Although this may be more up Abel Pharmboy's alley than mine, there was an article in the New York Times yesterday that indirectly demolished one of the favorite claims of advocates of "natural" medicines and cures. Appropriately enough, it appeared in the Business section. It also demonstrated just what a big business finding natural compounds with therapeutic properties.
The story opens with a description of Chris Kilham, ethnobotanist, a man who's searched the world for medicinal plants:
Part David Attenborough, part Indiana Jones, Mr. Kilham, an ethnobotanist from Massachusetts who calls himself the Medicine Hunter, has scoured remote jungles and highlands for three decades for plants, oils and extracts that can heal. He has eaten bees and scorpions in China, fired blow guns with Amazonian natives, and learned traditional war dances from Pacific Islanders.But behind the colorful tales lies the prospect of money, lots of money -- for Western pharmaceutical companies, impoverished indigenous tribes and Mr. Kilham.
Let's not forget this. Natural products to be used for supplements and medicines have become big business, and big pharma has has seen the potential for easy profits, mainly because "supplements" do not have to be subjected to clinical trials, as long as the health claims made for them are sufficiently vague:
Products that once seemed exotic, like ginseng, ginkgo biloba or aloe vera, now roll off the tongues of Westerners. All told, natural plant substances generate more than $75 billion in sales each year for the pharmaceutical industry, $20 billion in herbal supplement sales, and around $3 billion in cosmetics sales, according to a study by the European Commission.
Although the efficacy of some of the products the herbal ingredients go into is hotly debated, their popularity is not in doubt. Thirty-six percent of adults in the United States use some form of what experts call complementary and alternative medicine, CAM for short, according to a 2004 study published by the National Center for Complementary and Alternative Medicine, a division of the National Institutes of Health.
Yes, there's little doubt that herbal remedies are popular, but just because they are popular does not mean that they are efficacious. Because they are popular, however, does mean that the production of various herbal supplements can be very lucrative indeed, a fact of which big pharma has taken note. Of course, there's also no doubt that substances derived from plants have resulted in some of the mainstays of pharmaceutical treatments. Examples are numerous, including the anticancer drug Taxol (derived from the bark of the Pacific Yew tree), aspirin (willow bark), digoxin (foxglove), the anticancer drug vincristine (Madagascar periwinkle), morphine (the poppy plant), among others. True, pharmaceutical companies generally isolate the active compound from the plant and then usually develop a means of synthesizing it, mainly because it can be problematic to provide sufficient supplies of drug from natural sources, as was the case for Taxol. Early on in the history of Taxol, it was feared that it would not be possible to produce enough drug from the bark of the yew tree alone. In other words, ecological concerns alone can make it desirable to make synthetic versions of these drugs. After all, would we want to decimate the population of endangered plants just to supply these drugs? Moreover, the modifications to these chemicals are often undertaken to increase their activity or make them more readily absorbed by the gastrointestinal tract.
Unfortunately, as this article makes clear, there is the mistaken belief that just because a drug is "natural" or derived from a plant it must be safer, a belief that Kilham promotes in this article:
Mr. Kilham believes multinational drug companies underutilize the medicinal properties in plants. They pack pills with artificial compounds and sell them at huge markups, he says. He wants Westerners to use the pure plant medicines that indigenous peoples have used for thousands of years.
"People in the U.S. are more cranked up on pharmaceutical drugs than any other culture in the world today," Mr. Kilham said. "I want people using safer medicine. And that means plant medicine."
