Saturday, April 22, 2017

We Support The March For Science

In person or in spirit, scientists and science enthusiasts MARCH FOR SCIENCE today. Why? Science is the most reliable method that humanity has devised that teaches us how things work - it is the beacon that leads us to the truth. Truths that are often well-disguised, beyond our intuition, and shielded behind our preconceived notions. The truth can upset worldviews and bottom lines, but those who resist it cannot be allowed to jeopardize the reality reasonable people have come to accept. When we forego the evidence to maintain a faulty reality, we fail to progress. A world that doesn’t invest in science will pay for it with another Dark Age.

Support science, education, and evidence-based policy.

Friday, April 21, 2017

You've Gotta Learn to Walk Before You March

March For Science Logo
Saturday, April 22, 2017, is Earth Day. So it is appropriate that organizers have scheduled a large-scale march on Washington, DC (and over 500 other satellite marches planned), in support of evidence-based policy decisions. It is interesting that in the year 2017 we require marches to get across the point (hopefully) that scientific evidence should be a critical aspect of policy development. But alas, here we are.

So, in the spirit of marching along with our fellow scientists and science enthusiasts who understand the importance of scientific inquiry, and who want to advocate for sustained and predictable federal funding for science, we at THE 'SCOPE thought it would be fun to take a closer look at the funny (dare I say, silly?) way that humans, march: on two legs, or bipedally as it is called.

We briefly covered the evolution of bipedal walking in an earlier post, so we will not rehash the anatomical adaptations that allow for this type of locomotion. Suffice it to say that our skeleton has undergone several changes to the spine, pelvis, and lower limbs, that allow us to keep our knees under our center of mass while standing and walking. Instead, we will focus on HOW we accomplish walking along on two legs.

The phases of the gait cycle. From Anatomy Reference Center.
When walking, our lower limbs alternate between being planted on the ground and swinging through the air in order to be planted as the next step. We refer to these two different positions as the two phases of the "gait cycle": stance phase, or when the foot is planted; and swing phase, or when the foot is.... wait for it.... swinging.

Transfer of the weight across the foot during stance phase.
Let's now put the gait cycle "under the scope" for a moment. The gait cycle is defined as the period from stance phase of one limb to the next stance phase of the same limb - never mind for now that the other limb is in its own gait cycle! The stance phase begins when the heel strikes the ground, at which point the body weight is transferred from the heel to the lateral side of the foot, across the ball of the foot, and toward the base and ultimately distal end of the big toe (referred to as "push off" or "toe off"). At push off, the limb enters the swing phase, which itself ends when the heel strikes the ground again.

So as you can see, the stance phase accounts for a higher proportion of the gait cycle (about 60%) than does the swing phase. But remember this is for one limb only... the other limb is also in one of the two phases of the gait cycle. Over the combined gait cycles of both limbs, the two limbs together contact the ground (double support) only about 25% of the time. So roughly 75% of the combined gait cycles involves support over a single limb. As walking speed increases, the percentage of the gait cycle spent in single support also increases. During running, for example, there is no period of double support!

Even with the silly type of locomotion that humans employ, it is highly energetically efficient because bipedal walking is essentially a series of controlled falls over the supported limb (the limb in stance phase). In other words, the lower limb acts like an inverted pendulum which uses the force of gravity and the principles of angular momentum to propel the body forward. Combine the low input energy required to sustain level walking with the fact that 60-70% of the input energy is recovered through anatomical function of the lower limb that reduces the vertical and lateral displacement of the center of mass during the gait cycle, and what you have is a recipe for efficient locomotion on two legs.

So, to those who are marching on behalf of the scientific enterprise, remember this: you can stride a great deal before you tire out simply because you are the product of 6-7 million years of evolution for bipedal locomotion.

Jason Organ is Assistant Professor of Anatomy & Cell Biology at Indiana University School of Medicine. Follow Jason on Twitter.

Mochon S, & McMahon TA (1980). Ballistic walking. Journal of biomechanics, 13 (1), 49-57 PMID: 7354094

Lovejoy, C. (1988). Evolution of Human Walking Scientific American, 259 (5), 118-125 DOI: 10.1038/scientificamerican1188-118

Gait cycle illustrations from: Organ JM. 2017. Gait. Amirsys Anatomy Reference Center, Elsevier: Salt Lake City, UT.

Thursday, April 20, 2017

Unsung Heroes In Our Battle Against Infectious Disease

Humanity has always been at war with infectious agents, but it wasn’t until 1860 when Louis Pasteur famously theorized that microbes (first observed by Antony van Leeuwenhoek in the 1600s) cause disease. It took another 70 years before Alexander Fleming noticed that Penicillium mold produced a substance that killed bacteria. While most people are familiar with these luminaries in the field, have you heard of Francesco Redi, Ignaz Semmelweis, Theobald Smith, Mary Hunt, and a cow named Blossom? In this presentation, we celebrate some of the “unsung heroes” whose victories are often neglected from the infectious disease saga.

