Wednesday, November 19, 2014

Purdue professor Dr. Sanders responds to commentary about his Ebola interview with Fox News

Last month I analyzed the media coverage of Ebola in a post where I dissected an interview between Fox News reporters and Dr. David Sanders. I was recently contacted by Dr. Sanders, who wished to clarify a few issues that I raised in my article. The purpose of my post was to demonstrate how the media sometimes covers scientific issues in ways that exaggerate and oversimplify concepts, which can potentially mislead non-scientist citizens.

I stated that the way Dr. Sanders described his research sounded a little misleading. I intended to convey how I thought an average non-scientist listener might interpret the dialogue. However, Dr. Sanders points out that he was careful with his wording to avoid possible confusion. He explained, “as you have pointed out, one says one thing, and the media (and the Internet) render it as something else.  I would just like to point out that I carefully stated that Ebola can ENTER human lung from the airway side; I never said infect.  I also try to avoid the use of the term ‘airborne’ because of the confusion about its meaning.”

Also, he had several good scientific points about the validity of using pseudotyped viruses and the comparison to other viruses when considering the potential for a change in Ebola transmission.

“Pseudotyped viruses are used widely for studying viral entry, and I know of no examples where the conclusions on the cell biology of the entry of pseudotyped viruses have been contradicted by studies of entry of the intact virus despite such comparisons having been published numerous times.” 

“When we discovered that there was maternal-child transmission of HIV was that a new mode of transmission or merely a discovery of a previously unknown mode of transmission? How was Hepatitis C transmitted between humans before injections and blood transfusions? I don't know either. How is Ebola virus transmitted between fruit bats or from fruit bats to humans? Perhaps modes of transmission differ in their efficiency. The HIV comparison with Ebola ("HIV hasn't become airborne") is fallacious given the cell biology of entry for the two viruses.  The receptors for HIV (the CD4 attachment factor and the chemokine receptor) are present on blood cells and not on lung tissue.  The receptors for Ebola are present on a diverse set of cells including lung cells. In addition, Influenza A switches in real time from a gastrointestinal virus in birds to a respiratory virus in mammals--not that many mutations required.”

Additionally, he wisely pointed out that “precedent may be a valid argument in medical practice or the law, but it is not valid in science.” In fact, science seeks to uncover things that were previously unknown, and thus were without precedent.

I appreciate Dr. Sander’s response to my article. I think that rational and in-depth discussions about science need to happen more frequently in the media. Short, simplified stories with shock-factor headlines only detract from the important conversations that are necessary to find practical solutions to challenges like Ebola.

-Mike Allegrezza

Monday, November 10, 2014

Penn researchers identify neurons that link circadian rhythms with behavioral outcomes.

Our bodies evolved to alternate rhythmically through sleep and wake periods with the 24-hr cycle of the day. These “circadian rhythms” are controlled by specific neurons in the brain that act as molecular clocks. The experience of jet lag when we change time zones is the out-of-sync period before the brain’s internal clock re-aligns with the external environment.

How does this molecular clock work in the brain? Decades of research have uncovered that environmental signals, such as light, are integrated into a circadian clock by specific neurons in the brain. However, little is understood about how these circadian clock cells drive biological effects such as sleep, locomotion, and metabolism. A study by Penn researchers published earlier this year in Cell has discovered critical neural circuits linking the circadian clock neurons to behavioral outputs.

The researchers used the fruit fly Drosophila as a model organism because like humans, they also have circadian rhythms, yet they are very easy to manipulate genetically and many powerful tools exist to study the 150 circadian clock neurons in their brains. The study found that a crucial part of the circadian output network exists in the pars intercerebralis (PI), the functional equivalent of the human hypothalamus.

“Flies are normally active during the day and quiescent at night, but when I activate or ablate subsets of PI neurons, they distribute their activity randomly across the day,” describes the study’s first author, Daniel Cavanaugh, PhD, a post-doc working in the lab of Amita Sehgal, PhD. Importantly, the research showed that modulating the PI neurons lead to behavioral changes without affecting the molecular oscillations in central circadian clock neurons, indicating that the PI neurons link signals from the circadian clock neurons to behavioral outputs.

The study also showed that the PI neurons are anatomically connected to core clock neurons using a technique involving the fluorescent protein GFP. Cavanaugh explains, “The GFP molecule is split into two components, which are expressed in two different neuronal [cell] populations. If those populations come into close synaptic contact with one another, the split GFP components are able to reach across the synaptic space to reconstitute a fluorescent GFP molecule, which can be visualized with fluorescence microscopy.”

Additionally, their experiments showed that a peptide called DH44, a homolog to the mammalian corticotropin-releasing hormone, is expressed in PI neurons and important for maintaining circadian-driven behavioral rhythms.

While these new data are interesting for understanding general mechanisms of biology, they also have implications for human health and disease.

“People exposed to chronic circadian misalignment, such as occurs during shift work, show increased rates of heart disease, diabetes, obesity, cancer, and gastrointestinal disorders,” says Cavanaugh. “In order to understand the connection between circadian disruption and these diseases, we have to understand how the circadian system works to control the physiological outputs that underlie these disease processes.”

-Mike Allegrezza