The worst scientific idea of the decade: vaccines cause autism

The year and the decade are coming to an end, and top-10 lists are everywhere. These are hard to put together if you want to do it right. I’m opting for a simpler list: the top 1, and I’ll make it for the entire decade.

Of all the bad science, bad medicine, and pseudoscientific nonsense that human beings have come up with over the past decade, which is the worst? Of course, scientists have bad ideas all the time, and most of them never make it out of the lab. So for me, “worst” means a bad scientific notion that has emerged into the public domain and done more damage to civilization, or to public health, than any other idea of the past decade.

To answer this question, I wanted a belief or practice that rose to prominence during the past 10 years, which eliminates a large number of pseudoscientific practices and quack treatments that have been around much longer, including acupuncture, chiropractic, and homeopathy. So what idea has taken hold only recently?

And the worst scientific idea of the 2000's is: vaccines cause autism. This idea has caught on and spread like wildfire during the past ten years, thanks largely to the well-funded, well-publicized efforts of organizations such as Generation Rescue, led by the notoriously mis-informed celebrities Jenny McCarthy and her even more famous boyfriend, the actor Jim Carrey.

Strictly speaking, this terrible idea was first published more than a decade ago, in a now-discredited, notorious 1998 paper in The Lancet by Andrew Wakefield, a British gastroenterologist. This very small study of 12 children seemed to show a link between the measles, mumps, rubella (MMR) vaccine and autism, but it later turned out that the study had multiple flaws: Wakefield recruited the children to the study through a lawyer who was trying to build a case against vaccine makers, Wakefield himself received over $750,000 in consulting frees from the same lawyer, Wakefield didn’t tell his co-authors any of this, Wakefield had filed for a patent on an alternative, “safer” vaccine, and on and on. Although his co-authors repudiated the paper publicly and withdraw their conclusions in 2002, Wakefield has continued to this day to stand by his original claims. (See journalist Brian Deer’s website for a good summary of the Lancet scandal.) He moved to the U.S. after being forced out of his job at a London hospital, and he set up a private business in Texas from which he continues to promote his anti-vaccination claims.

Pfizer wants you to make a New Year’s resolution

“80% of you will fail to quit smoking with Chantix. “ That’s what the ad should say, but it doesn’t. Instead, it shows a smiling woman who “quit smoking with Chantix and support in June ’07” and it promises “with Chantix you can smoke during the first week of treatment.” Nowhere does it say how likely you are to quit smoking.

This is from a very large, full-page ad that’s been running for weeks, almost every day, in the Washington Post and other newspapers. The top 1/3 of the page is the “sell,” and the rest of the page contains the required safety information, which tells you some of the problems, including hostility, depression, suicidal thoughts or actions, and nausea. Naturally, the top of the page is in a larger font with a colorful picture.

Why is Pfizer (Chantix’s manufacturer) running these ads now? Well, quitting smoking is a very popular New Year’s resolution. It’s on many top-10 lists, even one from the U.S. government. Pfizer is trying to grab smokers’ attention now, so they’ll ask their doctors for a prescription, which I have no doubt they’ll get. These direct-to-consumer ads work, big time, and the drug makers know it. The U.S. should never have allowed drug makers to advertise directly to consumers – and Congress should re-institute laws prohibiting these ads.

Alcohol and cancer: journal editors say they got it wrong

In a recent editorial in the Journal of the National Cancer Institute, three scientists point out that I was correct in my February blog post, where I pointed out the errors - and the mistaken scare-mongering - in press reports of a new study on alcohol and cancer.

The JNCI editorial, titled "Promoting Healthy Skepticism in the News: Helping Journalists Get it Right" focuses on two studies, one of which is the article I wrote about. Journalists at the time, including Sanjay Gupta at CNN, reported "there is no level of alcohol consumption that can be considered safe when it comes to cancer." As the editorial points out, the journalists got it wrong. The authors point out that other explanations (other causes besides alcohol) might explain the increased risk. And it's nice to see that even though their own journal was partly to blame for the hype back in February, at least they're making an effort to correct it now.

They could have done more, though. They didn't dig into the article and report, as I did, that the minimum risk levels in the study were for light drinkers, who had 1-2 glasses of wine per week and who had a lower risk than non-drinkers. But at least they pointed out that the absolute increase in risk, even for heavy drinkers, was very small. In fact, they go on to say that under-reporting of absolute risk is a major failing of many biomedical journals.

So my advice for the holiday season is: drink up! The evidence for heart-healthy benefits of wine, especially red wines with high levels of procyanidins (as described in this article from Nature 2006), probably outweighs any risks. Happy holidays!

Crestor gets an undeserved boost from the FDA

The FDA planted a big, wet sloppy kiss on AstraZeneca this week. An FDA scientist told reporters that the benefits of Crestor, a cholesterol-lowering drug, outweighed the risks even for otherwise healthy people. Essentially, millions of healthy people with normal cholesterol levels could find themselves taking Crestor, if they listen to this anonymous FDA scientist and to Crestor’s manufacturer, AstraZeneca. This new recommendation was widely reported on Friday, appearing in the Wall St. Journal, in a widely carried AP report, and in a more skeptical Reuters report.

The new report isn’t based on anything new, though. It’s based on a study published a year ago – a seriously flawed study that I dissected at length on this blog in November 2008. The FDA took a year to review this study and then said yep, we agree. I should mention that the 2008 study has one condition before recommending Crestor: that the patients should have elevated levels of C-reactive protein (CRP). I described in earlier blog post the problems with this recommendation – including the fact that they study’s leader has a patent on the CRP diagnostic test.

Does it matter that, as I explained a year ago, the study was funded by AstraZeneca? How about the fact that this huge study found only a tiny benefit? That’s right: the benefit is so small that you’d have to treat 95 patients for 2 years in order to prevent one heart attack. As I wrote last year, and as others have pointed out, when the number needed (NN) to treat is over 50, the result is probably just statistical noise. Or to put it another way, if you take Crestor for 2 years, you have about a 1% chance of getting any benefit. Compare that to, say, taking vitamin C to treat scurvy, where the NN is about 1. With any decent drug, if you take it, you should have a very high likelihood of benefit.

We know who’s going to benefit here: AstraZeneca. Does it matter to them that there is a significantly higher risk of diabetes in people who take Crestor? There was also a higher number of deaths in the placebo group caused by gastrointestinal disorders, but the FDA dismissed this number because it didn’t reach statistical significance. (Kudos to the WSJ and Reuters reporters for highlighting these problems.) And no one besides me (see my Nov 2008 blog post) seems to have noticed some of the other problems with the study, such as the fact that the placebo group contained an excess in the number of patients with conditions that raise the risk of heart disease.

Does it matter that, as the FDA reported in 2005, “Rhabdomyolysis (serious muscle damage) has been reported in patients taking Crestor as well as other statin drugs.” Or that, as the same report said, “Kidney failure of various types has also been reported in patients treated with Crestor as well as other statins”?

So who the heck are these FDA scientists? After considerable searching, I found the lengthy FDA report here. It’s a “briefing document” for a FDA advisory committee that will meet on Dec. 15. It basically reviews the study in great detail and simply repeats the study results. What became clear to me once I downloaded the document, though, was that it was written by AstraZeneca! [Note: thanks to the first commenter on this blog, I also found the separate FDA-sponsored document - see comments.]

The reports from the AP, Reuters, and the WSJ I cited above mention an anonymous FDA reviewer, but apparently this “reviewer” did not want to be named on the record. It's too bad none of the reporters revealed the name of this anonymous FDA scientist, but the roster of the FDA panel reviewing Crestor is here.

It’s a shame that the FDA’s own scientists can’t take a more critical look at the evidence. Look for AstraZeneca stock to go up next week. Let me close with a video from Stephen Colbert, who had a great skeptical spoof of this last year on his show. Skip forward to about the 2-minute mark in this video to see the Crestor segment.

The Colbert Report	Mon - Thurs 11:30pm / 10:30c
Cheating Death - Women's Health
www.colbertnation.com
Colbert Report Full Episodes Political Humor U.S. Speedskating

As Stephen says in the video, "this is a great breakthrough in the battle to find things to prescribe to people who don't need them".

Nice.

Read this if you like shrimp

Shrimp are tasty little morsels, but for years I’ve limited my shrimp intake because they’re high in cholesterol, or so I heard. Recently, though, I heard that they might good for you, so I decided to investigate. The results are a bit surprising.

First, shrimp is high in cholesterol, very high in fact. The American Heart Association recommends no more than 300 mg per day for a normal adult, but a 5-ounce serving of steamed shrimp contains 590 mg. For comparison, 2 large eggs contain about 580 mg of cholesterol.

On the other hand, shrimp is quite low in fat. That same 5-ounce (150g) serving of shrimp has just 1.7 grams of fat, while the same amount of beef has 14 grams of fat. So it’s low in fat, but high in cholesterol. What’s a shrimp-lover to do? Luckily, there’s a bona fide scientific study that attempted to answer this question – but with a catch, as we’ll see.

