At a now famous conference in 1975, a group of biologists met at Asilomar State Beach in California to discuss a new technology called recombinant DNA. For the first time, scientists could stitch together genes from different species: bacterial DNA could be put into a plant, say, or a human gene put into a fungus. The Asilomar conference agreed on a set of guidelines to ensure responsible research, and (after a few years of heated debates) a new era of biology eventually blossomed. Human insulin made by bacteria and yeast helped millions with diabetes. Doctors got tests for infectious diseases through genetic probes that bound to the DNA of dangerous germs. And agricultural companies began producing genetically modified plants with built-in pest protection.
A similar step-change is under way now. Like recombinant DNA before it, gene editing has the potential to transform medicine, agriculture and more. CRISPR is now used by thousands of biologists in labs across the globe. A revolution in food crops could be around the corner. People with horrible diseases have been cured through alterations to their genes. With more CRISPR-based medicines in trials, some of which could benefit many millions of people, the number of edited people could soon increase.
Especially for therapies, hurdles remain. One is cost. Casgevy, the CRISPR cure for sickle-cell disease and beta-thalassemia, is expensive to make and to buy. Health-care systems in America and Britain have secured discounts and rebates to pay for it. Most people with these conditions live in African and Asian countries with much less buying and negotiating power. Another hurdle is old-fashioned regulation: many CRISPR medicines use the same components, but so far companies have been forced to test each component every time, limiting how many medicines they can invest in bringing to market. There are technical challenges, too: current methods can only send CRISPR to a subset of the body’s tissues, leaving brain and muscle diseases off the table for now.
All of this has resulted in a sour business mood, and a number of gene-editing therapy companies are struggling to stay afloat. Some have dramatically narrowed their pipelines and laid off staff. Others have gone under. Five years ago, there was a frenzy of investment into CRISPR and the next-generation tools that followed. Recently those same investors have wondered just how much time and money it will take to turn these tools into actual therapies.
CRISPR just is better than what came before
But you do not become a successful artist when someone first hands you a paintbrush. Scientists first saw the potential of CRISPR just 13 years ago. They have had not just to learn how to use it, but also find the right subjects on which to lavish their skills. In medicine, that means finding the right genetic switch to flick to get a therapeutic outcome. In agriculture, it can mean editing three genomes at once while accounting for the influence of a changing climate. In disease prevention, it is about working out how to withstand resistance from pathogens. When considering this learning curve, the fact that there is a CRISPR cure on the market, pig organs going into clinical trials and non-browning avocados coming to a taqueria near you is testament to pretty fast progress.
A wealth of patients
The early hubris of the gene-editing therapy companies has hurt them, and they will have to learn from it before biotech fully re-emerges from its slump. It may yet turn out that venture-funded startups and pharmaceutical giants are poorly suited to developing and producing high-cost CRISPR therapies for the rarest of genetic diseases. Non-profits and public institutions may have to step in to fill a void should the economics of such therapies continue to be formidable.
At the same time, new doors have opened. Regulators seem willing to make it easier to bring more CRISPR medicines to market, not just because of keen advocates (one of whom describes himself as “a soldier” for Jennifer Doudna, a co-inventor of the technology) but also thanks to CRISPR’s sheer potential. It just is better than what came before.
The deals between Vertex and public-payer healthcare systems in America and Britain reflect a willingness to bring cures to under-served groups, and new collaborations between the private and public sector aim to bring cures to rare diseases at a fraction of the cost of Casgevy. Outside of medicine, legislation to treat GE foods as different from GMO foods means the world might be able to turn a corner on a topic that had become needlessly contentious.
CRISPR has given scientists the means to get to know the biological world as never before. It has already carried research into a new, more productive era. That, alongside the work into delivery of ever-more-sophisticated editors, is what will fuel the next wave of CRISPR therapies, future-proof the world’s food supply and lead to new scientific breakthroughs. So, while scientists and companies cannot afford to be complacent, the world should not lose hope for the age of gene editing. The best may yet be to come.■