Friday, 8 February 2019

CRSIPR

Brave new world


I recently retired from my profession as a human geneticist. Mayhap I left a little too soon as very exciting developments are about to descend unto the world of genetics as new techniques unfold and revolutionise biology and medicine as we know it. One technique in particular, with the uninspiring acronym, CRSIPR, will play a major role in this revolution. Alas, I shall not be part of this revolution and it is fitting that I take my bow and decamp stage left to leave the intellectual arena for sharper and younger minds.

Before looking at how CRSIPR will be utilised in a practical way, it will be necessary to review a little bacterial genetics and biology. I will keep this to a bare minimum and try not to introduce too many concepts unfamiliar to the none geneticist.

First off, the acronym CRSIPR refers to the bemusing and beguiling: Clustered Regularly Interspaced Short Palindromic Repeats. Effectively this describes a genetic system present in certain bacterial species and is the basis of an anti-viral defence mechanism. Bacteria fall prey to bacteria specific viruses called ’bacteriophages’. These viral particles inject their genetic material into the bacterial cell. The inserted viral DNA then directs the bacterial genome to construct intact viral particles. Eventually, the bacterial cell lyses releasing the virus to infect anew. The CRSIPR bacterial system is an evolutionary response to viral predation and is concerned with the detection of viral DNA and its destruction, thus preventing infection. In a way, it is analogous to the complex cascade of the immune system present in higher animals, but it is nowhere near as sophisticated or as diverse. The importance of the CRSIPR system for genetic engineering revolves around its ability to cut, add, remove and edit DNA at precise locations with wonderful fidelity. I don’t want to turn this post into a biology textbook. I merely wanted to provide a simple outline of the biological process. There are plenty of resources on the internet for those interested in delving deeper into the basic genetics. This precise biological tool enables geneticists to permanently modify important genes in organisms or introduce genes. In this way, harmful genetic mutations can be corrected allowing for the treatment of disease at the cellular level.  

I can’t emphasise enough the myriad of uses this technology can be applied to. Here is but a slight meander into some of its most important applications.

The technology has the ability to treat and even cure single gene disorders. For instance, cystic fibrosis is a relatively common genetic disorder affecting lung and pancreatic function. Although conventional treatments have improved life expectancy over the past 50 years, few sufferers make it past their 40th birthday. CRISPR technology can be utilised to correct the harmful mutation in lung cells, in vitro (ie in the test tube), thus resulting in a fully functioning protein. The next stage involves human trials to assess the protocol’s efficacy. in vivo.

Modern cancer treatment is a medical success story and sadly, medicine’s greatest failure. While it is true that modern treatments are able to drive certain cancers into remission, it is also true that many cancers remain intractable to treatment. In the Western world, 1 in 4 will ultimately succumb to a malignant disorder.  Chinese researchers are utilising CRISPR to combat oesophageal cancer. Immune cells are extracted from the patient (T lymphocytes) and genetically modified by the CRISPR system. A particular gene, which encodes a tumour specific receptor, is switched off and consequently, tumour cells are no longer able to bind to the receptor. Normally, binding of the tumour cell to the receptor prevents the immune system cells from rallying and attacking the tumour. The genetically modified cells are then reintroduced into the patients allowing the invigorated immune cells to attack the cancer, unfettered. 

Furthermore, and in regard to other cancer applications, the technique has the ability to turn off cancer driving genes (oncogenes) and to activate genes involved in cancer suppression thereby preventing the initiation of the malignant event or curtailing cancer progression.      

The ultimate goal is to introduce ‘working genes’ into early embryos with an existing genetic condition (subject to ethical caveat below). In this way, a cure for the condition is possible as the rectified gene will be introduced into all the cells, including the cells responsible for producing the cells of reproduction (sperm and ova). 

The above is just a few of the applications and possibilities available to this extremely powerful technology. It all sounds a bit too dandy and rosy, doesn’t it? But there is always risks and pitfalls afoot when we try to artificially modify our genetic material. Although the technique appears to be remarkably specific, targeted and accurate, there is always the possibility that none target genes may become modified (? collateral damage). If this occurs, and depending on the gene or genes involved, there could be unintended consequences. For instance, the inactivation, or deletion of a tumour suppressor gene in a cell may direct that cell down a pathway ultimately resulting in cancer. Further research is required to weigh up the relative advantages and risks of the methodology- watch this space cadet. 

Safety is not the only concern to contend with and ethical considerations doth raise their weary head, once more. There is a worry that the technology could be used for purposes not originally intended. Currently CRISPR technology is limited, by government strictures, to alteration within somatic cells and thus consequent changes can’t be passed on through the generations. But as I’ve already mentioned, germline modification is technologically feasible. In such instances, none medical changes could be introduced into sperm, eggs or early embryo to enhance ‘desirable’ characteristics such as intelligence and height. Due to concerns about ethics and safety, germline and embryo genomic modification is currently illegal in many countries. However, not all nations abide by the rules.  

By necessity, this is but a brief exposition of a highly complex topic but I’ve hoped I’ve covered the salient issues albeit superficially. Nuff said, for now.


Brave new world



6 comments:

  1. Like you, Flax, I welcome all advances in technology which have the potential to eradicate or at least alleviate some form of human suffering. It's only when I look at human history with the likes of Josef Mengele and ShirĊ Ishii, that I have a vague sense of unease regarding the moral capacity to handle such advances. It just seems that wherever there is a scientific advance, there's always some arsehole somewhere who will mis-apply it, or develop hitherto unforeseen ways to utilise it in an evil manner. There is no clear answer as research cannot be abandoned. I wish that total arseholes could be identified in utero and dealt with suitably,

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    1. I didn't have the 'space' in the post to thoroughly discuss the ethical issues. It was 1,000 words long already and I always feel that if I witter on too long I will loose my audience. Civilised folk will act civilised (most of the time) and uncivilised folk will act uncivilised (most of the time). Rogue nations such as N Korea will do as they please. There is no easy answer I'm afraid.Perhaps I could post about the ethical dilemma inherent in such technology?



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  2. Will this technique also allow modification of, e.g., Ebola?

    (There have been suggestions that the "medical research facility" which was at the centre of the Ebola outbreak which killed approx 11 thousand in Africa, had been "weaponizing" the bug")

    Giving the evil empire additional tools to aid their mass-murdering global policies would seem a bad idea.

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  3. Yes, the technology could be used to modify disease organisms to make them more virulent or targeted (ie to ethnic groups) and I have no doubt that it will be used for such. Even so called civilised nations would probably weaponise organisms if past history is to be relied upon. There is no easy answer to such problems. The technology can't be undone and is not particularly difficult to apply. A lab, a couple of PhD scientists, and a bacterial culture would get things a going. Scientists when they develop their technology rarely contemplate beyond their own small contribution and rarely consider wider societal ramifications.

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  4. https://www.zerohedge.com/news/2019-02-22/gene-edited-crispr-twins-may-have-supercharged-brains-and-silicon-valley-wants-it

    Here we go!

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    1. No real surprise I suppose. Whether the technology will be applied by nations to boost the IQ of the population or add other enhancements is unlikely in my opinion. What I think is more likely is that rich folk will pay large sums to rogue scientists to enhance their offspring. Therefore, the net effect on society will be nil. The legit use to treat disease is a more interesting application of the technology. Let us see what the 'brave new world has to offer'.

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