Monday, June 30, 2008

Chemicals: morally neutral

The story of penicillin is an interesting one: Alexander Fleming discovered that a mold had contaminated his bacterial culture (legend has it that his lab was so dirty, it wasn't actually a culture). By serendipitous luck, he realized that there was a ring around the mold colonies around which no bacteria grew. Upon filtering the broth, he found that it could kill bacteria, wasn't toxic to mice, and had a broad range of activity, at miniscule doses.

The idea that World War II was the best thing that could have happened to the world has been tossed around by those with a historical bent. It wasn't until the Second World War that, given the success of sulfa drugs, penicillin's possibilities became recognized. By 1943, production was 800 million units of this drug by growing up massive cultures of mold and isolating it from the culture--being able to eliminate infected wounds and pneumonia was probably a powerful morale-booster (source: Napoleon's Buttons).

And then things went wrong. Or rather, they didn't go wrong: life happened. Doctors forgot that bacteria have been around for 3.5 billion years--and if they could survive the PreCambrian Extinction, the KT Collapse, the fall of the dinosaurs, and our nuclear testing, a molecule from a mold that they most likely evolved with over the course of the last 2 billion years would merely baffle them, at best.

Drug resistance to penicillin illustrates the premise that chemicals themselves are morally neutral. They are "good" or "bad" only depending on how we use them. A molecule of DDT has no more of a moral code than a brick. But apply it cautiously, or ruthlessly, and people either praise it, or loathe it depending on what value is at stake.

It therefore makes no sense to malign chemical additives, pesticides, and herbicides because of what they are. But that does not grant free license to contaminate our waterways with mercury and pour sulfuric acid into the air. Just because the molecules are morally neutral does not mean we can afford to be.

And here the problem lies in the fundamental "good" and "bad" of the whole Green movement. Just where do we draw the lines, what are the goals, how can we achieve them in a meaningful way? Any one aspect of the Green movement (fewer pollutants, less greenhouse gas, clean water, clean air, no GMOs, organic foods) ultimately fails to see the big picture, and usually fails to consider the social ramifications of what each one recommends.

For instance, if organic farming were to become the mainstay of food production tomorrow: yields of organic crops are usually lower than conventionally-grown produce (usually about 20-50%, depending on the crop, the farmer, the region, the weather), so an organic farmer would need to produce more in order to get the same amount. He must therefore spend more time tilling his fields with a motorized vehicle, adding more greenhouse gases to the environment than the conventional farmer. Now, of course, the amount of greenhouse gases emitted by the organic farmer most probably does less harm than the pesticides sprayed by the conventional farmer. But how much more, and if your goal is to reduce greenhouse gases, then the organic farmer loses out.

What the Green movement needs first is to define what it wants to achieve in no uncertain terms. Then it needs to look reality squarely in the eye and accept it for what it is.

And the reality is this: we like our bread soft and unmoldy after a week in our pantry; we like our pet's food in conveniently stored and handled packages. We like that our cars don't rust and our pet don't have fleas, that cleaners work without too much elbow grease and hassle. Chemicals, while they can do a lot of harm, can't be blamed for everything, not when the choices we make concerning them are so selfish when it comes to our own time, energy, and money. These choices lie with us, not with the chemicals.

Sunday, June 29, 2008

Environmentalism: chemistry edition

There is no question that environmentalism is important. But there is little consensus as to what it means to be environmentally conscious, what the impacts of our actions are, and where the ethical boundaries lie. There is even less consensus as to a definition of "reasonable lengths" one should go to in order to be "green".

These are big questions--I could probably blog for the rest of my life answering them (giving my version of the answers). However, having learned that it's better to be able to digest what you've chewed off, I've arbitrarily decided to focus on chemistry and environmentalism instead.

I say "arbitrarily" but my decision was based mostly on National Geographic's latest edition of the Green Guide. I love the National Geographic Society--that they can make the public aware of issues in countries like Myanmar (recently Burma) speaks to the immense power of photographs, and the prowess of the photographers they hire. I'll be frank and say that their articles are somewhat lacking for completeness, in that many of them do not cover the topics in the detail that I would like, but that's excusable, because nobody does, and it's a magazine, not a book.

