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About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline

« Buckyballs Prolong Life? Really? | Main | Making Their Own ALS Drug »

April 20, 2012

Buckyball Longevity - There's A Problem

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Posted by Derek

We have a problem here. The paper I blogged about yesterday, on life extension effects with C60 fullerene ("buckyballs") has a duplicated figure. This was first spotted by commenter "Flatland" yesterday. I was traveling all day, and when I came home in the evening I saw the comment and immediately realized that he was right. I've made the animation below (via Picasion) to illustrate the point:
picasion.com_26765994708ac1b7c3377a9ac9258d60.gif
These are from the part of the paper where they showed protective effects of C60 on animals that were being dosed with (toxic) carbon tetrachloride, and these are supposed to be the water/carbon tet control animal dosed by oral gavage (GAog) and by intraperitoneal injection (GAip). In other words, these are supposed to be separate animals, but as you can see, these are, in fact, the exact same histology slide. I've scaled the GAip image up about 120% and moved the two to correct the offset, but otherwise, I've done no image processing at all. The originals are screen shots from the PDF of the paper, the top two images of Figure 4.

This is, at the very least, very sloppy work, on both the part of the authors and the editorial staff at Biomaterials. I didn't catch this one myself, true - but I wasn't asked to review the paper, either, and I can assure you that I spend more time critically studying the figures in a paper under review than one I'm writing a quick blog entry about. Under normal reading conditions, most of us don't look at histology slides in a paper while constantly asking ourselves "Is this right? Or is this just a duplicate of another image that's supposed to be something else?"

And while this image duplication does not directly bear on the most surprising and interesting results of the paper - life extension in rodents - it does not inspire confidence in those results, either. I'm emailing the editorial staff at Biomaterials and the corresponding author of the paper with this blog entry. We'll see what happens.

Comments (54) + TrackBacks (0) | Category: Aging and Lifespan


COMMENTS

1. RB Woodweird on April 20, 2012 9:12 AM writes...

But Elsevier tells us they would really like to drop the prices of journals and they really really support the idea of open access but they really really really need to charge you five figures a year for your Biomaterials subscription in order to maintain high editorial standards.

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2. ScientistSailor on April 20, 2012 9:15 AM writes...

Obviously this paper is an April fool's joke that came out a bit late. Kudos to them, it's really quite funny. I've been thinking of doing the same thing myself.

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3. UICAlchemist on April 20, 2012 9:34 AM writes...

Good catch Flatland!

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4. PharmaHeretic on April 20, 2012 9:49 AM writes...

But biomedical researchers cannot survive without committing outright fraud, cherry-picking data and making unwarranted conclusions.

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5. Elaine Schattner on April 20, 2012 10:06 AM writes...

Great example of why peer review should be thorough and open.

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6. qetzal on April 20, 2012 11:06 AM writes...

Re-use of the same images could be a sloppy accident. However, I don't think you could say the same for rats that live 5 years! That's either true, or gross incompetence, or deliberate fraud.

I'd like to give the authors the benefit of the doubt, but given the image problem, as well as the seeming discrepancy between the median survival estimates and the actual data plots, well....

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7. David Formerly Known as a Chemist on April 20, 2012 11:09 AM writes...

Mmmmmmm...prosciutto!

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8. Bemused on April 20, 2012 11:24 AM writes...

This is all the evidence I need to stop taking reveratrol pills and start shoving bucky balls down my gaping maw. But who will sell it to me?!?

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9. PPedroso on April 20, 2012 11:41 AM writes...

Perhaps buckyballs extend life because of its gyre? :D

I really hoped this article to be true and accurate...

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10. Biotechtranslated on April 20, 2012 12:03 PM writes...

Hmmm... I think comment #6 nailed it.

If this were the only inconsistency in the paper, you could always blame a tired post-doc who mixed up biologic samples.