Searching the Web for shrimp and cholesterol, it’s easy to find lots of pages offering health and nutrition advice telling you that shrimp are good for you. But most of these webpages are from dietary advice “experts” who want to sell their books and diet plans, or from shrimp producers. Uh oh.

Science, medicine, and politics mix in new mammography and stem cell guidelines

Today's news included two stories that both illustrate how politicians almost always get science wrong. It never seems to be a good thing when politicians sink their teeth into a scientific or medical question: they are only too happy to distort the facts to achieve their political goals.

First, the new mammography guidelines. This was all over the news two weeks ago: an official federal advisory panel, the U.S. Preventive Services Task Force, recommended that women between 40 and 50, who had no risk factors for breast cancer, not have annual mammograms. This caused a firestorm of criticism from many quarters, because the previous guidelines recommended annual screening. The panel determined, after looking at data from the past decade and more, that the risks of excessive screening (many more false positives, and the resulting biopsies and even surgeries) were not justified by the small number of additional cancers detected.

This is a complex issue, and many other bloggers wrote about it, so I'm not going to discuss it in detail. My overall impression was that the panel weighed the evidence and made their recommendations based on the best available science, and I think their decisions were good ones. I'd also note something that the media seems to have missed: about ten years ago, when another panel was debating similar recommendations, there was tremendous political pressure to make annual screening the official policy.

Stimulus funds are promoting pseudoscience at Harvard Medical School

Another in an ongoing series of blog posts about wasteful spending by NCCAM, the National Center for Complementary and Alternative Medicine

In today’s competitive research environment, if the government offers money for something, then someone will do it – even if the research is worthless. This even happens at Harvard (where, it so happens, I got my Ph.D.).

Let's look at how, just recently, NIH funnelled more money to acupuncture. Bruce Rosen of the Massachusetts General Hospital and Harvard Medical School has secured two stimulus grants totalling $1.8 million to study acupuncture’s effects on brain activity. This was clever in two ways: first, Rosen took advantage of the fact that the National Center for Complementary and Alternative Medicine (NCCAM), the home of pseudoscience within NIH, had some stimulus funds that it had to spend quickly. Second, his studies simply use imaging techniques (fMRI) to look at patients’ brains during acupuncture. This virtually guarantees that he’ll find something: if you stick a needle into a person’s body, then of course the brain reacts! It hurts, doggone it! And if you compare this to sham acupuncture, where the pain is a bit different, then voila! you find that the fMRI looks different! Ergo, acupuncture must be activating some special brain functions. Clever!

Specifically, here are the stimulus funds that Rosen just landed:
2P01-AT002048-06 “Neuroimaging Acupuncture Affects on Human Brain Activity, $1,200,061
1P30-AT005895-01 , “Core Center for Multimodal Evaluation of Acupuncture Mechanisms”, $593,196

Here’s how Rosen introduces one of these projects:

“Acupuncture, a component of traditional Chinese medicine, has been used for thousands of years to treat a multitude of ailments. Recent scientific evaluation has suggested that this therapy may demonstrate clinical benefit for a number of conditions including chronic pain, though the mechanisms of action have not been well understood.”

Here we have, in his very first sentence: a classic logical fallacy (the “argument from authority”), right at the beginning of the proposal. Even if a treatment has been used for thousands of years (and let me note here that this is not true of acupuncture, despite numerous claims to the contrary), that doesn’t mean that it works. And of course, in ancient times people had a life expectancy of about 30 years, so we don't exactly want to go back to those days. Rosen follows this fallacy with the “suggestion” that acupuncture might work – and note how vague his claim is, using the phrase "may demonstrate" – despite the fact that all the properly-controlled studies show the opposite. In fact, recent studies show quite convincingly that “sham” acupuncture works just as well, even if the needles don’t penetrate the skin! And with placebo treatments, you get the benefit (such as it is) without the risk of infection from needle sticks.

Rosen has impressive credentials, with a Ph.D. in physics from MIT and an M.D. from Hahnemann Medical College. And he’s probably a really smart guy - who got taken in by pseudoscience somewhere along the way. A look at the publications on his acupuncture center’s website reveals almost no publications in the peer-reviewed literature since 2005. OK, maybe his web page is out of date, so I looked on PubMed and found two – only two – publications by Rosen on acupuncture and MRI in the past two years. Both were small, poorly controlled studies, and one appeared in BMC Complementary and Alternative Medicine, a rather pathetic excuse for a journal. With this kind of productivity, no wonder NCCAM gave him another $1.8 million!

But NCCAM loves this stuff. They even feature a picture from one of Rosen’s (two) studies on their website in their latest newsletter. It doesn’t matter if acupuncture works, as long as you can generate cool MRI images of people’s brains. Hey look, it’s an MRI – it must be science!

So Bruce Rosen is getting $1.8 million in stimulus funds to take worthless MRI images of patients’ brains while someone sticks them with needles. And this $1.8 million is merely a supplement to his ongoing NCCAM work – he’s been funded by NCCAM since at least 2003, (see the “06” at the end of that first grant number above? That means it’s in its 6th year of funding) and he proudly states that “our well-established group has been a leading force in acupuncture mechanism research for over a decade.” Great.

Finally, if Bruce Rosen reads this and feels I’m unfairly attacking him, well, he can reply on this blog (comments welcome!), or he can talk to me in person in February, when I’ll be giving a talk at Harvard Medical School, his home turf.

Merck hiding negative results about drugs, again

You’d think that after the Vioxx fiasco, Merck might be a little more careful about pushing drugs that don’t offer much benefit. Well, if you did think that, you’d be wrong. A new study in the New England Journal of Medicine this week shows that two very, very profitable cholesterol drugs are pretty much useless. Merck has been at least partly aware of this for 3 years, but they still don't want to admit it – not surprising given that sales of these drugs by Merck last year totalled over $4.5 billion. That’s “billion” with a "b." Merck has also been advertising these drugs heavily since they were approved by the FDA in 2002, and it has paid off.

So what are these drugs? They’re called Vytorin and Zetia, and first of all, they’re not statins (which many of you may have heard of), which are indeed useful at lowering cholesterol. The newer drug is called ezetimibe; Zetia is the brand name, while Vytorin is a combination of ezetimibe and a statin drug. Merck makes statins too, and they have been enormously profitable, but with statins I’d say the drug makers have earned their profits (at least some of them).

What did the new study find? Well, to quote the article itself, “niacin is superior to ezetimibe”, and the NEJM editors wrote that, “the findings, obtained in a modest sample of 208 patients, followed for only 14 months, show a clear superiority of niacin over ezetimibe.” That’s right, the use of inexpensive, non-prescription niacin (vitamin B) was clearly better that Zetia. It’s worth noting that the study wasn’t measuring the rates of heart attack; instead, it measured the thickness of the common carotid artery as a surrogate, on the assumption that thickening of the arteries leads to heart attacks. But there were also more heart attacks, and more deaths, in the patients on Zetia – not enough to reach statistical significance, but perhaps that was only because of the small number of subjects. The trial was halted early when it became clear that niacin worked better, and it might be harmful to the subjects to continue giving them Zetia (ezetimibe) instead.

I found another NEJM article from April 2008 that showed that combining Zetia with statins was no better than statins alone.

So what did Merck have to say? Astonishingly (or not?), they are continuing to promote Zetia aggressively, and they issued this statement a few days ago: “"The results of the small ARBITER 6 study do not, in any way, change our view of Zetia and Vytorin as effective medicines for fighting high LDL cholesterol," said Peter S. Kim, Ph.D., president, Merck Research Laboratories. “We encourage patients to continue taking their medication as prescribed by their physicians.” Really? The results don't change his view in any way?

This latest news comes just 3 months after Merck and Schering-Plough agreed to pay $41.5 million to settle a lawsuit that accused them of sitting on unfavorable results about Zetia and Vytorin for two years. That lawsuit was based on results released in January 2008, describing a study that ended two years earlier.

This is the kind of greedy, evidence-be-damned behavior that encourages conspiracy theorists to make wild accusations about drug companies. The problem is, sometimes their accusations are true, even if the drug companies do produce many beneficial products. One thing the U.S. should do is put a stop to direct-to-consumer marketing of drugs, ads like the one below, which claims that Vytorin is better than statins alone. Note how it doesn’t directly claim that Vytorin will reduce your risk of heart attacks, but it cleverly implies that it will:



Now that is insidious. We should never have allowed direct marketing of drugs, and we can still put a stop to it.

10,000 genomes – why?