But what irks me the most about the Green Guide is not the incompleteness, the logical fallacies, or their not thinking through the ramifications of their actions (or doing so in such a limited fashion that they fail to see the bigger picture--systems biolgoy, anyone?). It is, rather, that the language used assigns a moral standard for things that are "morally neutral" (a wonderful turn of phrase by J.K. Rowling). They imply that chemicals are bad for the environment, which is most likely true. But they also assume that natural products are good, which is most assuredly NOT the case.

This week I will be expounding on this dichotomy, in the hope that I might get some of you to think about the Green movement differently. I wholeheartedly encourage embracing the Green movement (in part because I no longer have to feel like the only twenty-six year-old in the Western World without a car*). But the messages that some of the groups tout are...not exactly doing the Green movement any favors.

To be discussed this week:

1) Chemicals are morally neutral
2) The extent to which we rely on chemistry
3) Natural as better--or not
4) Unintended consequences of greenery (strictly involving chemicals)
5) What it means to be green, the chemistry edition.

*Yes, that was meant in jest.

The Art of Connection

I won't pretend to be a cultural anthropologist--having taken one course, almost seven years ago, in my freshman year, in college, hardly makes me an expert. But I predict that, as with TCM, we will, within the next ten to twenty years, start seeing a resurgence in interest in African herbal medicine, and possibly in the traditional "cures" of South American tribes, as well. After all, if we can derive painkillers from poison dart frogs, it stands to reason that there might just be something behind all the shamanism and "pretenses" of healing.

I've titled this "The Art of Connection" because getting at the right information is an art. Taking a literal translation of the ancient Chinese texts is a mistake, as it turns out--one could say the same about taking the oral histories of African tribes literally, too. It amounts to parsing the meaning, and not just the information, out of the words.

To give you a better idea of what it means: I'm a native English speaker (I know a little Spanish and I'm reasonably fluent in Chinese, but English is my primary language), who moved to the Netherlands last year. I've had to learn Dutch on the fly, so to speak. The words themselves are not that difficult, but the way they are used still drives me crazy and renders my dictionaries useless, because the meaning they convey has (seemingly) little to do with the words that are used. In part, this is because the vocabulary of many other languages is small when compared to English--and therefore they rely on constructions to get the meaning across--but also because there are some words in Dutch that simply don't translate well.

Nowhere is this difficulty in translation more apparent than in the English translations of the Judge Di series. Rumor has it that van Gulik originally wrote it in Chinese, and then it was translated into Dutch, and then that was translated into English. While most certainly apocryphal, if you have a bad Dutch-English translation...suffice it to say you spend more of your time wondering why the translator couldn't do a better job.

And that's just between two languages with a common root (Teutonic). How one begins to approach the art of translating between Yoruba and English is something I can't even begin to fathom.

Still, it must be done. And more to the point, it must be done well. I'd like to think that the West paid for its arrogance when the British lost the Boer War, but that's really a pipe dream, as there continue to be so many shows of blatant ignorance and arrogance about how things "should" be (most notably, the idiotic movie made by Geert Wilders). But biology doesn't give a crap about what "should" be. It just is, and whether you like the treatment has little to do with whether it works, and conversely, whether you think it should work has little to do with whether it does.

I've said elsewhere that you can't win against biology. The whole macho-thing about conquering the West" presumes that life stops once you stop--that once you figure out this, you can solve that. It's only recently that we've realized how connected everything is--dust from the Sahara feeds orchids in the Amazon--and it'll take a while before we're able to fully appreciate those connections. Maybe we should get started now.

Saturday, June 28, 2008

Standardized plants

Desk ornaments

One of the biggest hurdles to phytotherapy is that plants are, after all, living things. Much like my two black (loveable) cats above, even though two plants may be growing side by side, they may still produce a different bouquet of molecules--and they are very different cats; one of them could be white--they're that different.

Some of the more practical amongst us may wonder whether or not it actually matters. After all, 5000 years of practical application have, essentially, confirmed that these plants work.

