Tuesday, August 17, 2010

Lou Gehrig Probably Died of Lou Gehrig's Disease

OR: Why news embargoes are bad for science.

In an example of mainstream reporting that is aptly described as a "jumbled ball of confusion", the New York Times claimed that baseball player Lou Gehrig (who died in 1941 and whose remains were cremated) might not have had Lou Gehrig's disease:
A peer-reviewed paper to be published Wednesday in a leading journal of neuropathology, however, suggests that the demise of athletes like Gehrig and soldiers given a diagnosis of amyotrophic lateral sclerosis, commonly known as Lou Gehrig’s disease, might have been catalyzed by injuries only now becoming understood: concussions and other brain trauma.

Although the paper does not discuss Gehrig specifically, its authors in interviews acknowledged the clear implication: Lou Gehrig might not have had Lou Gehrig’s disease.
Amyotrophic lateral sclerosis (ALS) is a horrible progressive disease that causes the degeneration of motor neurons that control the muscles. Patients with ALS gradually lose the ability to walk, eat, and breathe on their own. This can happen in a relatively short amount of time (Mitchell & Borasio, 2007):
The clinical features of amyotrophic lateral sclerosis are indicative of the loss of neurons at all levels of the motor system—from the cortex to the anterior horn of the spinal cord. Physical signs of this disorder thus encompass both upper motor neuron and lower motor neuron findings. Objective sensory findings are incompatible with a diagnosis of amyotrophic lateral sclerosis unless they can be accounted for by neurological comorbidity. The course of the disorder is inexorably progressive, with 50% of patients dying within 3 years of onset.
Gehrig died two years after his diagnosis.

What is the evidence that Gehrig might have died from brain trauma and not ALS? According to the New York Times, the forthcoming paper in the Journal of Neuropathology & Experimental Neurology presents postmortem findings from three patients:
...markings in the spinal cords of two players and one boxer who also received a diagnosis of A.L.S. indicated that those men did not have A.L.S. at all. They had a different fatal disease, doctors said, caused by concussionlike trauma, that erodes the central nervous system in similar ways.
From that limited evidence we see extrapolation to a dead sports hero who suffered a number of concussions during his playing career. Gary Schwitzer's HealthNewsReview Blog provides an excellent summary of what was wrong with this coverage, and I suggest you read beyond the excerpt below:
NYT's unfounded leap: Lou Gehrig might not have had Lou Gehrig's disease

This was one time when the headline was OK, but the story that followed had our heads spinning. "Study Says Brain Trauma Can Mimic Lou Gehrig's Disease" is a story that was troubling on a number of fronts. It reported on a study which at the time had not yet been published suggesting that some "athletes and soldiers given a diagnosis of amyotrophic lateral sclerosis...might have been catalyzed by injuries only now becoming understood: concussions and other brain trauma."

To be clear - and please don't anyone miss or miscontrue this point - this is an important and fascinating area of research.

But the story did not exhibit the best of health/medical/science journalism.
Why is it bad that the study has not yet been published? Because experts in the field are not able to read the article and report on what it actually showed. Because the news coverage gets worse, much worse. As in this outright lie printed by The Guardian:
Lou Gehrig killed by baseball not Lou Gehrig's disease, study finds

Player who gave his name to a type of motor neurone disease more probably died due to brain trauma
On the other hand, here's the more modest press release from the journal publisher:
Head Trauma in Pro Athletes Linked to Motor Neuron Disease

Released: 8/17/2010 11:50 AM EDT
Source: Wolters Kluwer Health: Lippincott Williams & Wilkins

Football Players and Boxers with ALS-Like Condition Show Specific Patterns of Protein Deposits in Brain

Newswise — Professional athletes with repetitive head trauma—and possibly others with a history of head injuries many years previously—may be prone the development of a motor neuron disease similar to amyotrophic lateral sclerosis (ALS or "Lou Gehrig's disease"), reports a study in the September Journal of Neuropathology & Experimental Neurology, official journal of the American Association of Neuropathologists, Inc...

"This is the first pathological evidence that repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease," according to the study by Dr. Ann C. McKee of Boston University School of Medicine and colleagues.

