May 6, 2007
From China to Panama, a Trail of Poisoned Medicine
By WALT BOGDANICH and JAKE HOOKER
The kidneys fail first. Then the central nervous system begins to misfire. Paralysis spreads, making breathing difficult, then often impossible without assistance. In the end, most victims die.
Many of them are children, poisoned at the hands of their unsuspecting parents.
The syrupy poison, diethylene glycol, is an indispensable part of the modern world, an industrial solvent and prime ingredient in antifreeze.
It is also a killer. And the deaths, if not intentional, are often no accident.
Over the years, the poison has been loaded into all varieties of medicine — cough syrup, fever medication, injectable drugs — a result of counterfeiters who profit by substituting the sweet-tasting solvent for a safe, more expensive syrup, usually glycerin, commonly used in drugs, food, toothpaste and other products.
Toxic syrup has figured in at least eight mass poisonings around the world in the past two decades. Researchers estimate that thousands have died. In many cases, the precise origin of the poison has never been determined. But records and interviews show that in three of the last four cases it was made in China, a major source of counterfeit drugs.
Panama is the most recent victim. Last year, government officials there unwittingly mixed diethylene glycol into 260,000 bottles of cold medicine — with devastating results. Families have reported 365 deaths from the poison, 100 of which have been confirmed so far. With the onset of the rainy season, investigators are racing to exhume as many potential victims as possible before bodies decompose even more.
Panama’s death toll leads directly to Chinese companies that made and exported the poison as 99.5 percent pure glycerin.
Forty-six barrels of the toxic syrup arrived via a poison pipeline stretching halfway around the world. Through shipping records and interviews with government officials, The New York Times traced this pipeline from the Panamanian port of Colón, back through trading companies in Barcelona, Spain, and Beijing, to its beginning near the Yangtze Delta in a place local people call “chemical country.”
The counterfeit glycerin passed through three trading companies on three continents, yet not one of them tested the syrup to confirm what was on the label. Along the way, a certificate falsely attesting to the purity of the shipment was repeatedly altered, eliminating the name of the manufacturer and previous owner. As a result, traders bought the syrup without knowing where it came from, or who made it. With this information, the traders might have discovered — as The Times did — that the manufacturer was not certified to make pharmaceutical ingredients.
An examination of the two poisoning cases last year — in Panama and earlier in China — shows how China’s safety regulations have lagged behind its growing role as low-cost supplier to the world. It also demonstrates how a poorly policed chain of traders in country after country allows counterfeit medicine to contaminate the global market.
Last week, the United States Food and Drug Administration warned drug makers and suppliers in the United States “to be especially vigilant” in watching for diethylene glycol. The warning did not specifically mention China, and it said there was “no reason to believe” that glycerin in this country was tainted. Even so, the agency asked that all glycerin shipments be tested for diethylene glycol, and said it was “exploring how supplies of glycerin become contaminated.”
China is already being accused by United States authorities of exporting wheat gluten containing an industrial chemical, melamine, that ended up in pet food and livestock feed. The F.D.A. recently banned imports of Chinese-made wheat gluten after it was linked to pet deaths in the United States.
Beyond Panama and China, toxic syrup has caused mass poisonings in Haiti, Bangladesh, Argentina, Nigeria and twice in India.
In Bangladesh, investigators found poison in seven brands of fever medication in 1992, but only after countless children died. A Massachusetts laboratory detected the contamination after Dr. Michael L. Bennish, a pediatrician who works in developing countries, smuggled samples of the tainted syrup out of the country in a suitcase. Dr. Bennish, who investigated the Bangladesh epidemic and helped write a 1995 article about it for BMJ, formerly known as the British Medical Journal, said that given the amount of medication distributed, deaths “must be in the thousands or tens of thousands.”
“It’s vastly underreported,” Dr. Bennish said of diethylene glycol poisoning. Doctors might not suspect toxic medicine, particularly in poor countries with limited resources and a generally unhealthy population, he said, adding, “Most people who die don’t come to a medical facility.”
The makers of counterfeit glycerin, which superficially looks and acts like the real thing but generally costs considerably less, are rarely identified, much less prosecuted, given the difficulty of tracing shipments across borders. “This is really a global problem, and it needs to be handled in a global way,” said Dr. Henk Bekedam, the World Health Organization’s top representative in Beijing.