On the other hand, standardized medications make dosing and scheduling much easier. Can you imagine the tizzy your family physician/GP would be thrown into if the New England Journal of Medicine suddenly recommended that every patient's aspirin be titrated to the optimal dose? Of course, this sort of individualized therapy is part of what makes TCM so powerful--that each and every patient receives a tailored concoction--but you can hardly expect a harried doctor (who's probably more worried about getting sued) with exactly 10 minutes of time, half of which is spent deciphering his colleague's handwriting, to give the sort of individual attention that personal dosing requires. Add to this the fact that a bad licorice season, or a factory being built within 500 feet of a ginseng field, can drastically affect the quality, growth, and compound within a plant, and you can see how things begin to go disastrously wrong if there is no standardization.

At the molecular level, there simply is no way to guarantee that batches of plant extracts from one plant (much less many) will contain exactly the same components, unless we are after only one compound. This is, in part, why we synthesize Taxol (the other part being that Pacific yew is an endangered tree). The best we can hope for, therefore, is an average of chemical signatures given by a particular plant--a "fuzzy fingerprint", if you will.

And this is what makes TCM so unsatisfying for Western physicians. From the Age of Enlightenment onwards, the philosophy of science and medicine has been that knowing more about how we (human bodies) work will lead us to understanding more about how to fix it* when it gets broken. Now, nobody will doubt that bodies get broken, in terms of the physical, physiological, and chemical. The human race has been fixing physical problems for as long as its history, but the physiological and chemical problems have had to wait for the advances of science before we could understand what the nature of the problem was. The history of diabetes provides a wonderful example of how, even in the face of knowing what was wrong, we were still powerless to do anything about it. We are so used to equating "disease" with "broken"--with one single concrete cause, and one single effective cure--that it's now wonder we are surprised when the magic bullet turns out to be a dud. Contrast that with the view TCM takes, that the body isn't really broken, it just needs help getting to where it should be--and that help can come in many, many forms, and they are not all the same for everybody--and you begin to see how the divergence in thinking begins to cause rifts.

This is not to suggest that any old ginseng or lavender plant will yield the right proportion of effective:noneffective ingredients. Maybe the difference matters, and maybe it doesn't. The fuzzy fingerprint may be as close as we will ever get to standardizing things chemically. But that doesn't mean we can't standardize what we can: the soil content and acidity, drainage and water availability, amount of light and darkness. It is even conceivable that air quality could make a difference.

Allow me to end on a note of conceit and ask, "Is there any better reason to ensure that our climate and environment are not going to go to hell in a handbasket?" Considering how much we already depend on it, how much it costs us when things go wrong, and that the potential to save lives could be floating around in some undiscovered plant (or some already-discovered plant), can we really afford to take the chance that the poisons we spew and the trash we discard doesn't have an effect?

*I usually try to avoid using when pimping books, but the synopsis is so wonderfully exact that I didn't think I could do it any better

Thursday, June 26, 2008

Big words

So far I hope I've persuaded you that TCM and other medical paradigms can only add to our knowledge base, that new ways of approaching the problem can lead to new solutions. We now come to a point where TCM and other alternative medical paradigms cannot help us: the pharmacologic theory of drug action.

Don't worry, I'm not going to start chucking about complicated equations and talking about kinetics and equilibrium. For starters, this is a blog, not a pharmacology course.

But models have their place in our knowledge base, too. Pharmacological modeling enables us to understand drug-drug interactions better, which allows us to better use the drugs that we have. In the case of plant extracts, it allows doctors to understand which drugs cannot be used with what plants. Multidrug pharmacy is already a major component of treatment regimens for a variety of diseases, most notably pediatric cancer. Unfortunately, most of the regimens in use today come about through trial and error--"experimental", indeed. And let's not forget the plethora of drugs being used "off-label", for other than their intended purpose. Anti-histamines, for instance, are sometimes used by desperate parents to get their kids to sleep.

And if you're using phytotherapy (because "herbal medicine" isn't science-y enough) rest assured that in each leaf of a plant there are easily a hundred compounds, most of them more benign than your average stick of celery. The effects of the few that aren't, however, are no laughing matter. St. John's Wort (you may remember me being surprised that it could be sold in a supermarket) actually has a long list of drug-drug interactions.