In the genomics world that I inhabit, a consortium has just published an intriguing proposal to sequence the genomes of 10,000 vertebrate species. It’s described an article in the current Journal of Heredity – unusual in that this is not a research article, but a proposal. Nonetheless, the article is full of interesting facts about what we know (and don’t know) about vertebrate species and how they’re all related. It makes a good read for anyone interested in evolution; for example, how many people know that all vertebrates have a common ancestor who lived about 500-600 million years ago? Perhaps more interesting, evidence is emerging that we all share about 10,000 genes – which means that these 10,000 genes are so useful that their functions have been preserved for 500 million years.

The consortium is led by a number of outstanding scientists, including UCSC’s David Haussler and NIH’s Stephen O’Brien, both of whose work I like and have followed for years. And some aspects of this proposal are terrific: for example, they want to start collecting DNA now from 16,203 vertebrate species. This will make a great specimen collection for future work. (Heck, maybe I’ll even sign on to the project myself.)

But this proposal is more than that: it is also the opening salvo in an effort to raise $50-100 million for the sequencing of these species. The paper was announced with press releases and news articles in both Science and Nature, demonstrating that it is clearly a lobbying effort for new funding. Fair enough – science takes funding, and sometimes you have to build support for new ideas. However, given that two of the three leaders of the consortium are primarily funded by NIH, I can only guess at who they’re expecting to cough up the money. The NIH's human genome funding has been led by NHGRI, which continues to look for new ways to justify maintaining the size of its three enormous sequencing centers (the Broad Institute, Washington University in St. Louis, and Baylor College of Medicine). Now, let me say here that genomes are the bread and butter of my own work, and these centers have done terrific work for the past 10-15 years - and I've often collaborated with them. And I hope they will continue. But it hasn’t escaped my attention that the new NIH Director, Francis Collins, was a key force in building up those centers while he was Director of NHGRI, and we all know that the centers are near and dear to him.

But wait a minute: 10,000 genomes, none of which are human? Exciting idea, sure, but not for NIH. The NIH-led centers are already participating in the 1000 Genomes project, which is attempting to sequence 1000 individuals (at a low-level “draft” quality). If NIH wants to scale up, there are 6 billion more of us available. Admittedly, not everyone wants to have his/her genome sequenced, but plenty of us would be happy to volunteer. Take a look at the Personal Genome Project, which was started by George Church at Harvard, and is trying to sign up 100,000 humans to have their genomes sequenced.

So I’m going to be the skeptic here: if NIH is thinking of throwing its sequencing dollars at 10,000 more genomes, I suggest that it focus on humans rather than a broad collection of other vertebrates. (I know, this should be obvious, right? But sometimes NIH gets distracted.) We still have only scratched the surface of what there is to know about the human genome, and there’s plenty of DNA sequencing to do in the human population. The 10,000 genomes project sounds like a great mission for the National Science Foundation, which has ceded much of large-scale sequencing work to the NIH in the past 10 years, except for plant genomes and some bacteria. In fact, maybe this is a chance for NSF to have its own large-scale sequencing center – I’d be all for that. But I’m not at all convinced that NIH should spend its biomedical research dollars on 10,000 vertebrates. Let’s see how this plays out.

Flu vaccine shortage

This is just a brief post to point out a news article on the wires today (from Agence France-Presse) quoting me at some length about the shortage of H1N1 (swine) flu vaccine in the U.S. The article discusses why the egg-based vaccine production method, which is woefully obsolete, needs to be replaced if we're to avoid such shortages. I also made a point about how risky it is for us (as a society) to be relying on chicken eggs for a virus that could wipe out chicken flocks. See the article at Yahoo news, here, or at the Daily Telegraph in the UK, here.

More misinformation on the flu from Mercola

As a followup to my post a few weeks ago on scare-mongering about influenza vaccines, I want to point out a beautiful dismantling of Dr. Mercola's latest nonsense by my colleagues over at Science-Based Medicine.

It seems that Mercola posted an article on his website titled "Do NOT Let Your Child Get Flu Vaccine -- 9 Reasons Why". (I'm not providing the link because I don't want to increase his web traffic, not even a tiny bit.) Not surprisingly, every single reason is wrong, misleading, stupid, or all three. As Dr. Joseph Albietz writes in his post, "There are so many mistakes, so much misinformation in so little space, it’s almost a work of art."

I don't want to repeat all of Dr. Albietz's dismantling of Mercola's bogus claims (I recommend reading his post for the full list), but I want to mention a couple, just to show how dishonest - or maybe just plain stupid - Mercola is. Here, then, are some of his reasons for not vaccinating your children:

"5. Over-vaccination is a common practice now in America. American children are subjected to 29 vaccines by the age of two."

Wrong and wrong. First, "over-vaccination" is a term invented by anti-vaccination groups. There is no evidence that you can over-vaccinate - all the vaccinations available today help to prevent infectious diseases. More vaccines simply prevent more diseases. Second, there are only 10 vaccines on the routine schedule in the U.S., not 29. Some of them require booster shots, but these are not separate vaccines. But in any case, this is irrelevant because even if there were more, the evidence shows that they are beneficial.

Mercola's sixth reason is this:

"6. Modern medicine has no explanation for autism, despite its continued rise in prevalence. Yet autism is not reported among Amish children who go unvaccinated."

This one I've seen before. Jay Gordon, well-known anti-vaccination doctor and Jenny McCarthy sidekick, said the same thing on Larry King Live last year. This too is wrong, as Dr. Albietz also pointed out. The Amish do have autism, and they do vaccinate. So this is just a complete non-sequitur. It has nothing to do with the influenza vaccine.

Perhaps the most outrageous scare-mongering is this one from Mercola:

"3. Adjuvants are added to vaccines to boost production of antibodies but may trigger autoimmune reactions. Some adjuvants are mercury (thimerosal), aluminum and squalene. Why would you sign a consent form for your children to be injected with mercury, which is even more brain-toxic than lead?"

Note the use of the incredibly hysterical phrase "brain-toxic". Scary indeed, if only it were true. But no, this is wrong, wrong, wrong. First, the tiny bit of truth: yes, adjuvants are small trace elements, including aluminum, that make vaccines more effective. Note that this allows vaccines to be effective with a smaller dose of the immune agent, and there's never been any evidence that adjuvants are harmful (they've been used in vaccines for 50 years). But there is no adjuvant in the H1N1 vaccine. That's right - so again this is a non-sequitur, since it doesn't apply to the flu vaccine. And thimerosal is not an adjuvant - it's a preservative used in multi-dose vaccine vials, to prevent bacteria from growing in those vials. So that's wrong too. But wait - there's no thimerosal in the single-dose vaccines, and there's none in FluMist (the nasal version of the vaccine) either. And even if there were, there's now a huge body of evidence (too much to summarize, but look here for a start) that thimerosal has no harmful effects whatsoever.

Mercola's scare-mongering seems designed to promote his own unscientific, unproven vitamin therapies, which he sells on his website. The webpage with his "9 reasons" also contains instructions on "How to protect yourself without dangerous drugs and vaccinations." Not suprisingly, his advice is to buy his vitamin supplements and other products.

I can't tell whether he's just ignorant or whether he's intentionally misleading people to sell his products, but either way, he's a threat to public health.

Taking advantage of cancer patients

How much is 10 months of your life worth? What if you only have 14 months to live?

How should we react to a doctor who takes advantage of some of the most desperate cancer patients to sell them a therapy that doesn’t work? What if, after scientific evidence shows it isn’t working, he continues to promote his therapy and offer it to patients? What if he chooses one of the most intractable cancers, pancreatic cancer, which is a near-certain death sentence, and tells patients to use his therapy instead of the one therapy that offers a small chance of working?
Is scorn a strong enough feeling for such a doctor? Shouldn’t we try to do everything we can to stop him? Well, please meet Nicholas Gonzalez, M.D., who, according to his very own website, treats pancreatic cancer with “diet, supplements (with proteolytic enzymes for cancer patients) and detoxification routines such as coffee enemas.”

Gonzalez invented the “Gonzalez regimen” nearly 30 years ago, and he claims on his website that pancreatic cancer patients in his care have experienced near-miraculous recoveries and far longer survival times than patients receiving normal care. After lobbying Congress directly (again, according to his own website), Gonzalez convinced NIH (with help from Rep. Dan Burton of Indiana) to fund a trial of his regimen, comparing it to the only available chemotherapy. The regimen is quite complicated, so I’ll reproduce it exactly here, from the NIH trials website:

”Patients receive pancreatic enzymes orally every 4 hours and at meals daily on days 1-16, followed by 5 days of rest. Patients receive magnesium citrate and Papaya Plus with the pancreatic enzymes. Additionally, patients receive nutritional supplementation with vitamins, minerals, trace elements, and animal glandular products 4 times per day on days 1-16, followed by 5 days of rest. Courses repeat every 21 days until death despite relapse. Patients consume a moderate vegetarian metabolizer diet during the course of therapy, which excludes red meat, poultry, and white sugar. Coffee enemas are performed twice a day, along with skin brushing daily, skin cleansing once a week with castor oil during the first 6 months of therapy, and a salt and soda bath each week. Patients also undergo a complete liver flush and a clean sweep and purge on a rotating basis each month during the 5 days of rest.”

