Genetics Ain't Everything: But it Does Matter

Image: Public domain

One of the concerns I have about the exploding field of genetics is that it becomes a lazy response to all manner of health challenges. Cholesterol too high? "Must be your genes." Autoimmune disorder? "That's genetic." Medicine has for a long time tried to explain away health problems by invoking mysterious, unavoidable forces. Once upon a time, fevers in the tropics were thought to be caused by "bad air" (it was humid and stuffy in the tropics). Physicians dubbed this cause with the Latin term mal aria. If you read that closely you can see malaria, now known to be caused by a germ foisted upon its unlucky victims by a mosquito.

Doctors thought anxiety and depression among women was caused by the uterus itself, thus medicalizing simply being a woman, and the Greek word hysterikós described the mental suffering that arose from the uterus, thought to be the cause of the malaise, moodiness, and general despair (that couldn't have possibly been caused instead by the constraints and frustrations of women contained in a patriarchal society, where everything was controlled by men, and women themselves were considered "property"). Right? No, it was caused by hysteria. Or so it was thought.

Then there was germ theory: "Germs cause disease," and before you know it, everything was being treated with antibiotics. What did that get us? Superbugs that can't be killed with any antibiotics.

Granted, medicine's made strides--at least we don't think "angry gods" cause disease anymore (well, most people don't). But it seems that the mystery of disease is either attributed to forces we can't control, or if we make an advance like germ theory or genetics, suddenly everything is attributed to that new theoretical cause. I'm happy to say that these days, clearer-eyed clinicians realize that the causes of disease are often complex and multifaceted, involving environmental factors, psychosocial factors, and even political and economic factors such as poverty and racism--the so-called "social determinants of health." 

Still, one's genetic programming is still thought to be--in my view--disproportionately ascribed as the cause of what ails folks, and yet we have failed to make significant progress in sorting out the "genetics" of things like heart disease, depression, diabetes, and many other conditions. But they keep looking. 

Image: Courtesy National Human
Genome Research Institute at genome.gov

With all this emphasis on genetics, I find myself wondering why more clinicians aren't doing genetic testing on their patients to understand what sorts of drug therapies might be best suited to them. Why is that?

Over the last two decades or so we have built a substantial knowledge base that specifies how people metabolize different drugs. Given the propensity of doctors to prescribe more and more drugs to everyone all the time, it seems to me that one would want to know how those drugs will be processed by the body. 

What should I avoid? What will work best with my own metabolism? Those seem to me to be reasonable questions. Within the last 10 years, there's been an explosion of genetic testing available that enables clinicians to know these things.

Genes determine how we metabolize drugs, how we process them in our bodies, because genes code for enzymes, and enzymes are what process drugs. These metabolic processes generally do two things with the drugs we take. One thing is that that they take prodrugs and turn them into active drugs that do helpful things. An example of this is the drug levodopa, used for Parkinson's disease. Levodopa isn't a "drug." It doesn't itself do anything. What the brain needs in Parkinson's disease is dopamine, but dopamine can't be given by mouth because stomach acid destroys it. It can't be given intravenously because it's too toxic to the heart in that form--and because would it really be useful if Parkinson's patients had to be on an IV drip all the time?

The body metabolizes levodopa into dopamine, in the brain, where it's needed, and this helps Parkinson's patients improve.

The other thing these processes do is take a drug and make it nontoxic so it can be eliminated from the body. If this didn't happen, drug would build up, and after helping us for a short while, it would then kill us! Not very therapeutic.

Some people are "normal" metabolizers, and a lot of drug dosing is based on this expectation. If things don't work out, say, the drug's action seems weak, we increase the dose. If the opposite happens, we get toxic side effects, we try lowering the dose. As one would imagine, this is a bit of trial and error, and the patient pays the price.

Wouldn't it be convenient if we could know before we prescribe how well a person is going to metabolize a drug? Wouldn't it make make prescribing more precise?

It would be great if we knew beforehand that a certain individual was a slow metabolizer and thus perhaps might not process a given dose very quickly, and possibly lead to significant side effects and toxicity. It would also be helpful to know if a person was fast metabolizer, and thus likely to need an increased dose or more frequent dosing in order to achieve therapeutic effects. It would be really useful to know if a person isn't going to benefit at all from a certain drug, because of their genetic programming.

