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The many ways leading to molecular errors in a cell. Cells won’t be able to survive, have they not managed ways to repair these errors. However, CRISPR manipulation can lead to types of errors that are unknown to evolution and cells may not be equipped to fix them. Image credit: Komor Lab, University of California San Diego

Peter Diamandis in the nice to read “20 technology and exponential Megatrends” published in Abundance 360° as well as the MIT Emerging technologies 2023 include the evolution of CRISPR as a game changing technology for this and the coming decades.

Peter makes a more general claim on CRISPR in its growing capacity to target several areas, from healthcare to agriculture, whilst the MIT is focussing on the possibility offered by CRISPR to target widespread conditions affecting human health. like excessive cholesterol.  Both are deriving their forecast from the ongoing evolution of CRISPR in terms of precision.

To understand this we need to backtrack.

Our bodies, and our health, is a sort of average that manages to carry  on (pretty well usually) in spite of local issues. It is estimated that within each of our cells at any time there may be some 10,000 to 1,000.000 “errors” in terms of wrong molecules meaning a molecule that should consist of certain atoms happens to have some of these out of place, missing, extra ones. Now, if that seems a big mess you should consider that the number of atoms (estimated) in a cell is in the order of 1,000,000,000,000 (1 trillion atoms) clustered in some 42 million proteins, hence, even in the worst case situation only 1 atom out of one million is misplaced!

However, if there were no mechanism to keep these “errors” in check and possibly fix them the situation will very quickly go sour. Evolution has taken care of this and cells are really good in detecting what is wrong and fixing it (we wouldn’t be here if that were not the case).

The figure represents the many reasons that can lead to “errors” in a cell and the ways the cell manages to fix those errors (notice that in  some cases a cell may not be able to fix the error and a pathology may rise, including cancer).

The problem in using CRISPR is that the kind of errors that might be induced in the process of cutting and pasting strands of DNA are of a new sort, something that evolution has not faced before and that have not led to some fixing strategy.

This  is what has so far raised many concerns in the application of CRISPR to humans (and to some extent to any other forms of life because of potentially unexpected result).

A more precise version of CRISPR, CRISPR 2.0, is now available and it has been applied in a variety of fields. Yet, it is not a silver bullet. However, progress is fast and a new version, CRISPR 3.0 is becoming available. It is able to change a single base in a gene and there are several pathologies that are linked to a single base change. This highly decreases the chances of unintended variations and errors. The progress is also fuelled by the application of artificial intelligence in understanding the genome sequences and analysing possible undesired outcomes of genomic variations.

A big issue, not technical but economical, remains. The procedure is very costly, easily reaching a 1 million $ for a cycle of “cure”. This is not that different (actually it lower) than the cost of a “classic” medicine. The problem is that the CRISPR “pill” is manufactured for that specific person and only that one, hence the cost is not divided by the many million of people that can use the cure.

Having a CRISPR based drug addressing a common pathology. like excess cholesterol, makes that “pill” usable by million of people thus dramatically decreasing its price). This becomes possible for those situations where there is a broad commonality, this unfortunately is not the case for many genetic or acquired genetic diseases that requires a specific “bullet”.

The future of personalised medicine, a clear trend in healthcare, will need to overcome these challenges to reap the full benefit from genetic manipulation.

About Roberto Saracco

Roberto Saracco fell in love with technology and its implications long time ago. His background is in math and computer science. Until April 2017 he led the EIT Digital Italian Node and then was head of the Industrial Doctoral School of EIT Digital up to September 2018. Previously, up to December 2011 he was the Director of the Telecom Italia Future Centre in Venice, looking at the interplay of technology evolution, economics and society. At the turn of the century he led a World Bank-Infodev project to stimulate entrepreneurship in Latin America. He is a senior member of IEEE where he leads the New Initiative Committee and co-chairs the Digital Reality Initiative. He is a member of the IEEE in 2050 Ad Hoc Committee. He teaches a Master course on Technology Forecasting and Market impact at the University of Trento. He has published over 100 papers in journals and magazines and 14 books.