Not an easy therapy for the patients, who had to consume over 100 pills a day in addition to the strict diet, enemas twice a day, and special baths. But does it work?

NO. In fact, the results of this trial were finally published just last month, in the Journal of Clinical Oncology – after 4 years delay – and we now learn that patients undergoing the Gonzalez regimen died in just 4 months, on average, compared to 14 months for patients in chemotherapy. Now 14 months might not seem like a good result, but when you only have 14 months to live, I’m sure you don’t want to die 10 months earlier while taking hundreds of pills and enduring twice-daily coffee enemas. This is quackery of the worst kind, killing the patients and making them miserable for the few months they have to live – according to the JCO article, patients had a worse quality of life under the Gonzalez regimen as well as having a much shorter survival time.

(Note that Kimball Atwood written extensively on the problems with the Gonzalez regimen, including links to his earlier posts on this subject, so I’ll try not to repeat too much of his excellent summary here.)

Not surprisingly, Gonzalez has had a major falling out with his collaborators on the study, who published the article without him as a co-author. So how did he react to these results? Did he have second thoughts, and perhaps consider whether he should stop selling his ineffective therapy (and offering false hopes) to pancreatic cancer patients?

Unfortunately, Gonzalez hasn’t changed his beliefs one bit, and he posted a lengthy “rebuttal” of the JCO article on his site soon after he learned about the article (which he apparently was unaware of until it appeared). In it, he boasts about how he alone was responsible for getting the study funded (“the grant was approved and awarded during a face-to-face meeting between me and the then NCI Director, Dr. Richard Klausner, held in the office of Congressman Dan Burton”), complains about being betrayed by the authors (his former collaborators), and maintains that it “implies falsely the study proves chemotherapy more effective than my treatment.” He goes on endlessly, complaining about how the scientists who ran the study at Columbia University mismanaged everything, and claiming that this is why the results didn’t show that his regimen worked. According to his diatribe, NIH, NCI, and the Columbia scientists were all part of a big conspiracy to hide the truth about his regimen. If there's any conspiracy here, it's Gonzalez's efforts to delay publication of this study and hide the results from his potential future patients (or should I say victims?). (And for those who want to blame "big pharma" for conspiring against Gonzalez, note that he proudly reports on his site that he has received millions of dollars in funding from two large for-profit corporations.)

The story of how this study got started in the first place is disturbing on many levels, and I will point readers again to a blogpost by Kimball Atwood’s for more details. Among other things, the investigators at Columbia University were warned repeatedly about violating IRB protocols on informed consent. And the basis for the study was a claim by Gonzalez – based on 11 patients whom he claims to have treated for pancreatic cancer – that he was achieving survival times substantially longer than standard therapy. It appears that he (in the most generous interpretation) chose selectively among patients to produce this claim.

Gonzalez has been investigated and put on probation in the past by the N.Y. medical licensing authorities, and has been sued successfully for malpractice, after recommending that a woman forego standard cancer therapy and take his treatment instead. (As Quackwatch documents, “he claimed that the cancer was cured even though it was progressing. It eventually damaged her spine and left her blind.”) Despite these past mishaps, he continues to offer his regimen to cancer patients, and his website today still contains claims of multi-year survival for many of his past patients.

Gonzalez is taking advantage of vulnerable, desperate patients and selling them a painful treatment that merely kills them faster. NIH deserves blame here too, as does NCCAM (the National Center for Complementary and Alternative Medicine), which funded this unethical trial, and especially Congressman Dan Burton, whose support for pseudoscience has in this case caused inexcusable harm to patients whose lives were cut short. And the physicians at Columbia who went ahead with the trial are not without blame either.

How should I react to Gonzalez? Should we give him the benefit of the doubt, and assume he’s just trying to do the best for his patients? Should we believe his claims of a conspiracy and fund more investigations into his elaborate regimen for treating pancreatic cancer? Or should we take away his license, and do anything else we can to prevent him from offering this therapy ever again? I know what I think. I am appalled.

Note: I also recommend Orac's article on this topic, titled "The Gonzalez protocol: worse than useless for pancreatic cancer."

Scare-mongering about the flu vaccine and cancer

I guess I shouldn't be surprised. The anti-vaccination activists, the same people who continue to claim that vaccines cause autism, despite the overwhelming evidence to the contrary, have invented a new way to scare people in order to prevent them from getting the vaccine against the new pandemic flu strain (aka swine flu). Here is the headline, which appeared yesterday on several websites:

"Another Shocking Warning About Swine Flu Vaccine"

The article begins with this gem: "The swine flu vaccine has been hit by new cancer fears after a German health expert gave a shocking warning about its safety." This "warning" was news to me: did you know that the vaccine can give you cancer? Neither did I. The source of this new claim is Wolfgang Wodarg, a German politician who is described in the article as a "lung specialist." The article on mercola.com (the website of Dr. Joseph Mercola, more about him below) calls him "Dr. Wodarg", but when I checked Wodarg's own websites, I found that he was a politician in the German parliament who claims to be an expert on health matters. Whatever his claims, though, he doesn't know beans about the flu.

Despite the lack of credibility of the source, I wanted to know where in the world this seemingly-crazy claim came from. Was there anything to it? The main claim is this: "The nutrient solution for the vaccine consists of cancerous cells from animals, and some fear that the risk of cancer could be increased by injecting the cells." Let's break this down.

There are at least two claims here: first, that the vaccine is grown in "cancerous cells from animals," and second, that "some" people are afraid that this could give them cancer. Let's deal with the second claim first. No references are given in the original story, and it appears to be completely invented. Mercola just repeats the invented claim, which in its original form read: "some people fear that the risk of cancer could be increased by injecting the cells." How can a reporter just make this up? My guess is that simply by stating that "some people" have this fear, the reporter has created a self-fulfilling claim - after reading about the "fear", it is entirely possible that some people will begin to fear the same thing. Whatever the case, it's extremely irresponsible to make this statement without providing any proof.

Now let's look at the first claim. Here there is a very tiny little speck of truth, grossly misrepresented and distorted. This is a common strategy among conspiracy theorists and quacks: find some little factoid and then make wildly distorted claims about it. Then when experts (real ones, not fake ones like Wolfgang Wodarg) are asked about the claim, they will endeavor to explain the truth, but in trying to be clear and accurate, they will give credibility to the original claim. I'm going to try to be clear and accurate here, but first I want to say that this entire story is complete and utter nonsense, and Wolfgang Wodarg is an irresponsible idiot for starting it. If people follow his advice, many will likely get very sick, and some people might die. There, got that out of the way.

So let's look at the "cancer cells" claim. First of all, the claim doesn't apply at all to the vaccines made in the U.S., which are grown in chicken eggs. It refers to a new vaccine manufacturing process that involves cell lines, which is being developed in Germany and in a few other European countries - and which will lead to much more rapid, efficient production of vaccines in the future. (The flu vaccine, as I've written in the journal Nature, is produced using out-of-date methods that are far too slow.) The Dr. Mercola website make no mention of any of this - possibly because Mercola is ignorant of it. But what about the German vaccine?

Here's the scoop: the company Baxter announced in August that it was testing its new H1N1 vaccine, grown in a Vero cell line, for safety and effectiveness. If it passes, it may be approved for use in Europe. Growing the virus in a cell line is much simpler, and faster, than growing it in eggs. The Vero cell line originally isolated in 1962, came from kidney epithelial cells from an African green monkey. These cell lines have been used for many purposes over the years, including vaccine development. And here's the grain of truth in Wodarg's claim: yes, Vero cells can be called "cancer" cells. Many cell lines are cancer cells, in that they divide and grow indefinitely (stem cells also have this feature). If they didn't, they wouldn't be much use as cell lines - the cells would simply die after a relatively short time.

However - and here's where Wobarg goes right off the rails - there is no evidence that Vero cells have ever caused cancer. These cells have been used in the past to produce other vaccines, including rabies and measles (references are easy to find), and no humans have ever gotten cancer from these vaccines. So there is no legitimate reason to believe that the flu virus will cause cancer. I'd probably have to write ten more pages to demonstrate why these cells don't pose a cancer risk, and there lies the insidiousness of the claims by Wodarg and Mercola: they made their outrageous claim with no evidence at all, but now, to refute it, I could spend hours and hours looking at the history of vaccines made using Vero cells.

And wait: there's a third claim buried in the sentence about the fear of cancer: by writing "some fear that the risk of cancer could be increased by injecting the cells", Mercola is claiming that cancer cells will be injected into your arm if you get the vaccine. Sorry, Dr. Mercola, that's not true. The vaccine is grown in a cell line, purified to remove the Vero cells, and then the virus particles themselves are killed. So this third claim is bogus too. But just like the others, to disprove it thoroughly, I'd have to dig through the literature on cell cultures, purification, and vaccine testing. Mercola didn't bother to look at any real science, as far as I can tell.

