My meeting with a world leader
Last week I met the person who will most likely have more influence over the future of the world than anybody else.
No kidding. You think Trump, Putin, Merkel and all the other politicians make much difference? Fortunately not. But Jennifer Doudna will go down in history as someone who changed the world.
In the not too distant future, a few decades maybe, we will have beaten many currently incurable diseases, we will easily be producing green energy, food will be abundant and we may even have revived extinct species. There may be some stuff that is not so good. Terrorists releasing lethal viruses, engineered to kill. Designer babies, born to meet the aesthetic requirements of Mum and Dad. Dogs created with two heads, just because it is possible.
In no more than the last five years – pretty much since the day I started this newsletter in fact – all of the above and much more has left the realm of science fiction and become very real. Key to this is the discovery of CRISPR, the revolutionary new method of editing DNA. Although many scientists have been involved history will probably credit Jennifer Doudna with its invention and now she is a worried woman.
Slim, blonde and elegant this Californian mum is all too aware of the potential of her invention. She knows that very few people (you and I excluded) understand what is going on and, a little reluctantly, she has left the sanctity of her UC Berkeley laboratory on a mission to explain CRISPR and join the debate about its use.
She has written a book, ‘A Crack In Creation’ which I highly recommend and will say more about next time, and she gave a talk last week at the Royal Institution in London.
A call out of the blue
She began with a bit of history. The first important steps on the path to editing life came in the 1970s when we discovered how to clone (i.e. copy) genes, which are of course strings of the A, C, T and G bases of DNA. On studying these genes we realised that they are constantly being damaged but are very good at repairing themselves. For a long time we had known that DNA codes for proteins which determine the function of cells (the ‘Central Dogma’).
So in order to alter cell function we needed to find a way of altering DNA, confident in the knowledge that the cells would incorporate any changes. In the 1990s the approach was to ferry DNA into cells on the back of viruses – so-called ‘viral vectors’- but this crude approach hit the buffers in 1999 when Jesse Gelsinger, a participant in a clinical trial, died when a massive immune reaction overwhelmed him just four days after treatment.
Rather than trying to ram some new DNA into a cell, a much better approach is to enter the cell and alter the bases as desired. Various methods such as Zinc Finger Nucleases and TALENs have been tried and with some success but they are cumbersome and expensive.
In 2006 Jennifer Doudna was telephoned out of the blue by another Berkeley professor, Jillian Banfield, who started talking about ‘crisper.’ In fact she was referring to Clustered Regularly Interspaced Short Palindromic Repeats, repeated DNA sequences that she had found in her study of bacteria.
It turned out that between these repeats were other DNA sequences that the bacteria were basically storing in their memory. They were a record of past attacks by viruses and they enabled the bacteria to fight back and destroy the DNA of the virus whenever it attacked again.
Doudna realised that this was nature’s way of cutting DNA and in 2012 she and her partners, most notably Emmanuel Charpentier, published a paper ‘A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity’ that described a method for making double-stranded breaks in the twisted ladder of DNA and ‘highlighted the potential to exploit the system for RNA-programmable genome editing.’
Researchers around the world seized upon this, instantly realizing that CRISPR has made gene editing simple, accessible, cheap and accurate. The genie was out of the bottle and progress has been more than rapid. In her talk Doudna repeatedly said that the new technology has been moving alarmingly fast, that it has ‘jumped all of its boundaries’ and that she was ‘unsettled by the pace of development.’
As Doudna said, this is a ‘universal technology’ applicable across all life sciences. Away from the intense scrutiny of human gene editing, plant and animal researchers are using CRISPR to develop tomato plants with stronger stalks, chickens that produce hypoallergenic eggs and mushrooms that resist browning.
Meanwhile the first cancer trial in which patients have been inject with cells that contain genes edited using CRISPR has commenced in China. Chinese researchers have already bred ‘designer monkeys’ by editing monkey embryos and they were also the first to use CRISPR to edit human embryos, albeit embryos that were unviable and could never become humans.
London’s Crick Institute has also started to use CRISPR to edit the cells of human embryos, albeit on the understanding that these are destroyed within seven days.
A race has started. In a famous meeting at Napa Valley in 2015 experts in the field called for a moratorium on gene editing of embryos, a view upheld by a recent report from the USA’s National Academy of Sciences. But, as Doudna pointed out, while CRISPR universally acceptable, regulation and ethics vary from one region to another.
Asian nations, she said, do not necessarily share Western views about the sanctity of life and she reported rumours of Chinese companies offering embryo-edited, designer babies for profit. When research work is conducted solely by academic institutions and regulated companies it is relatively easy to control. But CRISPR is available to home enthusiasts for use ‘in the garage’, it is available all over the world and it can be used for both good and bad ends. Undeniably this is alarming.
CRISPR is by no means 100% efficient. Not all cells receive the intended edits and there is also the problem of ‘off-target effects’. But Doudna played down the significance of the latter. She expressed confidence that the accuracy of CRISPR editing would improve and said that anyway the editing need not be 100% accurate. Like any medical treatment there might be some side effects but the judgement would be whether these were outweighed by the benefits.
Furthermore, she added, recent work has shown that for conditions like muscular dystrophy and cystic fibrosis patients will feel a therapeutic benefit even if only 10% of the relevant cells are corrected. ‘I don’t see accuracy as a bottleneck,’ she explained.
So really there seems to be nothing to stop CRISPR being used to change the function and appearance of any living thing, from the tiniest bacteria to you or I.
And of course, after the scientific breakthrough comes the commercial breakthrough. Companies are learning how to build sustainable business models based on CRISPR. Investors will be hearing more from them in the years to come.