Tag Archives: genetics

What we almost know

The impact of intestinal flora on health conditions is known, thus fecal transplants for numerous conditions. Last week I wrote about an experiment with mice verifying the impact on obesity.

As a consequence, there are numerous products being marketed as “probiotic.” We have no idea whether those products are helpful, harmful, or simply benign.Bacterial flora are an instance where we know some bacteria are essential, and we know some can be added beneficially, but we do not know which ones to add. There are promising studies with lactobacillus acidophilus shown: lactobacillus We almost know about GI flora, but not quite enough yet.

There are other topics where we are at a similar place. We know a lot about what mental illness is and isn’t. We know that increasing serotonin in the interstitial spaces of the brain helps with depression and that too much serotonin is associated with schizophrenia. As of this point, however, we don’t have imaging or blood tests or biopsies that will tell us who is mentally ill–we use written testing and observation not laboratory tests to diagnosis it. When physicians attempt to treat it, it is largely a matter of trial and error. We do not know beforehand whether a particular selective serotonin re-uptake inhibitor (SSRI), such as fluoxetine or venlafaxine will work with an individual, or if any SSRI will work. Some people will do better with buproprion, which uses a different mechanism. Others will do better with a serotonin–norepinephrine reuptake inhibitor (SNRI) such as duloxetine. Others will experience no clinical effect at all. We almost know about mental illness, but not quite enough yet.

These examples lead to a more general question about what we know and do not know. It is usually phrased as “nature vs. nurture,” but it is really genetics vs. environment. I am not sure if the the “versus” between them is appropriate–something else I do not know–as it is the relative interaction of the two rather than a false choice between them that is a more likely source of the truth about who we really are.

Researchers often conduct identical twin studies, controlling for genetic variation by comparing the environmental impact of twins with nearly identical DNA. Molecular computer graphic of DNA double helix However, the studies are limited: it is intriguing if they both smoke the same brand of cigarettes or like the same foods despite very different upbringings, but it does not neatly tell us which behaviors are genetic and which are environmental.

Similarly, we know that 3/4 of children of two bi-polar parents are likely to have bi-polar disorder, which seems to indicate a Mendelian genetic inheritance, but we only almost know about the inheritability of mental illness, not quite enough.

Even where we know that a trait is inherited, we often do not know what genes or constellation of genes are associated with a given, visible trait. We almost know about the human genome, but not quite enough yet.

As scientists or those of a scientific bent, we are obligated to say what we know and what we don’t know, being able to distinguish the difference. It is not always an easy distinction to make, but is central to our effort to know more, and eventually know enough.

Learning about fat people

When I was growing up, I had a first cousin who was morbidly obese, long before the efforts of the rest of the country to catch up with her. Her failure, and it was considered a failure, to lose weight was seen as evidence of a moral failing, a lack of willpower, only slightly less pejorative than the sin of gluttony in earlier times. There was some vague talk that she might have some hormonal imbalance, but it was clear that all around her considered her problem to be predominantly one of willpower.

Both alternative and scientific medicine have taken a recent interest in gastro-intestinal (GI) flora, or “gut bacteria.” The alternative medicine folks have favored “probiotic” supplements and yogurts fortified with bacteria. The probiotic movement began with Nobel laureate Elie Metchnikoff, known as the “father of probiotics,” who believed that longevity of rural Bulgarians and Georgians could be attributed to their consumption of fermented milk products.
Metchnikoff

Consideration of the impact of GI flora on diarrhea is not really new–a half century ago I can recall being given lacto-bacillus pills to counter the gastric distress resulting from penicillin. It is the potential impact of bacteria on obesity that is notable in the current focus. Recently National Public Radio (NPR) interviewed Jeffrey Gordon, a microbiologist and director of the Center of Genome Science and Systems Biology at the Washington University School of Medicine in St. Louis.

While I hope you will either listen to the embedded audio clip (about 12 minutes) or read the interview transcript, the short version is that there the research shows a recursive feedback loop between how the bacteria impact our appetite and how what we eat impacts the bacteria that are in our intestines. By eating the right or “lean” foods, we encourage the bacteria that help us maintain our weights at a healthy level. Now, there has been some experimentation with fecal transplants, having a similar aim, but that does not seem to be for everyone–particularly those of us who would be grossed out by the very idea. Eventually, we will probably have probiotics, which, combined with proper diet (they need to be fed or cultivated in our gut), can be delivered to our intestines in pill form, or at least a suppository rather than a fecal transplant.

Over time my cousin became estranged from nearly everyone in the family and died a few years ago, not having been seen by any family members in decades. Waxing philosophically, I cannot help but wonder how different my cousin’s life might have been had she been born a half-century or better a century later. And, I wonder how different my father’s life might have been had he survived his first heart attack and lived to see statin drugs.

It seems that much of our survival depends upon living just long enough for technology to address a mortal weakness in our genome. Nonetheless, it is encouraging to note that promising approaches to obesity may make it seem like nothing more interesting than a historical healthcare statistical blip rather than the crisis it appears to be as we live with it and address it.

Leptin and Ghrelin and Fat, oh my!

I am so embarrassed.

I have been confusing ghrelin and leptin, as we all do from time to time.

Still, I am very embarrassed.

I know that they are appetite-related hormones, and there was recent news about them. And, it seems I am not alone in the confusion.

But, first let’s go to the news desk.

An international team with principal investigator in the United Kingdom has published A link between FTO, ghrelin, and impaired brain food-cue responsivity in the Journal of Clinical Investigation.

In lay terms, as that is my language, what the study found was that individuals with the genetic indicator FTO, known for a tendency to obesity, are less satisfied after eating because of higher levels of ghrelin, a hormone that increases appetite.

Ghrelin has been known about since 1999, and there has been considerable debate about the possibilities of a ghrelin-antagonist to address obesity in a pharmaceutical. The alternative would be a leptin-stimulant as it is leptin that gives us the feeling of satiety after eating.

One of the two approaches, or both, is likely to lead to a very effective pharmaceutical approach to obesity.

But, back to my confusion for a moment. A 2010 Spanish study found that after weight-loss dieting, lower levels of ghrelin and higher levels of leptin were associated with gaining back the lost weight. Furthermore, the ghrelin was significant for men while leptin was statistically significant for women.

Oh, my. I am very confused.