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Sculpting Evolution: Engineering Biology To Address Global Disease Challenges

Date : 10/09/2020

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Akila

Uploaded by : Akila
Uploaded on : 10/09/2020
Subject : Medicine

Gene drives are a new technological advancement. They are now being used in many laboratories around the world, with one common goal: to increase resistance of mosquito-borne infectious diseases such as malaria, dengue and schistosomiasis. Dr Kevin Esvelt commenced the lecture by giving a basic overview of what gene drives were. Gene drives are designed to eliminate unwanted traits in insects and other animals. They work by pushing out genetic modifications through whole species until eventually every critter has been changed into something we have intentionally engineered. It is only very recently that advanced gene editing techniques have made human designed gene drives possible. And at the heart of this revolution is a new technique for precision engineering genes: Clustered Regularly Interspaced Short Palindromic Repeats- CRISPA for short. CRISPA uses specially designed molecules that run along the strands of DNA in an organism s genome and seek out specific sequences of genetic code. Once found they snip out the old code and paste in the new one. It is essentially a sophisticated biological search and replace technology that allows scientists to easily modify the genetic traits of an organism, such as replacing the parts of a mosquito s genome that allows it to host malaria causing parasites for instance.

However, there are some flaws to this new technology. Every time a CRISPA mosquito mates with a wild mosquito, the genetically modified genes are diluted down, meaning some of its offspring will still be able to carry the malaria parasite. This is where the genius of CRISPA-enabled gene drives come in. This implements an extra code which enables the continuation of search and replace parasite enabling DNA sequences. When a mosquito mates, the built in code would ensure that every single one of the offspring would inherit the same traits, as well as inheriting the CRISPA code that would ensure the anti-malaria gene is passed on to every future generation. In theory, this will be driven through the whole mosquito population, and eventually every mosquito would become a human designed malaria-free insect. This is not a technology that is strictly restricted to mosquitos, it can be used on any sexually reproducing organism. In laboratories, CRISPA gene drives are tested on worms, as they can be mass produced. These results are then quantified to simulate how it may affect different organisms.

Working out which genes to change is still an ongoing area of research, especially because CRISPA may modify more genes sequences than expected, or introduce unanticipated traits. Moreover, the effectiveness of this technology depends on how frequently the engineered species reproduces. For example, this technology is much more effective when being used on a rapidly reproducing species such as mosquitos, as opposed to humans.

Gene drives allow us to manipulate nature, and that raises social, legal, ethical and environmental concerns, which may hinder or slow further development, as it is after all, an advanced form of genetic engineering. For instance, we still do not know how this technology will affect ecosystems or whether it will create unexpected risks for other species (humans included). An important concern is whether these genetically engineered organisms are able to adapt to change. Whether or not natural selection tides in their favour is vital, as it affects the spread of this gene into future generations. If the species cannot adapt to change, they will be outcompeted by wild organisms of the same species, and the gene will eventually become diluted. Conversely, some agriculturalists could argue that the risks are worth the benefits as it is more economic and eco-friendly, in comparison to using pesticides and other chemicals.

Economically, there are concerns about whether this technology will be abused by entrepreneurs and tycoons, simply because they can. And legally, there are concerns that weaponised super mosquitos may be created to spread malicious diseases amongst the human population. A perhaps more worrying concern is the idea that maybe it is possible to create human gene drives, to create a desire future population. A question Dr Esvelt reiterated, was whether it is right to play around with nature? Invariably, his answer will always remain the same: it is fine as long as research is undertaken responsibly. Dr Esvelt also believes that synopses of these experiments should be given to the public, and they should be made aware about the ongoing research. He highly disfavours the idea of closed door experiments, because he believes that collectively, we can improve these technologies further, through the inputs of the public. Incrementally, he believes that through this, consequences for public opinion would be more favourable.

Professor Alphey, gave an insight into the practical application of CRISPR enabling gene drives, through his company Oxitec. His research team had travelled to the tropics to raise awareness of malaria, dengue and schistosomiasis. They had travelled to a plethora of countries where the threat of infectious disease was imminent, such as Brazil. More shockingly however, he gave statistical insight into such technology. There are on average 50-100 million dengue fever cases per annum, and this figure is increasing. This raised the question whether these technologies were really working. This coupled with the $5 billion burden of cost raises some eyebrows.

In conclusion, this lecture was fascinating and extremely insightful, being delivered by two of the most formidable scientists, working on some of the most complex yet complementary technologies the human race has ever seen. Many thanks to Dr Kevin Esvelt and Professor Luke Alphey.

This resource was uploaded by: Akila