If you’ve ever walked into an apothecary for traditional Chinese medicine (TCM), it’s hard to ignore the tang of dried herbs that are arrayed on the floor, lining the counter, and stacked on floor-to-ceiling shelves. There’s a good chance any brew you buy won’t taste great either. Despite the smell and taste, many people around the world swear by TCM, using it to treat various ailments or as supplements to bolster general health.
A large fraction of TCM ingredients come from plants, and the active compounds are their metabolites. Plants are amazing chemists—they can’t run from danger or environmental stressors, so they have no choice but to synthesize their way to survival. Their strategies include secreting bitter or toxic compounds to deter consumers in the wild. Occasionally, some of these chemicals are potent enough to treat human health conditions.
For as long as humans have been hunter-gatherers, our ancestors have foraged for plants to seek relief from their illnesses. Ancient China wasn’t the only civilization to tap into the vast medical potential of plants. What distinguishes TCM from other canons of herbal remedies is the early emergence of the written language in China, TCM experts say. The power of the written word allowed historical medical scholars to record, compile, and share thousands of years of medicinal wisdom.
Today, traditional Chinese herbal medicine is adopted all around East and Southeast Asia and among their diasporas. In China, TCM is well integrated into the health-care system; modern-day hospitals have entire wings dedicated to the practice. Herbs like ginseng and ginkgo are mainstay ingredients in household beauty products. Ancient TCM texts provide pharmaceutical companies with a treasure trove of promising would-be drugs to screen for. Nevertheless, TCM’s popularity is mainly confined to communities in or from the Far East. Outsiders are skeptical, arguing that because most TCM offerings haven’t gone through double-anonymized clinical trials, they may not be safe or effective.
“There is a tremendous cultural barrier,” says Jing-Ke Weng, a Massachusetts Institute of Technology plant biologist who studies how plants synthesize medically important molecules. “People will be reluctant to adopt something they don’t understand.”
The TCM label is a historical and cultural one; there is no unifying chemistry behind the diversity of TCM herbs. Some practitioners trained in TCM say the foundational principles are yin and yang, which roughly translate to “darkness” and “light.” Although outsiders may think these concepts are unscientific, they embody homeostatic balance, says Karl Tsim, a molecular biologist at the Hong Kong University of Science and Technology who researches the genetic and chemical properties of TCM. He explains that yin points to the body’s immune defenses, while yang refers to the body’s metabolic levels, notions that allopathic doctors can recognize.
On occasion, a prescription from the TCM classics can make a splash on the global stage. Perhaps the most well-known TCM herbal ingredient that became a pharmaceutical is the antimalarial molecule artemisinin, which is derived from Artemisia annua, or sweet wormwood. Its discovery is somewhat of a legend: In 1969, a Chinese herbalist named Tu Youyou began combing through the yellowed pages of 1,600-year-old medical tomes for a cure for malaria.
At that time, outbreaks were sweeping through southern China and its neighbors. The disease hit the soldiers in the Vietnam War especially hard. Making matters worse was the fact that the malaria parasite had grown resistant to chloroquine, the standard treatment of that era. North Vietnam asked China for help, and the Chinese government launched Project 523. As the operation’s leader, Tu discovered frequent mentions of sweet wormwood in the recipes that treated malaria-like fevers. Her team isolated the active ingredient from sweet wormwood and developed a low-temperature extraction that preserved the molecule’s bioactivity. Tu even volunteered as the first human medical test subject for the compound. Her discovery saved millions of lives and earned her a share of the 2015 Nobel Prize in Physiology or Medicine.
Identifying the active agent in other TCM prescriptions will be equally, if not more, challenging. A typical TCM brew contains upward of 10 plant ingredients, and that translates to thousands of metabolites.
Weng’s lab at MIT is among those trying to untangle the medicinal secrets of herbal TCM by linking plants and their metabolites to the biological effects they induce in the body with the help of modern science.
For example, a standard experiment is to feed cells with a TCM herb, use RNA sequencing to analyze the cells’ gene expressions, and see which biological pathways have been upregulated or downregulated. Weng speculates that machine learning may one day enter the fray to help parse the mountains of metabolomic data.
The complexity of a formula could make herbal TCM remedies a good option for treating complex diseases that involve many targets and multiple biological processes going haywire. TCM is usually slow acting and has long-lasting effects, so it’s suitable for chronic or preventive use against conditions such as inflammation and cardiovascular diseases, Tsim says. In contrast, “Western” medicine often focuses on finding a silver bullet for acute diseases. These differences make Western medicine and TCM complementary, he adds.
One group is taking a botanical approach to tackle the thorny disease of cancer. Researchers from Yale University and the company Yiviva are developing what could be the first herbal cancer drug. Derived from a 1,800-year-old TCM prescription, the four-herb formula, YIV-906, has demonstrated in preclinical and early clinical studies that it can boost the efficacy of chemotherapy drugs and reduce their side effects. The TCM-inspired oral formulation is currently being tested as an adjuvant in combination with other anticancer drugs in Phase 2 trials for liver-associated carcinoma.
With more herbs come more challenges for quality control and standardization of the ingredients, which are already problems that saddle everyday-use TCM herbs, Weng and Tsim say. These issues also threaten public trust for the broader adoption of TCM. It also doesn’t help that TCM’s bioactive molecules often come from endangered plants or once-common shrubs harvested to the brink of extinction.
To modernize TCM and prevent reliance on increasingly rare plants, Weng is turning to the manufacturing machinery of bacteria and yeast. He hopes that implanting herbs’ genes into these nonnative hosts will allow the active substances to be synthesized at scale in bioreactors. Such a tack “would be a major step forward to resolving the sourcing issue for these critically important medicinal molecules,” Weng says.
It could also solve another problem: the finickiness of plants as chemists. The molecules they churn out depend on regional terroir, just as the quality of wine from a vineyard does.
With global temperatures on the rise, quality control of TCM will become even more of a nightmare in the future. Tsim and his collaborators are rushing to profile the chemicals in TCM herbs according to their source, geography, and growth conditions so they know how the active compounds in herbs might shift with time—and how to reproduce these compounds if the need for greenhouse cultivation ever arises.
Without these urgent efforts, the immense herbal knowledge amassed over millennia could be yet another casualty of climate change. “It’s not for us. It’s for the next generations,” Tsim says.