This article was posted on mercola.com on September 8 (yestesday, as I write this), and it appears to be spreading quickly among the anti-vax movement, with postings on Facebook and elsewhere. Unfortunately, the likely effect of this is to reduce the number of people who get vaccinated for swine flu, which in turn will increase the severity of the pandemic as it continues to spread this fall. Even worse, nonsense like this increases the average person's overall distrust - or fear - of vaccines, which has even greater public health consequences.

Why does someone who claims to be a doctor (Mercola) do this? Why does he want to keep people from getting vaccinated? Is he so interested in money and self-promotion that he just doesn't care? Is he so poorly trained and ill-informed that he really believes this drivel? It would have taken him about 5 minutes to figure out that the Vero cell line isn't used for vaccines made in the U.S. - why didn't he point that out, rather than warning all of his readers (mostly in the U.S.) about this new "risk" of vaccination? To me, this kind of reckless disregard for the facts indicates that he just doesn't care.

I looked a bit further into "Dr." Mercola (an osteopath, not an M.D.), whose website is awash in self-promotion as well as offers to buy his books and other products, and he is more than just an anti-vaccination quack. He makes all kinds of unsubstantiated health claims about his products (and he has an entire website devoted to selling them), and it wasn't too hard to learn that he has violated federal regulations at least twice: in 2005 and again in 2006, the FDA ordered him to stop making illegal claims about multiple products he was selling on his website (see the 2005 FDA letter here, and the 2006 FDA letter here). Not surprisingly, these FDA warnings did little to slow this guy down.

Mercola is a conspiracy monger as well - he recently posted an article titled "Do Drug Companies Secretly Favor a World Flu Pandemic?" which claimed, in addition to its wacky title, that vaccines "don't work" and that they pose a "significant health risk" to children. And today he posted a video accompanied by the claim that "studies show that flu vaccines are unsafe and ineffective." This guy must have a few wires loose somewhere. Or he is one greedy, uncaring quack. Or both.

Why the ad hominem attacks, you ask? It's true that regardless of how much of a quack Mercola might be, that doesn't mean that everything he says is false. However, once we learn that someone is willing to lie in order to promote bogus medical treatments (see the FDA violations I mentioned above), we should view any future claims from that source with great skepticism. I can't stop Mercola from making his pseudoscientific statements, but perhaps I can convince a few people that they shouldn't believe anything they read on his site.

In the meanwhile, people, get yourself vaccinated against the flu!

Opening up influenza research with a new kind of journal

Today is the launch of a new type of online publication, a cross between website and a "real" journal, called PLoS Currents: Influenza. What is it? Well, it's a website for immediate publication of new findings about the influenza virus. Submissions are screened by a panel of moderators (I'm one of them) and if they are appropriate, we will publish them immediately - no delays - and they will be freely available for anyone to read. They will also be given a permanent, searching PubMed identification, just like a regular journal paper.

What's the difference between this and a regular journal? Well, first of all, submissions won't be thoroughly reviewed, which means they don't "count" as journal papers, but it also means you can publish them later in a peer-reviewed journal. The Public Library of Science has already bought into this model - they're sponsoring PLoS Currents, after all - and we expect other journals to do so also. So why publish, you might ask? That's easy: in a highly competitive field such as influenza research, different scientists are often racing to answer the same question. By publishing super-rapidly in PLoS Currents, you will get a citable, time-stamped reference that establishes your discovery, and most importantly, establishes when you made it.

The big win here, we hope, is that scientists will be empowered to announce their results to the world without worrying about being "scooped" - a common fear that leads to many results being kept secret for months while papers are prepared and revised. This in turn will speed up scientific progress overall, which is the real goal behind PLoS Currents.

Also, because we aren't looking for complete manuscripts (although those are fine too), we'll accept new observations, new data, and more speculative ideas (as long as they have some data to support them) in PLoS Currents.

We're also pioneering a new way to author papers, using the Google Knol software. After writing your contribution in Google Knol, submission will require little more than a few mouse clicks. To launch the journal, four of its moderators (with colleagues) have posted the first few contributions just these week. Check it out here.

If PLoS Currents: Influenza is successful, it will open the door to an almost unlimited set of new publications in virtually any scientific field. We chose influenza because, with the recent emergence of the new H1N1(A) pandemic flu strain, it became clear to many of us that waiting the typical 3-4 months (at best) for results to appear was just too slow. Similar delays occur in virtually every other area of biomedical research, and it's time we took fuller advantage of the web to speed things up.

Bad medicine at M.D. Anderson Cancer Center

M.D. Anderson Cancer Center (at the University of Texas) is one of the top cancer treatment centers in the United States, and probably in the world. This makes it especially disheartening to see that they have a new website, Cancerwise, that endorses pseudoscientific treatments; in other words, it promotes bad medicine. From what I can see, most of the site discusses perfectly reasonable topics, which makes their endorsement of “woo” especially insidious – how is a patient, or even a scientist from another discipline, supposed to distinguish the real science from the quackery?

What caught my notice in particular – although this is not the only example – is the article “The 3 Most Common Questions People Ask About Acupuncture” written by Lorenzo Cohen. As I and many others have pointed out in previous blog posts, and as the scientific literature shows quite clearly now, acupuncture does not work. When compared to placebo in published trials, the benefits of ‘sham’ acupuncture, where the needles don’t even pierce the skin, are the same as those for ‘real’ acupuncture. Likewise, when the needles are inserted in random positions instead of the ‘real’ acupuncture points, the effects are indistinguishable. So it doesn’t matter where you place the needles, and it doesn’t matter if they pierce the skin – in other words, the only effect is the placebo effect: if a patient believes in acupuncture, and he/she thinks he/she is getting treatment, then they report a mild, subjective improvement in certain types of pain.

With that in mind, here is a disturbing bit of pseudoscience from Cohen’s article:

“The effects of acupuncture also tend to be cumulative, so it's important not to expect too much too soon. At M. D. Anderson, we consider 8-10 treatments as one course, and for long-term problems, multiple courses may be necessary. I often tell patients with chronic conditions, ‘It's like fertilizing your garden -- don't expect the flowers to bloom tomorrow. In the long-term, though, you should end up with a better result.’ "

This is complete nonsense - there is no scientific data to support it. But what is a patient supposed to think when he/she reads that M.D. Anderson recommends 8-10 acupuncture treatments for their patients?

Cohen also throws in this canard, a quote from his own “integrative medicine” director: “"Can't hurt, might help, why not!" Here’s why: there are real risks to acupuncture, such as infection, and the scientific evidence says the benefit is zero. So here’s my reply: can’t help, might hurt, why do it?

Then, in the section titled “What should I use acupuncture for?”, Cohen writes:

“...it's always a good idea to recommend acupuncture when the patient is:
* Experiencing uncontrolled nausea, vomiting or pain.
* Experiencing side effects from treatment or medications.
* Has failed conventional treatment for symptom control.”

Always? Always? How about “never”? There isn’t a single well-done clinical trial demonstrating the effectiveness of acupuncture for any of these conditions. (For a summary of some of the evidence showing its ineffectiveness, see this link at Science-Based Medicine.) Other scientists at M.D. Anderson (are they even paying attention?) should step in and do something to make it clear that the institution doesn’t recommend pseudoscientific, unproven therapies for anything.

There are other articles promoting pseudoscientific methods on the Cancerwise site, including this one, which applauds Sen. Tom Harkin for his support of NCCAM (which I’ve written about multiple times) and alternative/integrative medicine. I’m sure we’ll see more such articles there, and it’s very dismaying to see woo-meisters like Lorenzo Cohen make progress in their attempts to drag us back into the past, when medicine was little more than guesswork and superstition.

One of our jobs in academia is to be especially critical of ourselves, so when we see an academic center making mistakes, we call them out on it. So I’m joining other bloggers in doing so – notably Orac, who wrote about this same topic last week. (I highly recommend Orac’s lengthy discussion – he thoroughly dismantles Cohen’s claims, including Cohen’s references to studies that supposedly support those claims.) I don’t know who at M.D. Anderson is responsible for the Cancerwise site, but they have a list of 18 authors on that page, and I hope that at least some of them will be concerned to know that they are endorsing pseudoscience.

Here's an idea for another article at Cancerwise: the title can be identical to one of Cohen's section headings: "What should I use acupuncture for?" And the article can be very short, just one word: nothing.

It’s the 2009 Mexican flu - or is it S-OIV H1N1(A)?

