China wants to rule the global pharmaceutical market and is mining its history to get there.
This is a new and surprising goal. For much of the past 300 years, China has never really cared whether Europeans or North Americans approved of its medical systems. “Chinese doctors were well aware of Western medicine, but they didn’t perceive of it as in any way superior,” says Volker Scheid, professor of East Asian medicines at the University of Westminster in London. As a result, since the advent of antibiotics (and what is thought of as “modern medicine”) China has fallen far behind in the pharmaceutical arms race. Of the 50 biggest global pharmaceutical and biotech firms, only one, Sinopharm, is Chinese. But China is now looking to take over a massively important (and lucrative) industry that has, to date, been centered in the West.
This revolution is starting in Dalian. If Dalian were in the United States, it would be the country’s third-biggest city, trailing only New York and Los Angeles. But in China, a city of 3.7 million people barely cracks the top 20. Residents of Shanghai and Beijing consider Dalian quaint—the “romantic city” of China, with well-manicured city parks and squares, and plenty of waterfront and beaches to stroll along.
That vacation vibe belies the fact that it’s at the forefront of global information research and development. At the city’s outskirts sits the Dalian Institute of Chemical Physics (DICP), which hosts the 15-year Herbalome Project, initiated in 2008. The project’s goal is to isolate every compound contained in all the medicinal herbs in the Chinese healing tradition, and to utilize modern pharmaceutical practices to turn these plants into more efficient—and more marketable—drugs. The globalization of traditional Chinese medicine (TCM) would be a tremendous public relations boost for the country, but there’s an even more significant goal here: If the Herbalome Project and other similar endeavors are successful, they could add billions to China’s gross domestic product—and might even shift the global pharmaceutical focus away from the West and toward eastern Asia.
“Once China obtains a competitive edge in the global drug market,” says Yanzhong Huang, a senior fellow for global health at the Council on Foreign Relations, “it could redefine the term affordable drugs and become a game changer for global health.”
Finding All the Piano Keys
Xinmiao Liang remembers, not so fondly, being given traditional medicines as a child. Most TCM concoctions are created by drying herbs, then boiling them in water for hours. The end results are often the color and consistency of coffee, and extremely unpleasant to ingest. “The taste was very bitter and tough to get down,” Liang says. “That was when I began hoping that one day Chinese medicine would be like Western medicine: convenient to take, with good effects.”
Today, Liang’s Herbalome Project has a team of about 20 scientists working toward that goal. It’s very serious and very tedious work. Currently there are over 10,000 herbs in the TCM canon, according to Olivier Civelli, a Swiss-born molecular biologist at the University of California, Irvine, who, in the mid-1990s, invented the “reverse pharmacology” process now being applied to that list of plants. And each of those herbs can be further broken down into dozens, sometimes hundreds, of testable compound samples. Liang says the scientists analyze 500 samples every day—and they’ve already touched almost 750,000 compounds.
Before he met Liang, Civelli had spent the majority of his professional career hunting for new neurotransmitters—the chemicals that convey messages between brain cells. Civelli’s process is complex, but can be dumbed down to this: Every neurotransmitter has its own custom receptor in the brain cell, and each of those neurotransmitter-receptor sets can tell the brain something specific about what the body should do. For example, when dopamine (a neurotransmitter) interacts with its receptor, it triggers positive feelings.
Scientists know about many, many receptors, but have discovered only relatively few neurotransmitters. It’s sort of like knowing where all the keys of a piano are, but only being able to press down (and hear the sound of) a few of them. Civelli wanted to figure out how to play the rest. He predicted that by working backward from the massive list of receptors, researchers might be able to find many new neurotransmitters that could treat some of the 157 mental illnesses listed in the DSM-5 (the Diagnostic and Statistical Manual of Mental Disorders, considered the bible of mental health).
And they did. After Civelli’s team proved that reverse pharmacology worked, lots of labs joined the search. Ultimately, at least a dozen new neurotransmitters found through this process went all the way through drug development.
But by 2004, the well ran dry. Researchers still had some orphan receptors—but couldn’t find any neurotransmitter matches for them. Civelli gave up the hunt until 2008, when Yan Zhang, who had been studying under Liang at Dalian, asked Civelli for a postdoctoral position in his lab. After they spoke, Civelli realized there could be an untapped gold mine of brain drugs to match the orphan receptors: traditional Chinese remedies. So they began to go through the canon.
It took a few years, but early in 2014, Zhang and Civelli’s team published a study in the journal Current Biology announcing their discovery that the corydalis plant contained a compound that suppresses both inflammatory pain (connected to tissue damage) and injury-induced neuropathic pain (at least in lab mice). It’s a major breakthrough. The compound doesn’t lose effectiveness over time, the way opiate drugs do. As a result, it could end up as a key treatment for those suffering chronic pain, who typically need painkillers for the rest of their lives.
This is no small thing. Health economists have estimated that the annual cost of treating chronic pain in the U.S. is as high as $635 billion, and the IMS Institute for Healthcare Informatics has reported that in 2012, pain medication was the fifth-most costly class of drugs—and that doesn’t even include over-the-counter pain relievers like Advil and Tylenol. If the Herbalome Project’s new corydalis-based pain drug can pass through the Food and Drug Administration approval process, it could be transformative. And all the profits would flow back across the Pacific.
Land of Silk and Drugs
In China, of course, medical practitioners have known for centuries that if you take the tuberous corydalis plant (known locally as yan hu suo), grind it up and boil it in hot vinegar, the resulting concoction can alleviate menstrual cramps and headaches, as well as backaches and other forms of pain.