However, I have a sneaking suspicion that this was more of a "wow, the buckyballs made the rats live longer, but the histology slides don't make sense... well this slide should look like the control so I'll just...."

Mike

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11. MoMo on April 20, 2012 12:19 PM writes...

Bemused! Look no More!

Now for sale, and GRAS too!

BuckyBall Pills-50 mg per Tablet!

Each Chewable Pill shaped like Buckminster Fuller's Head!

30-Day Supply- 89.99$!

Only from MoMo Laboratories!

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12. NorthwesternChemist on April 20, 2012 12:23 PM writes...

NEW C70 BuckyBall dietary supplements! Increase your energy levels and rid your body of pesky toxins! 117% more carbon then our competitors' C60 buckyballs!

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13. Rick Wobbe on April 20, 2012 12:27 PM writes...

From the header (Biomaterials xxx (2012) 1-11), it looks like this is a pre-print. If so, maybe it's not too late to pull it from the edition before the journal goes to press while the various oddities are sorted out.

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14. Anothermous on April 20, 2012 12:28 PM writes...

Dr. Charles Nichols: call your office please.

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15. Rick Wobbe on April 20, 2012 12:45 PM writes...

Sensational as it is, the alleged finding of this paper may well find its way into the popular press. Given the problems already pointed out fairly quickly by various contributors to this blog, this could be a disaster in the making. There's already too much science-bashing going on around climate change, evolution and vaccine safety. If this paper were published in its current flawed form, it would deservedly be ripped to shreds and no one's interests would be served, except perhaps the attorneys involved. I hope the journal acts responsibly and promptly to get this thing re-reviewed and either trashed or published with proper science.

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16. Chemjobber on April 20, 2012 1:12 PM writes...

Rick: Too late. Click my handle for PopSci's comments.

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17. TColnot on April 20, 2012 1:13 PM writes...

@13: Too late, just got published: Baati, T. et al. (2012), Biomaterials 33, 4936-46 (June edition)

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18. Phil on April 20, 2012 1:18 PM writes...

CJ: The PopSci article isn't overly sensational, but should they appear, reprints in the popular press probably will be. =\

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19. Rick Wobbe on April 20, 2012 2:00 PM writes...

@16-18. So it goes.

Thanks Derek for sharing this. I hope some good comes of it anyway. It was nice pretending, even for a little while, to have training, skills and experience that actually mattered again. Now, back to the trash heap to watch the people who really matter make some money off this.

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20. dave w on April 20, 2012 2:23 PM writes...

I suspect a spoof - I note the paper was specific on the geographic origin of the olive oil dosing vehicle, but seemed silent on the question of what variety of rats they were using...

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21. Rick Wobbe on April 20, 2012 2:30 PM writes...

Thanks Chemjobber, #16.

Yep, it's out there. Just check out these testimonials!!!

“Put some “soccer balls” in your olive oil and live into your late 150s” (hackingtheuniverse.com)
“To say these results are important is an understatement: the desire to live longer runs strong in many of us, and it's a feat scientists have been hoping to achieve for centuries.” (john-ray.blogspot.com)
“Chronic Buckyball Administration Doubles Rat Lifespan” (Extreme Longevity.net)
“Get Bucky Balls Hours of Magnetic Fun Highly Rated. Fast Shipping.” (ad on Longecity.org)
“Bucky Balls Could Double Your Lifespan” (gizmodo.com)
“Live longer. Eat buckyballs.” (sciencebuzz.org)
“it seems like humanity may have finally discovered the fountain of youth.” (city-data.com)
“Fullerene C60 administration doubles rat lifespan with no toxicity” (kurzweilai.net)

Oy vey.

Permalink to Comment

22. cynical1 on April 20, 2012 2:42 PM writes...

@ Dave W (#20): Having actually lived in Tunisia where some of authors are from, I can attest that their olive oil is pretty good stuff. Maybe that's why I'm not dead yet. Who knew?

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23. Ginsberg on April 20, 2012 3:20 PM writes...