Seventy years ago, medicine laced with diethylene glycol killed more than 100 people in the United States, leading to the passage of the toughest drug regulations of that era and the creation of the modern Food and Drug Administration.
The F.D.A. has tried to help in poisoning cases around the world, but there is only so much it can do.
When at least 88 children died in Haiti a decade ago, F.D.A. investigators traced the poison to the Manchurian city of Dalian, but their attempts to visit the suspected manufacturer were repeatedly blocked by Chinese officials, according to internal State Department records. Permission came more than a year later, but by then the plant had moved and its records were destroyed.
“Chinese officials we contacted on this matter were all reluctant to become involved,” the American Embassy in Beijing wrote in a confidential cable. “We cannot be optimistic about our chances for success in tracking down the other possible glycerine shipments.”
In fact, The Times found records showing that the same Chinese company implicated in the Haiti poisoning also shipped about 50 tons of counterfeit glycerin to the United States in 1995. Some of it was later resold to another American customer, Avatar Corporation, before the deception was discovered.
“Thank God we caught it when we did,” said Phil Ternes, chief operating officer of Avatar, a Chicago-area supplier of bulk pharmaceuticals and nonmedicinal products. The F.D.A. said it was unaware of the shipment.
In China, the government is vowing to clean up its pharmaceutical industry, in part because of criticism over counterfeit drugs flooding the world markets. In December, two top drug regulators were arrested on charges of taking bribes to approve drugs. In addition, 440 counterfeiting operations were closed down last year, the World Health Organization said.
But when Chinese officials investigated the role of Chinese companies in the Panama deaths, they found that no laws had been broken, according to an official of the nation’s drug enforcement agency. China’s drug regulation is “a black hole,” said one trader who has done business through CNSC Fortune Way, the Beijing-based broker that investigators say was a crucial conduit for the Panama poison.
In this environment, Wang Guiping, a tailor with a ninth-grade education and access to a chemistry book, found it easy to enter the pharmaceutical supply business as a middleman. He quickly discovered what others had before him: that counterfeiting was a simple way to increase profits.
And then people in China began to die.
Cheating the System
Mr. Wang spent years as a tailor in the manufacturing towns of the Yangtze Delta, in eastern China. But he did not want to remain a common craftsman, villagers say. He set his sights on trading chemicals, a business rooted in the many small chemical plants that have sprouted in the region.
“He didn’t know what he was doing,” Mr. Wang’s older brother, Wang Guoping, said in an interview. “He didn’t understand chemicals.”
But he did understand how to cheat the system.
Wang Guiping, 41, realized he could earn extra money by substituting cheaper, industrial-grade syrup — not approved for human consumption — for pharmaceutical grade syrup. To trick pharmaceutical buyers, he forged his licenses and laboratory analysis reports, records show.
Mr. Wang later told investigators that he figured no harm would come from the substitution, because he initially tested a small quantity. He did it with the expertise of a former tailor.
He swallowed some of it. When nothing happened, he shipped it.
One company that used the syrup beginning in early 2005 was Qiqihar No. 2 Pharmaceutical, about 1,000 miles away in the far northeastern province of Heilongjiang. A buyer for the factory had seen a posting for Mr. Wang’s syrup on an industry Web site.
After a while, Mr. Wang set out to find an even cheaper substitute syrup so he could increase his profit even more, according to a Chinese investigator. In a chemical book he found what he was looking for: another odorless syrup — diethylene glycol. At the time, it sold for 6,000 to 7,000 yuan a ton, or about $725 to $845, while pharmaceutical-grade syrup cost 15,000 yuan, or about $1,815, according to the investigator.
Mr. Wang did not taste-test this second batch of syrup before shipping it to Qiqihar Pharmaceutical, the government investigator said, adding, “He knew it was dangerous, but he didn’t know that it could kill.”
The manufacturer used the toxic syrup in five separate drug products: ampules of Amillarisin A for gall bladder problems; a special enema fluid for children; an injection for blood vessel diseases; an intravenous pain reliever; and an arthritis treatment.