Such testing exists, and for the last 10 years I have been advising my students that this version of personalized medicine is coming soon. But it is still not routine practice. It has become a lot more common in psychiatry, and that is the one medical field in which gene testing for drug metabolism has become something approaching "routine"--although I still see a lot of psychiatric prescribing that is still done the old fashioned way.

For the last year I have been offering this sort of testing to my patients. It is especially useful for those folks who have been put on a lot of medications by their various doctors. In many cases, we have found that some drug they are on should be swapped out for a drug better suited to their metabolism, or situations in which their side effects could be attributed to their "normal" dose, because they are slow metabolizers of that drug. There are cases in which a prodrug they were put on wasn't getting converted at all--they were taking a drug that couldn't do anything, because they are genetically programmed to not be able to convert it to the active drug, once ingested.

Image: Public domain

There are two really nice things about this type of testing: 1) It's more or less permanent. Once we
know your profile, it's not like your genes are going to change. Pharmacogenomic testing can be shared with whatever doctors one sees, and apply to many classes of medications commonly prescribed. 2) It's often covered by insurance, because even though a lot of medical authorities seem to feel that such testing adds little to planning medical care, insurance companies see the value in profile-guided, individualized drug prescribing because in the end, it saves them more money than it costs in terms of the costs of weakly-treated disease, or conversely, drug toxicity.

If you are on several medications, if you expect to be on medications, or even if you just want the security of knowing that you have scientific data to share with your clinician concerning medicines that are best suited to your genetic profile: Ask your doctor--or me--about pharmacogenetic testing!

Developments

It's been about nine months since I last wrote here, while I have been working on a book. That project is going well, with the first draft about half done. It is a lot harder to work on side projects during the school year, but I'm happy with how it is going. During Spring Break (ahh!), I thought I would take a few moments to comment on some developments since we were last here on this blog together.

COVID-19

This really does feel like it's in the rear-view mirror for a lot of folks! And yet...

It was three years ago, also during the University's spring break, that we first encountered COVID-19, and it ripped across the world. In the first 9-12 months of the pandemic, I found the disease highly responsive to homeopathic remedies, and usually a handful of specific remedies like Gelsemium, Eupatorium perfoliatum, Bryonia, and a few others. Case presentations were usually striking, intense, and similar to the features of remedies like these. People usually responded promptly and the course of the disease was usually shorter and with a decrease in symptom intensity.

Some time around the winter of 2020-2021, I started to see more cases with less intense symptoms that were more general, and as a result, the array of potential remedies expanded. By the summer of 2021, I was seeing a lot of cases that would only respond to their "constitutional" remedy, or the remedy that addresses the patient's whole system, a much wider array of remedies that requires longer case-taking. By the summer of 2022 I had already seen a number of cases of what would become known as "long-COVID," which I have found harder to treat. I also started seeing cases of people who--whether they had COVID or not previously--began to develop syndromes following immunization with any of the COVID-19 vaccines.

Now I'm not against vaccines. In one sense they are actually "homeopathic" in that they are "like" the disease they are intended to prevent! Nevertheless, as I frequently note: If it's strong enough to cure you, it's strong enough to kill you. Some folks absolutely eschewed immunization, fearing such consequences; a fear, I believe a little out of proportion to the actual danger. On the other hand, I think industry and the public health establishment have been a bit reticent about persistent symptoms that actually could reasonably be related to a covid shot. I suppose this was in an effort to reduce vaccine hesitancy during a time when we were still worrying about hospital overload and deaths. It may have also been simply a refusal to see what has been happening on the ground. In any case, I filed several reports with the Vaccine Adverse Event Reporting System. 

There's no agreement on the diagnostic criteria for long-COVID. I have been finding homeopathy helpful, but I have also found it can be tricky to treat.