What a load of tripe! This is nothing more than two fallacies. First is the appeal to ancient knowledge. Many indigenous peoples also believe in spirit worship or that praying can bring rain. Does that mean that spirits in fact exist or that praying will bring rain? After all, it's "ancient knowledge." Just because a practice is supported by tradition and hundreds of years of use doesn't necessarily make it superior to more recent developments. In fact, it doesn't even imply that it's effective at all. One only has to point to the persistence of homeopathy or Ayurvedic medicine to drive this lesson home. This is particularly true in the case of drugs, where confirmation bias and regression to the mean can provide the appearance of effectiveness even when none exists above that of placebo. Indeed, it was because of the recognized shortcomings of anecdotal evidence and personal experience in determining whether treatments were efficacious or not that medical scientists developed randomized, placebo-controlled clinical trials, which, after all, are a recent innovation in the scope of medical history. Plant-derived treatments discovered by indigenous peoples may be effective. Or they may not. If no data exists they have to be subjected to the same tests that any pharmaceutical company-produced drug does. Just because they are believed to be effective does not mean that they actually are. Worse, he's promoting the erroneous view that just because a drug is "natural" or "plant-derived" it must be safer. As I like to say, I have news for people who make these claims: Curare is all-natural, too, and cyanide is found in peach pits. Indigenous peoples seem to know what advocates of alternative medicine forget: that nature can produce some of the most deadly toxins known to humans.
Kilham demonstrates even more flawed thinking:
In Peru, Mr. Kilham is betting on maca, a small root vegetable that grows here in the central highlands -- "a turnip that packs a punch," he says, adding "it imparts energy, sex drive and stamina like nothing else."
That view is supported by studies carried out at the International Potato Center, a Lima-based research center that is internationally financed and staffed. Studies there show maca improves stamina, reduces the risk of prostate cancer and increases the motility, volume and quality of sperm.
Some peer reviewed studies published in the journal Reproductive Biology and Endocrinology backed up those findings.
And:
Today, Chakarunas organizes local growers to sell their maca to the French firm Naturex, which extracts it into concentrate. Naturex sells the concentrate to Enzymatic Therapy, a Wisconsin-based company that makes and markets the finished maca products.
I decided to see if I could find this peer-reviewed literature. After all, claims that a supplement "imparts energy, sex drive, and stamina" sounds more like a sales pitch on a late night infomercial than a finding in peer-reviewed scientific literature. There have been studies suggesting that maca extract can increase sperm count in rodents1, 2, 3, 4, possibly reduce prostatic hyperplasia1, 2, 3, and that it might have positive effects on depression and cognition1, 2. However, like any other drug, maca extracts may have side effects, as well, including a modest increase in diastolic blood pressure and liver function tests.
I couldn't find any indications that maca extract imparts "energy" or "sex drive," at least not in humans, given that all the studies I could find looking at these questions were done using rats or mice. Of course, few people will actually go and look at the peer-reviewed literature when someone like Kilham makes claims that sound more like a woo-meister than a scientist in assessing the potential pharmaceutical activities of various maca extracts. Consequently, people reading the NYT article may conclude that there is actually evidence to support his claims. There isn't, or at best it's spotty and based on animal studies. Indeed, the effects seen in rodent models were relatively modest, and it is not at all clear if they will translate into humans under controlled clinical trials with objective measurements.
What this article reminds me, at least, if no one else, is that the entire division of therapeutic drugs into "natural" drugs or "synthetic" or "pharmaceutical" drugs is wholly a false dichotomy. A drug is nothing more than a substance that has a reproducible physiological effect in the human body other than nutrition that can be used for therapeutic or harmful purposes. The body doesn't give a rodent's posterior whether the compound being used as a drug is derived from a plant, the end result of a complex chemical synthesis cooked up by the Dark Lords of Big Pharma themselves in order to bilk unsuspecting millions of huge sums of money for a "me-too" drug, or pulled out of someone's butt. It can't tell the difference. The drug will work by binding to a receptor or modulating some other physiological process on a purely physical, chemical basis. The true dichotomy is between pure drugs, whether derived from plants, chemically modified from a plant product, or de novo chemical synthesis that work reproducibly or impure plant extracts that may have hundreds of contaminants whose activity can vary from batch to batch. Does this mean that "natural" products and supplements are not useful or therapeutic? Of course not. Although rare, synergy between various components of an herbal concoction is a possibility. However, what all too many advocates of "natural" cures seem to want is that their favorite herbs and supplements be exempt from the same necessary scientific experiments and clinical studies to which pharmaceuticals are normally subject. However, if advocates are going to make claims of pharmaceutical activity for these supplements and herbal remedies by claiming that they are useful to treat disease, then these compounds should be subject to the same standards that any other drug would have to meet.