In April 2006, one of southern China’s finest hospitals, in Guangzhou, Guangdong Province, began administering Amillarisin A. Within a month or so, at least 18 people had died after taking the medicine, though some had already been quite sick.
Zhou Jianhong, 33, said his father took his first dose of Amillarisin A on April 19. A week later he was in critical condition. “If you are going to die, you want to die at home,” Mr. Zhou said. “So we checked him out of the hospital.” He died the next day.
“Everybody wants to invest in the pharmaceutical industry and it is growing, but the regulators can’t keep up,” Mr. Zhou said. “We need a system to assure our safety.”
The final death count is unclear, since some people who took the medicine may have died in less populated areas.
In a small town in Sichuan Province, a man named Zhou Lianghui said the authorities would not acknowledge that his wife had died from taking tainted Amillarisin A. But Mr. Zhou, 38, said he matched the identification number on the batch of medicine his wife received with a warning circular distributed by drug officials.
“You probably cannot understand a small town if you are in Beijing,” Zhou Lianghui said in a telephone interview. “The sky is high and the emperor is far away. There are a lot of problems here that the law cannot speak to.”
The failure of the government to stop poison from contaminating the drug supply caused one of the bigger domestic scandals of the year. Last May, China’s premier, Wen Jiabao, ordered an investigation of the deaths, declaring, “The pharmaceutical market is in disorder.”
At about the same time, 9,000 miles away in Panama, the long rainy season had begun. Anticipating colds and coughs, the government health program began manufacturing cough and antihistamine syrup. The cough medicine was sugarless so even diabetics could use it.
The medicine was mixed with a pale yellow, almost translucent syrup that had arrived in 46 barrels from Barcelona on the container ship Tobias Maersk. Shipping records showed the contents to be 99.5 percent pure glycerin.
It would be months and many deaths later before that certification was discovered to be pure fiction.
A Mysterious Illness
Early last September, doctors at Panama City’s big public hospital began to notice patients exhibiting unusual symptoms.
They initially appeared to have Guillain-Barré syndrome, a relatively rare neurological disorder that first shows up as a weakness or tingling sensation in the legs. That weakness often intensifies, spreading upward to the arms and chest, sometimes causing total paralysis and an inability to breathe.
The new patients had paralysis, but it did not spread upward. They also quickly lost their ability to urinate, a condition not associated with Guillain-Barré. Even more unusual was the number of cases. In a full year, doctors might see eight cases of Guillain-Barré, yet they saw that many in just two weeks.
Doctors sought help from an infectious disease specialist, Néstor Sosa, an intense, driven doctor who competes in triathlons and high-level chess.
Dr. Sosa’s medical specialty had a long, rich history in Panama, once known as one of the world’s unhealthiest places. In one year in the late 1800s, a lethal mix of yellow fever and malaria killed nearly 1 in every 10 residents of Panama City. Only after the United States managed to overcome those mosquito-borne diseases was it able to build the Panama Canal without the devastation that undermined an earlier attempt by the French.
The suspected Guillain-Barré cases worried Dr. Sosa. “It was something really extraordinary, something that was obviously reaching epidemic dimensions in our hospital,” he said.
With the death rate from the mystery illness near 50 percent, Dr. Sosa alerted the hospital management, which asked him to set up and run a task force to handle the situation. The assignment, a daunting around-the-clock dash to catch a killer, was one he eagerly embraced.
Several years earlier, Dr. Sosa had watched as other doctors identified the cause of another epidemic, later identified as hantavirus, a pathogen spread by infected rodents.
“I took care of patients but I somehow felt I did not do enough,” he said. The next time, he vowed, would be different.
Dr. Sosa set up a 24-hour “war room” in the hospital, where doctors could compare notes and theories as they scoured medical records for clues.
As a precaution, the patients with the mystery illness were segregated and placed in a large empty room awaiting renovation. Health care workers wore masks, heightening fears in the hospital and the community.
“That spread a lot of panic,” said Dr. Jorge Motta, a cardiologist who runs the Gorgas Memorial Institute, a widely respected medical research center in Panama. “That is always a terrifying thought, that you will be the epicenter of a new infectious disease, and especially a new infectious disease that kills with a high rate of death, like this.”