This isn’t the first time TCM has yielded a medicine that passed the rigorous standards of biomedicine. It’s also not the first time TCM has been mined for major global profits.
In 1805, a 21-year-old pharmacist’s apprentice named Friedrich Serturner was experimenting with the opium poppy plant, long used in Chinese medicine as a pain reliever and well known throughout Asia and Europe for its narcotic effects (the Opium Wars were just on the horizon). Eventually, Serturner isolated a compound with 10 times the power of the plant and named it morphine—to this day a standard in pain relief medication. This work spawned an entire class of painkilling medicine, opioids, which in 2012 generated $8.34 billion in sales in the U.S. alone.
In 1967, Mao Zedong initiated Project 523, a secret drug project to find a treatment for malaria. The initiative led to Tu Youyou’s 1972 discovery of the antimalarial effects of artemisinin, a compound derived from the sweet wormwood plant (or qinghao). Treatments based on Youyou’s findings have become the frontline treatment for malaria throughout the world; Coartem, an artemisinin-based combination therapy, is Novartis’s all-time best-selling drug, according to Mark Fishman, president of the Novartis Institutes for BioMedical Research.
But in years past, China hadn’t reaped the rewards of its own long-sought research and knowledge; years of local experimentation and careful documentation led to mostly foreign profits. In the 21st century, that’s changing.
The Next Blockbuster
“China’s interest in pharmaceutical R&D is part of a larger global movement where countries like India, Brazil and China have significantly increased their production of vaccines and other medical therapeutics,” explains Matthew Boulton, associate dean for global public health at the University of Michigan. “The opportunity to reduce costs and increase access were two of the drivers behind in-country production as opposed to relying on Western pharmaceutical firms.”
Investment in biomedicine research and development is widespread and growing: A recent study in The New England Journal of Medicine estimated that China devoted $160 billion to biomedical R&D in 2012. (Compare that to the $131 billion that the U.S. spent the same year). And that number is likely to go up: From 2007 to 2012, China increased spending in biomedicine research by about 33 percent—every year.
Civelli was amazed by DICP’s labs and equipment. ”They have decided to push science at any price,” he says. “They are supported much better than we are. Sometimes they are too well supported: They have machines they say they have to replace after three years. I’ve been using the same tool since 1997.”
For China it’s a win-win: homegrown drugs developed out of locally sourced plants focused on the unique health issues of its people—that can also be sold globally for massive profits.
Foreign entities see the potential, too. Novartis, for example, has invested over $1 billion in an R&D center in Shanghai; it is one of many Big Pharma companies building in what is fast becoming one of the world’s meccas for drug development. Nonprofits aren’t immune to the siren call of TCM either: The World Health Organization has established nine Collaborating Centers for Traditional Medicine in China.
Fear of Extraction
The push to decoct scalable and sellable drugs from TCM isn’t without its drawbacks. Some experts believe putting herbal remedies through the ringer of the drug approval process—where any given pharmaceutical must be shown incontrovertibly to work on a single disease—may lead to an irreversible reconfiguration of the TCM canon.
Mei Zhan, a medical anthropologist at the University of California, Irvine, recounts what she learned while studying in China. The people she worked with likened Western biomedicine to a lock and key, where “you identify the bad guys and you destroy them,” Zhan says. “In Chinese medicine it’s like cultivating a rose garden: It’s a long, slow process, and you help your own body to maintain itself and its well-being.”
Since the advent of the antibiotic era, TCM has generally focused on managing chronic conditions that do not have a single, identifiable cause (such as chronic back pain or sleep disorders). As a result, TCM has proved in many cases to be better than Western treatments for such illnesses. But it also may mean that some aspects of TCM are essentially incompatible with drug-approval processes in the U.S. and Europe.
If testing, for example, ends up not finding any compound in St. John’s wort that affects neurotransmitters, American, European and even Chinese patients may stop buying it as an over-the-counter herbal remedy for depression, opting instead for one of Big Pharma’s biomedically verified blockbuster drugs—even if the herbal remedy had been working for them for years.
This is the potentially detrimental consequence of the Herbalome Project and other like-minded endeavors: Because the biomedical extraction process is so laser-focused, it could accidentally lead the public (and the scientific community) to miss a potentially fecund source of healing. Liang himself has admitted as much. In 2011, he told Nature that the process his team was using was “not ideally suited to the task” because “TCM concoctions are mixtures of multiple compounds, and a typical Chinese medicine is intended to hit multiple biological targets.”
But on the flip side, the process has proved it can turn a complicated and obscure herbal mixture into a straightforward and replicable pain relief pill. And if, for example, testing discovers a new neurotransmitter hidden in St. John’s wort, it could become for depression what morphine is to pain, or what artemisinin is to malaria: a new, global, billion-dollar mega drug.
Chinese medicine, like any good system of science, is not (and was never) stable. In every generation, it adds new diseases and new treatments to its textbooks. Case in point: Shennong’s Materia Medica (Shennong bencao jing), the earliest known pharmacology text in China (compiled between 300 B.C. and A.D. 200), lists 365 potential medicinal ingredients; a survey in the late 20th century found 12,807 medicines in use across China. “Chinese medicine is resilient because it never forgets what was before; it simply adds to it,” Scheid says. “I see it as a very big toolbox that’s always growing.”
Liang admits his team has seen only mild success to this point. “Given the complexity and characteristics of traditional Chinese medicine,” he says, “the study of its foundation, research pharmacology, toxicology and medicinal theory can’t be done overnight.” At the same time, he is upbeat, believing that the Herbalome Project has the potential to yield big bucks, major public relations gains and a true impact on the public health of their families, communities, cities and country.
With translation help from William Ma and Michelle FlorCruz.