I was curious to learn more about this guy. The article coyly refers to him "being on faculty" at U Mass. I found a press release from the U Mass College of Natural Resources and Environment that terms him an "explorer in residence," an academic title that I, for one, have never encountered before. It turns out he is affiliated with the Plant Sciences department; his name is not mentioned in connection with the anthro department, which is where an ethnobotanist might be expected to show up. In fact, it appears he has no formal training to be either an anthropologist or a botanist. And finally, he seems inordinately interested in aphrodisiacs. Just thought you might like to know...
I'm sorry.... did they say the studies had been carried out at the International Potato Center??
Bwahahahahahaha!!!
Heh, heh....heh....
Whoo!
Rebecca - I know what you mean, but there are several centres like this, like CIMMYT and IRRI, for different crops. When I used to work on cereals, one of the other pathologists (Roy Johnson, in case anyone else knew him) worked a lot with plant breeders in developing countries. A lot of their breeding effort was based on CIMMYT lines - the lines would be sent out, and could then be crossed with local cultivars to improve yield etc. This certainly isn't big agribusiness at work, it's actually something that can make a practical difference.
Of course, the International Potato Center would do better if it marketed itself as Spud-U-Grow.
Bob
http://boilemmashmem.ytmnd.com/
Whenever people spout the "natural is good" I like to point out to them that Monosodium Glutamate was a naturally occurring byproduct of soybean fermentation and is an all-natural food additive. So are BHA and BHT (often added to preserve freshness) - those were discovered, I believe, as the reason why apricots air-preserve/dry without rotting. Once when I got into it with a "health food nut" I went to the trouble of researching a lot of the crazy stuff that's in foods and - not to my surprise - discovered that all the stuff they objected to was mostly naturally occurring. Even "partially hydrogenated fats" were originally an all-natural process before the food industry decided to make lots and lots of the stuff.
There are other all-natural medicines like psilocybin, rye ergot, ethanol, laudanum/opium, cocaine, and tobacco... Tobacco, to me, is the ultimate refutation of the "all-natural" weenie's position. It's not good for you, it's "all-natural" and it was an indigenous tribal medicine. It has shortened vast numbers of lives, prolonged the institution of slavery, and produced untold millions of wealth for another unpopular "all-natural" industry: big tobacco.
@Rebecca, Show some respect, this is the year of the potato.
A problem with natural products chemistry is finding a cheap way of determining what useful, medicinal activity is present in any natural product. Consider someone looking for a new antibiotic, it is generally trivial to make extracts from a hundred plants and expose bacteria to them in culture. On the other hand, to the best of my knowledge (which is old), the only way to test antipsychotic drugs is in long-term (i.e., expensive) clinical trials; so one cannot afford to examine 100, random extracts.
Ethnobotany is intended to substitute for the screening process; but it uses testimonial as a substitute for controlled experiment. Some natural products (or derivatives) passed clinical studies for the same conditions as they were used in folk medicine; but I wonder how many do so. Moreover, if a natural product used for, say, fever is found not to have that property; it should not be discarded because it may have some other useful activity. I don't know if yew bark was a folk remedy; but I am sure that, even if the ancients understood cervical cancer (which I doubt), taxol is not orally bioavailable and yew bark would not have worked.
In short, I question the track record of ethnobotany (or its relative, pharmacognosy) in identifying new drugs. I hope Abel weighs-in on this, I really don't know the answer to that question.
