Monday, March 16, 2015

I Don’t Believe It

There are too many myths in biomedical science. I think that our fears are misplaced and if we just address the real threats, e.g. inflammatory vegetable oils, we can enter the New Year with realistic hopes for good health.

Don’t Worry about Genetic Predispositions to Disease

Mendel was wrong in asserting that there is one gene for each phenotype. Modern clearinghouses of genes reveal the relationships between gene sequences and numerous protein functions. In the Human Protein Reference Database (HPRD), for example, each human gene is listed with all of its synonyms. The synonyms frequently reveal that genes lead multiple, unrelated lives and have sundry tangled relationships with dozens of other proteins. So the idea that there is one gene for each physical trait, phenotype, is a misleading simplification.

The good news is that the complexity would only be a problem, if our individual genetic composition was important to our health. In most cases, I think that our individual genetic predispositions to disease would only be important, if we stress our bodies (usually with an inflammatory diet) to the point of failure. With a healthy diet and lifestyle, I don’t think that most genetic predispositions to disease would ever affect health. To be specific, most people should be able to live until 80 with few physical compromises. This is very hopeful.

Don’t Worry about Drug Side-Effects (avoid the need for drugs)

Drugs have many side effects, simply because we don’t know enough about the interactions of small drug molecules with all of the possible protein targets. Take heparin, for example. Heparin is one of the most commonly used drugs to inhibit blood clotting. There is a clotting assay to measure how well heparin blocks clotting and injecting more heparin makes clotting slower. It appears that heparin binds to a protein involved in clotting. Heparin does bind to anti-thrombin, which in turn inhibits thrombin that is needed for clotting. Heparin also binds to several other proteins required for clotting and also binds to a dozen proteins involved in the complement system needed to kill pathogens or infected cells. Heparin binds to hormones, growth factors and their cell surface receptors. There are hundreds of proteins that use heparin to facilitate attachment to other proteins, to change shape and activity or to enter or leave cells. The point here is that heparin is a vivid example of a drug used to treat blood clotting, while at the same time dozens of other major interactions are ignored.

All drugs have multiple interactions with myriad proteins, but during screening, a drug is identified as having a significant desired affect. All drugs have side effects, because they are not completely specific. The side effects are often exploited as off-label uses for the drugs. Statins, for example, can impact lipid metabolism and change LDL blood levels. Unfortunately, research shows that lowering LDL does not affect heart disease. Fortunately, statins also lower inflammation and inflammation causes heart disease, so statins can be used as very expensive anti-inflammatory drugs.

The hopeful side is that most drugs are not necessary and there are other approaches that are more effective and cheaper to prevent and treat disease.

Don’t Worry about Your Gut Flora

There is a major NIH initiative to identify all of the bacterial species that live in or on the human body. That sounds potentially very useful in the context of all of the hype about pre- and probiotics. Your gut flora are important and people are doing very dumb things by killing off the bacteria that protect their skin from pathogens. The problem is that the concept of species of bacteria is wrong. In your gut, there is so much transfer of DNA between all of the different types of bacteria, that the idea of bacterial species doesn’t work.

Consider the pathogenic, toxin-producing E. coli strain. E. coli gets a bum rap, because we have created a new bacterium by treating cattle with antibiotics. The antibiotics increase fat accumulating in the beef, by altering the gut flora. The antibiotics eliminate some bacteria that normally live by adhering to the rectal areas of the cattle. E. coli can colonize the vacancies, but only if the gut lining releases nutrients and the E. coli is resistant to the antibiotics. The solution comes in the form of a plasmid from another bacterium. The plasmid is a small segment of DNA that carries genes for resistance to several different antibiotics and a toxin that causes intestinal cells to leak. The cattle don’t care much about the new Frankenstein E. coli, but if that plasmid-toting E. coli goes from cowpie to hamburger, and replaces your natural E. coli, it can be deadly.

The point is that the bacteria needed to fill all of the niches in your gut environment are created by approximation from the myriad genes of your whole gut flora community. You are constantly creating new “species” of bacteria. The problem is that you produce your own gut flora based on what you eat and by interactions with your gut. Those interactions can make you healthy or keep you sick. A single bottle of formula, for example, can permanently compromise the gut flora of a breastfed baby. We are learning how to control the development of healthy gut flora, probiotics, by supplements containing particular polysaccharides and oligosaccharides, i.e. prebiotics.

The hopeful side is that diets that have been shown to be healthy also produce healthy gut flora. That isn’t much of a surprise.

Don’t Worry about Toxins

The world is a dangerous place, but people have been there and done that. Plants have been standing around synthesizing a witch’s brew of natural toxins for millions of years. They are so good at it that even the most highly evolved species, bacteria, can’t eat them and survive. You can find a plant toxin that will interact with every human protein. That is why most human drugs are derived from plant toxins.

We know not to eat green potatoes, but pregnant women who make the mistake of eating rotten potatoes will regret the birth defects in their babies. There are so many toxins in plants that we have to be careful to watch what toddlers put in their mouths and every poison control center has to be able to identify plants over the phone to recommend emergency treatment. Pregnant women have a built in system to avoid plant toxins during the embryo’s most vulnerable first trimester. It is called morning sickness. A healthy diet during this time is to avoid vegetables and stick to meat and starch. Women build up baby fat to get through this sensitive time without exposure to plant toxins that their bodies may not be able to detoxify.

The happy thought here is that environmental toxins of human origin are not what make us sick, any more than eating plants generally is not a problem. With a healthy diet, even one modestly contaminated, we will not get sick. With a diet that compromises our health, even natural toxins become a threat.

Don’t Worry about Environmental Estrogens (except to save the rest of the animals)

There is an abundance of synthetic molecules that mimic human sex hormones, but once again, plants have been producing estrogen mimetics for millions of years. The second most abundant biological polymer (macromolecule), after cellulose, is lignin. Lignin is what makes up a large part of plant tissue and is what permits plants to be stiff. Lignin is also the “organic” material in fertile soil. This polymer is black in soil, because it is so complex that it has molecular structural components that can absorb all wavelengths of light. Lignin has no defined structure, but rather it is essentially a combination of thousands of structures.

Now imagine the mucky, black, lignin-laden banks of a forest stream. Tons of complex organic molecules leach into the stream and many of those molecules can mimic the shape of estrogens and bind to human molecules, receptors, that would normally bind to estrogen. It is possible to have excess estrogen leach from a sewage treatment plant, because it is not specifically targeted for removal, and the estrogens could temporarily reach a level to affect sensitive aquatic species, but there are already so many natural sources of estrogenic compounds, that the impact on humans would be expected to be unmeasurably small.

It is certainly possible for humans to pollute streams with other molecules, antimicrobial toothpaste ingredients, for example, that have unusually high environmental stability and bind with unnatural strength to estrogen receptors. Those would be problems like DDT. It would make sense to avoid exotic compounds and use natural plant products where possible, just because biological systems can digest them more readily.

The hopeful perspective here is that we already have ways of avoiding most of the problems with manmade estrogens and although these may be environmental hazards, they probably won’t affect human fertility.

An Anti-Inflammatory Diet and Lifestyle Is the Simple Solution

Prevention is the easiest way to stay healthy and since chronic inflammation is the foundation of degenerative, autoimmune and cancer diseases, an anti-inflammatory diet and lifestyle avoids most of the diseases. These same diseases also provide a modern description of aging, i.e. the consequences of mismanaged chronic inflammation. A healthy body is also the best protection from environmental threats, genetic weaknesses and the dangers of modern medicine.

The hopeful perspective for the New Year is eating and living well can keep you healthy and physically fit into your eighth decade.

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