In the talk below, Dr. Bill Sullivan, a professor at the Indiana University School of Medicine, takes us on a fascinating tour through medical history, answering these questions and more:

How did we figure out that microscopic creatures can make us sick?
Why were milkmaids considered to be so beautiful and what does that have to do with vaccination?
How were starfish important to the discovery of the immune system?
What do you penicillin wasn't the first antibiotic?

Thursday, March 23, 2017

Bugs To Drugs: Can Probiotics Treat Depression?

Depression is a debilitating mental illness that affects up to 15 million Americans in the US alone, yet we are far from understanding the root cause. Multiple genes have been associated with depression, but whether these genes produce symptoms depends on the individual’s environment. New research is showing that one of the biggest environmental factors impinging on mental health comes from within.

Our body is home to trillions of microscopic creatures, mostly bacteria, which are collectively referred to as our microbiota. As unsettling as that may sound, these microbes are not necessarily the kind we want to evict from our body. The bacteria dwelling within our gut serve many important functions; for example, they help digestion, produce vitamins, and keep other types of microbes that cause disease at bay.

Our microbial inhabitants bring countless additional genes into our body called the “microbiome.” These microbial genes can be considered an extension of our own DNA – a so-called “second genome.” In other words, your body is not only influenced by the genes in your DNA, but it can also be affected by genes carried by your microbiota. These microbial genes not only affect physical health, but may also alter your mood and personality.

It is convenient to refer to species of our microbiota as "good" or "bad", but in reality they are neither. There are bacteria that can cause serious disease, like C-diff, but usually only after the microbiota has been disrupted (e.g. after prolonged antibiotic treatment). Likewise, "good" bacteria like E. coli can cause life-threatening disease under the right circumstances.  
Our microbiota help produce surprising amounts of neurotransmitters – chemicals that function in brain signaling. When laboratories produce “germ-free” mice by raising them in sterile environments, the mice exhibit strange neurological issues. Lacking their gut microbiota, germ-free mice do not respond to stress properly. These studies have given rise to the concept of the “gut-brain” axis, a conduit of biochemical communication between these organ systems. Such an axis exists in people too, as researchers have noted a strong correlation between intestinal problems and mental illness. For example, anxiety and depressive disorders are associated with both irritable bowel syndrome and ulcerative colitis.

A study by Ioana A. Marin and colleagues at the University of Virginia, published on March 7, 2017 in Scientific Reports, provides new evidence that intestinal bacteria influence mental disorders such as depression. In this experiment, mice were subjected to unpredictable chronic mild stress (UCMS), which involves strobe lights, irritating noise, cage tilting, and crowded conditions. Kind of like being shoved into noxious nightclubs against your will at random times throughout the day.

Unlike Disco Mickey, laboratory mice become stressed out when subjected to stimuli that resemble your average nightclub.
Over time, mice subjected to UCMS begin to show symptoms that resemble depression in humans. The researchers look for “despair behavior,” which can be detected in a number of ways. In this study, the mice were placed in a tub of water to evaluate despair behavior. Unstressed mice quickly swam to a platform and escaped, but the stressed mice did not make a strong effort to escape and had to be rescued from the tub.

The researchers then compared what the intestinal microbiome looked like in stressed versus unstressed mice. The different species of bacteria comprising the microbiota can be determined by sequencing the DNA in mouse droppings. Each species has a signature DNA sequence that serves as an identifier for that type of bacteria.

The results showed that stress altered the mouse microbiome by reducing a type of bacteria called Lactobacillus. It might have occurred to you that stress could have simply changed the eating habits of the mice, which in turn would affect the composition of the microbiome, but the researchers did not observe any change in eating habits or weight of the stressed mice. Furthermore, when they administered Lactobacillus as a probiotic, the symptoms of depression improved.

Why would stress cause changes in the microbiome? No one knows for sure, but this could be a result of altered brain chemistry making the gut less hospitable to some bacteria. Researchers also noted that intestinal physiology was altered in the stressed animals, which could have played a role in microbiota changes.

When someone consumes a probiotic they are ingesting live bacteria. That concept should no longer gross you out. Probiotics include the so-called "good" bacteria that have been shown to confer health benefits in some studies. These bacteria can be delivered into your body in numerous ways, including food (like yogurt) or pills.  
Does this mean you should rush out to purchase probiotics to battle depression? There are important caveats to studies like this that should be considered. The study was performed in a mouse model of depression, which may not fully represent the condition in humans. The microbiome of controlled laboratory animals is more uniform than humans, who tend to have vastly different bacteria in their guts depending on such things as diet, geography, illness, and age.

However, a 2016 meta-analysis (a study of studies) concluded that “probiotics were associated with a significant reduction in depression [in humans], underscoring the need for additional research on this potential preventive strategy for depression.” While that sounds encouraging, we are far from understanding how certain bacteria may ameliorate depression and whether this affect holds up in diverse patient populations. Probiotics certainly should not replace the more rigorously established treatments for depression recommended by health professionals.

Bill Sullivan is a professor at the Indiana University School of Medicine. Follow him on Twitter @wjsullivan.