It's a coincidence how the sloppy accidental duplication of images always supports the narrative of the authors.

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24. I'll leave my name out on April 20, 2012 4:13 PM writes...

TBH this almost happened on my last paper, duplicated figure (very similar looking graphs) got past the reviewers. Luckily I gave the whole thing a once over after I uploaded my edits. It's a pretty easy mistake to make when you're just uploading figures onto a website. This was in a quality journal, by the way - not an Elsevier printing press.

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25. Want SSF Usnea on April 20, 2012 6:23 PM writes...

I heard an AM radio host hyping the story last Wednesday -- so it's apparently already worming its way through the popular press.

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26. johnnyboy on April 20, 2012 9:40 PM writes...

I'll go with #24 and think this is an honest mistake. Anyone who's written a manuscript with multiple contributors and many images will know that it's all too easy for mistakes to happen in any of the many, many steps involved in the back and forth between authors, then with later changes after reviews and photo editor changes, etc... In the days of hard prints it was difficult to switch one photo for another, but nowadays with electronic files it's just too easy for confusion and switches to happen. Sure, it should have been picked up by the authors or reviewers - big surprise, shit happens. I'm certain none of the commenters here have ever made a mistake, right ?

Permalink to Comment

27. newnickname on April 20, 2012 9:58 PM writes...

Am I reading the chronic exposure (life extension) experiment correctly?

1. Each gavage dose was 0.8 mg C60 in 1 mL olive oil. (I guess the C60 was suspended in oil, centrifuged at 5000 g for 1 hour, filtered thru 0.25 um filter and, I hope, adjusted, somehow [HPLC analysis?], to get the 0.8 mg/mL final concentration). 1 mL of suspension per dose = 0.8 mg C60.

2. The dosing schedule was daily for 7 days (d); weekly for the next 7 weeks (w); once every two weeks for the next 20 weeks (b); then stopped (due to development of tumors in a control rat, possibly induced by gavaging).

Month 1: d d d d d d d w w w
Month 2: w w w w
M3: b b
M4: b b
M5: b b
M6: b b
M7: b b
M8 to M58: no more C60

A total of 24 doses; 24 x 0.8 mg = 19.2 mg C60;
19.2 mg C60 / 720 mg/mmole = 26.7 umoles
= 1.6 x 10^19 buckyballs, TOTAL over 7 months.

The oldest rats then survived for an additional 50 months after treatment stopped?

If a 450 g rat needs 19.2 mg to almost double their lifespan, a 60 kg human only needs ~2.56 grams of C60! They started dosing rats at 10 months of age which is about 25 years old in human years.

Until further evidence is produced, I'll accept the "submitted the wrong photo" hypothesis. If it was just a mix-up, I hope others will try to reproduce this result.

Permalink to Comment

28. Zach on April 21, 2012 2:38 AM writes...

I, too have had proofs come back with completely screwed up figures. The worst offenders are journals that require you to upload the figures one at a time, and those that require artificial figure names like "fig1.eps," "fig2.eps," etc.

In this case, the figure in question looks like a montage of several photographs, so it's likely that there was only one image file, prepared by the author. There are 20 photographs in the montage, so the possibility that one photo got included twice by accident is credible.

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29. Zach on April 21, 2012 3:01 AM writes...

I will also note that the duplicated figures appear to be two examples of the water control group. In a case of misconduct, wouldn't you expect the screwed up figures to include the buckyball group?

Permalink to Comment

30. Vince on April 21, 2012 4:07 AM writes...

Great catch, Derek and flatland.

@ 14, Anothermous: Haha, clever. thanks for the laughs!

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31. carac on April 21, 2012 4:12 AM writes...

I would really like for somebody that is an experienced statistician (and not just proud to have passed a medical statistics course that result in the vast medical published studies being wrong on statistics) to look at the claims raised by this paper - I find very interesting the numbers seen for only oil vs oil+C60 but IMHO those certainly do not suggest the conclusion claimed by this study!