A lot of people I know who use herbals are looking for more of a low-tech, low-cost medicine. It isn't always some kind of new-age bias. It can also be just the realities that the same researching, isolating, refining, concentrating, producing, regulating and testing that assure safety and effectiveness adds a lot of cost. Natural is good when it's in their budget, and when they can diagnose and treat themselves instead of an expensive doctor visit. Ideally, they would see that it can cost more in the long run to use questionable, unregulated methods, but it isn't always the case. Unless we want to involve the government a lot more in people's personal decision making, there isn't much that can be done. I think letting people make their own choice even if it's stupid is the lesser of two evils.
As a pastry afficianado, I know the real reason for partially hydrogenated oils. It makes them solid at room temperature, which in addition to being convenient for storage, is vital for the production of pastry. Pastry is leavened by the use of trans fats, which melt during baking, leaving voids behind. Traditionally, natural trans fats were used -- butter, lard, suet, goose fat. Meat shortages during wartime created a huge market for a synthetic alternative -- and one which, as it happens, was touted as being much healthier because it was made from vegetables. Thus, margarine and vegetable shortening were born.
Those are great examples of "all natural" things that are bad for you. I like to mention hemlock, personally. ;-)
As Orac is a Whovian, I should mention that there's a good dig against this "natural is good" argument in the pilot of the new Sarah Jane Adventures. The story revolves around a new soft drink called Bubble Shock, sold as an energy drink containing the all-natural 100% organic secret ingredient Bane. Which, it turns out, really is all-natural and 100% organic. And totally evil, of course. :-P
Kilham is an adjunct lecturer in the plant, soil, and insect sciences department at UMass Amherst, but without a university email address.
http://www.umass.edu/psis/personnel/personnel.html
I can't find him listed as the instructor of any course in the course schedule for this semester or the last 4 semesters, nor is he in the directory.
I think letting people make their own choice even if it's stupid is the lesser of two evils.
I am totally in favor of letting people make their own choices, as long as they don't bitch if it turns out to be a wrong decision, or expect me to finance their recovery from their mistake. Perhaps doctors need to put signs up in their offices like they have in some redneck garages:
"Repairs: $50/hr. If you worked on it first, $100/hr."
I take it back.
He taught a one-credit course fall 07 called Ethnobotany I: The Shaman's Pharmacy. "Explore traditional, plant-derived medicines among various world cultures, based by first-hand knowledge from field research. Learn about beneficial compounds in plants, and about medicinal plant preparation. See, touch, smell, and taste herbal potions. View extraordinary slides from the Amazon, India, China, and other cultures, and learn about environmental preservation, shamans, medicine men and women, and nature's bounty of beneficial plants."
@zyan "A lot of people I know who use herbals are looking for more of a low-tech, low-cost medicine."
I hope they are happy with a low-effectiveness, low safety-tested products. Read Dan Hurley's "Natural Causes"
http://www.amazon.com/Natural-Causes-Politics-Americas-Supplement/dp/07…
Manduca, I would love to take a class like that, especially as a toxicologist. Finding the active compounds (if any) would be very exciting, especially if they were useful as is. Most drugs don't show up that way, as they are often poisons produced as the chemical weapons of evolution. You really can only eat plants that your species has evolved to be capable of detoxifying (including those with few such protections).
One of my favorite drugs is camptothecin (CPT) (dissertation work involved it). It was originally isolated from the Chinese Happy Plant, an ornamental tree. It is an incredible anticancer drug in vitro, and works beautifully in a wide variety of animal models. Problem is, humans have a difference in the blood protein serum albumin, not shared with test animals. The albumin strongly binds CPT, so one has to give a monstrously high dose to get a useful done into the patient. At this point, it becomes very easy to end up with an overdose. In the end, organic chemists went back and did a lot of great work that decreases the albumin binding, and later CPT analogs make decent anticancer drugs (lots of problems still associated with them). CPT cannot be used in humans unless it is modified. Natural is simply not safe or effective.
