This article is part of the series — Tech in the New Decade.
Genes are the blueprint of life. Today, with many effects of genetic mutations — as well as tools to introduce or correct such mutations — being known, we are at the cusp of a new age of gene editing therapies for humans. This has not been without controversy. He Jiankui, the Chinese researcher who was the first in the world to conduct a medical experiment leading to CRISPR-babies, was sent to prison for unethical and illegal medical practices. His defence was that these experiments could confer resistance to HIV-infection in these unborn babies with HIV-positive parents, by mimicking a natural mutation in the CCR5 gene that prevents entry of the HIV virus into cells. This sparked outrage partly because it was poorly done, partly because it was unnecessary, but would we think differently if he were instead trying to correct an incurable genetic disease?
Would it not be better to have a one-time gene-editing solution that introduces protective mutations into susceptible people?
Since gene-editing of unborn babies has the potential to go to their reproductive cells (germline editing) and thus transmit to future generations, it is most controversial. Editing cells that will not carry through to subsequent generations (somatic editing) is less so and is a likely component of future therapies. However, would it not be better to have a one-time gene-editing solution that introduces protective mutations into susceptible people? To illustrate, we know that natural nonsense mutations in the PCSK9 gene protect against high cholesterol. Subsequent work has led to PCSK9 inhibitors that reduce cholesterol and cardiac deaths if taken regularly. In monkeys, introduction of such mutations into the liver succeeded lowering LDL cholesterol by 60%. While there were some off-target effects and inflammation caused by viruses used to deliver the gene therapy, these are expected to be fixable by additional research. The real question now is not whether such therapeutic gene editing is possible, but rather — do we want it and are we ready for it?
The field of genetic editing has three levels of risk. First, to the individual; second, to society; last, to humanity. The risk to the individual is primarily due to unforeseen consequences of tinkering with a system evolved over millions of years. This consideration is least when we are correcting a known disease-causing mutation, and most when we seek supra-physiological or cosmetic enhancement. The risk to society, interestingly, will become greatest when the risk to individual becomes least. If gene editing becomes a safe and final solution, society risks becoming progressively more unequal — not just in opportunity but in capacity — in a self-reinforcing fashion, creating new social orders and caste systems. The risk to humanity is an extension of the risk to society: once we become confident enough in the technology to move from somatic editing to germline editing. While removing ‘bad’ genes from the gene-pool may sound sensible, it is not. Loss of genetic diversity would leave us genetically fragile — susceptible to new threats that may wipe out a homogenous humanity. These technical, moral, ethical and foresight issues will need to be resolved before gene-editing become widely accepted.
The field of genetic editing has three levels of risk. First, to the individual; second, to society; last, to humanity.
In view of extreme positions on human gene-editing by constituent members and a clear dual-use research concern, the World Health Organisation has been working on a governance framework based on responsible stewardship and equitable access. However, previous experience with stem cell therapy suggests that there would be much heterogeneity in ability, acceptability, and incentives across the globe. Sovereign nations may choose to overlook such frameworks, so as to pursue leadership of this frontier area, with consequent political and economic benefits. There is a clear risk that such competition may take place outside the purview of rigorous clinical trials meeting global ethical standards, be hidden from the public eye, and fail to reveal harms in a timely manner. Nevertheless, it is hard to imagine a future where editing of genomes, in some form or the other, does not become widespread. The exact path is difficult to predict and the emergence of a consensus will take time. Until then, while science takes its course, we must prepare by engaging people in thinking deeply about the key issues above, in order to equip institutions and society to make better choices at every fork of the road.
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