The development of mathematical models for drug activity really only began early in the last century. Modifications to the theories over the years has given us a powerful way of predicting the efficacy of drugs, but a model for two drugs, much less many, is still lacking. It is a matter of having the computing power, but also recognizing the need for models, and minimizing the damage on our way to new treatments.

Wednesday, June 25, 2008

Systems biology: everything's connected

On the second point of TCM, which is the theme of the week

"Systems biology" sounds complicated--hell, biology sounds complicated. It's the study of life, after all, and what could be more complicated? There are massive numbers of articles published on the opioid receptor, for instance, and that's on three different proteins with relatively well-defined roles. If that's one, imaginee how complicated a system must be.

But that's what the big picture is starting to look like: everything's connected. Jared Diamond illustrates this principle very well in the book Guns, Germs, and Steel, which I highly recommend reading if you like having your brains boggled. Chaos theory's butterfly effect, while formulated to describe a system's dependence on initial conditions, best illustrates the phenomena of a little change blowing up into something big.

Which is precisely what drugs do. You take a pill--by the time it gets into your stomach it's already dissolving. Maybe half of the active molecules make it through the acid bath. Then it gets neutralized, and absorbed into the bloodstream, where it may or may not bind to proteins in your blood, rendering them inactive. It has to get past the liver, which filters out all the crud that's in your blood; it get sloshed around by the heart, possibly ending up however many thousands of miles away from its site of action, all the while being degraded by the heat of the body and whatever enzymes are running rampant throughout your body, hell-bent on destroying any and al invaders. It's a wonder, if you think about it, that any drugs at all work, much less as well as they do.

"Well" might be pushing it--given the very long list of side effects of drugs such as Lexapro (which I've taken for a year) and the very short list of intended actions, let's just say that I don't know of a single boss who would accept that kind of performance from a person. Is this because the drug was specifically designed for the purpose of inhibiting one receptor? Is this why "dirty" drugs, which work on an array of receptors, are currently being explored as therapies?

This is systems biology: you can't touch one without touching everything. And in this respect, TCM, which strives more for "balance" than an actual treatment mechanism, has a lot to teach us in terms of how to view diseases. If you need an example, consider how the treatment paradigm for stomach ulcers has changed: it used to be that you drank milk, or chalk (how else to describe antacids?)--it was thought that the acid in the stomach was the problem, and you had to neutralize it. Or lessen it--I'm sure we all know of at least one person who has been told to "relax" because their ulcers would start "acting up". Then we figured out how to turn off the acid pumps in the stomach--good for the pain, bad for digestion. Then a single maverick doctor from Australia decides that Helicobacter pylori is actually the causative agent for ulcers, proves it by drinking a shot of the bugs. Stomach ulcers are now routinely treated with a course of antibiotics, with acid-lowering agents to manage the symptoms until they heal. But herbalists of all stripes, not just TCM practitioners, have been using licorice to manage ulcers. As far as how it works exactly isn't quite known--there are literally hundreds of active components in licorice, but the main compound, glycerrhyzic acid, is an anti-inflammatory agent--which might help the immune system destroy the bugs, as well as soothe some of the pain.

The point is not to suggest that herbs make for better medicine than drugs developed with a specific purpose in mind. It is merely that focusing on one aspect of the disease (stomach acid) can be counterproductive when trying to find new treatment regimens. It is likely that licorice, because it has hundreds of other active compounds, influences the body in ways that a specifically targeted drug cannot, and therefore "brings it into balance" again. It's like trying to center a tarp over a target using only rope. If you have one very strong rope, you can easily yank the tarp from A to B, but trying to center it can be very difficult. Whereas if you have lots of ropes, you can pull on it in all the right directions, and therefore center it quite easily.

Losing sight of the connections with everything else leads, ultimately, to a myopic view of health and the human body with a knowledge base that is still sorely lacking (ever wonder why we sleep? so do scientists). When you understand the connections, you don't eliminate the holes, but you see other ways to fill them in. Ultimately, nobody can know everything. But knowing more is never a bad thing.

Tuesday, June 24, 2008

A difference of philosophy

Yes, I know, this is a Bhodisattva. It was the closest representation of thinking and meditation I could find.

