T. rex protein degrades further

An article in Science this week casts fresh doubt on the Tyrannosaurus rex "proteins" that were extracted from a 68-million-year-old fossil. The new report by Pavel Pevzner and colleagues argues that the T. rex peptides (protein fragments) represent statistical artificacts rather than genuine T. rex proteins. The original study by Mary Schweitzer, John Asara, and colleagues, which appeared in Science in 2007, claimed that the authors had discovered 7 peptides from T. rex, all from the collagen protein, which is the most common protein in bone. The story, which received tremendous publicity at the time, has been slowing falling apart ever since. Asara and Schweitzer continue to defend it, including a response in Science this week, but let's look at how the story is collapsing:

1. After the original report, Pevzner (privately) pointed out statistical problems, and the authors revised their findings, admitting in a letter to Science in September 2007 that one of the peptide fragments was a statistical artifact. One down, six remaining.
2. In January 2008, Science published a new Technical Comment in which 27 authors (Buckley et al.) used a standard set of authentication tests developed for ancient DNA, and reported that the T. rex sample failed those tests. (Another sample from mastodon, also reported by Asara but 100 times younger, passed the same tests.)
3. In July 2008, Thomas Kaye and colleagues published a report that re-examined the microscope evidence of the T. rex "soft tissue". The original findings by Schweitzer were based on this soft "tissue" being original T. rex organic material. Kaye et al. report that the soft material was a bacterial biofilm - not original material at all. They also report on carbon dating of the biofilm showing it to be modern, not ancient.
4. Pevzner et al. report this week that the peptide mass spectrometry evidence - which Asara and Schweitzer repeatedly used to defend their results against the earlier criticism - are also flawed. One way to resolve this, Pevzner points out, is to release the mass spec data, which is a common practice in that community. This would allow others to re-interpret the data and test more rigorously for statistical artifacts. However, Asara and Schweitzer refuse to release their data. Instead, they wrote another response which simply gives more details about how they ran the software to search their spectra against a peptide database, but doesn't really answer Pevzner's questions.

This ongoing controversy reveals some of the worst behavior I've seen on the part of Science. (Disclaimer: I've published repeatedly in Science myself.) They published two articles by Schweitzer and Asara, grabbing all the publicity they could, although they knew about the problems. The second article appeared this past spring - long after they received Pevzner's article (which was received on January 7, 2008, according to the Science website) and after they received and published the criticism by Buckley et al. What I find most reprehensible on their part is that they published both the Buckley et al. and the Pevzner et al. critiques as "Technical Comments" - which means they appear online only, not in the print edition. Both the Asara and Schweitzer articles, by contrast, appeared in the print edition, which means they will be read more widely.

If Science truly cared about getting this story right, they would publish the critiques just as prominently as the original article. It seems that Science is eager to get publicity for a "discovery", but not so eager for publicity when it turns out the discovery is false. Yes, it's true that they did publish the critiques, but they should have done better.

Finally, I recommend Rex Dalton's story in Nature on this controversy, which does a good job of summing it up, with links to all the articles. We'll see what happens next, but it appears that Schweitzer and Asara will keep defending their claims. The mounting evidence seems to show that they were wrong - wrong about the soft tissue, wrong about the mass spec identifications, wrong about the age of the sample, and wrong to continue to refuse to release their data.

Associated Press turns a story on critical care into commentary on religion

A news story from the Associated Press (and carried by CNN) illustrates how the media can focus on whatever they want to in a scientific or medical article, and create a headline that doesn't seem to match the article. Here's the CNN headline: "Survey: Many believe in divine intervention". The URL is even more telling: god.vs.doctors. The first sentence reads: "When it comes to saving lives, God trumps doctors for many Americans."

Well, this isn't too surprising - Americans tend to be religious, and the results were gathered by a survey, which might have biases. But the surprising element of this story is what the original article in the journal Archives of Surgery really contains. It is a survey by three doctors titled "Trauma Death: Views of the public and trauma professionals on death and dying from injuries." The main result is that a majority of the public prefer palliative care (i.e., making the patient as comfortable as possible) when "aggressive critical care would not be beneficial in saving their lives." The study also found that most people trust a doctor's recommendation to withdraw treatment when there is no hope for improvement. These findings are presented first.

However, the authors also asked a question about religion in their survey - they asked both the public and trauma professionals if "divine intervention" could save a person after medical professionals determine there is nothing left to do. Not too surprisingly, over half (57.4%) of the respondents from the public said yes, while only 19.5% of professionals did.

I'm not sure why the authors of the study included this question - maybe they knew it would be a "hot button" that would get them headlines. But it seems the point of their study was to educate doctors about what patients think. CNN turned this into a story that claimed "God trumps doctors," although the article didn't say any such thing. The CNN headline suggests that people would prefer "God" to doctors, but in fact the story says that most people trust a doctor's recommendations for treatment.

