Synthetic Life Makes Synthetic Proteins

The genetic code is the metabolic instructions by which the genetic information in the DNA is translated into a protein. The fact that almost all organisms use the same code is prime evidence that all life is related in its evolutionary past. The code is considered to be "conserved" and "universal". Of course, the concept of universality may be challenged by exobiology's explorations of Mars, Europa, and Titan, but the conservative nature of the genetic code, with the exception of a few Archaebacteria, has always been a cornerstone of biological science.


But the reality of course is that the Genetic Code is like the Cobal language of computer science. The Genetic Code is old (over 3.5 billion years). Of course life on this planet is not going to update the genetic code anytime soon - it is thriving using the old code, but evolution is a weird thing, if something better comes along, and a mechanism to adapt to that change exists, the out with the old and in with the new. Until recently it appeared to be metabolically impossible to "update" the code. But one species, Homo sapiens, may have discovered a way to fast-track the process.

The basic tenants of the genetic code is that the information coming from the DNA, in the form of messenger RNA, is "read" by a ribosome three units (also called a codon) at a time. Each codon codes for an amino acid, the building blocks of a protein. Proteins are the workhorses of the cell - everything depends on them. In other words, genes code for proteins. While we have had the ability to change genes for some time, using recombinant DNA technology and genetic engineering, until recently we were always confined to the use of the same old programming language.

Earlier this year, independent teams of researchers at Harvard University and the University of Cambridge have found ways to alter not only the genetic code, but also the cellular machinery responsible for deciphering the code - the ribosome. (see Synthetic biology: Rewriting the code for life by Linda Geddes, 2008). This process is called synthetic biology, and due to the efforts of biotech giants such as Craig Venter, this is no longer science fiction. We now have at our fingertips the technology to create new forms of life that are designed for specific missions and environments.

These advances open up unbelievable possibilities, and the potential for unimaginable nightmares. It may soon be possible to manufacture proteins that were not possible from a biochemical perspective just a few years ago. This could create new drugs that could finally eradicate some of our specie's biggest problems, such as cancer and HIV. It could also allow us to develop plants that tolerate salt water, or grow on toxic waste. A new programming language means endless possibilities. It also could spell our demise as a species. After all, the evolutionary history of life on this planet tells us that if something better comes along, the old is replaced... even if it is us. Let us not be so egocentric to think that we are special from an evolutionary perspective. Unless of course, you believe that our purpose on Earth is to generate our own successors.

My Friend, E. coli

While as a geneticist my vote would go to Drosophila melanogaster as the greatest organism of all time, I do recognize that Escherichia coli is probably one of the most beloved organisms of the biomedical research community. This versatile little microbe can be found in teaching and research labs from high schools to research institutions and large biomedical facilities. We probably know more about E. coli than almost any other organism on the planet, including ourselves. Many of the advances in medicine and drug development would probably not be possible if it were not for this wonderfully versatile little bacteria. But, as we are all aware, E. coli has a dark side.

The March 24 issue of New Scientist features an article ("Mystery Food Poisoning Traced to Salads") which presents statistics on the increase in the rate of food poisoning associated with salad greens. While the article does not specifically mention E. coli, if you asked the common person on the street what was causing the food poisoning in spinach and lettuce, most would guess this bacterium. In fact, E. coli is probably the only microbe, or any other organism for that matter, that most people know by its scientific name! Unfortunately, that recognition is not a good one. From baby diapers and water parks in the 1990s to ground beef and salad greens in this decade, E. coli has earned a reputation as a menace.

I have found that most students are surprised to find out that their intestines contain more bacterial cells than there are human cells in their bodies. Most are disgusted by the thought, and some actually pale when I mention that one of the leading organisms is E. coli. I have even had a few ask if they can get antibiotics from the campus health clinic to rid them of these "parasites."

After a brief discussion of why these little creatures are present in our system, and the benefits that they provide us by protecting us from harmful bacteria, synthesizing necessary vitamins, and stabilizing our blood glucose levels, most of the students develop a real appreciation for E. coli. From that point we can proceed to discussions on how important it is to keep your intestinal bacteria content by reducing unnecessary use of antibiotics and consuming plenty of fiber. It is then relatively easy to understand why probiotics, such as yogurt and Acidophilus pills, work as supplements. With a little public relations work, E. coli is transformed from the villain to a misunderstood hero.

Why is any of this important? In the March 1 edition of Science News, science writer Janet Raloff ("Nurturing Our Microbes") presents an intriguing possibility that someday it may be possible to reprogram our natural flora of microbes to combat disease. She first discusses how probiotic supplements may be used to increase the efficiency of intestinal bacteria in enhancing our immune system, by increasing the absorption of nutrients such as calcium and by regulating weight. Raloff then presents comments by Jeremy Nicholson of the Imperial College in London, who said that future drug therapies might one day be directed at the bacterial inhabitants of the intestinal system.

As a researcher, I think that is an important advance for medicine. We all know of the problems that have plagued large-scale implementation of gene therapy. Given the number of bacteria in the lumen of the gut, it should be possible to achieve a higher rate of transformation than is experienced in in vivo eukaryotic cells. Furthermore, by having the bacteria produce the drug of interest, it may be easier to get the drug directly into the bloodstream than traditional oral routes that need to navigate the hostile environment of the stomach.

And since this is an election year, and at least some of the focus appears to be on health care, the use of genetically modified E. coli may reduce the cost of certain medicines, since once transformed the individual would have a constant, renewable source of the drug.

However, before we proceed with the development of drug-producing recombinant bacteria, I would like to make a suggestion. If the drug companies state that they are ready to produce a genetically altered bacterium, especially one named E. coli, the general public is going to have a revolt.

Movies such as I Am Legend have not presented a pretty picture of genetically engineered organisms. Recent public responses to cloned meat, and once again to certain forms of immunizations, reveal that the general public is not convinced that we know what we are doing.

So my suggestion is this — start a public relations campaign on behalf of E. coli. Get E. coli, or its agent, on The Daily Show and Good Morning America. Start thinking about how to spin the benefits of E. coli to an increasingly research-phobic public. Work the media, begin ad campaigns, and most importantly, get the message out to the science teachers to incorporate it into their curriculum. For if we don't, this promising medical advance may be a tremendous waste of money.

Note: this article first appeared in the April 10, 2008 issue of BioWorld Perspectives, and is reproduced here by permission of AHC Media, LLC