Monthly Archives: September 2013

What we almost know

Posted by on September 25, 2013 Comments Off on 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

Posted by on September 16, 2013 Comments Off on 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.

Three research pieces with a lot of heart

Posted by on September 10, 2013 Comments Off on Three research pieces with a lot of heart

Often the most heartening news comes from health research. The past couple of weeks have revealed three worthy of note. All three involve prevention measures, two before a heart attack, and one after.

First, the US Centers for Disease Control and Prevention estimate that 200,000 deaths from heart attacks can be avoided annually. The preventable deaths are concentrated in three areas.

The first area is age, where preventable deaths are concentrated in the 45-64 age cohort.
Preventable deaths by age

The second area is race, where African-American men are at the highest risk of preventable death, 143 out of 100,000.

Preventable deaths by race

Finally, the deaths are concentrated geographically in the South-Central Region.
Preventable deaths by region

Second, a study from Britain and India, published in the Journal of the American Medical Association (JAMA) found that a single pill or “polypill” with fixed doses of aspirin, anti-hypertensive, and cholesterol-lowering drugs was statistically more effective than offering separate prescriptions. While physicians point out that this approach limits flexibility, greater variation of dosage combinations in polypills is a promising approach.

Polypill study

Third, a study in JAMA Internal Medicine found that even after a heart attack, better diet, as measured with Alternative Healthy Eating Index (AHEI 2010), resulted in lowered mortality.

The good news is that either before, or failing that, after a heart attack, the good practices of medication adherence and reduction of risk factors such as poor diet, can improve our survival as individuals. Furthermore, we can move the needle in a better direction by focusing our educational and interventional efforts on those under 65, African-American, residing in the South-Central United States.

Herd Immunity — How vaccines avoid thinning the herd

Posted by on September 3, 2013 Comments Off on Herd Immunity — How vaccines avoid thinning the herd

Part of the difficulty in making a case for universal vaccination against dangerous disease is a lack of understanding of probability. Since there are few certainties in life, except its eventual end for individuals, we are constantly calculating probabilities. What is the probability that I will get to the other side of the street before that oncoming car arrives? What is the probability that the wheel stop on my number or that I will draw the card needed to complete my hand? What is the probability that the game I am going to attend will occur or get rained out? And, of course, what is the probability that the suggested intervention will cure my disease rather than kill me or leave me permanently debilitated?

Some probabilities are more difficult to calculate than others: what are the odds that I will die from prostate cancer, and what are the odds that the operation will leave me impotent? how do I calculate the best course when my choices are an operation with an 80 percent success rate that leaves another 15 percent paraplegic and 5 percent dead? How about the same operation with 93 percent success, 5 percent paraplegic, and 2 percent dead?

The more complex the alternatives, particularly when they are being balanced against complex outcomes from non-intervention, the more difficult it is for us to make a rational decision.

That leads to a discussion of vaccination. Let’s consider a disease such as smallpox, which has killed 100s of millions of people. Not everyone got smallpox. Not everyone who got smallpox died from it–estimates are that about 30 percent, or 3 out of every 10 died. Now, consider that not everyone who gets a vaccination gets 100 percent immunity. Some people get partial immunity. Some very small percentage may not produce antibodies in reaction to the vaccine. Some people actually die of the side effects of the vaccination.

As an individual, you might think, well, it’s not great but 70 percent odds of surviving are better than none, and maybe it will miss me altogether, so why should I vaccinate? Of course, smallpox has been eradicated, and we don’t have to make that kind of determination any more since the dangers of side effects from the vaccination exceed the danger of contracting smallpox, particularly in the United States where the last documented case appeared in 1949.

If you were a free individual, not part of a society, not part of the possible transmission stream of a disease, then no one is likely to care too much what you decide? However, if you are reading this, you are part of a society providing this message to you via a societal mechanism. As part of that society, you have obligations to others in the society, including children, yours and others, who once were considered private property but are now considered individuals with rights, albeit limited compared to adult rights.

The concept of “herd immunity” goes directly to the questions posed and to your obligations within the society.

Herd Immunity Concept

Those who are vaccinated provide a barrier to illness for those who are not:

Consider:

Assume you have 5 friends who do not know one another, and that everyone has 5 such friends.

Assume that vaccinations give almost 100% immunity and that the corresponding disease gives almost 100% probability of infection if you come in contact with a person who has it.

Now, if 80 percent of people are immunized against the disease, it is quite possible that one of your friends is not immunized. However, if 80 percent of that person’s friends are immunized, there is now only 1/5 times 1/5 or 1/25 = 4 percent chance of the disease vector reaching you. It may be that you friend’s friend has friends with 100 percent immunity, all five of them immunized, and the further you are socially from the source of infection, the lower your odds of becoming infected–even if you are not immunized. You are protected by herd immunity.

However, consider if only 60 percent of people are immunized, then 2/5 times 2/5 is 4/25 or 16 percent chance of becoming infected. That is 4 times your chance of infection from a secondary friend, as in the first example. The degree of herd immunity is a complicated calculation depending upon the percent immunized and the way the disease is transmitted. Your chance of infection depends on those factors as well as your social distance from the source of the infection.

For an animated look at the concept, click on “Play Animation” in the three scenarios of The History of Vaccines: Herd Immunity.

Here are the thresholds for different diseases as estimated by the Centers for Disease Control (CDC):

Herd Immunity Thresholds CDC

Think about flu shots for a moment:

  1. The vaccine is based upon recent mutations of the virus, so you might catch a virus that is not part of the vaccine.
  2. Not everyone gets 100 percent protection from a vaccine–it may be sufficient to protect against some strains and give partial protection against others
  3. In part, because of herd immunity, not everyone exposed to influenza is infected

So, we have friends and relatives drawing the wrong conclusions (e.g. the vaccine caused me to get influenza), based on an association of factors that are coincidental or subject to an alternative explanation, such as a new strain or partial immunity. For most young people, the flu is an occasional inconvenience rather than life-threatening; however, their failure to vaccinate exposes others whom they could be protecting by a simple annual injection. Let’s spread the word–it might not save those young individuals–just an older person, or an asthmatic standing close to them.