Monday, April 18, 2016

Nature: a drug pusher?

Some time ago, I was talking to a friend of mine. She stunned me when she affirmed that "drugs" are not the same as "natural" remedies. Drugs which she bought at the drugstore were "chemicals", while plants and flowers were gentler, kinder, almost harmless, medicines. I tried to explain.
But but but… I know, it is confusing! And I am a scientist!!!

While I do not advocate taking home remedies to cure life-threatening ailments, it would be unscientific not to recognize that many active ingredients used in several drugs available at the drugstore were originally found in plants or animals.

Darwin's grandfather, a physician, used to prescribe digitalis (foxglove) to his patients with heart disease. Digitalis is the principal natural source of the cardiac glycosides digoxin and digitoxin; foxglove therapeutic effects are known since at least the late 1700'.
Colchicine, penicillin, quinine, and digoxin are all very potent and effective drugs which were isolated from plants or moulds, sometimes by trial and error (most of them), sometimes by error (penicillin - this is the greatest example of accidental discovery - and Fleming's genius).
Anecdotal evidence was a very important drive in the discovery of such drugs before the scientific method took over and standardized drug discovery protocols. But we all know that when we are desperate enough, we would try anything to make the pain go away.

My favourite plant is the belladonna, also known as the deadly nightshade. Belladonna ("beautiful woman" in Italian) is named after the use that in the past women made of the plant (including, according to Wikipedia, Cleopatra, the queen of Egypt).
Having large, languid eyes was considered an attractive trait (maybe it still is; I am not keeping up with fashion lately); ladies used an extract of the plant to dilate their pupils, so that they could achieve that elusive look (not without side effects such as blindness, increased heart rate, and the like), and snatch general Antonius (in ancient times), or poor Mr. Darcy (more recently). Fast forward to our century, and the same compound found in belladonna (atropine) is used as a mydriatic by ophthalmologists; in other words, it is still used to dilate the pupils. From fashion to medicine, from ancient times to modern day!
The deadly nightshade, as the name implies, is... deadly, duh. Eating even a small amount of the plant can cause serious problems, and while it still has great potential medicinal properties, it has to be used very, very carefully, because, as in any other plant, the concentration of active ingredients is highly unpredictable. A nightshade leaf could kill a person, or just cause a little tummy ache.
Rumour has it that the nightshade was the queens' favourite poison.
Give me poison ivy instead, it feels less dangerous...

Another favourite of mine, and a lot less deadly, is salicylic acid. As the name impies, it was first isolated from the willow tree (genus salix). If I remember my plant physiology classes correctly, plants use these chemical compounds to communicate between different parts of the plant ("hey roots, are you doing OK today?" - "No, there is an ant infestation" kind of conversation), and also to fight the proliferation of parasites. You should not be surprised to know that the curative properties of the willow bark have been known for several centuries, and even animals know about it - at least, my plant physiology book reported this fun fact about animals eating willow bark. As with the example above, dosing salicin (precursor of salicylic acid) from the willow bark is a hit or miss endeavour. Too little, and nothing happens; too much, and you'll have a hole through your stomach (wild animals do not have lawyers to sue a willow tree for damages). Besides, a little chemical modification (the addition of a methyl group on the side of the molecule) increases its transport through the stomach lining and makes it easier on the stomach. So aspirin was born in 1897.

The greatest obstacle with herbs and plants is that it is extremely difficult to get the correct dose of the active ingredient. Plants produce different compounds according to environmental variables, so they are not very consistent; many of these chemicals are a response to parasites or viruses, so they are only produced when a plant is under stress. Plants, of course, do not only produce the chemical we need, but also a number of other chemicals, which may have side effects and can cause more trouble than they are worth. Many chemicals are not stable, and are quickly degraded by heat and long storage time.

So, yes, drugs are very often totally natural chemicals (we should all know by now that everything is a chemical). Of course, we can try to improve on what nature has provided, but I totally embrace the notion of sipping chamomile tea to relax at the end of a busy day.

For more serious occurrences, I'll err on the side of caution, and pay a trained pharmacist to prepare my drugs with exactly the right amount of active ingredients, and dispense them safely. I am not a risk taker: playing Russian roulette with such dangerous plants is not my type of game...

Wednesday, April 6, 2016

Wishful thinking

OK, it is time to come back with a roar! I just read a news headline that shocked me: a couple has been charged with manslaughter (I am not sure of the legalese here) for letting their child die from complications from an ear infection. The charge? They tried to cure the child with homeopathic and herbal remedies delaying proper medical care. This is very sad, but I do not want to make a political statement; I want to take this opportunity to explain why homeopathy is just wishful thinking.