At the other end of the spectrum is a traditional remedy made from a particular plant in Africa. If administered during a case of mono, can lead to Burkitt's lymphoma. Talking with my brother, who is teaching medicine in Kenya, he mentioned that Burkitt's rates have decreased where people can be convinced not to use this "medicine" anymore. One interesting property of Burkitt's is that the tumor dies off very quickly during treatment. He described the breakdown as something you could watch over the course of a day, as the tumor causes visible bulges under the skin. The rapid tumor cell killing can actually be dangerous to the patient.
Calli Arcale: I think you are confusing "saturated fats" with "trans fats." Saturated fats are so-called because they've got a hydrogen atom everywhere there's a spot to put one. You want saturated fats to make your pastries. "Trans" (as opposed to "cis") describes how the hydrogens are distributed. There is no reason that a trans fat needs to be fully saturated, and many (although admittedly not all) naturally occurring saturated fats are cis rather than trans. However, the ratio of trans fatty acids to cis fatty acids goes up when the fats are artificially hydrogenated. I expect that what we're looking at here is a case of the dose makes the poison.
Orac: When it comes to biologically active compounds, a natural version has one advantage over synthetic versions. You know what stereoisomer you're getting. Biological systems generally only produce one. Lab synthesis can produce as many as the compound has in a racemic mix. Vitamin E, for example, apparently has 8 stereoisomers, two of which are biologically active, and those two don't have the same activity. If there's no good way to separate out the desired isomer, the dosing protocols need to be adjusted to take that into account.
This particular issue is something that I noticed when I came across a rant by an altie about synthetic vitamin E in a major clinical trial that showed no benefits. Said altie happened to identify the vitamin E used as d,l-alpha-tocopherol, but didn't really explain what any of the terminology meant. Ignorant li'l ol' me assumed that there were two stereoisomers in the supplements and figured that that might be enough to skew the results. I only found out later that there are eight stereoisomers that need to be taken into account which would definitely skew the results.
I do wonder sometimes, how many alties have any concept of isomerism at all or just knee jerk "natural good, synthetic bad." OTOH, mainstream medicine does need to be aware of how different isomers of the same compound can have different effects and what isomers lab synthesis produces.
Inquisitive Raven has clarified things, but there's still a problem here.
Cis- and trans- apply only to unsaturated chains, which is to say those with a double bond. Saturated fats have no double bond (by definition) and can't be cis or trans.
In more detail, in a double bond the two carbons and the four things attached to them are all in the same plane; in the cis configuration the two hydrogens are on the same side of a line through the carbons; in trans, on opposite sides. Single (saturated) bonds aren't planar, and they rotate freely, so there's no same & different sides.
Are there trans fats in nature at all? If they exist, they are uncommon; so much so that the usual fat-breakdown enzymes for double bonds just don't work on trans fats. So they told me in biochem class a long, long time ago. Maybe this is obsolete? Anyone know?
Get this: the professor in that class said he'd never eat partially hydrogenated fats, because who knew what the hell happened to the trans-bonded sections when there were no known emzymes to break them down properly? He preferred to stick with the evils we understood, like butter. Here's the get-this: that was in the spring of 1964. (UC San Diego, for the record, but I've no idea of his name.)
As the immortal Mr. Berra noted, sometimes you can observe a lot by just watching. (I'll spare you the account of the HeLa cell contamination I encountered in 1959.)
Inquisitive Raven:
Mainstream medicine has been aware of isomerism since the Thalidomide incident, just look at cisplatin. It is my opinion that stereochemistry is the most growing discipline in medical chemistry.
Trans-fats are natural, just not abundant, and they are metabolized normally. The problem with them is that they are bit worse than saturated fats when it comes to forming "bad" cholesterol.
