Unraveling the Genetic Mysteries of the Opium Poppy
(Inside Science) -- In any list of plants that have had a significant impact on humanity, the poppy is close to the top. Evidence shows that people have relied on its sap since Neolithic times to soothe pain and ease coughs. In the 1800s, the humble plant was the catalyst for two wars between China and the British Empire. Today, opioid painkillers made from poppies are still the most effective and cost-efficient available -- and some of the most dangerous for addiction.
Now, understanding the past and future of the powerful plant may become easier. Today, an international team of scientists published a paper in the journal Science detailing the poppy genome. The research helps unravel how the plant's evolution led it to produce key drug compounds and may help researchers develop new drugs that are reliable and cheap. It could also help forensic scientists identify where street drugs originate.
"We've been quite fascinated for decades as to how plants have evolved this complexity of chemistry that occurs inside them," said Ian Graham, a plant biologist at the University of York in the United Kingdom who helped decode the genome. Plants are fixed in the environment, so they have to use chemicals to protect against predators like herbivores and microbes, and different chemicals to attract pollinators like bees, he explained. "Basically, it's a chemical warfare that plants use to protect themselves."
The scientists identified a large cluster of 15 genes that encode enzymes involved in the pathways humans are most interested in: one for the cough suppressant noscapine, and another for the painkillers codeine and morphine. Even though the poppy genome is similar in size to that of a human, 70.9 percent of the genome was repeated elements, which the scientists had to wade through.
According to the study, the pathway for the painkilling drugs evolved around 7.8 million years ago, meaning that the compounds the poppy has inside it today may have evolved long ago to protect the plant against environmental dangers, Graham said.
Pharmaceutical companies have struggled to come up with painkilling drugs that are as cheap, plentiful and effective as what poppies can produce. One reason is the complexity of the morphine or codeine molecule, said Graham, which has a chemical structure that's challenging to mimic.
Synthetic biologists have been successful in making morphine, codeine or noscapine by taking genes from plants and putting them in yeast. But the technique produces very small amounts of the drug at a high price tag, Graham said. The low cost of a poppy crop is hard to beat. "In plants, you can produce a kilogram of codeine for a few hundred dollars."
Armed with the knowledge of how the poppy genome is constructed and arranged, it's possible for scientists to start modifying plants to become even more robust drug factories. "Like every other species of plants, poppies are subject to disease by mildew," said Graham. "In the future, we could get higher yields of the drugs in a controlled way through disease-resistant crops."
While more opiates may sound dangerous in the U.S., the study authors point out that non-Western countries have very little access to medicines for palliative care. In the U.S. and Canada, there are far more painkilling drugs than needed, but in India only 4 percent of people who need morphine have access, and in Nigeria it's just 0.2 percent of people. "Addressing the lack of access to pain relief or palliative care especially among poor people in low to middle income countries has been recognized as a global health and equity imperative," the authors write in the paper.
The genome may also lead to better counter-terrorism efforts, said Michael Marciano, who applies molecular biology to national security at Syracuse University in New York and was not involved in the new research. Marciano was part of a group that developed a method to extract poppy DNA from heroin -- something called forensic geosourcing. They published their research earlier this year.
"Having a referenced genome makes the work that we're involved in more valuable," said Marciano. Finding DNA in street drugs is a challenge because the refining process is harsh and damages DNA, leaving it "very degraded," he said. The new work, he said, opens up possibilities in identifying the exact country, region or field that grew the poppy.
The social and political history of opium is not lost on the research team, which includes collaborators from China, Australia and the U.K. "A British team and a Chinese team working together is quite interesting because the British army wanted to sell more opium to China in the 1800s," said Kai Ye, a study author from Xi'an Jiaotong University in China. "And now, we are working together and trying to make the best science for the benefit of all human beings."