CRISPR ‘it has incredible potential to improve our world
The 15 kilometer cross-country ski race at the 1964 Winter Olympics should have been a close race. But in fact Finland’s Eero Mäntyranta streaked over the line fully 40 seconds ahead of his closest competitor.
His secret? He was born with a mutation of the EPOR gene, which regulates the production of the erythropoietin protein. In turn this determines the production of red blood cells, which are crucial for physical endurance.
Disgraced cyclist Lance Armstrong achieved the same outcome by taking erythropoietin as a drug. But in future – if indeed it has not already started – athletes may go straight to the root of the matter and mutate their own EPOR gene, to give themselves the same advantage that Mäntyranta was born with. How could this possibly be detected?
That athletes will turn to gene editing is, in my view, a certainty. We have the tools to manipulate genes and we know at least some of the genes that code for the sort of physical attributes that athletes crave. Here is a picture of the Belgian bull.
This ‘double muscled’ specimen has a natural mutation of the gene that codes for the protein myostatin and the result is uninhibited muscle growth. For farmers that means lots of lean meat. But for weight lifters it could be a short cut to an Olympic medal.
A crack in creation
This is just one of the ethical dilemmas unleashed by our newfound ability to edit the genome. As I described last week Jennifer Doudna of UC Berkeley is credited with the discovery of CRISPR, the technique that has made gene editing considerably faster, cheaper, more accurate and accessible, and today I want to tell you a little more about her new book ‘A Crack in Creation.’
Much of it covers the voyage of the discovery of CRISPR – the hypotheses, the laboratory tests, the international conferences, the chance meetings between researchers and the occasional flashes of inspiration. The book also tells us exactly how CRISPR works.
You may have to read this several times before getting your head around it but essentially CRISPR was adapted from the method that bacteria use to identify and cut the DNA of viruses that are trying to attack them – ‘a pair of designer molecular scissors that homes in on a specific twenty-letter DNA sequence and cuts apart both strands of the double helix.’.
Today we are able to use CRISPR to disable target genes and to add new stretches of DNA. One of the impressive aspects of Doudna’s book is her confidence in these techniques.
Scientists tend to be circumspect, but not here. ‘Scientists have succeeded in bringing this primordial process (of the evolution of life) fully under human control. Using powerful biotechnology tools to tinker with DNA inside living cells, scientists can now manipulate and rationally modify the genetic code that defines every species on the planet. And using CRISPR an organism’s entire DNA content has become almost as editable as a piece of text.’
That is not to say that CRISPR can achieve anything. Many traits are the result of numerous genetic interactions and may be too complicated to affect. And CRISPR is not perfect. DNA does not always get altered as desired, and there are ‘off-target’ effects that hit other areas of the genome.
Then there is the challenge of delivering the CRISPR mechanism into cells. This is hard enough when the cells are in the laboratory but even harder when the cells are still inside the human body. We are finding ways of making gene editing more accurate, but a certain amount of inaccuracy may not matter anyway.
Most medical treatments have some unforeseen consequences and the judgement is not whether they are perfect but whether the advantages outweigh the disadvantages.
We must though draw an important distinction between the editing of germline cells and of somatic cells. Germline cells contain DNA that is handed down to the next generation. Somatic cells (sometimes called adult cells) are all the others.
Suppose that I have muscular dystrophy, a disease that can be tracked down to specific genetic mutations. If CRISPR is used to correct these mutations then there may be off-target effects that could affect the function of my cells and body in unwelcome ways. But this is my problem alone.
However if in trying to correct a specific gene in germline cells there are off-target effects then these will be passed on. This, it seems to me, is highly problematical.
And yet Doudna believes that germline editing is something that we should accept, arguing that since our genes are constantly and randomly changing as our cells divide and copy, a few extra CRISPR-induced changes won’t make much difference.
What this tech can do
What can this new power over the living world do for mankind? First, it can enable us to understand it. The best way to find the function of a gene is to disable it and see the result.
Once we discover the genetic mutation responsible for, say, Huntingdon’s or cancer we can create cells or laboratory mice with this same mutation as use them as models upon which to test potential therapies. Already we have numerous examples of the potential of gene editing.
In human medicine CRISPR has already been used to develop potential cures for diseases including cystic fibrosis, sickle cell disease, muscular dystrophy, HIV/AIDS and even Alzheimer’s. Tests have been conducted on laboratory cells and animals and, in some pioneering cases, in humans.
CRISPR is critical to cancer immunotherapy, which sees immune cells engineered to recognize cancer cells. Elsewhere we have made barley that is resistant to powdery mildew, tomatoes that do not rot as soon as they are picked, mosquitoes that are unable to transmit malaria, ultra-muscular police dogs and cows with no horns. On the horizon are pigs that can serve as donors of human organs and even woolly mammoths and unicorns.
This all sounds great and yet Doudna is worried. The availability of CRISPR means that it could fall into villainous hands. She is worried that the same ignorant outcry that has hampered the progress of GM crops could impede the progress of gene editing. And she concedes that ‘CRISPR is forcing us to confront difficult, perhaps unanswerable questions, many of which boil down to conundrums about the relationship between humans and nature.’
But mankind has for ever tried to conquer nature and Doudna clearly believes that gene editing is in many ways superior to techniques we have used in the past. In the realm of agriculture historic practice has been to bombard plants with chemicals or radiation in order to cause random genetic changes.
When this has thrown up a plant with superior traits then we have bred from it. Is it not better to identify the desired trait, work out its genetic cause and then deliberately engineer the gene? And if we have hunted the great auk to extinction, should we not use genetic engineering to bring it back?
The most pressing debate concerns germline editing. When allied to established practices like In Vitro Fertilization and pre-implantation testing it is highly likely that we will be able to ensure that babies do not carry the genetic mutations that in some cases virtually guarantee a life of suffering.
Of course these same techniques could be used to create ‘designer babies’ and yet Doudna favours their approval. ‘I don’t believe there’s an ethical defence for banning germline modification outright, nor do I think we can justifiably prevent parents from using CRISPR to improve their chances of having a healthy, genetically related child, so long as the methods are safe and offered in an equitable manner.’
If we have the tools to prevent suffering, surely we should use them. Doudna argues that some existing practices like PGD (pre-implantation genetic diagnosis) that allow parents to choose the sex of their baby or abort those with Down’s syndrome are already facilitating forms of designer baby and that ultimately matters of conception are best left to parental choice.
Finally Doudna dismisses the argument that germline editing should be banned because it ‘unnatural’. As she points out ‘natural ‘ evolution has not been entirely benign and, ‘in the world of medicine the line between natural and unnatural blurs to the point of disappearing….In my mind the distinction between natural and unnatural is a false dichotomy, and if it prevents us from alleviating human suffering, it’s also a dangerous one.’’
So this book is both a description of the extraordinary possibilities of gene editing but also, if indeed the horse has not already bolted, a plea for its acceptance. We should, Doudna believes, be bold and brave. ‘Few technologies are inherently good or bad; what matters is how we use them’ – and in the case of CRISPR ‘it has incredible potential to improve our world.’