Here are some other things I have found interesting: There's a recent shift on public immunization for COVID-19: the vaccines are about go commercial, which means they won't be "free" anymore. There's concern about that; maybe the virus will surge again? I doubt it: Another interesting thing I have found is that some people are re-catching covid whether they were immunized, or had it, or both, sometimes catching it several times! Related to that is that several folks (myself included) can't seem to catch covid again, no matter how exposed to it they are, even if they had their first exposure (illness or vaccine) over 18 months ago. It seems there are things about immunity we're not paying enough attention to. Just exactly who should get re-vaccinated and how often? Instead, the Advisory Committee on Immunization Practices and the Centers for Disease Control are working toward a recommendation of annual, bivalent (two-strain) immunization, much like influenza. Why? Because "annually" is an easy public health message, I suppose. 

I could support this except for the fact that some cases of symptoms after the shot have been when the person had a prior immunization within mere months (as successive evolutions of products were launched) or when the person had covid within a year or more prior. It makes me suspect we're messing with people's immune systems without sufficient knowledge of what else we're doing.

Drug Prices

This past week, the pharmaceutical firm Eli Lilly, one of only three manufacturers of insulin in the U.S., announced that they are going to cap prices at $35 a vial (about a month's worth for most people with diabetes), consistent with the Inflation Reduction Act of 2022. I would imagine that they see the writing on the wall. Insulin prices in America are way higher than they are in the rest of the world. It takes about $10 to make a vial of insulin, and companies are charging up to $400 per vial. Now a lot of folks maybe didn't really notice this: insurance companies aggressively negotiated for lower costs, but even so, the final cost was higher than it needed to be. People should be clear that this still has effects on their pocketbooks. One effect is that even the insured are paying higher premiums because of this price-gouging (what else could I possibly call it?), and people without insurance are literally going without a life-saving drug because of this excess.

Lilly, Sanofi, and Novo-Nordisk, like all drug companies, have "patient assistance" programs for the uninsured/under-insured, but they are often difficult to apply for, and in any case, is this really how we want health care to work? "Oh, you can get the drug you need to keep you alive for less money, but you have to fill out this complicated online form, and we can change the terms of the program at any time." Anger over this system of greed and graft has been growing, and one commentator recently suggested that Lilly is just trying to stay ahead of the pitchforks, as it were, calling to mind the torches and pitchforks of ordinary folk who have just had enough. Shortly after Lilly announced their--what else can I call it, capitulation?--Senator Bernie Sanders (I-VT) sent letters to Novo-Nordisk and Sanofi, strongly suggesting to them they follow suit. I suppose that is fair warning, as more members of Congress hear from angry constituents about drugs that have been around forever, drugs that are easy to make, being priced into the stratosphere for no reason other than the companies can get away with it.

Climate Change, La Nina, and Vasomotor Rhinitis

I have been hearing from a lot of people lately about "allergies" acting up. It is true that some people get wintertime allergies, usually due to mold, or dust, as we're stuck in our warm homes against the weather. But locally, we have been seeing one of the warmest winters--not quite a record warm winter yet, but getting there. La Nina, in the Pacific, has been creating wild swings in our weather, due mostly to changes in the jet stream that guide weather systems as they cross west to east. I've been hearing that allergists are seeing an increase in people asking to be tested for allergies, and yet the allergy testing isn't coming up with any conclusive allergens.

It's well-known in medicine that wild swings in barometric pressure and weather can cause symptoms that seem like they are related to allergy, mainly nasal stuffiness, sneezing, and cough from post-nasal drip. Yet they don't actually have a viral infection, and they aren't actually allergic to anything new. We know this from simple history-taking and physical examination, as well as allergy testing, as I noted above. One of the nice things I like about having homeopathic and herbal medicines in my toolbox, is that I have additional options to aid people suffering from vasomotor rhinitis, or inflammation of the nasal and upper respiratory passages, due this year in this part of the country, from these wild swings in our weather. If you find you are having respiratory symptoms from what you believe are allergies, maybe from this early spring, and yet antihistamines like Zyrtec or Claritin don't seem to work, consider that it might just be the weather. It might be time to ditch the Allegra and try something else--whether allopathic, homeopathic, or another healing system that can address the strange and surprising ways our bodies can respond to something as ordinary as weather!

Be well!

Springtime at the orchard. Coming soon!