How is biotechnology changing medicine?

What are the limitations of treating patients with the clot-busting drug TPA, made by biotechnology? We opened this chapter with the story of Janet’s stroke, pointing out how important it is to treat stroke patients quickly. An analysis published in 2014 of many studies done in the 20 years since TPA was first clinically used showed that the probability of having no significant disability is 75 percent higher in people who get TPA within 3 hours of stoke onset compared with people who don’t get TPA. This benefit is reduced if a patient gets the drug later, and is almost nonexistent at 6 hours poststroke.

One of the problems that arose when TPA treatments were initially administered was that the drug tended to break down rapidly in the bloodstream after injection. Biotechnologists solved this problem by altering the TPA gene slightly so that the protein gets glycosylated (adding sugars), which leads to a longer lifetime in the bloodstream. As other drugs are developed by biotechnology, the TPA story is being repeated: initial success, problems with the chemistry, and then modification.

While the commercial production of drugs by DNA biotechnology has had some successes, the examples are relatively limited and certainly not as notable as those in traditional biotechnology, where bacteria and other microbes are manipulated by their environment to make large amounts of molecules, such as antibiotics. However, as we described, DNA manipulation technologies such as mircoarrays and CRISPR hold great promise to profoundly change medical diagnosis and treatment.

Future directions

A striking example of “old” biotechnology (in which a microorganism is coaxed into making a valuable product) merging with “new” biotechnology (which uses recombinant DNA) is the emerging field of cyanobacteria-produced plant secondary metabolites. Plants make these small-molecule metabolites to protect themselves against infections, injuries, and environmental factors. Many of the metabolites are strong antioxidants that react with and eliminate harmful oxidants such as oxygen atoms with unpaired electrons (superoxides) in cells under stress. Because human cells in disease states produce such oxidants that harm tissues, there is intense interest in using certain secondary metabolites that plants produce as drugs. Unfortunately, it takes a huge quantity of plants to obtain enough of a given antioxidant for clinical use.

This is where cyanobacteria come in. Cyanobacteria (sometimes incorrectly called blue-green algae) are photosynthetic single-celled organisms that grow well under light conditions in ponds or vats in the lab. Although they are not plants, cyanobacteria have genes encoding some of the enzymes involved with secondary metabolite production. Using recombinant DNA technology, genes from plants that encode other needed compounds in the pathway of certain antioxidants (specifically, phenylpropanoids) have been inserted into cyanobacteria, turning these organisms into factories that produce plant metabolites for clinical use.