“For there is nothing either good or bad, but thinking makes it so,” Shakespeare once wrote in his famous play, ‘Hamlet.’ The philosophical questions “What is good?” and “What is bad?” have been discussed over many centuries, and it seems like humanity will not have a clear answer for it any time soon. As much as we think we are absolutely capable of figuring out what is good and bad, and try to manipulate other people’s lives according to our made up definitions, in reality we should try to humble ourselves by remembering that what we, as humans, define as good or bad is actually a very one-dimensional perspective about the absolute truth. Although these kinds of discussions are generally brought up more often for topics related to social sciences, I want to take a peek into biology, and observe the same principles at work. The aspect of biology I want to discuss is the bacterium Escherichia coli.

The genera Escherichia is thought to have emerged around 102 million years ago and is known as a gram-negative pathogenic bacteria mostly found in the intestines of warm blooded animals [1]. German pediatrician and bacteriologist Theodor Escherich discovered E. coli in 1885, and for many years the bacterium was simply considered to be a commensal organism of the large intestine. It was not until 1935 that a strain of E. coli was shown to be the cause of an outbreak of diarrhea among infants [2]. The reason its pathogenic properties were discovered so late is that many of its strains are harmless. However, virulent strains of E. coli can cause various diseases in humans and in domestic animals, and are also sometimes responsible for product recalls due to contamination. Gastroenteritis, urinary tract infections, and neonatal meningitis are the most commonly observed diseases in humans, and in rare cases virulent strains are also responsible for haemolytic-uremic syndrome, peritonitis, mastitis, septicaemia and Gram-negative pneumonia [2]. Various outbreaks all around the world have been caused by E. coli, causing millions of deaths and sick people and billions of dollars have been spent fighting it. Even though death rates have decreased with the evolution of modern medicine and the discovery of antibiotics, the outbreaks are still a major concern for all countries, such as the recent outbreak in Germany in 2011 affecting 3,950 people and killing 53 [3].

Its reputation has not been one of great dignity, and it has ruined the reputation of many. You may recall in 1993, the fast food chain restaurant “Jack in the Box” suffered a major corporate crisis involving E. coli O157:H7 bacteria. Four children died of hemolytic uremic syndrome and 600 others were reported sick after eating undercooked patties contaminated with fecal material containing the bacteria at locations in Seattle and the Pacific Northwest, USA. The chain was faced with several lawsuits, each of which was quickly settled but left the chain nearly bankrupt and losing customers.

But don’t these creatures have any properties to be appreciated, I wonder...

Compared to eukaryotic cells, bacteria have a pretty basic mechanism of functioning. They don’t have sophisticated organelles, and they do not have a cell nucleus where their DNA is stored. Everything is floating along all together in the cell cytoplasm (which shocks me when I reflect upon how such a small and simple organism can cause such severe pain on “highly evolved modern humanity”). It has the basic metabolic tools for survival. And even though, at first sight, it is tempting to look down on its simplicity, today we know that it is this simplicity that gives us space for making many modifications and experiments on it, whereas in more complicated cells, like animal cells, the moment a modification is made, the entire system reacts to that and causes much trouble in the process.

The turning point of E.coli making a huge impact on our lives was in 1973, when Stanley Cohen and Herbert Boyer discovered the “Recombinant DNA Technology.” This technology allowed specific genes to be isolated from one organism and cloned to another organism by the help of bacterial plasmids. The first commercial product to be synthesized by this technology was human insulin, which is used for the treatment of diabetes [4]. This brought an amazing amount of recognition and appreciation for the technology, as the practical aspect of the technology was now proven to be commercially profitable. For the insulin to be produced, the DNA sequence that encodes human insulin was synthesized and transplanted into a plasmid that could be maintained in a non-pathogenic strain of E.coli [4]. Now the bacterial host cells acted as biological factories for the production of the two peptide chains of human insulin, which, after being combined, could be purified and used to treat diabetics who were allergic to the commercially available porcine (pig) insulin, or for diabetics from certain religious groups who abstain from pork products such as Muslims, Jews, some Christian groups, and many more who have similar concerns.

This was only the start of an incredible new technology which used bacteria to produce different proteins or enzymes to cure human diseases. Today more than 200 new drugs have been produced by recombinant DNA technology and have been used to treat over 300 million people for diseases such as cancer, multiple sclerosis, cystic fibrosis, and stroke, and to provide protection from other infectious diseases. Over 400 new drugs are in the process of being tested in human trials to treat such diseases as Alzheimer disease and heart disease (to name only two) [4].

