By: Heather Williams

When you think about a bacterial infection, nothing pleasant comes to mind.  You might imagine sickness, illness, and all kinds of nastiness best avoided.  When you think of E. coli, most consider this a terrible bug to be avoided.  We think meat contamination, dirt, or all kinds of symptoms that leave you stuck in the bathroom for an undetermined time period.

While E. coli can be harmful, not all strains cause illness.  There are naturally occurring non-toxigenic E. coli species that live peacefully and do no harm.  Additionally, there are also genetically modified E. coli that are actually working to do some good and heal the body.  This “worker bacteria” is just the thing scientists are trying to make happen.

A study taking place by Synlogic of Cambridge, Massachusetts is using a methodology they call “synthetic biotics” as a way to use bacteria that are engineered to carry out specialized duties in the recipients’ stomach.  These gene-modified E. coli bacteria were created with genes specifically designed to clean up ammonia in the gut of people who cannot get rid of the compound.  These scientists are working to find ways to “harness the microbiome” to help the body with functions that it may be deficient in.

This particular mutant helps those suffering from disorders of the urea cycle.  For some, the liver cannot get rid of the excess nitrogen, causing a buildup of ammonia in the body.  This ammonia is just like the hazardous ammonia you may find under your sink, and just as unhealthy to build up in the body as it is to consume straight from the bottle.  While rare, those suffering from this illness end up requiring a liver transplant as a result of the damage caused.

At this time, this concept is in the safety trial period and not yet tested on sick patients.  What does that mean?  A study is currently underway involving otherwise healthy individuals that have volunteered to take the drug (genetically modified E. coli) and live in the testing facility for as long as three weeks while being monitored and providing fecal samples for DNA analysis.  At this time, 50 people are participating in the trial.  Many have already taken the new GMO (genetically modified organism) pill, while some selected at random have received a placebo as control subjects.

How Does Genetic Modification Work?

Most people think of food products when the term “genetic engineering” comes up.  In science, there are many additional applications for genetic modification beyond crops’ resistance to parasites, standardized size for ease of harvest, or even increased production of particular plants or animals to increase value and return on investment.  In research, many times genes are removed from one organism and transplanted into another to better understand it, or even to use the abilities that the gene codes for in another cell.

Let’s take a step back and talk about what all of this means.  Each cell contains DNA, or deoxyribonucleic acid.  This is the building block of the cell and the organism that it makes up.  DNA is composed of amino acids (adenine, thymine, guanine, and cytosine – affectionately known as A, T, G, and C).  These amino acids code for genes.  Think about the amino acids as letters in the alphabet and genes are the words made up of those letters.  Each gene contains the “genetic language” used to create the proteins that the organism uses to live and thrive.  The collective of all of the genes present in an organism is called the genome.

To genetically modify a cell, a segment of DNA containing the gene that the scientist wishes to incorporate into the DNA is isolated from an organism.  This segment of DNA, or gene, is spliced into the new cell.  The gene of interest is removed through a molecular process using restriction enzymes, or a kind of genetic scissors.  A piece of the DNA of the new cell is also cut with restriction enzymes to create a place for the gene to go.  The gene is then introduced to the recipient cell in the presence of DNA ligase, a kind of molecular glue, to paste the gene into the cell.  Once this process is complete, the cell contains the new DNA that can code for proteins to do a particular job.  This is just one of the methods a scientist can use to incorporate new genes into existing DNA.  Some applications use electricity to shock the new gene in place, while others use commercial chemicals to handle the process.  Whatever the vehicle, the outcome is the same.  DNA not native to the cell added to the organism creates a genetically modified organism.

 Other Companies Using the Synthetic Biotics Approach

Synlogic is not the only company to consider genetic modification of a harmless bacteria to treat an illness.  Synthetic biology is a way of manipulating an organism’s metabolism to produce beneficial and productive compounds such as perfumes, fuel, drugs, and other chemicals.  In fact, ActoGenix, another biotech company in Europe, modified the genome of the bacterium Lactococcus lactis to release a protein drug.  Marina Biotech, an American company is using genetically modified bacteria to create an anti-cancer bacterium and has made it to the small safety test part of the research process.

When Can We Expect to See This Drug on the Market?

The U.S. Food and Drug Administration (FDA) has fast-tracked Synlogic’s application to begin human trials.  The current timeline is to have trial information determining the safety of the biological drug by December and offering studies to actual patients next year.

Beyond Synlogic, I expect genetic medicine to continue to grow in the future and synthetic biotics using genetically modified bacteria as a new way to treat common ailments.  Soon treatment will be as simple as swallow a pill and letting the worker bacteria do their job.  This type of medicine allows a chemical free pharmaceutical approach and a customized treatment process specific to the needs of the individual.  Genetic medicine is fast approaching mainstream.  And it all starts with this little pill of E. coli.