What would you think if after a heart attack your doctor prescribed capsules of extracts of ginseng, Chinese scorpion, cockroach, leech, peony root, sandalwood and turpentine? I suspect this might evoke a touch of skepticism. But believe it or not, that is just the treatment that 1899 Chinese heart attack patients received to prevent further complications. The goal was to test the potential efficacy of an ancient remedy that goes by the name “Tongxinluo,” with the name deriving from the Chinese words for “open,” “network,” and “heart.” The reference was likely to opening non-existent “energy channels,” not the coronary arteries. But judging by the results of the study, which were published in the highly respected Journal of the American Medical Society, the concoction may have some sort of effect on the channels we call the coronary arteries.
Before modern medicine evolved, essentially within the last two hundred or so years, civilizations around the world relied on various potions produced from natural substances to treat ailments. There is no question that plants contain an array of compounds with potential physiological activity, and via trial and error, various extracts made it into the medical armamentarium. For example, in ancient China, preparations made from the Ma Huang plant were used to treat asthma. These actually worked since the plant contains ephedrine, a bronchodilator. Many of the “remedies,” however, were complex mixtures of plant and animal products. In all likelihood they started out as a single component, and if that didn’t work, something else was added. Eventually a substance may have been included that had some efficacy and a medicine was born. The assumption then was that all the components worked together to produce results. That would seem to explain why so many of the 13,000 or so ancient Chinese medicines that have been compiled in traditional pharmacopeias are complex mixtures, with “Tongxinluo” being a prime example.
Why did researchers decide to treat heart patients with this bizarre mixture? They were intrigued by historical anecdotes from Chinese herbalists and their patients about benefits for the heart. Anecdotes do not science make, but they can be a springboard to science! Yarns about tea brewed from the foxglove plant easing palpitations prompted British physician William Withering to carry out a trial that resulted in the discovery of digitalis as a treatment for congestive heart failure. Investigation of anecdotes rarely yields significant results, but there is always the possibility of finding a diamond in the rough. So, did the Chinese doctors find one? Maybe a somewhat flawed diamond.
There is no question that the trial, which was randomized, placebo-controlled and double-blind, was well-conducted. After a year, the experimental group experienced major adverse cardiovascular events at a rate of 5.3% versus 8.3% in the placebo group, and a cardiac death rate at 4.5% versus 6.1%. Although these differences are not earth-shaking, they are statistically significant. There are caveats, of course. The patients also received standard treatments including statins, aspirin, beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), but not uniformly. That makes it difficult to tease out the effectiveness of Tongxinluo. And what that effect may be due to is a further mystery. A cockroach extract is unlikely to be beneficial, but a leech isolate may have some “blood thinning” effect. Ginseng contains a number of ginsenosides that conceivably could impact heart function. In any case, pharmaceutical companies are not going to start raising cockroaches, leeches or scorpions to reproduce Tongxinluo, but they may start investigating whether any of the components have some potential application. Maybe eventually something will come out of this study. As it did out of an investigation of another ancient Chinese remedy, one for malaria.
Malaria is a terrible disease caused by a mosquito transmitted parasite. It kills over a million people every year despite the availability of drugs to treat the disease. A major problem is that the parasite has developed resistance to the classic chloroquine drugs that have been very effective in the past. This was already a problem during the Vietnam War when North Vietnam asked China for help given China’s reputation for traditional medicines. Pharmaceutical chemist Tu Youyou took on the task of combing through ancient texts to look for any mention of treatment of malaria. She found repeated allusions to Artemisia annua, commonly called sweet wormwood, a plant from which her team isolated “arteminisin,” a compound that indeed proved to be an effective treatment for malaria. Arteminisin saved millions of lives and garnered Youyou a share of the 2015 Nobel Prize in Medicine.
While arteminisin is an effective medication, its extraction from the plant is a complex process and yields are low. This makes it an expensive medication, unaffordable by most people in countries where malaria is a problem. Science, specifically synthetic biology, has stepped in to help. Synthetic biology refers to the manipulation of living organisms to produce a desired outcome. In this case, that desired outcome is the production of arteminisin, and the organism that is manipulated can be a bacterium or a yeast.
How does the Artemisia plant produce arteminisin, was the first question researchers asked. Plants are veritable chemical factories that take water, carbon dioxide from the air, and minerals from the soil to produce all sorts of compounds as directed by genes in DNA, the proverbial “blueprint of life.” Genes tell a biological system which proteins to produce including enzymes which are specific proteins that act as catalysts for the chemical reactions that piece together molecules.
Amazingly, the genes that code for the enzymes needed to make artemisinic acid, the plant’s precursor to arteminisin, have been identified and have been inserted into the genome of a bacterium or a yeast. When these organisms are fed glucose, they produce arteminisic acid that then with a simple chemical reaction is converted into artemisinin. What human ingenuity can do is just amazing! Those microbes that have been cleverly manipulated by synthetic biology are now saving millions of lives. And it all started with some ancient Chinese anecdotes! It remains to be seen if Tongxinluo follows a similar path.
