put that another way, if you are at low risk of heart disease, then there is a 99.9% probability that taking statins for a year will give you no benefit. Even so, given that statins have minimal side effects, you might think it's a reasonable preventative treatment, even with such a small benefit. The skeptic in me says that if there was even a tiny amount of bias in some of the trials, that apparent benefit might actually be zero.

On this question, we need more data from completely unbiased studies. In an editorial for the Cochrane Reviews, Carl Heneghan wrote that "Interventions targeting CVD risk reduction in low-risk population should be undertaken in the context of a randomised controlled trial; preventing scarce healthcare resources going to waste."

He's right. Statins might have a small benefit, but before we start prescribing them to tens of millions of people - and before I start taking them myself - I'd like to see unbiased studies conducted exclusively in low-risk populations.

Searching for the cause of chronic fatigue syndrome: XMRV turns out to be another blind alley

Chronic fatigue syndrome (CFS) causes severe fatigue that can last for months at a time. CFS is difficult to diagnose and even more difficult to treat, and its cause has long been a mystery. In 2009, in an apparent breakthrough, scientists reported that a virus found in mice, called XMRV, might be the long-sought cause of chronic fatigue. Their results were reported, with great fanfare, by Judy Mikovits and colleagues in the journal Science (Lombardi et al., Science 2009;326:585), with reports in respected outlets such as the New York Times making it seem that the answer had been found.

Now it turns out that, like many initially exciting reports, this one has a much more mundane explanation: contamination.

As happens all too often when a "surprising" discovery is announced, the result turns out to be an experimental error. Contamination is a common type of error in modern molecular genetics, because nothing is actually visible to the naked eye, and we have to rely on very sensitive methods (such as PCR) to detect what is present. In this case, the experimenters had a common mouse cell line in their lab (not unusual), and it turns out these mouse cells were contaminated with a virus called MLV, which looks a lot like XMRV.

The new study by Hue et al. from University College London (Retrovirology 2010, 7:111) is titled "Disease-associated XMRV sequences are consistent with laboratory contamination." The title pretty much tells the story, but here's a brief synopsis.

XMRV (Xenotropic murine leukaemia virus-related virus) is the virus in question - the one that Mikovits claimed is the cause of chronic fatigue syndrome. It's a retrovirus, and it is very similar to another mouse virus called MLV-X. It turns out the the PCR method for detecting XMRV uses short DNA sequences ("primers") that will also detect MLV-X. These primers were previously believed to be specific to XMRV, but they're not. Therefore, if you are looking for XMRV in a tissue sample, and the sample contains MLV-X, you'll think you found XMRV. But what: why would human patients have MLV-X? Perhaps MLV-X is a cause of chronic fatigue? Good question.

Well, it turns out that a common tumor cell line called 22Rv1 is infected with MLV-X. It also turns out that all the XMRV sequences from human patients are far more similar to the exact same strain of MLV-X that is in the mouse cell line. The tumor cell line was in the lab doing the experiments: ergo, it's contamination. Elementary, my dear Watson. Or, as Hue et al put it:

"We provide several independent lines of evidence that XMRV detected by sensitive PCR methods in patient samples is the likely result of PCR contamination with mouse DNA.... We propose that XMRV might not be a genuine human pathogen."

The initial Science paper by Mikovits and colleagues generated three published "Comments" in the journal, an unusually high number, which alone is enough to raise some red flags. The comments pointed out multiple methodological problems, including the possibility of contamination. In one of them, the authors (van der Meet et al) warned that

"Over the past few decades, we have witnessed a long series of papers claiming the discovery of the cause of CFS. None of these claims has been confirmed. Each time, this gives false hopes to large numbers of patients who seek a solution for their suffering. Shortcomings in the study by Lombardiet al. now raise concerns about the role of XMRV in the pathogenesis of CFS."

After the 2009 Science paper, several other studies looked at patients with chronic fatigue syndrome and failed to find anyone with XMRV (for example, this study from the CDC last summer). This was strikingly different from Mikovits' report that 67% of patients had XMRV. The latest report, by explaining where the false positive results came from, should put the final nail in the coffin for the XMRV hypothesis.

In retrospect, Science shouldn't have published the flawed study, and you could argue that peer review failed. On the other hand, the final resolution illustrates the self-correcting mechanism of science at its best. All of this is very reminiscent of the scientific response to Andrew Wakefield's notorious 1998 study claiming that autism was associated with the MMR vaccine: multiple followup studies, most of them conducted far more carefully, failed to reproduce the results. But in that case, bad scientists (Wakefield) aided by gullible journalists and non-scientists (Jenny McCarthy, Jay Gordon) have kept the story alive, causing continuing damage to children in the form of preventable illnesses and even deaths. Even after the story last week in the journal BMJ that explained Wakefield's outright fraud, he continues to push his discredited notions. (I love the title of the BMJ's editorial: "Wakefield's article linking MMR vaccine and autism was fraudulent.")

CFS has less visibility than autism, so I hope that scientific evidence will carry the day here. We still need to find the cause of chronic fatigue syndrome, and there's no telling right now where the answer lies.