Cure your ills with yogurt! ORLY?
I came across an article which prompted my BS meter to go into overdrive this morning. This is via a “Business Report” in the San Francisco Chronicle entitled “Antidepressant-infused yogurt with mail-order DNA.” Let’s look for the wrong in this article!
First a summary: the article describes the claims of Tuur van Balen, a Belgian bio-engineer, who has been on the motivational speaking circuit and telling audiences that yogurt might be infused with antidepressant properties. His premise is that the bacteria that are used to make yogurt might have novel properties added to them in the laboratory, by adding new DNA sequences to their genomes. The recombinant bacteria then might produce useful chemicals while forming a delicious breakfast treat! The premise on its own is realistic, and currently there is a large number of on-the-market foods that contain genetically modified organisms among their ingredients. The example given in his presentation (available via Youtube) got my ire up.
His video presentation showed audience members how to engineer yogurt which produces antidepressants, specifically Prozac. This claim bugged me, because it didn’t seem plausible. I watched the video, and the implication from it was that a single DNA sequence of just over 800 nucleotides would be sufficient to accomplish this task, however in truth it would be far more difficult to do this for many compounds, and it turns out that it would be impossible to accomplish using Lactobacillus.
Prozac is a small molecule, which is thought to operate by inhibiting the reuptake of the neurotransmitter serotonin. Although the chemical structure of Prozac is not particularly complex, it is not something that could be synthesized biologically and involves over a dozen organic synthesis steps. Consequently, it is fallacious to claim that the introduction of a single DNA sequence (presumably encoding one enzyme) might be able to introduce a biochemical pathway that could generate this compound in vivo. Now, bacteria can and have been engineered with a number of exogenous DNA sequences that add a novel biochemical pathway. I discussed one such example on this blog, where E. coli was engineered to produce the small molecule antibiotic erythromycin. It’s a lot of work, and takes a lot of careful planning, and is not likely a DIY project.
So let’s consider then an approach that might be more fruitful, and potentially more DIY than this proposal to “have yogurt bacteria make Prozac.” Fortunately for us, alternatives exist! One way to accomplish this is through a new-ish technology called RNA interference, which was the subject of the 2006 Nobel Prize for Medicine or Physiology to Andrew Fire and Craig Mello. With this technique, synthesized pieces of RNA are introduced into an organism, where they can bind to messenger RNAs made by the cell. This can have the effect of “silencing” that RNA, resulting in loss of expression of the gene. It is a temporary measure, and as the cell continues to grow, the “silenced” gene may start to be expressed again. The technique as originally used by Fire and Mello was used to study gene expression in the roundworm Caenorhabditis elegans.
Student researchers at York College are using these animals to study the effects of losing the function of specific genes. It is actually quite simple to do; the worms eat bacteria (E. coli) which have a DNA cassette added to their genome that encodes for the gene-specific interfering RNA. The interfering RNA then enters the worm cells, and affects expression of the gene.
How could this be applied to humans? We could eat yogurt containing live cultures of recombinant, RNA interfering-expressing Lactobacillus. As indicated above, the drug Prozac acts to inhibit the internalization of the neurotransmitter serotonin at nerve synapses. This uptake process requires a membrane transporter that captures serotonin on the outside of the cell, and brings it inside the cell. Prozac presumably blocks the hole, preventing efficient uptake of serotonin. Instead, an interfering RNA might be introduced that decreases the level of the membrane transporter, accomplishing the same thing as introduced Prozac, but with only a single step!