Understanding TCM requires understanding Chinese culture; it is impossible to appreciate the full scope of TCM within the paradigm of Western medicine

This was the first point of the TCM seminar on Monday, that in order to understand TCM you have to understand the culture, or at the very least, the philosophy of medicine that pervades TCM.

When you read Chinese texts, there's a lot of talk about energy channels, "hot" and "cold", "yin" and "yang". Most doctors would laugh at you if you tried to explain your stomach ulcer in terms of "hot" and "cold", and they'd be right to. There's no more of an "invasion of cold" as there is an invasion of Easter Bunnies (well, unless you live in South Park). So if you read the texts literally, it sounds like a lot of hocus-pocus bullsh!t that vaguely resembles the humoral theory of health that was popular during the Renaissance.

The difference? TCM works in a way that the humoral theory never did.

That alone explains the staying power of TCM, even more so than the pseudo-New-Age language it's often surrounded in. And while we're talking about the language, let's just clear one thing up--Chinese is an extremely contextual language. The same word, used in two different sentences, can take on two entirely different meanings. It's an art, for a Westerner, to be able to read the words AND get the meaning right. But also, as anyone who has ever tried t'ai chi or yoga, there is simply no scientific way to explain that flowing sensation you get when you've practiced for a while. Sure, you can call it a supersensitive spell in newly invigorated neurons, but that doesn't make any more sense than a "flow" of energy in the context of how it feels.

And that is what Western medicine lacks--the words to describe the sensations of sickness, the beginnings of imbalances. Without words, it is almost as if these sensations don't really exist. I don't think it's that Chinese doctors and patients are any more sensitive to the sensations of sickness--I think it's that TCM provides a platform for expressing the problem in a common language that both patient and doctor can understand.

I actually do not think the bridge between Eastern and Western medicine is impossible to cross. But it does require that Western doctors stretch the boundaries of their conventional models of sickness and health in order to accommodate the slew of information that TCM (and other ancient medical systems) has to offer.

Monday, June 23, 2008

Traditional Chinese Medicine

I attended a seminar today on Traditional Chinese Medicine (TCM) and integration of that system of thinking with Western medicine. Throughout this week, I will be discussing some of the more salient points.

The highlights of the seminar:

1) Understanding TCM requires understanding Chinese culture; it is impossible to appreciate the full scope of TCM within the paradigm of Western medicine
2) We need to view disease processes through a "systems biology" (or, "everything's connected") point of view; one drug for one receptor will not suffice
3) Better mathematical models for understanding drug-drug interactions (antagonsim and synergy) are needed.
4) Better methods of standardizing plant-derived biologically active compounds, regardless of the cultural background, are also needed
5) Traditional pharmacoepaeia the world over needs to be evaluated for efficacy; this is especially the case in developing nations, where the culture might already have the tools needed to cure their own diseases at fractions of the cost of importing Western drugs.

One of the burning questions that was discussed later was whether TCM medications should be fast-tracked through the approval process. On the one hand, they've essentially been in human clinical trials for 5000 years. On the other hand, nobody knows how they work.

One big idea that got lost in the midst of all the excitement over how awesome these drugs are (and, make no mistake about it, they are drugs) is the fact that European herbal lore also has a rich array of pharmacologically active drugs, and nobody seems to object to St. John's Wort being sold in the supermarket (where I get mine). What's the difference?

Monday, June 16, 2008

New thingum

I've decided that I need to come up with a better way to update this. In a nutshell, working, a two-hour commute, and needy cats are not conducive to coming up with timely articles, and definitely not conducive to researching them to the degree that I would like.


While I would ideally come up with a new article every day, I'm going to lay off that ambitious goal, because a) I need to sleep, too; b) I have several other writing projects floating around, too; and c) I also need to cook, clean, and fulfill my social obligations.

Furthermore, I've realized that I tend to write a lot. I have big ideas. They require big pieces. Or, lots of little ones.

Meaning: Starting next week, I'm going to start serializing my posts, break them up into bite-sized chunks, easily digestible, and hopefully interesting to read.

That's all for now. Time to cook.