Bacterial heroes and viral villains – snipping the way to the future

spider man By: Emily Brown, PhD

The most recent Spider-Man film grossed nearly $800 million worldwide, and cinemas are set to unleash a new and improved Spider-Man 2 this May. Whilst the great charm and beauty of actors Tobey Maguire and Kirsten Dunst most likely helped fuel the initial success of the film series, our fascination with the part-man-part-beast concept has spanned far beyond the glitter of Hollywood. Peter Parker’s DNA may have flashed before our eyes as his body assimilated superhuman powers, but the idea of genetic modification existed in both the fantasy and real worlds long before the advent of such impressive computer generated images. Wikipedia, arguably the source of all valuable knowledge, lists 85 characters, comics or films that involve some form of genetic engineering. Ranging from the less suspecting (Tracy Strauss, Madelyn Pryor, Julian Bashir) to the more ridiculous (Shaggy Man, Venus Bluegenes, The DNAgents), these characters share in common a possession of extraordinary powers, and sometimes the adoption of highly colourful and figure-hugging body suits.

But how exactly is the acquisition of such power explained by the respective literary proponents? Peter Parker’s body-wide changes are initiated by radioactive mutagenic enzymes present in the venom of the lethally irradiated spider un(fortunate) enough to bite him. Not long after this bite does Parker start to display spider-like characteristics -superhuman strength (the jumping spider can for example hold 170 times its own body weight), reflexes, balance, a subconscious sense of danger (the so-called ‘spider-sense’) and the ability to cling to any surface. No doubt all highly desirable traits. But as unlikely as this might sound, the suggestion that enzymes can alter DNA is not such a wild idea. Genetic modification, the direct manipulation of an organism’s DNA, requires the DNA to first be cut so that it can then be joined or spliced together with DNA from another source. A restriction enzyme is an enzyme that cuts DNA at or near specific recognition nucleotide sequences, known as restriction sites. These ‘molecular scissors’ are routinely used for DNA modification in laboratories and are a vital tool in molecular cloning.

Over 3000 restriction enzymes have been studied in detail, and more than 600 are available commercially. Whilst the idea of an irradiated spider might seem far-fetched, restriction enzymes are naturally found in bacteria and archaea (a group of single-celled microorganisms). Here they provide a defence mechanism against invading viruses; the foreign viral DNA is cut up by the restriction enzymes, while the host DNA is protected by an enzyme that modifies the DNA and blocks cleavage. The term restriction enzyme originates in fact from the studies of phage l (a virus that infects the bacteria Escherichia coli, better known as E. coli). In the early 1950s, in the laboratories of Italian scientists Salvador Luria and Giuseppe Bertani, it was discovered that a phage could grow well in one strain of bacteria, yet fare significantly worse in another. In the latter case, the bacterial host cell was evidently capable of reducing the biological activity of the virus (in a process known as restriction), although the exact mechanism remained unclear. This mystery was solved in the 1960s, this time in the laboratories of Werner Arber and Matthew Meselson, where it was shown that the restriction is caused by enzymatic cleavage of the phage DNA. Unsurprisingly, the enzyme involved was termed a restriction enzyme.

The restriction enzymes studied by Arber and Meselson were type I restriction enzymes that recognise a restriction site, but cleave the DNA at a non-specific point located some distance away. Another decade later, in 1970, Hamilton O. Smith, Thomas Kelly and Kent Welcox isolated and characterised the first type II restriction enzyme, HindII, found in the bacteria Haemophilus influenzae. This type of restriction enzyme differs in that it cleaves DNA at the restriction site, and in doing so serves to be much more useful in the laboratory. Cohesive end cutter type II restriction enzymes cut the two DNA strands (most DNA molecules are double-stranded helices) at different points within the restriction site. The result is a staggered cut that generates a short single-stranded sequence or overhang, known as the sticky or cohesive end. These overhangs become very useful in genetic engineering, since the unpaired nucleotides that make up the sticky end can pair with other overhangs made using the same restriction enzyme. If DNA from two different sources are cut with the same enzyme, it is highly probable that the two DNA fragments will splice together because of the complementary overhang. The product is a recombinant DNA molecule, composed of DNA from two different origins, created by DNA technology.

Since the first discovery of restriction in the 1950s, the use of recombinant DNA technology has become commonplace, as new products from genetically altered plants, animals and microbes have become available. In 1997, Dolly the sheep dominated the headlines as the world’s first animal to be cloned from an adult cell. Whilst her early death may have left some scientist ‘wooly’ on the cloning issue (thanks to Jim Giles and Jonathan Knight for this clever pun), the technology has since gone on to bring advances to various areas of life, from treatments for cancer to transgenic insect-resistant crops. As far as is known however, we are yet to see the technology confer super-human strength and power. Thankfully we are not currently at risk of encountering deadly villains and their counterpart heroes on a daily basis, sporting their ridiculous costumes and egos. Instead, we are surrounded by the unseen heroes, the special enzyme molecules that battle to fight invading viral villains, and the scientific geniuses that brought them to light. Mr Muscle may argue that bacteria are best destroyed, but we should also thank these microorganisms for opening a whole new realm of our world, whatever that world may hold.

Emily Brown, PhD

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