From China to Panama, a Trail of Poisoned Medicine
By WALT BOGDANICH and JAKE HOOKER
The kidneys fail first. Then the central nervous system begins to misfire. Paralysis spreads, making breathing difficult, then often impossible without assistance. In the end, most victims die.
Many of them are children, poisoned at the hands of their unsuspecting parents.
The syrupy poison, diethylene glycol, is an indispensable part of the modern world, an industrial solvent and prime ingredient in antifreeze.
It is also a killer. And the deaths, if not intentional, are often no accident.
Over the years, the poison has been loaded into all varieties of medicine — cough syrup, fever medication, injectable drugs — a result of counterfeiters who profit by substituting the sweet-tasting solvent for a safe, more expensive syrup, usually glycerin, commonly used in drugs, food, toothpaste and other products.
Toxic syrup has figured in at least eight mass poisonings around the world in the past two decades. Researchers estimate that thousands have died. In many cases, the precise origin of the poison has never been determined. But records and interviews show that in three of the last four cases it was made in China, a major source of counterfeit drugs.
Panama is the most recent victim. Last year, government officials there unwittingly mixed diethylene glycol into 260,000 bottles of cold medicine — with devastating results. Families have reported 365 deaths from the poison, 100 of which have been confirmed so far. With the onset of the rainy season, investigators are racing to exhume as many potential victims as possible before bodies decompose even more.
Panama’s death toll leads directly to Chinese companies that made and exported the poison as 99.5 percent pure glycerin.
Forty-six barrels of the toxic syrup arrived via a poison pipeline stretching halfway around the world. Through shipping records and interviews with government officials, The New York Times traced this pipeline from the Panamanian port of Colón, back through trading companies in Barcelona, Spain, and Beijing, to its beginning near the Yangtze Delta in a place local people call “chemical country.”
The counterfeit glycerin passed through three trading companies on three continents, yet not one of them tested the syrup to confirm what was on the label. Along the way, a certificate falsely attesting to the purity of the shipment was repeatedly altered, eliminating the name of the manufacturer and previous owner. As a result, traders bought the syrup without knowing where it came from, or who made it. With this information, the traders might have discovered — as The Times did — that the manufacturer was not certified to make pharmaceutical ingredients.
An examination of the two poisoning cases last year — in Panama and earlier in China — shows how China’s safety regulations have lagged behind its growing role as low-cost supplier to the world. It also demonstrates how a poorly policed chain of traders in country after country allows counterfeit medicine to contaminate the global market.
Last week, the United States Food and Drug Administration warned drug makers and suppliers in the United States “to be especially vigilant” in watching for diethylene glycol. The warning did not specifically mention China, and it said there was “no reason to believe” that glycerin in this country was tainted. Even so, the agency asked that all glycerin shipments be tested for diethylene glycol, and said it was “exploring how supplies of glycerin become contaminated.”
China is already being accused by United States authorities of exporting wheat gluten containing an industrial chemical, melamine, that ended up in pet food and livestock feed. The F.D.A. recently banned imports of Chinese-made wheat gluten after it was linked to pet deaths in the United States.
Beyond Panama and China, toxic syrup has caused mass poisonings in Haiti, Bangladesh, Argentina, Nigeria and twice in India.
In Bangladesh, investigators found poison in seven brands of fever medication in 1992, but only after countless children died. A Massachusetts laboratory detected the contamination after Dr. Michael L. Bennish, a pediatrician who works in developing countries, smuggled samples of the tainted syrup out of the country in a suitcase. Dr. Bennish, who investigated the Bangladesh epidemic and helped write a 1995 article about it for BMJ, formerly known as the British Medical Journal, said that given the amount of medication distributed, deaths “must be in the thousands or tens of thousands.”
“It’s vastly underreported,” Dr. Bennish said of diethylene glycol poisoning. Doctors might not suspect toxic medicine, particularly in poor countries with limited resources and a generally unhealthy population, he said, adding, “Most people who die don’t come to a medical facility.”
The makers of counterfeit glycerin, which superficially looks and acts like the real thing but generally costs considerably less, are rarely identified, much less prosecuted, given the difficulty of tracing shipments across borders. “This is really a global problem, and it needs to be handled in a global way,” said Dr. Henk Bekedam, the World Health Organization’s top representative in Beijing.