Millions of people have already been infected by the new pandemic influenza virus, and the number may well climb over a billion. The CDC recently estimated that up to 40% of U.S. citizens may be infected over the next year, a startlingly high number. Close to home (for me), several children in my neighborhood came down with influenza just last week. They all recovered, fairly quickly. They almost certainly had the new H1N1 pandemic strain, which seems to be spreading rapidly despite the fact that flu season is normally in the winter. A postdoc in my lab was the first person I know who caught the new pandemic flu – he came down with it in early May, and was very sick for a week. (He stayed home, and no one else was infected, as far as I know.)

But the media are still calling this “swine flu”, in headlines all over the world. Government authorities decided early on to call it 2009 H1N1(A), a catchy name if there ever was one. In one of the earliest scientific publications, CDC scientists called it S-OIV, for “swine-origin influenza virus”.

Nice try, but the media aren't buying it. The problem with the name "swine flu" is that it’s not a swine flu any more. Once an influenza virus has become established in humans, it’s a human flu. If you catch the “swine flu”, you’ll get it from another human – not from a pig. So what to call it?

The choice of a name is actually pretty clear: each of the three 20th-century flu pandemics was named after the geographic location where people believed it originated: the 1918 Spanish flu, the 1957 Asian flu, and the 1968 Hong Kong flu. As best we can tell, the new H1N1(A) virus originated in Mexico, and therefore we should call it the 2009 Mexican flu. This will be accurate and consistent with historical precedent.

And by the way, this idea has already been proposed, but the Mexican government objected, so government health authorities, including the WHO, immediately backed down and looked for a more politically acceptable name. Several countries have already started using the term Mexican flu, including Belgium and Israel, as the AP reported yesterday – although the English-speaking world is still using “swine flu.”

As a side note, we now know that the Spanish flu should have been called “American flu” or possibly “Kansas flu” (where it really started), but during World War I, the U.S. didn’t want to admit that it had a serious health crisis, nor did any of the European countries involved in WWI. The Spanish got stuck with the name – incorrectly – because they didn’t try to hide the fact that they had a pandemic on their hands.

So a note to headline writers in the media: I don’t blame you for calling it swine flu and ignoring alternative names such as S-OIV and H1N1(A). But it’s misleading to use the term “swine flu”, which is already used to refer to influenza viruses circulating among pigs. Calling it “swine flu” also led to the foolish decision by some countries to slaughter large numbers of pigs, which was completely ineffective at controlling the spread of the new virus.

It’s a human flu, and it started in Mexico, so let’s call it Mexican flu.

Stimulus funds for pseudoscience

The stimulus funds that the U.S. Congress recently gave to NIH will include $31 million in additional funding for NCCAM, the National Center for Complementary and Alternative Medicine. This is in addition to the $125 million they already had in the current year’s budget. Great. If we spent those funds digging holes and filling them in again, at least a few people might get some exercise, which would benefit their health. That would be a better use than giving the money to NCCAM. Why? Because funding bad science is worse – in many ways – than not funding anything at all. NCCAM continues to provide a home for all sorts of pseudoscience, quackery, and practices that are really no different from voodoo or witchcraft. Allowing NCCAM to operate out of NIH not only gives it an unearned veneer of respectability, it also damages the reputation of NIH. I hate to see this, because NIH is the crown jewel of our biomedical research system.

Let’s look at what NCCAM features on its home page right now. It features the headline “Take charge of your health” followed by six topics. A visitor to the site would have every reason to expect to find sound, science-based advice that would benefit your health under each of these topics. Alas, this is not the case. The first topic is acupuncture, so let’s look at what NCCAM says about it.

The NCCAM accupuncture page is, frankly, an embarrassment. It is one long apologia for acupuncture, dancing around the facts while trying not to admit that the evidence for acupuncture is nonexistent. Indeed, it appears that the authors of the page know that acupuncture doesn’t work, and are trying, in a tortured way, to avoid admitting the truth. The NCCAM's “Key points” on acupuncture are:

“(1) Acupuncture has been practiced in China and other Asian countries for thousands of years. (2) Scientists are studying the efficacy of acupuncture for a wide range of conditions. (3) Relatively few complications have been reported from the use of acupuncture. However, acupuncture can cause potentially serious side effects if not delivered properly by a qualified practitioner. (4) Tell your health care providers about any complementary and alternative practices you use.“

Interesting – the key points don’t include any specific benefits! That’s because every study done has shown that acupuncture doesn’t work any better than placebo, and of course placebo treatments don’t require sticking needles in your body. Let’s look at those key points more closely: the first one is merely an “argument from authority” – i.e., people have been doing this for a long time, and we are supposed to infer that therefore it works. Hardly! If we used the same medical practices that were used in China thousands of years ago, we’d have the same life expectancy – perhaps 30-40 years. Not good. Point 2 just states that studies are under way (funded by NCCAM, I might add), but doesn’t point out that all the studies are negative! The third point just says that you probably won’t be injured by acupuncture (but you never know). So it seems that the NCCAM folks know that science doesn’t support any benefit from the use of acupuncture, but they can’t just say that on their website – why? Because NCCAM’s staff view its mission (apparently) as the promotion of “alternatives” to medicine, even if those alternatives are nonsense.

Ah, but you might have heard that acupuncture does help to control some types of pain – that’s what its proponents argue. NCCAM has a lengthy page devoted to this topic. What are the key points here? Let’s look:

“(1) People use acupuncture for various types of pain. Back pain is the most commonly reported use, followed by joint pain, neck pain, and headache. (2) Acupuncture is being studied for its efficacy in alleviating many kinds of pain. There are promising findings in some conditions, such as chronic low-back pain and osteoarthritis of the knee; but, for most other conditions, additional research is needed. The National Center for Complementary and Alternative Medicine (NCCAM) sponsors a wide range of acupuncture research. (3) Acupuncture is generally considered safe when performed correctly. (4) In traditional Chinese medicine theory, acupuncture regulates the flow of qi (vital energy) through the body. Research to test scientific theories about how acupuncture might work to relieve pain is under way.”

These points are a pathetic attempt to apologize for acupuncture, without admitting that it doesn’t work. First they say that lots of people use it – true enough, but are we supposed to believe that means it works? In that case, why do any science at all? Why not just look at what people are doing, and follow their lead? Then they say that acupuncture is being studied by NCCAM, and they claim “promising” results in some conditions. But “additional research is needed” for others. Sorry, NCCAM, but more research is not needed – multiple studies have shown that acupuncture doesn’t work. If it weren’t for lobbying efforts by acupuncturists and their ilk, who have a major financial interest in seeing these studies continue, this topic would be dead. And point (4) about qi is just embarrassing. There's never been any evidence that qi exists, and NIH/NCCAM should not even mention it.

Recent studies have shown that “sham” acupuncture, where the needles are inserted in random locations, works just as well as “real” acupuncture. Furthermore, it doesn’t even matter if the needles pierce the skin! The patients get the same benefit as long as they think the needles went in. See a longer discussion of this at Science-Based Medicine, where Steven Novella describes one recent trial on acupuncture for back pain – exactly what the NCCAM site claims it works for. Novella expresses the results eloquently:

“Imagine if we were evaluating the efficacy of a new pain drug. This drug, when tested in open trials (no blinding or control) has an effect on reducing pain - it is superior to no treatment. When compared to a placebo, however, the drug is no more effective than the placebo, although both are more effective than no treatment.

Now imagine that the pharmaceutical company who manufactures this drug sends out a press release declaring that their drug is effective for pain, but that their research shows that a placebo of their drug is also effective (FDA applications are pending). Therefore more research is needed to determine how their drug works. Would you buy it?

That is the exact situation we are facing with acupuncture research.”

Despite the claims at the NCCAM site, acupuncture has not been shown effective for any type of pain, and it does have potential side effects – infection from improperly sterilized needles, for example. Why risk infection for a treatment with no benefit?

But wait, I’m not done. Recently, NCCAM proudly announced two new members of its Advisory Council. One of them, Xiaoming Tian, is an acupuncturist. (By Congressional mandate, a majority of the NCCAM board must be selected from proponents of “CAM”. Hmm, voodoo is an "alternative" medicine - I hope they included a voodoo-ist.) So who is this new advisor? His bio says that he is Director of the Academy of Acupuncture and Chinese Medicine at Wildwood Acupuncture Center in Bethesda, Maryland. It’s hard to find much about this school, or Mr. Tian, except from his bio on the website where it says he “has been practicing acupuncture and Chinese herbal medicine in Bethesda, Maryland since 1986” and he is “considered one of the leading researchers in acupuncture and Chinese herbal medicine.” However, he doesn’t seem to have any serious credibility as a researcher: I could locate only one study on which he appears as the second author. And in that study (R.E. Harris et al. The Journal of Alternative and Complementary Medicine. August 2005, 11(4): 663-671) the authors used acupuncture and sham acupuncture to treat fibromyalgia, and found no difference between the “real” and sham versions. That’s because all acupuncture is a sham.

