Obstacles in cancer research – funding, evaluation, & complex disease

Posted on September 26, 2012 by biochembelle

Yesterday morning, director of the National Cancer Institute, Harold Varmus, addressed the National Press Club on the achievements and challenges of cancer research. Varmus covered quite a few topics, but here are a few highlights that stood out for me:

  • If budget sequestration goes into effect, NCI may be facing a 40% reduction in new grant awards. When asked to elaborate, Varmus basically responded, You do the math; our objective it to stop this from happening.
  • Varmus (an NIH as a whole) is concerned about the issue of reproducibility in research. Is there a rush to publish in the current climate? Why are replicative experiments failing? But also how (and who) defines failure to reproduce?
  • Scientists need to rethink how we evaluate others’ achievements. Publishing in “particular journals” (he subsequently named Cell, Nature, and Science specifically) is being used as a marker of success, but important work is also found in other journals. It’s time to get back to judging the science by the research not where it’s deposited. (Related to this is an editorial by Ron Vale in the American Society for Cell Biology’s journal.)

You can watch the full videocast on CSPAN. It’s an hour long but worth a watch. I think it serves as a good primer for non-scientists on the way biomedical research works and why progress is often slower than we want.

Posted in biomedical research, conduct of research, grants, NIH, publishing, responsibilities, troubles of science | Leave a comment

Course correction: What you never thought you’d need to know

Posted on September 4, 2012 by biochembelle

It’s that time of year again. Students are flooding back onto campuses, resuming their courses of study or embarking on a new path.

Research runs similar lines – following up and taking new directions. And sometimes it leaves me wishing I had learned more _______ as a student. There’s hope for those who are still students – and in the digital age with things like free online courses and CodeAcademy, there might even be hope for the rest of us. Here are a few on my list:

  • Statistics – really, why isn’t this required for every science degree, from BS to PhD? We tend take p-values as a statement of truthiness of research results, but how well do most of us understand them?
  • More calculus – If you get into any sort of quantitative biology, derivatives and integrals are going to haunt you.
  • Linear algebra – Goes along with ‘more calculus’ and the realization that computers operate in matrices.
  • Computing – Along with previous 2, if you’re doing quantitative analysis, chances are you’re going to find yourself entrenched in R and/or MATLAB. You might also find that you’re running, editing, or writing code, so speaking the language (e.g. Python, which seems to be taking over bio applications) is be a huge benefit.

Ten years ago, as I was finishing up my BS, I never imagined how much some of these things would be infiltrating my life. From my view, these things certainly are not going to become less useful in the future – of my research or the field.

What’s on your list?

Posted in Uncategorized | 13 Comments

Morning musing: Decline of the doctorate?

Posted on August 18, 2012 by biochembelle

Of late, I have noted, among a subset of scientists, a disposition that the quality of the PhD candidate and/or PhD training declined.

Of course, this is based on purely subjective measures – usually centered on the degree of independence and engagement.

I posit that there is, always has been, and always will be a distribution in these areas, and that perceptions of decline are either: (a) just that, perceptions colored by general negative feelings about the academic system today, or (b) a result of the increased volume of PhD candidates and recipients (i.e. the raw numbers have increased, but the distribution remains the same).

But maybe I’m just an optimist …

What say you?

Posted in attitudes, biomedical workforce | 4 Comments

Churning (fake) butter: More safety questions for food manufacturers

Posted on August 14, 2012 by biochembelle

In case you missed it, check out this post for context.

August seems to be turning into a month of popcorn toxicology. While doing a bit of house blogkeeping this morning, I ran across a release about a new study on a diacetyl substitute.

After manufacturers started reducing and removing diacetyl from their fake butter recipes, they switched to a series of closely related compounds, simple extensions of the carbon chain. National Institute of Environmental Health & Safety and National Institute of Occupational Safety & Health have now assessed the toxicity of one substitute, 2,3-pentanedione, in rodents. Given the structural similarity to diacetyl, both groups thought the respiratory effects of 2,3-pentanedione should be explored. The NIOSH study, published online today, also looks at neurological effects because a related compound, 2,4-pentanedione is neurotoxic.

I won’t go into the detail that I did for the diacetyl Alzheimer’s post, because I am not a pathologist, and pathology is the meat of these papers. But here’s the gist: Inhaling 2,3-pentanedione injures the respiratory epithelium of rats and mice. Based on the NIOSH results, acute respiratory toxicity is comparable for diacetyl and 2,3-pentanedione.

However, 2,3-pentanedione creates some other major problems in rats. It damages to olfactory neurons, inducing degeneration and apoptosis. The compound also increases mRNA expression* of inflammatory genes – in the brain. Presumably it’s crossing the blood-brain barrier and dispersing throughout the brain; the authors observed changes in mRNA expression in the olfactory bulb, hippocampus, striatum, and cerebellum.

* The changes for the inflammatory genes IL6 and NOS2 are significant… but I suspect Alejandro would yell at them for using only one reference gene for their RT-qPCR

As is typical for early stage toxicology studies, concentrations of 2,3-pentanedione used were moderate to high – 200+ ppm (or 200 mg/L air) administered continuously –  but both neural and respiratory effects were observed within 6 hours of continuous exposure. Although rats are not humans, these studies highlight the importance of establishing exposure limits and proper engineering and personal protection controls for industry workers.

