Move Over Poppies, Genetically Engineered Yeast Can Now Make Painkillers Too

Back in 2007, the New York Times shared the story of Zainabu Sesay, a woman dying of breast cancer. She suffered in terrible pain until the day she died because she had no access to the painkillers that we here in the West take for granted. And she is not alone.

As of 2012, an astonishing 5.5 billion people had limited or no access to the painkillers that can deal with the sort of pain that Zainabu endured. And that's one reason why a recent report out in the prestigious journal Science is so important.

In this report, published earlier this month, a group of Stanford researchers led by Dr. Christina Smolke engineered yeast to make small amounts of an opiate called hydrocodone from sugar. This may ultimately provide an alternative to poppies for developing painkillers, such as morphine.

While this yeast makes too little of the opiate to be useful right now, it shouldn’t take too long to coax it into making more.

When asked how long it would take to get the yeast to make the 100,000 times more hydrocodone it needs to be competitive with the current crop of poppies, Dr. Smolke said the process "will be ready for scale up and competitive with poppies in about 2 years." But the product won't be ready to enter the market for some time after that.

In other words, we are potentially just a few years away from being able to get opiates from giant vats, instead of from the fields of Afghanistan and Tasmania. And if researchers can get yeast to make it even more cheaply than current procedures, then these medicines may become more accessible to sufferers worldwide.

This isn’t the only benefit to making opiates in yeast. Because we can manipulate the genetics of yeast so easily, scientists may be able to more quickly discover new opiates with different and hopefully better properties. Perhaps we will be able to discover less addictive opiates in a shorter time now that we make them in yeast.

If scientists can develop a less addictive opiate, this would have a huge global impact. One of the major hurdles in getting people in many countries access to painkillers like morphine is the widespread fear of addiction.

But this isn't a perfect solution. Yeast cranking out opiates conjures up an image of Walter White from Breaking Bad growing this strain for some drug cartel somewhere. The only difference would be that the expertise needed in this case would be biology rather than chemistry.

The Stanford researchers have done everything in their power to make it difficult for someone to get ahold of this yeast strain. They have also started a dialogue on how best to deal with the pitfalls of this kind of “synthetic biology.”

It is a good idea to have these discussions but they shouldn't mask the real good synthetic biology can do. In the very near future we will be using it to discover, improve, and/or make lots of different medicines to treat a wide variety of illnesses. The benefits are almost certainly worth the risks.

Genetic Tour de Force

Synthetic biology is essentially the process of engineering living things to perform tasks they can’t do naturally. An early primitive example is making human insulin in bacteria. These engineered bacteria have been around for decades and have been a boon for people suffering from diabetes.

These bacteria were tricky to engineer in the 1970’s, but would be pretty straightforward nowadays. In fact, the hope is that eventually engineering-living things will be as easy to as creating electrical circuits.

Basically in this "plug and play" world, scientists would be able to order sets of standardized biological parts and connect them together to create intricate biological pathways. They'd simply have to grab a circuit they needed off the shelf and plug it into their organism rather than having to make the circuit from scratch.

There are even groups already creating standardized parts that can be combined to create complicated biological pathways. But making opiates in yeast is just too complicated for this “plug and play” model of genetic engineering.

When asked about applying these methods to problems of this magnitude, Dr. Smolke said that it would be some time before "things at this scale and complexity are plug and play."

"For pathways of this complexity there are many unknowns that are encountered," she added.

In other words, there is just too much going on in a cell and everything is too interconnected to be able to plug and play the 23 genes from rat, various poppies, bacteria and yeast needed to make the opiate hydrocodone in yeast. And it could be quite a while before making something this complicated becomes a trivial task.

For example, a key step in the process required the yeast to tweak a molecule called (S)-reticuline. Poppies can do this but scientists didn’t know how they did it. The gene hadn’t been discovered yet that performed this task.

So to make this complicated circuit, these researchers had to actually discover and synthesize this new gene. There is no way to get a standardized part from something that hasn’t even been discovered yet! And this is just one example.

It took the researchers ten years to get this far. So for now, synthetic biology at this scale is more 'artisan creation' than 'assembly-line.'

But scientists keep getting better and better at engineering new traits into living things. And now that researchers have a toehold with a yeast strain that can make at least some hydrocodone, they can work on increasing production -- this is likely an easier task.

My hope is that yeast-made opiates will soon be in a hospital near you, and eventually throughout the world.