NCCAM is worse than a waste of money. By allowing it to operate within NIH, Congress is giving a false veneer of respect to all sorts of bogus treatments that range from worthless to harmful. To those who argue that some of its funding goes to useful research: if a treatment is promising and scientifically sound, it can be funded by the existing NIH institutes and centers – it doesn’t need the special “free pass” for low-quality research that NCCAM offers. Let's find a better use for that $156 million that NCCAM is getting this year.

Dinosaur proteins from T. rex and hadrosaurs

The controversy over the finding of Tyrannosaurus rex proteins in a fossilized bone
continues, with a long article in Wired magazine this week exploring the issue. The Wired reporter, Evan Ratliff, takes a refreshingly skeptical view through much of the article. It's a good read, and I recommend it.

But first, an update on the science: Mary Schweitzer, John Asara and colleagues published a new report in Science on May 1 describing their analysis of an 80-million-year-old fossil from the dinosaur Brachylophosaurus canadensis, a hadrosaur that is 12 million years older than T. rex. Once again, they found fragments from collagen, the protein that is a major component of bone, and as with their original T. rex study, they claim that these represent original dinosaur proteins. And as before, they found that the dinosaur proteins most closely resemble modern birds – in particular, ostrich.

The new study spends a significant amount of effort addressing the question of contamination. This question has been raised in at least two ways. Tom Kaye and colleagues reported in PLoS ONE that the soft tissue found by Schweitzer could be explained as a bacterial biofilm, rather than as preserved dinosaur tissue. I still like the biofilm explanation, and I don’t see how the new study refutes it. The study contains many microscope photos showing how the fine structure of the fossilized bone resembles modern ostrich bone, but preserved physical structure is not in question. The real question is, did dinosaur proteins survive for 80 million years in these bones?

The second contamination question emerges from this: Marty McIntosh discovered – after Asara released his mass spec data to the public – that the original T. rex sample contained hemoglobin. This finding has been discussed in the mass spec community, and privately among a group of scientists (including me) following this story, but it has not been published (as far as I know) until the Wired article.

Hemoglobin! Now, from what I know, we don’t expect to find much hemoglobin in bone tissue, and we sure don’t expect to find it in 68-million-year-old fossils. Could this be another big discovery? Or could it, perhaps, be that the sample is contaminated with modern proteins, perhaps from ostrich?

Upon further inquiry, a number of scientists learned that John Asara’s lab had indeed used its mass spec equipment to analyze samples of ostrich bone. Asara reports (in the Wired article) that the ostrich sample had been analyzed long before either of the dinosaurs:

“Asara conducted his ostrich and T. rex experiments a year and a half apart, separated by roughly 1,500 mass spectrometry runs. According to Asara, none of those spectra, nor samples of the soil surrounding the fossils, nor his daily control runs—in which he sequences known solutions to check for contaminants—turned up any ostrich hemoglobin.”

The new Science paper on the hadrosaur proteins doesn’t mention the (unpublished) hemoglobin fragments in the T. rex data, so this important question was not addressed. Well, if Asara’s lab handled ostrich material, then I remain skeptical of their assurances that ostrich couldn’t have possibly contaminated the original T. rex samples. And Marty McIntosh explained to the Wired reporter that “a chemical modification on the hemoglobin makes it more likely to be contamination.” McIntosh submitted a paper on his results to Science, but they rejected it – perhaps because it called into a question a finding that Science’s editors have obviously endorsed. That’s too bad.

If the T. rex sample was contaminated, that throws all the results into question. It also throws into question the new hadrosaur results – if contamination was a problem before, it might be still. The best way to resolve this is for an independent group to take the original fossils and repeat the study. I know that there are groups trying to do exactly this, but the fossils are controlled by paleontologist Jack Horner, who thus far has refused to share them with anyone but Schweitzer.

Extraordinary claims require extraordinary evidence, as any good skeptic knows. The finding of intact collagen protein in dinosaur fossils is certainly an extraordinary claim, and the finding of hemoglobin is even more stunning. Alas, the alternative explanations (statistical artifacts - see my earlier blogs and Pavel Pevzner's article in Science - and contamination by bacteria and/or ostrich tissue) are much more likely. I'd love for these results to be true - intact dinosaur proteins! Think of all the evolutionary comparisons we could do if we can reconstruct the past 80 million years directly from the molecular record! But I'm afraid I remain skeptical.

Alt meds for pets? Really?

The Washington Post has had two articles this week on "alternative" treatments, both of them very poorly researched, both written by reporters who just couldn't gush enough over the possibilities for cures promised by promoters of treatments such as Reiki, homeopathy, acupuncture, and Chinese herbs. It's too painful for me to repeat the claims of the first article - which was little more than marketing hype, focusing on a physician who was offering these treatments to her human patients - so I'll just mention today's article, which is titled "Going Beyond the Usual Rx for Rover: Alternative Treatments Gaining Acceptance."

According to the article, veterinarians who believe (despite the complete lack of evidence) "that such alternative therapies as acupuncture and Chinese herbs can help animals struggling with arthritis and allergies are finding growing acceptance from some peers and an eager reception from pet owners." The article quotes several veterinarians (is it really accurate to call them vets? I wonder) in northern Virginia who now specialize in acupuncture and homeopathy for pets.

The evidence for these therapies, when they've been studied properly, is that they offer no benefit other than the placebo effect. For treatment of pain, patients who think they're getting almost any treatment (including acupuncture) tend to report that they are feeling somewhat less pain - even if the treatment is a "sham" treatment such as a sugar pill or sham acupuncture. That's fine for people, but what about pets? You can't explain to Fido why the good doctor is sticking needles into him. Ouch!

These treatments aren't cheap - "alt vets" charge about $100 for an acupuncture session, according to the article. One doctor in Bethesda, Maryland offers ozone therapy to treat cancer and kidney failure. I wonder what that costs? Do these vets know that the American Cancer Foundation strongly advises cancer patients against ozone therapy (yes, it is heavily marketed for people too), noting that "there is no evidence that ozone is effective for the treatment of cancer"?

From the Post article, it's pretty clear that the placebo effect is once again operating, but it's affecting the pet owners, not the pets. Several owners are quoted saying how they saw their pets improve after homeopathy or acupuncture. One dog owner brings her border collie in for an "acupuncture tuneup" (no, I'm not making this up! if only I were so clever) every three months. The owner, who obviously believes this works, reports that "after a session here, she [the collie] runs like a puppy." I would too, after escaping those sharp needles for another three-month reprieve!

Frightening quack autism treatment

One of the most bizarre and frightening "treatments" being promoted for autism is a drug, Lupron, which suppresses testosterone. Treatment with Lupron is also known as "chemical castration," and as you can imagine, it's a very serious and potentially harmful drug. But Mark and David Geier have decided - despite the complete lack of evidence for this - that excess testosterone causes autism, and that (therefore) Lupron will cure it.

The Geiers have been promoting this for years, but a recent article in the Chicago Tribune caught my attention. The title of the article is ' "Miracle drug" called junk science', and the Tribune deserves some credit for producing a reasonably skeptical article. "Lupron is the miracle drug," says Mark Geier, who doesn't hesitate to make outrageous claims. Mark Geier has an M.D., although he is not qualified in the specialties (such as pediatic neurology) that he would need to understand autism. His son, David Geier, has only an undergraduate degree in biology. Despite this, they are marketing their "Lupron protocol" around the country, happy to profit from this outrageous, harmful treatment. The Geiers have filed for a patent on their Lupron treatment, and they charge $12,000 to autistic patients for initial diagnostic tests, plus $5000-$6000 per month for the Lupron therapy.

The Tribute article was prompted by an appearance made by the Geiers in the Chicago area, where they were speaking at the Autism One conference. Here is a quote from the Geiers' abstract of their presentation:

"Finally, attendees will be presented newly published peer-reviewed clinical studies on over 200 patients diagnosed with autism showing that interventions designed to lower or significantly reduce the functionality of testosterone (and other androgens) were observed to significant improve clinical outcomes. The new information presented may provide an important alternate treatment course for many patients diagnosed with autism that are presently administered psychiatric medications. "

It sounds reasonable - but only if you don't know anything about the Geiers' history, or the profits they are making from their supposed "cure."

As evidence for their Lupron treatment, the Geiers often cite a study they published themselves several years ago, which experts have pointed out is deeply flawed. (Somehow I doubt that they ever point out that some of their published research was subsequently retracted by the journal Autoimmunity Reviews.) The Tribune reporter interviewed Dr. Paul Kaplowitz, chief of endocrinology at Children's National Medical Center in Washington, who pointed out that the Geiers don't seem to understand that the blood tests they used in their study did not show elevated testosterone. Kaplowitz asked, "Is Dr. Geier just misinformed and he hasn't studied endocrinology, or is he trying to mislead?" Admittedly, it's hard to know in cases like these whether the quacks are truly ignorant, or whether they know they're peddling nonsense and just don't care.