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32. Micha Elyi on April 21, 2012 7:14 AM writes...

There's already too much science-bashing going on around climate change, evolution and vaccine safety.

(15) Rick Wobbe

"Science-bashing" or a demand that there be some science there?

Permalink to Comment

33. Watson on April 21, 2012 9:00 AM writes...

I have to wonder if there is any connection with the authors/universities of the Tunisian "serial plagiarists" recently given a blog entry over at Retraction Watch.

http://retractionwatch.wordpress.com/2012/04/19/whistling-the-same-tunisia-serial-plagiarists-plague-the-oncology-literature/#more-7348

Permalink to Comment

34. M. Bachmann on April 21, 2012 3:55 PM writes...

I just spoke to a mother who said her daughter was given an injection of buckyballs and because of that she now suffers from mental retardation.

Just like the authors of this fine paper.

Permalink to Comment

35. Justin on April 21, 2012 6:34 PM writes...

#34: your comment is offensive and totally inappropriate

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36. Justin on April 21, 2012 6:34 PM writes...

#34: your comment is offensive and totally inappropriate

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37. Chemjobber on April 22, 2012 11:14 AM writes...

30, 14: I agree, very, very clever. (I wish I could do that guy's weird accent. "You're getting rather dasperate, Mr. Gerard.)

Permalink to Comment

38. BOB on April 22, 2012 2:26 PM writes...

Does this mean I should stop eating buckyballs now?

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39. Hap on April 22, 2012 9:33 PM writes...

If it's simply a duplication of figures by double loading the same file, why the offset? (They don't appear to be the same image, but two pictures of the same tissue taken with different focus points.)

Unless the authors submitted two pictures of the same tissue, either to allow the editors to choose the best one for publication or to highlight different points of the same sample, it doesn't appear to be as innocent as a simple computer mistake.

Permalink to Comment

40. Biotechtranslated on April 22, 2012 9:54 PM writes...

Did they really gavage the rats with 1 mL of olive oil as a carrier? Is that typical? It seems to me to the be equivalent of a human drinking a cup of olive oil.

I can remember doing testing of rats and when you washed a drug out of a central line into the rat, you had to watch your volumes. 1-2 mL of saline and rat would start foaming at the mouth from the pulmonary edema.

Mike

Permalink to Comment

41. idiotraptor on April 22, 2012 10:47 PM writes...

@40

I have not read the actual paper, only the string of comments posted here. 200 microliters is the volume I use when gavaging mice. Adult lab strain rats are 10-20x the weight of adult lab strain mice (20g); 1ml gavage for use with the former species sound credible (but not the most conservative volume).

As highlighted in the posts above, there are other aspects of the published report that prompt serious doubt...

Permalink to Comment

42. mad on April 22, 2012 11:59 PM writes...

Having done a lot of image work I often end up with so many images of different sections of different slides that I can see this happening as a legit mixup especialy if the person who did the imaging was not active in authoring- but still its sloppy.

Question: how bad is a lab rats diet that olive oil alone vastly improves life expectancy! :)

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43. bacillus on April 23, 2012 7:47 AM writes...

@27. Who is going to be side tracked into trying to replicate an experiment that will take 5+ years to perform? To quote Carl Sagan "Extraordinary claims require extraordinary evidence". This paper does not match up to such criteria. I wonder whether Biomaterials was their first choice, or if they trawled it around the glamour mags first? I'd be surprised to see this study survive the test of post-publication peer review.

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44. Virgil on April 23, 2012 7:55 AM writes...

I've seen enough of these types of cases to be 100% sure this is not an innocent mistake. Straight copying of the same figure maybe innocent enough, but anything requiring actual image manipulation, such as re-sizing/cropping/resolution/brghtness/contrast, is usually evidence of intent to deceive. Just take a look over on abnormalscienceblog.wordpress.com for some absolute howlers!