What does this mean for the consumer? Like diacetyl, the FDA lists 2,3-pentanedione as GRAS, “general recognized as safe” under normal consumption conditions. If 2,3-pentanedione levels in food are comparable to diacetyl, then a single bag of microwave popcorn emits less than 1 mg, with about 80%  immediately upon opening.

I, for one, would continue to enjoy my popcorn. But it might be wise to adapt example of a former U.S. president: Pop but don’t inhale.

References

Daniel L. Morgan, Micheal P. Jokinen, Herman C. Price, William W. Gwinn, Scott M. Palmer, & Gordon P. Flake (2012): Bronchial and bronchiolar fibrosis in rats exposed to 2,3-pentanedione vapors: implications for bronchiolitis obliterans in humans. Toxicological Pathology. DOI: 10.1177/0192623311431946

Ann F. Hubbs, Amy M. Cumpston, W. Travis Goldsmith, Lori A. Battelli, et al. (2012): Respiratory and Olfactory Cytotoxicity of Inhaled 2,3-Pentanedione in Sprague-Dawley Rats. The American Journal of Pathology. DOI: 10.1016/j.ajpath.2012.05.021

Jacky A. Rosati, Kenneth A. Krebs & Xiaoyu Liu (2007): Emissions from Cooking Microwave Popcorn, Critical Reviews in Food Science and Nutrition. DOI: 10.1080/10408390701638951

Posted in Uncategorized | 2 Comments

Science, reporting, & communication

Posted on August 13, 2012 by biochembelle

Last night, I posted about a basic research paper that has gotten some press attention. As is often the case, much of the nuance and context of the original work is missing from the press coverage or buried at the end of the stories.

I am a self-proclaimed protein science junkie, and my career has centered on proteins in  immunity. However, while doing my PhD in Chemistry, I also learned a bit about toxicology. My uni had a good program in the field, and part of my PhD supervisor’s lab worked on molecular and cellular toxicology – which is really biochemistry and cell biology with a dash of pharmacology. I picked up enough to be skeptical of claims as broad as “Popcorn linked to Alzheimer’s”.

Another element added to my skepticism. My PhD mentor, well-versed in toxicology, was a popcorn fanatic. So our lab got the rundown when manufacturers announced they would be changing their microwave popcorn formulas due to safety concerns regarding diacetyl. (Note this announcement came very shortly after the first account of a consumer  experiencing adverse effects under rather rare circumstances.) So my mind jumped to diacetyl when I first heard about the current story from Jason Goldman on Twitter:

https://twitter.com/jgold85/status/233325825997561856

I clicked the link and found this example of how to do make a hash of science reporting:

MINNEAPOLIS, Minnesota (KTLA) — Next time you’re at the movies, you may want to think twice before asking for extra butter on your popcorn.Scientists at the University of Minnesota have found that an ingredient in fake butter, known as diacetyl, may triggerAlzheimer’s disease.In addition to microwave and movie popcorn, diacetyl is also used in margarine, snack foods, candy, baked goods, pet foods and other products such as beer and chardonnay wine.

The study also found a link between the flavorant and lung damage in popcorn factory workers.

What exactly did KTLA do wrong?

  • Not only was there no link or citation for the paper, the piece didn’t even list the journal where the work is published or the lab that did the work. I suppose we should be grateful that they mentioned the institution, which allowed me to find the paper via Google Scholar.
  • Only 1 sentence out of 4 actually addressed the current study. And that one sentence was a substantial generalization and overstatement of the work done.
  • The last sentence is false – the findings stated are correct but the result of medical research from other groups more than 5 years ago.
  • There is no qualification of dose – that (as was noted in the paper’s abstract) this is proposed as a potential hazard for industry workers who are chronically exposed to very high levels of diacetyl (as compared to the typical consumer).

The original press release is pretty reasonable. And other news outlets did a better job of covering the story, for example, this CBS health story. My major qualms with most media coverage are the overly broad headline (I realize creating statements that are both concise and accurate isn’t easy) and every lede I saw started with consumer focus when the research is about industry exposure.

Don’t get me wrong. Understanding the effects of industry exposure levels of chemicals is necessary and important. Such studies inform corporate and regulatory policy. But, as seen here, the media* can (and often does) misconstrue study findings, sometimes giving the impression of data that simply isn’t there. This adds to the challenge scientists face of communicating research to the public and to policy makers. It seems at times we are expected to deal in absolutes, but in science, there are subtleties and unknowns.

It reminds me of an admonishment Captain Kirk laid before Spock one time: “Insufficient data is not sufficient, Mr. Spock! You’re the science officer. You’re supposed to have sufficient data all the time.” In reality, scientists don’t have sufficient data all the time. Data are sometimes incosistent, sometimes nonexistent. We keep pushing forward – combing the literature, designing the next experiment, looking for that next bit of data, adjusting our models – to come up with the most complete and logical answer within our power and ability. Usually it leaves us wanting more – and in some ways, part of the beauty of science is that it’s never really done.

* Clarification: Here I am referring mainly to mainstream media health and science coverage, not science journalism. It’s been noted in many conversations that bad science coverage is often the result of a journalist covering topics all over the map who has maybe 15 or 20 minutes to digest a press release and write something up. There is a lot of good science journalism out there. The case study here is simply an example of why scientists should pay attention to how the media is reporting research.

Related post: Check out Doctor Zen’s thoughts on food & trust at Neurodojo.

Posted in communication, public outreach, science literacy | Leave a comment