I started reading the comments to the story, and it quickly appeared evident that people do not have the faintest clue of what homeopathic medicine tenets are. They confuse homeopathy with herbology; and naturopathy for pharmacology, which is a bit like confusing a chihuahua for a great Dane, and Grumpy Cat for a tiger.

First of all, it is useful to define what we are talking about*. Homeopathy is based on two assumptions:
1) a disease can be cured by using a chemical (I use this word deliberately, everything is a chemical compound, called "remedy" in homeopathy) which triggers a similar response to the symptoms one is trying to cure, presumably by "priming" the body to react to the trigger; this is called the Law of Similars, or "like cures like";
2) the chemical is more potent when it is used in very high dilutions.

A third requirement is that the solution must be shaken vigorously a certain exact number of times by bashing the vial against an elastic surface (honestly, I am not sure how this can be ever enforced; what if I run to catch the bus, and I have a vial of homeopathic remedy and a "leather-bound" book in my bag? Does that count?).

The chemical used can be anything, even a mix of chemicals: vanillin, vitamin C, plant extracts, honey, whatever; as long as taking it will give the same symptoms of the disease to cure. Trouble sleeping? Take some caffeine. Fever? Find something that will increase one's body temperature. Watery, itchy eyes and sneezing? Take something that makes you cry (an onion, in this case)… Supporters of homeopathy sometime maintain that this is the way vaccines work.

However, this is NOT the way vaccines work. I repeat: this is NOT the way vaccines work. Simplifying a very complex process**, vaccines work by stimulating the production of immune cells. Some of these immune cells are memory cells; their role is to "remember" the encounter with the trigger, and stimulate the production of more immune cells and antibodies next time the same trigger is identified. Given that the original trigger in the vaccine is a weakened or dead form of the pathogen that gives the disease (sometimes a little piece, depending on the type of vaccine), it causes a milder version of the disease that can be easily handled by a healthy person. Bonus point: in the process, those memory cells are created and kept around for years, sometimes decades, ready to spring into action when the real disease is encountered. Heck, I still had antibodies against measles 30 years after my vaccination (and never caught the disease - thanks mum)!

On the other hand, the same symptom can have many different origins. Headache can be a symptom of a vascular problem, a neuropathy, a brain tumour, or a stressful husband. Should we treat these conditions in the same way?***

In common homeopathic practice, the original solution is diluted by a factor of 10^6 (ten to the power of 6), that is, 1 mL of the active principle has to be diluted in 10^6 mL of solvent, usually water or alcohol, and the creator of homeopathy (Hahnemann, for the curious folks) recommended a factor of 10^60. To illustrate how enormous these numbers are, we can imagine to flip the coin in the opposite direction.
If I invested 1 dollar in a lottery ticket, and then won 10^6 dollars (1,000,000 dollars - forgive me the commas, I am not sure how else to keep the number together) in the next lottery draw, I would be very happy. We all agree that if I had 1 billion dollars (in scientific notation 10^9 dollars), I would not need to work anymore and I would be considered a very wealthy person. I am sure I'd make many new friends very quickly. If I had 10^60 dollars, well, that's a really big sum, and I do not think that much money even exists. But if you think about my 1 dollar investment versus 1 million dollars, that's the dilution we are considering here - or even higher.
If I were to pick 1 random dollar bill (remember, in homeopathy one only takes a small amount of "drug"; in this example, 1 dollar = 1 mL) from my pile of one million and one 1-dollar banknotes, it would very improbable I would pick exactly the one I invested in the lottery. Even if I were to increase the odds by using 100 one-cent banknotes (if they existed) instead of the original 1 dollar bill to at least grab a little bit of the original note, the chances would be very unfavourable.
In lay terms, this means that whenever somebody takes a homeopathic remedy, they are just drinking pure water, or pure alcohol.  To ingest enough active ingredient to even be registered by the human body, a person would need to get seriously drunk (if taking the alcohol dilution) before that happens. Uhm, suddenly homeopathy does not look so bad after all ;-)

* always read about anything; it is good knowledge even if it sounds very unlikely and it is 100% hogwash. I double checked on the National centre for homeopathy to get the latest information.
** which takes reading books and books for an immunologist to fully understand!
*** rhetorical question, of course.