This is another illustration of how careful scientists and doctors need to be in presenting their work to the public. The reporter in this case (an un-named AP reporter) gathered quotes from a number of medical professionals, none of whom supported the article's lead sentence. Reporters sometimes decide for themselves what the story is - which clearly seems to have happened here - and they are only too happy to "shape" a story from the scientific literature to support their pre-determined conclusions.

Preserved T. rex or bad science?

Science has published several articles in the past year or so, with much publicity, announcing that researchers had found preserved soft tissue from Tyrannosaurus rex that contained fragments of the original collagen proteins from T. rex. The researchers leading the research, J.M Asara and M.H. Schweitzer, claimed (Science 2007 Apr 13;316(5822):280-5) that the T. rex protein fragments were more closely related to birds than to reptiles. Very plausible, of course - and if correct, yet another bit of evidence linking modern birds to dinosaurs.

However, even though birds almost certainly are descended from dinosaurs, this series of articles is a textbook case of how even the best journals - Science, in this case - can publish bad science. The mass spectrometry in the Asara et al. articles was poorly done, and even they had to admit - in a letter published in Science last fall - that at least one of their protein fragments was falsely identified. Despite this admission - and they only had 7 fragments to begin with - Science published a second article this past winter by the same authors. What did that article (Organ et al., Science 2008 Apr 25;320(5875):499) contain? Nothing new about the T. rex material, but instead some additional analysis of crocodile and ostrich proteins and a repeat of the claim that T. rex is closer to birds. The title of the article, though, is "Molecular phylogenetics of mastodon and Tyrannosaurus rex" - astonishing, if you expect Science to publish only the best science. But maybe not so astonishing if seen in the light of the publicity that Science is always hungry for. Still, it's too bad.

But why am I so skeptical? Well, don't take it from me. In a comprehensive examination of the T. rex material and methods, Buckley et al. reported - in Science, no less (2008 Jan 4;319(5859):33) that the "ancient" DNA reported by Asara and colleagues failed all the standard tests for such material. In other words, it's a contaminent.

Now, the most recent news on this story, published in PLoS ONE (Kaye TG, Gaugler G, Sawlowicz Z 2008 Dinosaurian Soft Tissues Interpreted as Bacterial Biofilms. PLoS ONE 3(7): e2808 doi:10.1371/journal.pone.0002808), shows that the most likely source for this DNA is a bacterial biofilm. Not really surprising, but it's great to see this correction of the record. Unfortunately, the Science articles got so much play in the press that they will likely be hard to "erase" from the public's memory. I suspect that far more scientists will have heard of the "T. rex tasted like chicken" stories (yes, that's how some of the press stories were headlined) than the new PLoS ONE article.

For a more detailed discussion of the biofilm story, see Tara Smith's recent blog post on this same topic.

So my conclusion about the original (2007) article in Science: those 7 protein fragments weren't from T. rex at all. They were bacterial contaminents. Asara, Schweitzer, and colleagues were simply wrong - perhaps wishful thinking clouded their vision. The article never should have passed peer review, and Science should make an effort to correct the record. Sometimes even the best journals screw up, and that's what happened here.

Victor McKusick, R.I.P.

The genetics world lost one of its pioneers this week - Victor McKusick died of cancer at age 86, at his home in Baltimore. McKusick was a professor of genetics at Johns Hopkins University for most of his career.

Dr. McKusick was known as the father of medical genetics, and became famous for his tireless efforts, beginning in the 1960's, at cataloging all human genes associated with disease. Eventually he compiled these into a book, Mendelian Inheritance in Man (the first edition appeared in 1966), which later became the widely-referenced database Online Mendelian Inheritance in Man, or just OMIM. OMIM is so central to research that it moved, many years ago now, to NIH's National Center for Biotechnology Information, which also houses GenBank. Over the years, this collection has grown from just a few genes to 18,850 entries today. (Many genes are linked to more than one disease.)

McKusick "retired" from Hopkins in 1985 but continued working, and was a big presence when I joined the faculty there in 1989. I only met him briefly, and I wish I'd had the chance to get to know him. He was a true visionary. I recommend the extensive Wikipedia entry to anyone who wants to know more about Victor McKusick.

Influenza vaccines and free sharing of flu data

I don't usually discuss my day job on this blog, but this week there's some overlap between the two. My comments in this blog back in November 2007 drew the attention of the editors of the journal Nature, and they invited me to write a Commentary for Nature on the flu vaccine and issues surrounding the open exchange of influenza data.

My Commentary appeared this week as part of a special Nature section on "Flu fighting" in the journal. See this link for the Editor's summary of the special section. The summary has links to my article and to other articles included in the special section. If you can't get the articles (a subscription may be required), then you can get a reprint of my article from my home page, under "Editorials and opinion pieces."

Coming soon to this blog: should doctors prescribe statins for overweight children?

And what else is acupuncture good for?