Local Chicago-area doctor Mayer Eisenstein, who is making the Lupron protocol available and who supports the Geiers, was also interviewed by the Tribune. Eisenstein has his own pseudoscientific claims, and he too is a featured speaker at the Autism One conference. His speaker abstract states:

"if children do not get polio because of the polio vaccine but later die of a cancer caused by the SV40 virus received as a contaminant in the vaccine, the risk may outweigh the benefits."

Ouch. There's no evidence that the polio vaccine causes cancer - none whatsoever. That doesn't seem to be a concern for Eisenstein, whose bio on the Autism One site proudly claims that "he has formulated natural pharmaceuticals which can be used to treat many chronic medical conditions." These are modern snake-oil salesmen. Maybe Eisenstein is really so ignorant that he thinks the polio vaccine was a bad idea, but I think he just doesn't care.

By the way, if you want a guide to autism quackery, take a look at the Autism One conference site. But be warned: if you care about science, you might be in for a painful experience. I couldn't take it for long myself.

Also quoted in the Tribune was Dr. Simon Baron-Cohen, a professor of developmental psychopathology director of the Autism Research Center at Cambridge University, who said "The idea of using it [Lupron] with vulnerable children with autism, who do not have a life-threatening disease and pose no danger to anyone, without a careful trial to determine the unwanted side effects or indeed any benefits, fills me with horror." Well said.

What's hard for me to understand is how the medical profession can allow someone like Mark Geier to continue to practice medicine. One of the principals that all medical students are taught, supposedly, is "first, do no harm." Apparently, Mark Geier didn't learn that one.

Merck paid Elsevier to create fake medical journal

In a delightful case of hypocrisy, the mega-academic publisher Elsevier produced a fake medical journal - with the superficial appearance of legitimacy - for money. Apparently the pharmaceutical company Merck needed another journal to publish favorable articles about Vioxx, and Elsevier was happy to oblige. This is on top of Merck's activity paying doctors to list their names as authors on studies favorable to Vioxx - studies that the doctors had little or no involvement in - which I blogged about in May and October of last year.

The new findings were reported recently in The Scientist (free subscription required), and they came to light in The Australian a few weeks prior to that. We only learned about this fraud - and that's what it is - because of a lawsuit filed by an Australian man who suffered a heart attack while on Vioxx. In testimony at the trial, a medical editor testified that

"Only close inspection of the journals, along with knowledge of medical journals and publishing conventions, enabled me to determine that the Journal was not, in fact, a peer reviewed medical journal, but instead a marketing publication for MSD[A]." (MSDA is a subsidiary of Merck.)

The fake journal is called The Australasian Journal of Bone and Joint Medicine, and it is published by Elsevier.

Why is this especially hypocritical? Well, it shows that large publishers, including Elsevier, who have been opposing open access so vigorously, are, well, just blowing smoke in our eyes (to put it politely). Elsevier and others claim that they are guardians of academic quality and integrity, and that they provide an invaluable (or at least very expensive) service by editing the many journals that they sell to libraries and scientists around the world. As the open access movement has gained momentum, they even created an anti-open-access lobbying group, PRISM which they claim will help "to safeguard the scientific and medical peer-review process."

Right.

Now it turns out that this is just the tip of the iceberg. As The Scientist reported last week, Elsevier published not one, but at least 6 fake journals since the year 2000, all sponsored by (still-unnamed) pharmaceutical companies. Remarkable.

As a fellow blogger commented:

"The bitter irony is that Elsevier, along with the other major academic publishers, have spent the last few years ceaselessly lobbying against the open access movement, on the grounds that open access journals can’t be trusted to maintain the high quality of peer review that the commercial publishers provide."

The hypocrisy is breathtaking. It's stories like these that feed the paranoia of anti-big-pharma groups and other conspiracy theorists. Once in a while, there really is a conspiracy.

p.s. the blogosphere has many posts on this episode. See Jonathan Eisen's post, which has links to others.

Password foolishness

This is not one of my usual topics, so pardon me for the digression. I'm more than a bit annoyed about all these passwords I'm supposed to use and remember, and I've just got to say something about this latest one - and practice a little civil disobedience at the bottom of this post.

Let me explain. (And apologies for an “inside the ivory tower” blog this week. If you're not an academic, you might want to read one of my earlier posts instead.)

I’m a member of a panel—called a study section—that reads and reviews research proposals to the NIH. In the past, NIH used to send us a large box (by FedEx) with all the proposals, but for a few years now they’ve been sending us the entire set on CD, which is far more efficient.

Last year, someone at NIH got the bright idea to password-protect every proposal on the CD. This means that even though I have the CD, I can’t open and read any proposal without the password. To get the password, I have to login to the NIH website using another password. The CD password, mind you, is a one-time password that only works for this CD – at each meeting of the study section, we get a new CD and a new password.

We have to type in the password EVERY time we open a proposal. This means that when we have the actual meeting, each of us is frantically typing in the password every time we try to open a proposal. At the first meeting after NIH came up with this brilliant idea, every member of the study section protested to our NIH program officer (the guy who runs the panel), and he said he would pass on our plea. Not surprisingly, the response from the NIH bureaucracy was: nothing.

So here’s what drove me over the edge. I’m at a conference this week, and I figured I could use the travel time to start reading proposals for my next study section meeting. I’d loaded the proposals onto my laptop, and I thought I was all set. But then I tried to open the first one. “Please enter a Document Open password” stared back at me. What the heck? I had forgotten about the password protection on the CD, and I was without an Internet connection, so I had no way to read the proposal.

This is ridiculous. Does NIH want us to read the proposals, or not? The password protects one CD, for use at only one meeting. This is nothing more than security “theater” – imposing bogus security measures to give the appearance of improving security, while in fact doing nothing but making the reviewers’ job more difficult.

Well, I’ve had enough. I’m putting the password to my NIH CD right here, and I encourage members of every other study section to join me in this bit of civil disobedience. Maybe we’ll get the security zealots at NIH to stop it.

The password for my NIH study section’s CD is: AJAY$1JAIN

Okay, now I’m in trouble.

A tale of two pigs

I don't usually mix my own research into this blog, but I make exceptions for influenza. As everyone knows (if you're awake and sentient), there's been a huge outbreak of swine flu recently, starting a few weeks ago in Mexico, which has now spread all over the U.S., Europe, New Zealand, and elsewhere. You can read all about it in the major news media, so I'll just focus on a couple of things you might not find elsewhere.

First, the swine flu has been reported to be a mixture of human, avian, and swine influenza viruses. Although the source of these reports is the CDC, that's not an accurate picture. I read today in The Washington Post that this epidemic started when a single pig was infected simultaneously by bird, pig, and human viruses. That's a reasonable inference from the reports in the media, but it's not true.

In fact, as a number of researchers have now discovered, the new swine flu is a mixture of two different swine flu viruses. It's definitely a novel strain, but it's pretty clearly a mixture of two already-circulating pig strains. That sounds less exotic than the "human-bird-pig" theory, and it is. The reason for the "triple reassortant" story is a bit complex, but (to simplify a bit): the history of one of the two parental swine flu strains indicates that part of that strain originated in birds - well over a decade ago. That strain is sometimes called "avian-like" as a result, but it's not an avian flu strain now. Second, the history of the other strain includes a small piece (one gene) that appears to have originated in humans - over 15 years ago. Again, it's a swine flu virus now, but there's a piece of it that might have come from humans. The event that created today's swine flu - the one we're worried about - is a combination (called a reassortment) between two pig strains, pure and simple.

The other point I wanted to make is about data sharing. The sequences from the U.S. isolates have been deposited in GenBank - the public DNA database - immediately, and this allows people like me to start our analysis without delay. Many of us have been arguing for years how important it is to get the data out to the community fast, in order to accelerate the pace of scientific discovery. However, the isolates from Mexico have NOT been put into GenBank, even though these sequences first went through the CDC. Instead, they went into a database called GISAID, which was originally set up to facilitate sharing of avian influenza. Unfortunately, GISAID changed their data release policy about six months ago, and there's no guarantee that sequences deposited there will ever become public.

The CDC has been depositing influenza sequences in GISAID as if this were equivalent to making them public. It's not, and they shouldn't pretend otherwise. The CDC has not always been supportive of publicly releasing flu data - in fact, for years they deposited some of their sequences in a private database. They've recently made public statements about their commitment to public data release of influenza sequences, but it doesn't seem that they are following through with this commitment for all of the sequences from the swine flu outbreak. (Don't get me wrong: the CDC is doing a fantastic job in trying to track and understand this outbreak, and their work is incredibly important to public health, especial concerning the flu. I'd just like them to be a big more open with their data.)

One last note, a technical one. I've looked at the Mexican sequences (I have a GISAID account) and the California sequences, and they are virtually identical. So it would appear that any differences in virulence are due to differences in the people being infected, not to the virus itself. At least that's what it looks like so far - the situation is changing rapidly.