Permalink to Comment

45. David Formerly Known as a Chemist on April 23, 2012 11:02 AM writes...

You guys scoff, but the results are true. I started ingesting buckyballs daily back in 1884, waaaaaayyyy before buckyballs were cool!

Permalink to Comment

46. Evan on April 23, 2012 1:13 PM writes...

Also, in this composite the images on pg 7 of the paper are supposed to be labelled GAog to GEog, but note GD is repeated twice, and there is no GE.
Same goes for GAip to GEip, with a typo lp for ip compounding the problem.

I suspect the person who did the image processing in photoshop was supplied with the raw data, and messed it up - and the editors focused on the printed text, and did not spot the errors in the images. Still, such sloppiness does not inspire confidence in the data in the rest of the paper.

To Dave W : The rats were Wistar.

Permalink to Comment

47. Evan on April 23, 2012 2:12 PM writes...

Interesting article on fullere 60 in relation to an earlier comment about its use in foods as an antioxidant:
http://www.vkm.no/dav/732f564c58.pdf

Permalink to Comment

48. Evan on April 23, 2012 7:21 PM writes...

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676811/
This 2007 study is interesting as an overview:
"Medicinal Applications of Fullerenes"

What piqued my interest is the observation that fullerenes concentrate inside mitochondria....and that they have a catalytic action against ROS.

Do the fullerenes become involved in the electron transport chain in the mitochondria? Or are they just generalist ROS scavengers in the mitochondria? Either way, their action could be related in some way to the mitochondrial theory of ageing.

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49. ratkin412 on April 24, 2012 7:44 AM writes...

1: The study says they used a ".25 UM porosity filter to filter the supernatant. In my research, I have only seen .22 and .45 size filters. I suspect they mean .45 um filter. Could this be true?

2. They say to make the C60 solution, they added 50mg of C60 to 10 ml olive oil. That is only 2 teaspoons worth of olive oil!! In order to get the .8mg/ml dosage they tout throughout the study, my math says they would need to use 62.5 ml olive oil to get the .8mg/ml dosage. Am I misunderstanding something?

3. They also record weights for the rats long past the time they last mention specifically that the rats were still alive, yet the never mention that the weights are calculated using a formula (like they mention doing with their lifespans). Is is possible that the weights are real and the rats lived longer than the last reported "live" date (month 38)?

4. They say they gave the rats 1ml dosages (that would mean that they were working with 1 pound rats). They also say they gave the rats 1.7mg/kg of weight. The rats weighed various weights according to the chart. Is this an error in the report or a conventional standard?

Permalink to Comment

50. A. R. on April 24, 2012 1:46 PM writes...

Anyone else notice how small the sample sizes are?

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51. Anonymous on April 24, 2012 3:19 PM writes...

Rumor has the editor-in-chief of Biomaterials is very greedy....

Permalink to Comment

52. Hugo on April 25, 2012 2:22 AM writes...

Everyone commenting about the errors in tracking and numbers for this study seem to forget that the study was not intended for rat life extension. As they were looking for toxicity from the Buckyballs, not for life extension, so of course the data is not going to fit correctly. Mistakes are made on image uploads, and editors also make mistakes. All in all, I do not see any "smoking gun" of deceit or forgery. Just parts of a different study put together to try and explain an unforeseen outcome. Relax, take a Buckyball cocktail and post in the morning.

Permalink to Comment

53. Ben Harris on April 25, 2012 8:38 AM writes...

I noticed the same thing about the filters, I cannot find a .25 micron Millipore filter, I can find 0.025 micron.

I have emailed the author asking how he mixed the C60 and olive oil. I assume it was with a test tube rocker. 10 mL is not enough to use a magnetic stirrer.

Permalink to Comment

54. Brendan on May 10, 2012 12:02 PM writes...

another just for fun: http://chemscrapes.blogspot.com/2012/05/when-allotropes-of-carbon-clash.html

Permalink to Comment

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