Today E.coli is frequently used as a model organism for all kinds of microbiological experiments. In the lab, E. Coli. is one of the first micro-organisms that is thought of for testing a biological experiment. The reason is that E.coli cells are cheap to purchase and to sustain. They grow easily and rapidly in lab conditions and have non-pathogenic strains, so they are not dangerous for the researches doing the experiment. Whereas purchasing more complicated cells such as cancer cells or stem cells may be very costly, and moreover, may need special lab conditions to be sustained; so before more complicated cells are purchased, the experiments are usually tried out with E.coli or some other kind of model organism. More importantly, E. coli was one of the first organisms to have its genome sequenced; the complete genome of E. coli K12 was published by Science in 1997 [5]. Other areas in which modified E.coli has helped humanity are vaccine development, bioremediation (fighting pollution), and production of immobilised enzymes [6].

One specific example of the benefit of recombinant DNA technology for the environment is its use in the paper industry. Before the 1970’s, when there wasn’t much environmental awareness in the paper producing industry, poisonous chlorine compounds were conventionally used to achieve pulp brightness of a high order in the manufacture of high-quality paper products [7]. This chemical bleaching technique precipitated a tremendous environmental concern considering the magnitude of the industry. Plants treated with elemental chlorine produced significant amounts of dioxins. Dioxins are highly toxic, and their health effects on humans include reproductive, developmental, immune and hormonal problems. They are also known to be carcinogenic. Over 90% of human exposure is through food, primarily meat, dairy, fish and shellfish, as dioxins accumulate in the food chain in the fatty tissue of animals [7]. One alternative for these chemical bleaching processes is the use of the enzyme “xylanase,” which degrades the linear polysaccharide beta-1,4-xylan into xylose, thus breaking down hemicellulose, one of the major components of plant cell walls. Even though the use of xylanases in this industry has increased significantly with the discovery of Viikarri et al. (1986), the enzyme needs further improvements for it to be commercially acceptable [6]. To ensure the commercial utilization of hemicellulosic residues in the pulp and paper industries, the production of higher xylanase yields at low capital cost is required [6]. Such studies are ongoing with the purpose of partially mutating the amino acid sequence for the purpose of especially increasing the thermal stability of the enzyme and also increasing its metabolic activity. The gene mutation and gene expressions are generally done in either E.coli or yeast cells. Davoodi et al. has mutated the enzyme up to the point where the transition temperature increased 12 0C by introducing disulfate bonds in the enzyme [8]. The wonders this enzyme can do for the health of the environment is breathtaking, and is an area which should be further studied until finding the commercially viable kind that will eliminate chemicals from the paper industry during bleaching.

Even though some controversy remains on gene transferring, its tremendous positive impact on humanity cannot be denied. I personally think that it does need constraints and strict regulations, but this technique is one of the most remarkable techniques discovered in modern times, and E.coli has no doubt played a great role in the availability of this technology.

Even though condemning E.coli and stating its “evilness” seems like the most obvious path, we all ought to appreciate the variety and uniqueness of these creatures which also allow us to produce such large varieties of drugs. We ought to appreciate its simplicity, which allows it to have a chance of producing such sophistication. We ought to reflect upon the fact that something can be classified as “good” or “bad” only by the means in which we perceive it, and the reality of it may be completely opposite of what we had thought initially.

McPen is a freelance writer in natural sciences, Montana, US.

References

1. Battistuzzi FU, Feijao A, Hedges SB. 2004. "A genomic timescale of prokaryote evolution: insights into the origin of methanogenesis, phototrophy, and the colonization of land". BMC Evol. Biol.
2. Todar, K. "Pathogenic E. coli". Online Textbook of Bacteriology. University of Wisconsin–Madison Department of Bacteriology.
3. "German-grown food named likely culprit in deadly outbreak". CNN. (5 June 2010).
4. Glick, Bernard, Jack Pasternak, and Cheryl Patten. 2010. “MOLECULAR BIOTECHNOLOGY Principles and Applications of Recombinant DNA . 4th Edition.” Washington,DC: ASM Press, pp. 3-13.
5. Blattner FR, Plunkett G, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y (September 1997). "The complete genome sequence of Escherichia coli K-12". Science 277 (5331): 1453–62.
6. Cornelis P. 2000. "Expressing genes in different Escherichia coli compartments". Curr. Opin. Biotechnol. 11 (5): 450–454.
7. Beg, Q.K., M. Kapoor, L. Mahajan, and G.S. Hoondal. 2001. "Microbial xylanases and their industrial applications: a review." Springer.
8. Davoodi J., Wakarchuk W.W., Carey P.R., Surewicz W.K. 2007. “Mechanism of stabilization of Bacillus circulans xylanase upon the introduction of disulfide bonds.” Biophysical Chemistry, 125 (2-3) , pp. 453-461.