Seventy years ago, medicine laced with diethylene glycol killed more than 100 people in the United States, leading to the passage of the toughest drug regulations of that era and the creation of the modern Food and Drug Administration.
The F.D.A. has tried to help in poisoning cases around the world, but there is only so much it can do.
When at least 88 children died in Haiti a decade ago, F.D.A. investigators traced the poison to the Manchurian city of Dalian, but their attempts to visit the suspected manufacturer were repeatedly blocked by Chinese officials, according to internal State Department records. Permission came more than a year later, but by then the plant had moved and its records were destroyed.
“Chinese officials we contacted on this matter were all reluctant to become involved,” the American Embassy in Beijing wrote in a confidential cable. “We cannot be optimistic about our chances for success in tracking down the other possible glycerine shipments.”
In fact, The Times found records showing that the same Chinese company implicated in the Haiti poisoning also shipped about 50 tons of counterfeit glycerin to the United States in 1995. Some of it was later resold to another American customer, Avatar Corporation, before the deception was discovered.
“Thank God we caught it when we did,” said Phil Ternes, chief operating officer of Avatar, a Chicago-area supplier of bulk pharmaceuticals and nonmedicinal products. The F.D.A. said it was unaware of the shipment.
In China, the government is vowing to clean up its pharmaceutical industry, in part because of criticism over counterfeit drugs flooding the world markets. In December, two top drug regulators were arrested on charges of taking bribes to approve drugs. In addition, 440 counterfeiting operations were closed down last year, the World Health Organization said.
But when Chinese officials investigated the role of Chinese companies in the Panama deaths, they found that no laws had been broken, according to an official of the nation’s drug enforcement agency. China’s drug regulation is “a black hole,” said one trader who has done business through CNSC Fortune Way, the Beijing-based broker that investigators say was a crucial conduit for the Panama poison.
In this environment, Wang Guiping, a tailor with a ninth-grade education and access to a chemistry book, found it easy to enter the pharmaceutical supply business as a middleman. He quickly discovered what others had before him: that counterfeiting was a simple way to increase profits.
And then people in China began to die.
Cheating the System
Mr. Wang spent years as a tailor in the manufacturing towns of the Yangtze Delta, in eastern China. But he did not want to remain a common craftsman, villagers say. He set his sights on trading chemicals, a business rooted in the many small chemical plants that have sprouted in the region.
“He didn’t know what he was doing,” Mr. Wang’s older brother, Wang Guoping, said in an interview. “He didn’t understand chemicals.”
But he did understand how to cheat the system.
Wang Guiping, 41, realized he could earn extra money by substituting cheaper, industrial-grade syrup — not approved for human consumption — for pharmaceutical grade syrup. To trick pharmaceutical buyers, he forged his licenses and laboratory analysis reports, records show.
Mr. Wang later told investigators that he figured no harm would come from the substitution, because he initially tested a small quantity. He did it with the expertise of a former tailor.
He swallowed some of it. When nothing happened, he shipped it.
One company that used the syrup beginning in early 2005 was Qiqihar No. 2 Pharmaceutical, about 1,000 miles away in the far northeastern province of Heilongjiang. A buyer for the factory had seen a posting for Mr. Wang’s syrup on an industry Web site.
After a while, Mr. Wang set out to find an even cheaper substitute syrup so he could increase his profit even more, according to a Chinese investigator. In a chemical book he found what he was looking for: another odorless syrup — diethylene glycol. At the time, it sold for 6,000 to 7,000 yuan a ton, or about $725 to $845, while pharmaceutical-grade syrup cost 15,000 yuan, or about $1,815, according to the investigator.
Mr. Wang did not taste-test this second batch of syrup before shipping it to Qiqihar Pharmaceutical, the government investigator said, adding, “He knew it was dangerous, but he didn’t know that it could kill.”
The manufacturer used the toxic syrup in five separate drug products: ampules of Amillarisin A for gall bladder problems; a special enema fluid for children; an injection for blood vessel diseases; an intravenous pain reliever; and an arthritis treatment.