Specific Brain Abnormalities Linked to Motor Neuron Disease in Athletes with Head Trauma
The researchers used sophisticated neuropathology techniques to study specific proteins, called tau and TDP-43, in brains obtained at autopsy from twelve former athletes. Eleven of the athletes had been professional football players or boxers; one was a hockey player.
The study actually included neuropathological findings from 12 brains {all 12 had chronic traumatic encephalopathy, but only 3 had ALS}. The embargoed paper is likely to be very good research on an important topic. In addition, there is good evidence that mild traumatic brain injury IS a risk factor for neurodegeneration, as shown by the same group of investigators (Gavett et al., 2010).

The overblown and downright erroneous claims propagated by the press are unfortunate. Will more people read, click, and buy [and fund research] if the name of a historical baseball figure is invoked? I guess so. Some of the blame must be shared by the senior author of the paper, Dr. Ann McKee, who offered up the following quotes in an interview:
“Here he is, the face of his disease, and he may have had a different disease as a result of his athletic experience.”

. . .

“If we can create this in laboratory mice, which are easily genetically altered and breed quickly, we can learn about the pathogenesis of this disorder, and then provide treatment,” Dr. McKee said.
Three postmortem cases --> genetically altered mice --> treatment.

Uh, aren't we jumping the gun just a bit? Even though the chronic traumatic encephalopathy (CTE) variant of ALS-like disease may have a different etiology, drug development will not be easy. According to the ALS Association:
Present treatment of ALS includes one drug, riluzole (Rilutek©) and is aimed at symptomatic relief, prevention of complications and maintenance of maximum optimal function and optimal quality of life. Most of this, in the later stages, requires substantial physical caregiving. Click here for more information on Rilutek.

For information on drug development and clinical trials, click here.

Riluzole slows the progression of ALS but is not a cure. Neurodegenerative diseases exact a terrible toll on patients and their families. Sufficient funding for the development of effective treatments is of critical importance. But do we have to warp the news coverage to obtain such funding? Such is the sorry state of scientific research today.


Gavett BE, Stern RA, Cantu RC, Nowinski CJ, McKee AC. (2010). Mild traumatic brain injury: a risk factor for neurodegeneration. Alzheimers Res Ther. 2:18.

Mitchell JD, Borasio GD. (2007). Amyotrophic lateral sclerosis. Lancet 369:2031-41. Review.

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At August 18, 2010 7:33 AM, Anonymous Ivan Oransky said...

Thanks for a provocative and insightful post. I think questioning the emphasis of the Times story, and its claims, as you and Gary Schwitzer have done, is important. You have both done that very carefully and rigorously.

I do want to raise a point about your alternative headline, however: "Why news embargoes are bad for science."

I think that headline may be confusing an embargo with the inability of outside experts to comment. You write:

"Why is it bad that the study has not yet been published? Because experts in the field are not able to read the article and report on what it actually showed."

According to the story, however, the Times clearly used the time between when they received the embargoed materials and the embargo lift to solicit comment from outside experts, in this case "Dr. Brian Crum, an assistant professor of neurology at the Mayo Clinic in Rochester, Minn.," and "Dr. Lucie Bruijn, the chief scientist for the A.L.S. Association."

You can certainly argue about whether the Times chose the right experts -- or was able able to get the right people to call them back in the middle of August -- but it's not true that experts were unable to read the article.

In fact, one of the arguments journals and societies use to justify embargoes -- and a read of my blog, Embargo Watch, should confirm that I'm hardly an apologist for them -- is that reporters can take the time to contact such outside experts and write more-informed stories. Here at Reuters Health we routinely send embargoed materials to such experts, of course under embargo, before we publish stories.(That's why I find short embargoes so maddening.)

So whatever this story's problems, I don't think they are a good example of why embargoes are bad for science.

Perhaps you meant to argue that embargoes should hold until some time after studies are widely available to the scientific community. I wouldn't agree, since that would put an unreasonable block on reporters' ability to keep their readers and viewers informed -- particularly about taxpayer-funded research that may have clear clinical implications. But that argument would be consistent with the important "no ability for outside comment" problem I think you're concerned about, and I'd welcome the opportunity to explore it.

Ivan Oransky, MD
Executive Editor, Reuters Health
Adjunct Assistant Professor, New York University's Science, Health, and Environmental Reporting Program
Treasurer, Association of Health Care Journalists
Clinical Assistant Professor of Medicine, New York University School of Medicine
Blogger, Embargo Watch http://embargowatch.wordpress.com (a blog independent of Reuters that does not necessarily reflect its views)
Blogger, Retraction Watch
http://retractionwatch.wordpress.com (ditto)

At August 18, 2010 12:55 PM, Anonymous George C said...