@Oskar
Ahem, we have been aware of the importance of isomers since at least the time of Pasteur.
"Tobacco, to me, is the ultimate refutation of the "all-natural" weenie's position. It's not good for you, it's "all-natural" and it was an indigenous tribal medicine. It has shortened vast numbers of lives, prolonged the institution of slavery, and produced untold millions of wealth for another unpopular "all-natural" industry: big tobacco."
Just as an aside, I believe that tobacco in its 'natural' state is far more benign than that which is finally marketed with the plethora of and/or manipulation of chemical additives by tobacco companies. Perhaps this is an instance where natural is indeed better?
Bex - that is a classic example of the naturalastic fallacy. Combustion products, especially from the sort of incomplete comustion you get from burning leaves. Natural tobacco still contains nicotine because it is a natural insecticide. The North American indiginous people did not suffer as many adverse health effects because they used it ceromioulsy and did not smoke it all day long. The dose makes the poison. In fact smoking reduction programs targeted at natives often emphasize the sacred nature of the traditional use of tobacco to frame cigarrette smoking as sacriligous.
Joe
I take it that you are talking about stereoisomers not just any old isomers.
Pasteur was in fact the one that was first isolated enantiomers from tartaric acid in 1848 and Biot discovered rotation of polarized light in sugars in 1815, but to say that we "knew" the importance of enantiomers in that day is simply wrong, they figured out that they had something strange but their peers did not listen that much it was not until much later that it became popular in chemistry.
In 1957 when thalidomide was given to pregnant women, people had no idea that enantiomers could have such a different and sometimes catastrophic biological effect, if they did know about it they would never have given humans the drug.
I seem to remember that asymmetrical catalysis in organic chemistry took a giant leap in the eighties and has been a hot topic ever since in medicinal chemistry, and I suspect that Mother Nature whether she is a bitch like Sam Harris says she is will have a few Aces up her sleeve yet regarding the importance of enantiomers.
Oskar
I may have chosen an unfortunate example (history is not my forte); but appreciation of the importance of stereochemistry in biochemistry (medicine) goes back way before thalidomide (1957).
Emil Fischer won the Nobel Prize in 1902 (in part) for showing that sugars with different biological properties are isomers. I do not know when the non-nutritive value of D-amino acids was realized; but it was long ago.
You are correct that asymmetric catalysis took-off in the 80s; but non-catalytic asymmetric synthetic methods pre-dated it by 10-20 years.
Orac,
"Yes, there's little doubt that herbal remedies are popular, but just because they are popular does not mean that they are efficacious."
To add to this: Even if they are effecive in specific cases, why does everyone think they would have a clue as to how/when to use it effectively?
Orac,
There are a few instances where the natural products can differ from the synthetic which is beneficial. My mother had thyroid issues, and after experimenting for a long time with various medications, she eventually determined that the most effective for her were the animal produced hormones despite the problems of high variance of strength between lots.
The synthetic hormones were very consistent in strength, but her body did not react nearly as well to them -- something to do with an inability to process or break down the synthetic version (I admit I don't know the details).
Schwartz -
To add to this: Even if they are effecive in specific cases, why does everyone think they would have a clue as to how/when to use it effectively?
Because at one time, they were pretty much the sum total of medicine. Right or wrong, there are entire pharmacopias of plant's and their claimed uses. Interspersed among them are several plants that actually do work, most of which work better when they are synthesized, some from the plant itself, others in a completely synthetic form. Of course, there are rather more plants that are ineffective, or effective, but highly toxic in their natural form, in those same pharmacopias.
Ultimately, they worked these things out by trial and error - with an emphasis on error.
re: Tobacco. Nicotine is a really nice drug; it increases cognitive processing, stimulates memory and so forth, while avoiding the jangly effects of cocaine and similar stimulants. This might be why it was used ceremonially before and during native peoples' tribal councils.
The problem is not the drug, it's that the delivery system sucks.