Since the 1960’s, the drug noscapine has been used in many parts of the world as a non-narcotic cough-suppressant. Recently, biomedical researchers have learned that that noscapine (and chemically-modified derivatives of this drug) has potential as a cancer drug. And that is nothing to sneeze at.
The use of the drug for nearly a half century as a cough suppressant means the safety of noscapine has already been established. In fact, pre-clinical studies indicate that noscapine has fewer side effects than many anti-cancer drugs.
Unfortunately, the source of noscapine is opium poppies. Even though tens of tons of noscapine is isolated each year from thousands of tons of raw plant material, biochemical engineers question if the agricultural supply line can meet the extra demand if noscapine finds use as an anti-cancer agent. Estimates indicate that the amounts of noscapine needed for cancer treatments would be about ten times the amount currently produced for its use as a cough suppressant. Complicating matters are the extensive regulations and bureaucratic red tape associated with growing poppy plants and extracting chemical materials from them.
It takes about 1 year to grow mature poppy plants. And once grown, the process of isolating pure noscapine is time intensive and expensive. This drug has to be separated from narcotics and other chemicals found in the opium extract, and then purified. Because poppy plants are an agricultural product, considerable batch-to-batch variation occurs for noscapine supplies.
Chemists have developed synthetic routes to make noscapine. But, these chemical routes are too complex and costly to scale up for large scale production of this drug.
But, researchers from Stanford University believe that they have come up with a solution to the noscapine supply problem. They have genetically engineered brewer’s yeast to produce large quantities of noscapine.1 This work demonstrates the power of synthetic biology to solve some of the world’s most pressing problems. But, the importance of this work extends beyond science and technology. This work has significant theological implications, as well. This work provides empirical proof that intelligent agency is necessary for the large-scale transformation of life forms.
Genetically Engineered Yeast
To modify brewer’s yeast to produce noscapine, the Stanford University research team had to: 1) first, construct a biosynthetic pathway that would convert simple carbon- and nitrogen-containing compounds into noscapine, and then, 2) add genes to the yeast’s genome that would produce the enzymes needed to carry out this transformation. Specifically, they added 25 genes from plants, bacteria, and mammals to this microbe’s genome. On top of the gene additions, they also had to modify 6 of genes in the yeast’s genome.
Biosynthetic pathways that yield complex molecules such as noscapine can be rather elaborate. Enzymes form these pathways. These protein machines bind molecules and convert them into new materials by facilitating chemical reactions. In biosynthetic pathways the starting molecule is modified by the first enzyme in the pathway and after its transformation is shuttled to the second enzyme in the pathway. This process continues until the original molecule is converted step-by-step into the final product.
Designing a biosynthetic route from scratch would be nearly impossible. Fortunately, the team from Stanford took advantage of previous work done by other life scientists who have characterized the metabolic reactions that produce noscapine in opium poppies. These pioneering researchers have identified a cluster of 10 genes that encode enzymes that work collaboratively to convert the compound scoulerine to noscapine.
The Stanford University researchers used these 10 poppy genes as the basis for the noscapine biosynthetic route they designed. They expanded this biosynthetic pathway by using genes that encode for the enzymes that convert glucose into reticuline. This compound is converted into scoulerine by the berberine bridge enzyme. They discovered that the conversion of glucose to reticuline is tricky, because one of the intermediary compounds in the pathway is dopamine. Life scientists don’t have a good understanding how this compound is made in poppies, so they used the genes that encode the enzymes to make dopamine from rats.
They discovered that when they added all of these genes into the yeast, these modified microbes produced noscapine, but at very low levels. At this point, the research team carried out a series of steps to optimize noscapine production, which included:
Genetically altering some of the enzymes in the noscapine biosynthetic pathway to improve their efficiency
Manipulating other metabolic pathways (by altering the expression of the genes that encode enzymes in these metabolic routes) to divert the maximum amounts of metabolic intermediates into the newly constructed noscapine pathway
Varying the media used to grow the yeast
These steps led to an 18,000-fold improvement in noscapine production.
With accomplishment, the scientific community is one step closer to have a commercially-viable source of noscapine.
Synthetic Biology and the Case for a Creator
Without question, the engineering of brewer’s yeast to produce noscapine is science at its very best. The level of ingenuity displayed by the research team from Stanford University is something to behold. And, it is for this reason, I maintain that this accomplishment (along with other work in synthetic biology) provides empirical evidence that a Creator must play a role in the origin, history, and design of life.
In short, these researchers demonstrated that intelligent agency is required to originate new metabolic capabilities in an organism. This work also illustrates the level of ingenuity required to optimize a metabolic pathway once it is in place.
Relying on hundreds of years of scientific knowledge, these researchers rationally designed the novel noscapine metabolic pathway. Then, they developed an elaborate experimental strategy to introduce this pathway in yeast. And then, it took highly educated and skilled molecular biologists to go in the lab to carry out the experimental strategy, under highly controlled conditions, using equipment that itself was designed. And, afterwards, the researchers employed rational design strategies to optimize the noscapine production.
Given the amount of insight, ingenuity, and skill it took to engineer and optimize the metabolic pathway for noscapine in yeast, is it reasonable to think that unguided, undirected, historically contingent evolutionary processes produced life’s metabolic processes?
Yanran Li et al., “Complete Biosynthesis of Noscapine and Halogenated Alkaloids in Yeast,” Proceedings of the National Academy of Sciences, USA(2018), doi: 10.1073/pnas.1721469115.
During my freshman year of college, I took two classes in economics: microeconomics and macroeconomics. (I aced both courses, by the way.) Those courses...