In April 2006, one of southern China’s finest hospitals, in Guangzhou, Guangdong Province, began administering Amillarisin A. Within a month or so, at least 18 people had died after taking the medicine, though some had already been quite sick.
Zhou Jianhong, 33, said his father took his first dose of Amillarisin A on April 19. A week later he was in critical condition. “If you are going to die, you want to die at home,” Mr. Zhou said. “So we checked him out of the hospital.” He died the next day.
“Everybody wants to invest in the pharmaceutical industry and it is growing, but the regulators can’t keep up,” Mr. Zhou said. “We need a system to assure our safety.”
The final death count is unclear, since some people who took the medicine may have died in less populated areas.
In a small town in Sichuan Province, a man named Zhou Lianghui said the authorities would not acknowledge that his wife had died from taking tainted Amillarisin A. But Mr. Zhou, 38, said he matched the identification number on the batch of medicine his wife received with a warning circular distributed by drug officials.
“You probably cannot understand a small town if you are in Beijing,” Zhou Lianghui said in a telephone interview. “The sky is high and the emperor is far away. There are a lot of problems here that the law cannot speak to.”
The failure of the government to stop poison from contaminating the drug supply caused one of the bigger domestic scandals of the year. Last May, China’s premier, Wen Jiabao, ordered an investigation of the deaths, declaring, “The pharmaceutical market is in disorder.”
At about the same time, 9,000 miles away in Panama, the long rainy season had begun. Anticipating colds and coughs, the government health program began manufacturing cough and antihistamine syrup. The cough medicine was sugarless so even diabetics could use it.
The medicine was mixed with a pale yellow, almost translucent syrup that had arrived in 46 barrels from Barcelona on the container ship Tobias Maersk. Shipping records showed the contents to be 99.5 percent pure glycerin.
It would be months and many deaths later before that certification was discovered to be pure fiction.
A Mysterious Illness
Early last September, doctors at Panama City’s big public hospital began to notice patients exhibiting unusual symptoms.
They initially appeared to have Guillain-Barré syndrome, a relatively rare neurological disorder that first shows up as a weakness or tingling sensation in the legs. That weakness often intensifies, spreading upward to the arms and chest, sometimes causing total paralysis and an inability to breathe.
The new patients had paralysis, but it did not spread upward. They also quickly lost their ability to urinate, a condition not associated with Guillain-Barré. Even more unusual was the number of cases. In a full year, doctors might see eight cases of Guillain-Barré, yet they saw that many in just two weeks.
Doctors sought help from an infectious disease specialist, Néstor Sosa, an intense, driven doctor who competes in triathlons and high-level chess.
Dr. Sosa’s medical specialty had a long, rich history in Panama, once known as one of the world’s unhealthiest places. In one year in the late 1800s, a lethal mix of yellow fever and malaria killed nearly 1 in every 10 residents of Panama City. Only after the United States managed to overcome those mosquito-borne diseases was it able to build the Panama Canal without the devastation that undermined an earlier attempt by the French.
The suspected Guillain-Barré cases worried Dr. Sosa. “It was something really extraordinary, something that was obviously reaching epidemic dimensions in our hospital,” he said.
With the death rate from the mystery illness near 50 percent, Dr. Sosa alerted the hospital management, which asked him to set up and run a task force to handle the situation. The assignment, a daunting around-the-clock dash to catch a killer, was one he eagerly embraced.
Several years earlier, Dr. Sosa had watched as other doctors identified the cause of another epidemic, later identified as hantavirus, a pathogen spread by infected rodents.
“I took care of patients but I somehow felt I did not do enough,” he said. The next time, he vowed, would be different.
Dr. Sosa set up a 24-hour “war room” in the hospital, where doctors could compare notes and theories as they scoured medical records for clues.
As a precaution, the patients with the mystery illness were segregated and placed in a large empty room awaiting renovation. Health care workers wore masks, heightening fears in the hospital and the community.
“That spread a lot of panic,” said Dr. Jorge Motta, a cardiologist who runs the Gorgas Memorial Institute, a widely respected medical research center in Panama. “That is always a terrifying thought, that you will be the epicenter of a new infectious disease, and especially a new infectious disease that kills with a high rate of death, like this.”
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