"Unclear whether acupuncture helps fertility"

I love this headline from Yahoo News/Reuters! It just appeared today on the Yahoo News site. So acupuncture doesn't boost pregnancy rates? What a surprise! I can't resist the obvious: acupuncture also doesn't help cure back pain, headaches, infections, depression, or cancer. In fact, the list of conditions that acupuncture doesn't help is endless!

But the Reuters reporter wasn't just making this up - there really was a presentation in London by a researcher, Sesh Sunkara, who conducted a review of 13 other studies (a meta-analysis) and found that "the current available evidence is not conclusive" on acupuncture's benefits on fertility. She apparently reported her results at the conference of the European Society of Human Reproduction and Embryology. The findings were also reported online by reporter Mark Henderson at the Times, under the headline

"Acupuncture has 'no effect' on pregnancy rates following IVF, say experts"

The Times reports that there was a reason for this study, which otherwise might raise eyebrows (why on earth do a study for which there's no plausible reason to find a positive effect?): in England, and maybe elsewhere, "acupuncture has become the most popular complementary therapy" for infertility. A number of hospitals in England have on-site acupuncture services for their patients, charging hundreds of pounds for the sessions.

Dr. Sunkara is quoted in the Times story as saying:

...every day we have patients who ask whether they should have acupuncture to improve their success rate. There have been all sorts of papers saying that sticking pins and needles increases the pregnancy rate, which have been widely reported in the media, and we are looking at women who are very vulnerable, who want to do everything possible to increase their pregnancy chances.

It's sad but true: practitioners of quack medicine - in which I include acupuncture - are quite happy to profit from the desperation of naive people who are looking for medical help. Kudos to Dr. Kundara.

And a big fat raspberry to Paul Robin, the chairman of the British Acupuncture Society, who is shocked, shocked to hear these results: "I've been treating people for 20 years and in my experience treatment does seem to improve their chances of becoming pregnant." Right, Mr. Robin - so will you be finding some other occupation now? Or maybe reducing your fees? Somehow I doubt it.

I invite readers of this forum to suggest other headines on treatments that don't work. How about "Homeopathy doesn't cure common cold"? The possibilities are endless.

NCCAM is funding quack vitamin cures

It's been a while since I looked at what the National Center on Complementary and Alternative Medicine (NCCAM) is spending our tax dollars on, so I took at look and found a newly funded proposal (grant R43AT003025) called "Medical Food Cocktail for Alzheimer's Disease." The title raised suspicions right away - what the heck is a medical food cocktail, and why would it help treat Alzheimer's? Is it some new miracle treatment? I was skeptical - after all, this is NCCAM, the NIH center dedicated to wasting our valuable research funds on bad science.

A second red flag was raised by the official email address of the Principal Investigator (PI), Curt Hendrix - rather than a university or a company, his address is a personal email account. Very strange. So what is the study going to do? From the NIH website, we find that

The overall goal ... is to formulate and conduct initial feasibility tests of a medical food cocktail composed of standardized herbal extracts, vitamins, and minerals that are demonstrated in the basic science and clinical medical literature to impact the biochemical and pathophysiological processes involved in Alzheimer's Disease. The first Specific Aim will be to formulate and standardize the cocktail, which will include extracts of tumeric, green tea, black pepper and vitamins and other nutritive ingredients.

Once they formulate this cocktail, they'll test it on mice. What? Tumeric, green tea, black pepper, and vitamins will cure Alzheimer's? That would be great if it were true, but there's no evidence to support it. (And if it were true, we'd have sub-populations of humans that had very low Alzheimer's rates, since these are common components of many people's diets.)

So who is the company that NCCAM has given this award to? It's Akeso Health Sciences, LLC, in Westlake Village, California. I've never heard of them, so I did some quick checking. It only took a few minutes to find that Akeso is another name (or a front) for a company called Migrelief that sells vitamin supplements: http://www.migrelief.com. ("Migraine relief," get it?) They used to call themselves MigraHealth, and they sell vitamin supplements that they claim help cure migraines.

Akeso Health Sciences is also quoted in a testimonial on a website called The SBIR Coach, a company that helps other companies win NIH grants. Their motto - prominently posted at the top of their website - is "We know this game." That's right, they teach companies how to play the "game" and win small business grants (called SBIRs) from the federal government. So we have one scammer (SBIR Coach) helping out another (Migrelief, also known as Akeso Health Sciences) to get funding from NIH.

How can a purveyor of vitamins for migraines re-brand themselves and get NIH money? That's what happened here: Migrelief used their alter ego, Akeso Health Sciences (sounds like they do science, right?) and wrote a proposal to NCCAM. Because NCCAM has far lower standards than the rest of NIH, and because their mission includes the promotion of pseudoscience, they funded this ridiculous proposal. What a colossal waste of funds. And I can imagine that Migrelief will soon be selling their supplements to Alzheimer's patients, offering them false hope of a cure so they can make a fast buck.

NCCAM should be closed down. Any scientific proposal worthy of funding should have to go through one of the legitimate NIH institutes. And while we're at it, we should shut down the SBIR program too; that'll have to be the subject of a future blog.