Tag Archives: Clinical Trial

Nature’s Way: Whole Plant Works, Most Active Compound Fails: Why?

The villagers queue in a long line, a hundred or more of them, in front of the traditional healer’s hut in the south of Mali. It is the rainy season, and nearly all of them have malaria.

Chief Tiemoko Bengaly learnt traditional medicine from his grandfather. Perhaps soon nobody will learn traditional African medicine any more, as modern medicine arrives, along with manufactured Chinese herbal medicines.

Bengaly hands out dried Mexican prickly poppy, Argemone mexicana, tells his patients to drink as much tea made from the plant as they can for a week. The parts of the plant have different uses, as it contains powerful toxic alkaloids; the seeds are dangerously poisonous.

Mexican prickly poppy, Argemone mexicana.
Mexican prickly poppy, Argemone mexicana.

As Brendan Borrell reports in the June 2014 issue of Scientific American (pages 49-53), the results were dramatic: 89% of the patients recovered from their malaria, compared to 95% for the current best treatment for the difficult disease, Artemisinin-Combination Therapies or ACT.  The trial was done in 2010 by Dr Bertrand Graz and Dr Merlin Willcox, and their approach was highly unconventional.

ACT consists of a drug obtained from another plant, sweet wormwood, Artemisia annua, discovered by testing plants used in Chinese herbal medicine, in combination with one or more of the many other drugs used against malaria, but which the malaria parasite has invariably developed resistance to over the years. Thus it has come about that ACT has become the last best hope against a slippery, shape-shifting parasite that has defied half a century of work by the world’s biggest drug companies and medical research foundations. All attempts at an anti-malaria vaccine have foundered on the parasite’s ability to change its biochemical spots, while all the drugs have similarly started to fail as the parasite (actually several related species, causing different malarias) becomes resistant, finding ways to continue growing in the presence of chemicals designed specifically to target vital parts of its metabolism.

One of the most remarkable things about the success in Mali – apart, that is, from its very low cost compared to traditional drug discovery, and its use of ethnobotany and a retrospective treatment outcome (RTO) study rather than a double-blind controlled clinical trial (all remarkable features of the work), was this: if the plant had been tested the conventional (I nearly said ‘traditional’) Western way, it would have failed.

The conventional Western approach would have isolated each compound that had any pharmacological activity – in other words, that did anything useful against malaria – and then tested it, alone, “in vitro” (in a test tube) to see how well it worked. It would then pick the most effective one, and try it against malaria in mice, and if that worked well and safely, then try it against malaria in humans.

The most effective substance in Argemone is berberine, and it fails against the malaria parasite. But the whole plant, as administered by healers like Bengaly in Mali, is life-saving.

Somehow, observational study in the style of ethnobotany succeeded where conventional Western medicine’s protocols for drug discovery – clinical trials and all the other paraphernalia for bioprospecting and pharmaceutical research (a jaw-cracking combination of long words derived from Latin and Greek) – would have (or actually) failed.

There is something both humbling and inspiring about this. We humans come from an incredibly clever but stupid species. Alexander Pope had it right:

 Born but to die, and reas’ning but to err;
Whether he thinks to little, or too much;
Chaos of Thought and Passion, all confus’d;
Still by himself, abus’d or disabus’d;
Created half to rise and half to fall;
Great Lord of all things, yet a prey to all,
Sole judge of truth, in endless error hurl’d;
The glory, jest and riddle of the world.

Translated, we might read Pope to say “You do your science by analysis, which is hugely effective, but it leaves you prone to endless error, for you are ignoring all the subtle side effects, interactions and combinations of effects that together make up almost everything that is worth having in the world.” Science is not wrong – it is a marvellously precise application of common sense (try whatever it is with the factor X and without, and see what difference factor X makes) – but the world is such a complex place, and the combinations of X and Y and Z and A and B and C are so many, that it will take forever to analyse everything.

In that case, integrated approaches such as traditional herbal medicine, even if they are often somewhat ignorant and wrong in places, have something important to offer. But like many other things that we are accidentally wiping out, like thousands of species of plant and animal in rainforest, ocean, mountain, grassland and marsh, we’d better be quick to study herbal medicine before it vanishes from the face of the earth for ever.