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.

Former NIH director Bernadine Healy joins ranks of pseudoscientists

It’s very sad to learn that someone in a position of scientific prominence has thrown her support to irrationality, unreason, and pseudoscience. This has happened before – as when noted physicist Peter Duesberg became a prominent AIDS denialist - but I still hate to see it. Perhaps I just have high expectations of people with scientific training.

Today’s topic is Bernadine Healy, former Director of the National Institutes of Health, who has very publicly joined pseudoscientist Andrew Wakefield and his compatriots who support the claim that vaccines cause autism, despite overwhelming evidence to the contrary. (Actually, Wakefield is worse, since he’s the person who nearly single-handedly invented the claim and made it public with his poorly done, and probably fraudulent, 1998 study in The Lancet.)

Bernadine Healy now writes a blog for U.S. News & World Report, and in her most recent posting she comes out very publicly in favor of “more research” on the link between autism and vaccines. Actually she’s been singing this tune for quite a while – she wrote a similar article a year ago. Healy’s argument is that she is in “the crossfire” in this debate, and she wants to pretend that she’s just being reasonable, trying to mediate between two passionate advocacy groups. “These are all reasonable issues, and considering them with some flexibility would go a long way to resolving many of the frictions aired by Larry King.”

What?? [Excuse me while I take a few deep, calming breaths.] Dr. Healy, do you seriously believe that we should let Larry King determine the direction of public health research? How the heck did you ever get the job of NIH Director? (Actually, this is easy to find out – she got it because she was a prominent Republican – unlike other NIH directors, she was never a highly-regarded biomedical scientist. She went on to run, unsuccessfully, for the U.S. Senate. She only lasted 2 years as NIH director. She later became head of the U.S. Red Cross, but only lasted 2 years there as well. End of digression.)

After setting herself up as a supposed "reasonable" voice, Healy goes on to make a series of poorly reasoned arguments, repeating some wildly misleading claims and outright falsehoods, making it clear where her sympathies lie. Healy has swallowed the pseudoscientific nonsense of the anti-vaccinationists hook, line, and sinker. Her article reads like a manifesto of the prominent anti-vax group Generation Rescue, whom she cites as if they are a source for scientific data. (I guess the former NIH director doesn't know how to use NIH's PubMed literature database.)

Of course, other anti-vaccinationists love this stuff – and they love her. David Kirby, the journalist who makes his living by scaring people about vaccines, has applauded her on his Huffington Post blog. (The Huffington Post has provided a platform for many anti-vaccinationists, unfortunately.) Age of Autism, another prominent anti-vaccination group, made her their “Person of the Year” in 2008 – which any decent scientist should be ashamed of.

Let’s look at just two of Healy's many false arguments. She writes that “shockingly, a study comparing groups of vaccinated and unvaccinated children… is long overdue.” Here, she is parroting a call by Jenny McCarthy for such a study – nice job, Dr. Healy, taking your scientific advice from a former Playboy playmate. The fact is that this study has already been done – multiple times, in fact. Studies in the 1990’s and 2000’s involving over one million children have compared groups of vaccinated and unvaccinated children and found no link between vaccines and autism, and no link between thimerosal and autism. That’s right, Dr. Healy – you could look it up if you cared, but apparently you don’t.

Second, she asks “are we overvaccinating our children?” This is right out of the Generation Rescue talking points list. There is no scientific evidence that "overvaccinating" is a problem – the word itself is an invention of the anti-vaccination groups. In fact, we have dramatically reduced the rates of many childhood illnesses, some of them fatal, through the wide use of vaccines. There are millions of people alive today who would be dead if not for vaccines. Ever heard of polio and smallpox, Dr. Healy? But that’s not enough for Healy – she just wants to perpetuate the myth that this is a serious scientific question. Without any scientific evidence to support her, she questions the need for vaccines against chicken pox, hepatitis A, hepatitis B, diphtheria, tetanus, and pertussis – ignoring the enormous public health benefits that we have derived from vaccines against these illnesses.

She even throws in outright falsehoods such as “Influenza vaccine [is] mandated here starting at age 6 months.” Sorry, but no, Dr. Healy, the flu vaccine is not mandatory. The CDC recommends the vaccine, but that is a far cry from “mandating” it. In fact, the CDC recommendation is necessary in order to get health insurance companies in the U.S. to cover the vaccine. This is ridiculously easy to look up, so I have to conclude that Healy just doesn’t care.

Bernadine Healy is using her status as a former NIH Director to give her credibility on the vaccine-autism question. Sadly, it seems to be working - she's certainly attracted a great deal of attention, and all because of her implied claim to expertise on any biomedical issue. But it appears that she's more interested in the media attention (Larry King Live!) than the facts.

For more on this issue, I highly recommend Orac’s recent post on this topic. He eloquently expresses the excruciating pain that many of us feel at the inexcusable stupidity expressed by ex-NIH Director Healy. And kudos to blogger Josh Witten for adding Bernadine Healy to his “Festival of Idiots.” I couldn’t agree more.