I have to disagree with you criticisms. The Times article - and the snippets you quote - plainly say over and over 'may have' and 'might have'. You state yourself agreement. So what did they do wrong?
This science is yet another indicator that concussions in sports, in combat, are a far more serious event than used to be thought. It's vital this message gets through.
One complaint is that such a conclusion might result in less funding & fewer donations towards ALS research. This is just a reminder that there's an unfortunate competition for funds for ALL medical research. Everyone supports the disease that's touched home, and not the broader ideal that all medical science needs funding.
But if you must cost-benefit each condition, I would guess debilitating concussion-related problems cost society more, but on the other hand, I don't see how research into the differences between ALS & ALS-like disease from concussion would be to the detriment of either condition. I personally can only see how it would aid understand both.
Again, and most seriously, since the article DOES continually pose Gerhig's tragic case as a hypothetical (illustrated with just a few of his ball field head traumas) not to mention the other medical folks and case histories presented, the Times has 'covered' itself. It explained that both these conditions warrant more study to differentiate, understand, treat, and of course possibly prevent these terrible conditions.
I just don't get the complaints at all.
Unless this is all about funding.

At August 18, 2010 1:55 PM, Blogger The Neurocritic said...

Ivan - Thanks for your comment. I'm a fan of Embargo Watch and Retraction Watch. I admire what you're dong there.

I understand your concerns and can be sympathetic to a point, but as a scientist and a blogger I disagree. I realize that the Times did contact two experts in the field to comment on the work, although from the vagueness of their statements it's unclear whether they read the journal article. I trust that's standard procedure, and perhaps any further details were edited down to sound bites. Or maybe that's all they said.

My issue is that I (and other scientists/bloggers) am unable to read the journal article to verify the findings. Granted, I am not a leading expert in tauopathies and no media outlet would ever solicit my opinion. But I am able to provide a very well-informed summary of what was reported in the still-unpublished paper.

So maybe the problem is really that of of two embargoes - it's fine to have a press embargo for journalists to solicit expert comments, but once they publish a story in the mainstream media then the embargo of the originating source should be lifted and the journal article should be published simultaneously with the news article. So then the wider community can comment. [This point was made by Sandra Kiume in an e-mail]. PNAS is among the worst violators in this regard. Sometimes the paper isn't posted until a week after the press coverage.

At any rate, I do not want to add any more fuel to the "journalists vs. bloggers" fire...

George C - No, the complaints are not all about funding. They're about confusing the public. I agree with you that increased awareness of concussion-related problems in sports is a very positive development, and it's great to see the NFL acknowledging this.

But the NY Times story has created all sorts of misconceptions. Just go on any social networking site and see what people are saying. "Lou Gehrig did not die from Lou Gehrig's disease." Other media outlets less "cautious" than NYT have only reinforced this notion.

I'll again refer to Gary Schwitzer's HealthNewsReview Blog for his excellent summary of why the article was confusing:

1. It was based on a study of 3 people. (The ALS Association says there are up to 30,000 people in the US living with ALS.)

2. It stated, "Lou Gehrig might not have had Lou Gehrig's disease." (No evidence for this was provided. He also may not have been a great left-handed hitter. That may have been an optical illusion.)

3. It said this could "perhaps lead toward new pathways for a cure." (After a suggestive finding in just three people?)

4. The story later says, "The finding's relevance to Gehrig is less clear." (Hedging already after a bold earlier statement in the story.)

5. But just a few paragraphs later, the story says, "The new finding...suggests that Gehrig might not have had (ALS)." (Head spinning yet?)


At August 18, 2010 2:01 PM, Anonymous Sandra Kiume said...

Hi Ivan - Press embargoes are useful for journalists to prepare stories, but once they're published in the mainstream media then the embargo of the originating source ideally would be lifted and the journal article published simultaneously with the news article. A wider community is then able to read details without a frustratng lag, and comment further in social media.

At August 18, 2010 2:59 PM, Anonymous George C said...

