Anthrax, false research, triglycerides, mea culpa, cellphone freedom

Accidental anthrax

Which is the more likely threat to public safety?  A single big release of deadly organisms by terrorists, the nightmare that fuels much bioweapons research and a string of lookalike novels that are nearly a genre in themselves? Or a series of much smaller accidental releases “from the high-level biodefense labs that have proliferated in the wake of the anthrax attacks of 2001″? Christine Gorman asks this at Observations, the SciAm editors blog.

Bacillus anthracis. Credit: Centers for Disease Control and Prevention

Bacillus anthracis. Credit: Centers for Disease Control and Prevention

The data argue that we are in far more danger from accidents emanating from well-meant research efforts to protect ourselves. To date there have been no bioterrorists. The 2001 attack killed 5 and was probably carried out using a research anthrax strain from a US lab. Several incidents occurred in the 1970s. In 1978, smallpox escaped from an English lab killed a photographer. A similar 1971 release from a Soviet lab killed at least three; it’s not known whether that was an accident or deliberate. The accidental 1979 release of anthrax at Sverdlovsk may have killed as many as 100.

Gorman’s brief history of lethal microbial escapees from research labs was prompted, of course, by last week’s news from the Centers for Disease Control and Prevention that at least 75 of its staff members may have been exposed accidentally to live anthrax as it was transferred from one lab to another. This because safety procedures that were supposed to be followed were not, and why they were flouted is not known.

Nobody has turned up sick yet, but the incubation period has not quite expired, according to Susannah Locke’s updated report at Vox. David Malakoff’s June 19 report at ScienceInsider has a lot of details.

 

“Most published research findings are false”

John Ioannidis’s 2005 PLOS Medicine article, the one with the forthright but startling title, “Why Most Published Research Findings Are False,” reached a milestone earlier this year: a million page views, the first PLOS article to attract that much traffic. To celebrate, the PLOS Blog Network published a brief interview with Ioannidis carried out by PLOS’s Erica Kritsberg.

Ioannidis, who is Professor of Medicine, of Health Research and Policy, and of Statistics at Stanford, says he sent the paper to PLOS Medicine because the journal was new and seeking to be adventurous. “Given the breadth and importance of the topic, specialty journals would certainly find it uninteresting.”

Ouch.

He emphasizes that his results apply mostly to what he calls “silo” research, where a single principal investigator “is trying to outpace the others, finding significance in his/her own results without sharing and combining information. The opposite holds true when scientists join forces to examine the cumulative evidence. Sadly, in most fields the siloed investigator writing grants where he promises that he/she alone will discover something worthy of the Nobel Prize is still the dominant paradigm. This sort of principal investigator culture is a problem, especially for popular fields where the literature is flooded with tens of thousands of irreproducible papers.”

Last year Ioannidis joined with Daniele Fanelli, of the University of Edinburgh, in a PNAS paper arguing that studies involving behavior were more likely to claim extreme effects, to exaggerate their results, especially if the authors were based in the US. Why? “Our preferred hypothesis is derived from the fact that researchers in the United States have been exposed for a longer time than those in other countries to an unfortunate combination of pressures to publish and winner-takes-all system of rewards” They also forecast that researchers outside the US would likely soon catch up in the bad behavior department. Ivan Oransky analyzed the paper at Retraction Watch.

John Ioannidis. Why is this man smiling?

John Ioannidis. Why is this man smiling?

For more on Ioannidis and his dispiriting contention that scientific results are, for the most part, untrustworthy, see a post by Julia Belluz, who blogs at Science-ish for Maclean’s magazine in Canada. She reports on a session Ioannidis gave early this year at the Harvard School of Public Health, educating a roomful of doctors on the bad news about the state of science.

It does make one wonder what we’re all doing here.

 

Loss of function

I wonder what John Ioannidis would make of the New England Journal of Medicine papers reporting on mutations that silence the APOC3 gene and prevent formation of fats called triglycerides. This, they say, reduces the risks of heart attacks and strokes by 40 percent.  There are two of them, conducted independently but reporting similar results. The fact that the two studies from two different research groups come to similar conclusions does suggest they may be on to something.

At Forbes, the very reliable Larry Husten doesn’t challenge the papers, but he is doubtful about their interpretation by some researchers and science writers. These sources have promoted the idea that the heretofore ambiguous role of triglycerides has now been clarified and reveals that they are important in development of cardiovascular disease. The papers have also been interpreted as downgrading the importance of high-density lipoprotein, HDL, the “good” cholesterol, which has been thought to protect the cardiovascular system.

Husten argues that the papers suggest “that it may be very difficult to link the effect of APOC3 to its specific impact on triglycerides.” The loss-of-function mutations that shut down APOC3 do accompany a reduction in triglycerides, he notes. But low-density lipoprotein, LDL, the “bad” cholesterol, is also reduced–and HDL goes up. “So it may be hard to figure out exactly what APOC3 is doing, and it’s probably too soon to dethrone HDL and elevate triglycerides. We just don’t know enough at this point.”

