Green, of the CDC, had previously developed an inexpensive field test for detecting fake artesunate pills. In Atlanta, for the Jupiter Operation, his lab separated, identified and measured the contents of the pills. The fakes contained an astonishing variety of drugs and chemicals, some of them downright toxic. There was metamizole, a drug that can cause bone marrow failure and is banned in the United States; the outmoded drug chloroquine, which might have been added to create the bitter taste that many Asians associate with effective antimalarials; and acetaminophen, a pain reliever that can dull such malaria symptoms as pounding headaches and fool patients into thinking they're getting better. Jupiter Operation analysts also found safrole, a carcinogenic precursor to MDMA—better known as the illicit narcotic Ecstasy. The traces of safrole suggested that the same criminals who produced party drugs were now producing fake antimalarials.
Making matters worse, some of the bogus pills contained small amounts of genuine artesunate—possibly an effort to foil authenticity tests—which could cause the malaria parasite, spread by mosquitoes, to develop resistance to the leading drug treatment for the disease in Southeast Asia. That would be a public health disaster, researchers say. "We were shocked to find out how serious the problem was," says Newton.
The chemists also found that the fake drugs could be identified by their excipient—the inactive substance that carries the active ingredient in a tablet. The main excipient in Guilin artesunate is cornstarch. But geochemists on the team identified the excipient in some counterfeits as a particular type of calcium carbonate mineral, called calcite, which is found in limestone. That discovery would later take on greater significance.
The Jupiter Operation was the first time that palynology—the study of spores and pollen grains—was employed to trace counterfeit drugs. Plant species produce millions of pollen grains or spores, which end up almost everywhere. If a pollen grain's dispersal patterns (what palynologists call "pollen rain") are known, along with the locations and flowering times of the plants, then pollen can indicate where and when an object originated. Trapped in air filters, pollen can even reveal the routes of planes, trucks and cars.
Dallas Mildenhall is an expert (some would say the expert) in forensic palynology. Working from his lab at GNS Science, a government-owned research institute, in Avalon, New Zealand, he is a veteran of more than 250 criminal cases, involving everything from theft to murder. In 2005, Paul Newton asked him if he could extract pollen samples from antimalarials. "I was fairly certain I could," Mildenhall says. He views the trade in fake antimalarials as his biggest case yet. "It is mass murder on a horrendous scale," he says. "And there appears to be very little—if any—government involvement in trying to stamp it out."
In the fake drugs, Mildenhall found pollen or spores from firs, pines, cypresses, sycamores, alders, wormwood, willows, elms, wattles and ferns—all of which grow along China's southern border. (The fakes also contained fragments of charcoal, presumably from vehicle tailpipes and fires, suggesting the phony drugs were manufactured in severely polluted areas.) Then Mildenhall discovered a pollen grain from the Restionaceae family of reeds, which is found from along the Vietnam coast into southernmost China. That location matched the source of the calcite identified by Jupiter Operation's geochemists.
"A mine close to the China-Vietnam border is the only place in the world where this type of calcite is mined," Mildenhall says. The investigators now had two pieces of evidence for the general location of the counterfeit-drug-manufacturing facilities.
Based on their analyses, Jupiter Operation researchers determined that 195 of the 391 random samples were counterfeits. The pollen signatures from nearly all of them suggested that they'd been manufactured in the same region of southern China. The researchers then created a map, pinpointing where each of the 14 fake holograms had been found. The locations suggested the counterfeits were made and distributed by two separate trafficking networks. One encompassed a western region (Myanmar, the Thai-Myanmar border and northern Laos); the other an eastern area (southern Laos, Vietnam and Cambodia). What's more, metronidazole (an antibiotic) and small amounts of artesunate were detected exclusively in the western samples, while erythromycin (another antibiotic), erucamide (an industrial lubricant), sulphadoxine and pyrimethamine (older antimalarials) were found only in the eastern counterfeits.
At this stage of the investigation, the Jupiter Operation had done all that it could to locate the counterfeiters' production facilities. "We were able to pinpoint only a general area," says Mildenhall. "We were now totally dependent on the local law enforcement agencies to target that area and find out the precise spot."
With evidence from the Jupiter Operation in hand, Ronald Noble, the secretary general of Interpol, met in March 2006 with Zheng Shaodong, China's assistant minister of public security. During the meeting, Noble stressed to Zheng not only the threat to public health, but the potential profit losses for Chinese pharmaceutical companies.