August 11, 2012
Bioshock

So this is my ‘break’ from the heart-stopping terror that is Dead Space (it’s a tense game OK?)

Bioshock.

A game I never did complete when I initially got it some time back, but still one of my all time favourites. Such a deep, thought-provoking, scary and philosophical game - a real triumph of interactive story telling. It’s set in such an immersive (no pun intended) world - an amoral, decadent, dystopian art-deco style city under the sea, called Rapture. A place where science and medicine are not bound by ethics.

A place where advancements in genetics enable people to modify themselves by purchasing and injecting themselves with ‘plasmids’. A free economy, full of ruthless businesses all plugging their genetic modifications. In the game, the vision for Rapture was innovated by one Andrew Ryan, who has a big-brother/God like presence.

When your character first discovers Rapture by swimming towards a tower after his plane crashes in the Atlantic Ocean, he enters a bathysphere. on this bathysphere is a television set which rolls your first experience of Andrew Ryan, in a quaint 50’s style video reel. In one of the most memorable and compelling starts a video game I have come across, Andrew Ryan says:

 "I am Andrew Ryan, and I’m here to ask you a question. Is a man not entitled to the sweat of his brow? ‘No!’ says the man in Washington, ‘It belongs to the poor.’ ‘No!’ says the man in the Vatican, ‘It belongs to God.’ ‘No!’ says the man in Moscow, ‘It belongs to everyone.’ I rejected those answers; instead, I chose something different. I chose the impossible. I chose… Rapture, a city where the artist would not fear the censor, where the scientist would not be bound by petty morality, Where the great would not be constrained by the small! And with the sweat of your brow, Rapture can become your city as well."

I guess it’s a take on the American dream, and the fundamentals of capitalism. But what intrigues me so about the concept of the game is how it ties this basic system to science and medicine. The doctors are also scientists, experimenting with their patients. Advancements in medical sciences, not just to cure disease, but to apparently improve aesthetics. Genetic technology is for sale to improve people at their mere whim. It’s only a matter of who can afford what.

But moving away somewhat from the fictitious world of Rapture, and into the factitious world of modern times, this does bring us to the shady world of human genetic modification.

 I think the idea of medical genetic modification is exciting, and to some extent it’s a reality that isn’t too far off. siRNA’s are short interfering RNA molecules which interfere with protein production by inhibiting the function of messenger RNA (mRNA) molecules - the functional transcripts of DNA which actually turn the message encoded in DNA into something biologically functional (a protein). These can potentially be used to control viruses, cancers and other disease states. But, this isn’t so much genetic modification as it is genetic interference. (I wrote a post on siRNA’s waaaay backGenetic Interference).

The citizens of Rapture genetically modify themselves with plasmids - but what actually are plasmids? In science, plasmids are circular, non-essential loops of DNA which contain extra genes which can enhance  an organisms’ survival repertoire. These are very prominent in single celled organisms such as yeast and bacteria, where certain plasmids may respond to certain environmental conditions and activate, enhancing the chance of survival during times of environmental stress. For example, some bacterial plasmids contain antibiotic resistance genes. Of course, in reality, injecting oneself with plasmids would probably do little more than make you ill.

In research, organisms which have had genes added (knock-in) or genes removed (knock-outs) are known as transgenic organisms. Adding and removing genes to and from laboratory animals is an important research method, as it allows scientists to understand the molecular mechanisms behind diseases. Drugs treat disease by acting at the molecular level. As a result, it is vital to understand the chemical, molecular and genetic basis of disease.

Transgenesis in mammals is most often done in mice. Up until recently, it was difficult to implement transgenic methods on rats and higher mammals due to instability of embryonic stem cell recipients of transgenes (the foreign gene to be inserted). Generating transgenic animals for the laboratory is a long and difficult process. With rapidly breeding species such as mice, the process takes around a year.  I also highly doubt the current laboratory method would be implemented in humans. Why? Well, decide for yourself:

How to generate a transgenic mouse

  1. Obtain a gene vector. This is a plasmid bearing the gene of interest that you wish to add to your organism. We shall name this gene the ‘transgene’.
  2. Insert and integrate the plasmid into a culture of mouse embryonic stem cells.
  3. Isolate the blastocyst (basic ball of stem cells initially formed following fertilisation of egg. These will become a new baby mouse) from a pregnant female, and inject your modified embryonic stem cells into the blastocyst.
  4. Obtain a pseudopregnant female mouse by mating her with a sterile male.  Pseudopregnant - because she needs to be ready to support the development of offspring, but not actually bearing any young.  Insert the blastocyst into the pseudopregnant female mouse. As she is ready to support developing young, she will accept the blastocyst and propagate its development.
  5. From mixing the modified stem cells with the normal blastocyst, and allowing them to develop in a female, there are now cells from two organisms with two distinct genomes developing into a single organism. You have created a chimera. A chimera is a single organism made up of two or more populations of genetically different cells. 
  6. Once the chimeras have developed, been born and matured, breed them so they produce young which are homozygous for the desired transgene. What do we mean by ‘homozygous’? Remember, mice and humans have two sets of chromosomes in every single cell except in sperm and eggs which only have one set of chromosomes. An organism homozygous for the transgene would have both sets of chromosomes carrying the transgene.  As a result, it would be completely transgenic (i.e. genetically modified, fully expressing the new gene). An organism with one set of chromosomes carrying the transgene and one set of normal chromosomes would be heterozygous. To achieve this homozygosity, you must breed the various chimeras with each other. Mating a male chimera with a female chimera should produce fully transgenic offspring, if transgene-bearing sperm fertilise a transgene-bearing egg. The offspring will thus have the full two sets of chromosomes, each bearing the transgene.
  7. The homozygous (i.e. the transgenic) offspring contain all of the genes from the transgenic cells of the chimeric parent. This can be confirmed with DNA screening.
  8. You have created a transgenic organism.

Humans aren’t ready for genetic modification not only due to technological limitations of not having a technique which doesn’t involve a massive, complicated breeding programme, but also because our species just isn’t ready to accept it yet. There is some enlightenment to go, and there are ethical questions which must be brought to light.

How far would it be acceptable for humans to genetically modify themselves? My initial response is, it depends on societal norms at the time the technology is available. There was a time when questioning your gender was unthinkable, now sex changes are relatively more accepted, with people of atypical sexuality coming out and being respected. Perhaps in an era where people are more informed of the implications (both good and bad) of genetic technologies. But of course, there is still much to consider. Who is eligible for modification? What does this mean for the practice of medicine? I think the controversial, but valid, question should be; should there be a limit to what can be painted on the potential canvas that is our genome, and if there should be one - where is this limit? 

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