Husten quotes leading cardiologist Harlan Krumholz as saying the research, “has absolutely no implications for clinical practice. It might one day be seen as a pivotal study that led to the development of remarkable drugs, but that is far away.”

 

Mea maxima culpa

That emphasis might please Knight Science Journalism Tracker Paul Raeburn, who uses Gina Kolata’s New York Times piece on the two papers as a jumping-off point for a mea culpa. Raeburn is distressed that Kolata’s emphasis (as is the case in nearly all journalism about medical research developments) is on the potential for therapy, especially drug therapy. The stories usually caution (as this one does) that the potential therapies might not pan out. (As, indeed, they rarely do.)

Raeburn acknowledges that he has often said the same sort of thing, and he is not alone. I certainly have, and so has everyone who writes about this stuff. Mea maxima culpa.

So we should all take to heart his suggested revised approach to getting rid of this promise-of-therapy reflex. “I think we need to step away from the boilerplate promise-and-unpromise paragraph that we’ve written so often, and query researchers more carefully about exactly how and when their research might lead to new treatments. What problems remain to be solved? What are the potential side effects? How much might it cost? Would the FDA be likely to approve it? Does it raise ethical questions?”

While I’m up, I feel compelled to draw attention to an unrelated but really odd blog comment on the triglyceride papers. Recall that the gene alterations under study are loss-of-function mutations that shut down APOC3 activity. From Uncommon Descent, an “intelligent” design blog:  “Is this Darwinian evolution in action? No, because loss of function is the opposite of gain in function, which is what Darwin’s theory (natural selection acting on random mutation) proposes to explain. Loss of function is a form of evolution, but is[sic, I expect they mean "its"] resources are very limited.”

Huh?

 

Fourth of July holiday: freedom from mobile phone searches

Next Friday, July 4, is Independence Day, our most important national holiday here in the US. So I will not be bringing you On Science Blogs because I will be celebrating the birth of our freedom. You, too, I hope.

Our freedom was epitomized this week by the US Supreme Court’s unanimous ruling–especially astonishing because this is not a Court that does much of anything unanimously– [more mea culpa, see comments below] that police can’t search people’s cellphones without a warrant.

While you are lazing away the long weekend, or even sooner, you will want to read the incomparable Linda Greenhouse on the cellphone ruling. Her analysis: The justices came together in this case because they all own mobile phones.

Yay, freedom. Back in two weeks, Friday, July 11.

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5 Responses to Anthrax, false research, triglycerides, mea culpa, cellphone freedom

  1. John Gever says:

    Wait a minute, why wasn’t the 2001 anthrax attack bioterrorism? It was certainly no accident. Yes, the strain probably came from a research lab, and your overall point is well taken. But to say “To date there have been no bioterrorists” is simply false and it undermines your otherwise excellent post.

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    • Tabitha M. Powledge says:

      As I recall, the chief suspect in that case was a scientist who worked with anthrax, now dead, and his motive (or one of them anyway) was believed to be to raise the alarm, to make it clear how easy it would be to kill people with a deadly microbe. That doesn’t seem to me to be bioterrorism exactly. Meta-bioterrorism, maybe. And not a lab accident certainly, so I won’t argue the point passionately. Mea culpa? Perhaps. But not maxima this time.

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      • John Gever says:

        Geez, killing a bunch of people in order to “raise alarm” about an issue isn’t “exactly” terrorism? I suppose you’re hesitating because the issue in this case was, itself, bioterrorism, and not a more conventional political grievance. I think you’re splitting hairs. Killing people to make a statement or point is terrorism, period.

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  2. Bob Roehr says:

    Re: especially astonishing because this is not a Court that does much of anything unanimously

    I know it was a throw away line, but in fact, nothing could be farther from the truth; 9-0 is in fact THE most common ruling by the US Supreme Court, occurring roughly half the time. For better or worse, what gets attention and sticks in our mind is disagreement, not agreement.

    Justices Agree to Agree, at Least for the Moment http://www.nytimes.com/2013/05/28/us/supreme-court-issuing-more-unanimous-rulings.html?_r=0

    So Much For Politics: More Than Half Of Supreme Court Decisions Unanimous http://www.forbes.com/sites/danielfisher/2012/06/01/so-much-for-politics-more-than-half-of-supreme-court-decisions-unanimous/

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    • Tabitha M. Powledge says:

      Talk about mea maxima culpa. Maxima indeed. Apologies all ’round. I read that Times piece late last night, ground my teeth, and put a fix on my mental ToDo list for today. Then Life arrived this morning and the list got majorly revised. So, Bob, much obliged for the proxy fix, which is in any case more complete than mine would have been.

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