Not to go in a circle, but its fair to point out that we agree the Times was cautious, period. I don't know how we can expect that caution to be passed onto others. Surely you're not saying the Times should've 'shut up' because it should KNOW its report would be misrepresented elsewhere.
(The Times does it's own share of misrepresentation.)
I understand your frustration as a scientist. However, you seem to be expecting Journal-level science in the 'popular press.'
This is apparent in your comment that the article is 'vague'. Well, whether they read the journal or not, they write for a general readership. They're not going to satisfy you as a scientist or blogger.
I would suggest that someone in those roles - and anyone with interest - would certainly (& easily these days) look for deeper sources once the general media draws their attention to something. YOU'LL comb the journals!
I'm not saying your standards are too high. I'm saying your standards are too high for a general readership organ.
The Times, they're vague but not outright wrong. They're cautious. That's as much as we can ask for its audience.
Put it this way - I might well have skipped the link to your blog if I hadn't had my interest peaked by the Times article.
I'll leave it stand there.
Thanks and be well

At August 18, 2010 3:24 PM, Anonymous Ivan Oransky said...

Neurocritic and Sandra:

Thanks for the thoughtful responses.

I don't think we disagree on whether journals should release studies as soon as the press embargo lifts. I covered that in an early Embargo Watch post back in March, prompted by Ed Yong:


(Pardon the bullet point about anonymous bloggers, Neurocritic. I hope I made it clear I'm not condoning the extra layer of scrutiny, simply saying it's likely. And I think commenters on my post made excellent points about that.)

It drives mainstream journalists who like to link to original studies -- and that includes us at Reuters Health -- bananas too. I hate having to link to a journal's homepage instead of to an abstract. That's not a good service to readers.

So yes, it's probably a case of two embargoes and of consistency, and I think we agree.

I'm not a fan of the bloggers vs. journalists "debate" either, by the way. If it were up to me, I'd make embargoed material open to far more people, including bloggers:


Great discussion -- thanks.


At August 18, 2010 4:11 PM, Anonymous Ivan Oransky said...

Apologies -- in my last comment, the parenthetical about anonymous bloggers referred to the second link I included, about who gets access to embargoed studies, not the first one about the PNAS problem.

At August 18, 2010 8:06 PM, Blogger PalMD said...

To those focusing on the "hedge" language, please try to remember that the "mights" serve to protect the writer's conscience, rather than to clarify the topic.

For example, our president "might" be a foreign born muslim, not that i'm saying he is, but other people like him have been and maybe yada yada.

At August 18, 2010 9:02 PM, Blogger Dirk Hanson said...

Speaking of the writer's conscience, and setting embargoes aside, why does no blame fall on the scientist who wrote the paper and who provided the misleading analogy herself? How is this entirely the fault of the journalist who wrote the story?

At August 19, 2010 1:00 PM, Blogger The Neurocritic said...

Ivan - I appreciate your carefully considered views on the embargo issue. I went back and read the pieces you linked to (along with Ed Yong's post on the PNAS policy). I have several posts on problems I've encountered when trying to write about unavailable PNAS papers, my favorite being The PNAS Word.

I've never considered applying for press credentials from AAAS or EurekAlert! It's not only because I'm a pseudonymous blogger, but because blogging is a "hobby" for me and not a source of income. There's always plenty of non-embargoed material out there for me. But it is annoying when papers are not available in a timely fashion, as you and Ed and Vaughan Bell have noted.

The Wikileaks release of the Afghanistan War Logs might be considered an extreme example of the press embargo/then immediate publication policy [I see you've already written about this]. Wikileaks granted exclusive access to the massive collection of documents to 3 media outlets (NYT, Guardian, and Der Spiegel) for ~4 weeks to analyze, research, and write up their stories. Simultaneous with publication of the media articles, Wikileaks made the entire archive available to the general public. Now I know some people weren't happy with the press embargo in the first place, saying the public had a right to see the materials at the same time as the media.

George C - See PalMD.

Dirk - I did blame the scientist who granted the interview:

Some of the blame must be shared by the senior author of the paper, Dr. Ann McKee, who offered up the following quotes in an interview:

“Here he is, the face of his disease, and he may have had a different disease as a result of his athletic experience.”

. . .

“If we can create this in laboratory mice, which are easily genetically altered and breed quickly, we can learn about the pathogenesis of this disorder, and then provide treatment,” Dr. McKee said.

At August 21, 2010 11:12 AM, Anonymous Amiya said...

Interesting! Idrocilamide is another new drug that may be used to treat the condition, in addition to Riluzole.

At July 23, 2020 1:21 PM, Blogger Ethan Tara said...

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