Researchers have developed an easier and potentially cheaper method of synthesizing heparin, a widely used blood thinner that is typically made from pig intestines or cow lungs. While a form of synthetic heparin is already available, the animal-derived version is cheaper and dominates the market; it costs about $5 to $35, versus $50 to $60 for the same dosage of the synthetic. The new technique might also lead to the development of new kinds of heparin, which could be useful for treating asthma and other disorders that are not related to blood clotting.

The worldwide heparin market requires about 700 million pigs per year, and many of the raw materials derived from the pigs come from China. But overseas production makes it difficult to control quality. In 2008, a contaminated batch of the drug from China killed more than 200 people, making the need for an easy-to-produce synthetic version even more evident.

Now, roughly 10 years after the first fully synthetic heparin was developed, a team of academic researchers has figured out a way to simplify the manufacturing process, reducing 50 chemical steps to a more manageable and affordable 10 to 12 steps.

The key, the researchers found, was bacteria. Chemical synthesis of heparin is challenging because it requires repositioning several chemical entities called sulfate groups. By bioengineering bacteria to produce the drug’s chemical precursor, the researchers achieved a more optimal starting structure and eliminated most of the manual chemical steps. Instead of having to carefully add and subtract the various sulfate groups, they simply mixed in the necessary enzymes and cofactors and let the bacteria-derived structure do the rest.

“The bacteria are actually smarter than the chemists in this case,” says Shaker Mousa, a professor at the Albany College of Pharmacy and Health Sciences in New York and a coauthor of the new study, which is published in this week’s Science.

The bacteria-based process, known as chemoenzymatic synthesis, produces a relatively high drug yield of about 40 percent, which is important for keeping manufacturing costs down. The resulting compound is not exactly identical to the existing synthetic heparin, called Arixtra, so the drug will still need to be tested in human clinical trials before it can reach the market. But the researchers showed that their heparin is nontoxic and works well as an anticoagulant in animals.

To make a commercial product, researchers will need to scale up the chemoenzymatic method from the milligram level of the university laboratory to the kilogram level of a pharmaceutical company. “That’s the big challenge,” says Jian Liu, a medicinal chemistry researcher at the University of North Carolina, Chapel Hill, and one of the lead authors of the study. “But theoretically this opens the door, and hopefully industry will realize the importance of this method.”

If all goes well, animal-derived heparin could be phased out within five to 10 years, says Jeremy Turnbull, a heparin expert at the University of Liverpool in the U.K., who wrote an editorial accompanying the study. “The new availability of chemoenzymatic options could be valuable for a number of disease treatments, including cancer,” he says. “It should be possible to scale the process up to kilogram level or higher, but no doubt it will take further effort.”