The Soviet Union’s successful launch of Sputnik I, the world’s first artificial satellite, in 1957 caught the Western world off guard. Yet within a dozen years, a U.S. astronaut was walking on the moon.
I fear that the West is losing today’s version of the “space race” — this one to use and control gene editing. That worries me because the nations that gain control of the most effective gene-editing technologies will, quite literally, control the world.
As someone who helped give birth to the gene-editing field 30 years ago, I have a unique perspective on the changes that have been happening in the six years since CRISPR-Cas9 opened the eyes of every biologist, life scientist, and biomedical researcher to the power over life that gene editing represents. And what I see concerns me.
In the early 1990s, there were so few people in the gene-editing field that all of us could have had dinner at the same table. In 1999, when I co-founded Cellectis, the gene-editing club was still relatively small. For years we quietly went about our business with the technologies at hand. Transcription activator-like effector nucleases (TALEN) were used for the first person whose life was saved by gene editing, a 1-year-old girl who was dying from leukemia. Zinc finger nucleases were used in the first gene editing in a human, a 44-year-old man with a genetic condition known as Hunter syndrome. And my company is now using TALEN to create the first gene-edited consumer food product about to be sold commercially, a high oleic soybean oil.
The range of applications for gene editing is almost limitless, from curing or controlling a variety of diseases to using silkworms to make spider silk for bio-Kevlar and other applications to improving industrial fermentation and crop yields. It’s not hard to imagine that any species could someday be the target of gene engineering, opening the gate to the rising new field of synthetic biology.
The emergence of CRISPR in 2012 energized the gene-editing field. Since then, the number of new gene editors has been growing exponentially. That explosive growth has triggered a shift in the balance of research and development power, with Eastern Asian countries beginning to dominate the research. Researchers in these countries have been engineering living species one after another in series of different applications, filing patents, and conquering unexplored spaces.
Scientists in this region are receiving unprecedented amounts of government support. The Chinese government, for example, is rumored to be investing $300 billion in gene-editing technologies, and China’s Natural Science Foundation has funded nearly 300 projects in the past four years. It’s part of their bid to gain control of the most important new technology to come along in this century — or perhaps in any century.
In the last five years, the sheer quantity of research publications on gene editing from Eastern Asia has grown exponentially. Try this experiment: Head to PubMed and search for “gene editing” or CRISPR or TALEN. (Here’s a prepopulated search for those terms and more.) In the hits that emerge, note the country of origin of the lead authors. The real innovation is coming from Chinese, Japanese, and Korean scientists.
Methodology: All publications with “gene editing” (including local languages) in the title or abstract. Publications from Korea include dissertations, local target journals, and monographs. Sources: China Academic Journals full-text database (CNKI); Japan’s Scholarly and Academic Information Navigator (CiNii); PubMed; Research Information Service System (RISS) which provides access to more than 2 million journal articles published by Korean scholarly associations and university research institutes.
Another indicator of the changing nationality of gene-editing work is the location of CAR-T trials. Five years ago, there were no such trials being conducted in China. Then the Chinese government made it easier to set up and conduct this kind of trial. As of August 2018, there were 21 trials being conducted in Europe, 123 in the United States, and 148 in China.
As Eastern Asian countries put the pedal to the metal with billions of dollars and an army of Ph.D. scientists, the United States is barely keeping pace in furthering gene-editing research and deploying gene editing. Europe, as usual, is seating itself on the sidelines by harshly regulating, if not outright banning, gene-editing technologies from its territory, sentencing its population to a technological winter that may never see a springtime renewal.
The pendulum will continue to swing in Asia’s direction unless the West wakes up and acknowledges that something must be done about it.
What can be done? The West’s emphasis on regulation — and overregulation — is leaving us far behind countries whose governments are more open to the idea of unrestricted or less-restricted research. We must be willing to ease up on the burdensome restrictions that make it difficult to operate clinical trials or conduct gene-editing studies.
Patient safety, of course, is of utmost importance, and we must do everything possible to protect it.
One way to keep the West in the gene-editing race would be to focus on vector technologies. While the concept of correcting a DNA mutation that causes cystic fibrosis is easy to imagine, delivering a gene-edited therapy to a patient’s lungs to fix the mutation is a highly challenging endeavor. You need to harness a vehicle that will take the new genetic material to the right cells, target enough cells in the lung, and ensure that the gene-edited cells have a persistent therapeutic effect. Yes, this is rocket science.
While gene-editing technologies are beginning to make an impact, I believe they will reach their full potential in the second half of the 21st century. By then, scientists will be generating incremental improvements at high speed. The FDA and other Western regulators must adapt to allow a selective inclusion of the flow of these incremental innovations in trials and in applications in order to stay competitive.
Clinical trials of innovative technologies such as cell therapy, gene therapy, and gene editing take at least seven years from filing an investigational new drug application (IND) to the biologics license application (BLA). In that time, though, technologies used at the IND filing will become obsolete by the time of the BLA. Regulators will have to adapt to these new kinds of rapidly evolving technologies and allow their incremental inclusion during the course of trials in order to allow the product candidate to hit the market with state-of-the-art technologies. Cell and gene therapies are much different than molecular therapies, where the innovation is made at inception and will not evolve during the course of the trial.
I’m not the only one concerned about global competition in gene editing. Immunotherapy pioneer Carl June, the director of translational research at the University of Pennsylvania’s Abramson Cancer Center, told the journal Nature that a 2016 gene-editing advance by Chinese scientists “is going to trigger ‘Sputnik 2.0,’ a biomedical duel on progress between China and the United States.”
If such a “biomedical duel” increases competition, and thus innovation, I’m all for it. But if the West allows the bulk of the work to be dominated by Asian researchers and lets these technologies slip through its fingers, it may be decades, or even centuries, before we are able to make up for lost time and lost innovation. The truth of the matter is that every species on earth could be subject to gene editing, and the country that invests the most in this race will gain control over life as we know it on this planet.
Where on the planet will the first human 2.0 with an updated genome be born? If I had to bet right now, I would say 2040 in Asia.
With unprecedented potential for reward, we must not be so focused on risk that we lose the opportunity to forge ahead in this field.
André Choulika is the founder, chairman, and chief executive officer of Cellectis, a biopharmaceutical company focused on oncology.
I’ll pass on your Brave New World / Gattaca remix.
The Trump admin appears completely dedicated to “old “ science, it’s chemistry
and application to products derived. It is unlikely he cares and U.S. will not progress
I’m not sure that quantity of trials and looser regulations in East Asia necessarily guarantee Asia will be leading genome editing innovation. There’s more to the story than those two variables.
Plus, freer experimentation via limited regulation comes at a high cost to patients. The difficult conversation must deal with the fact that patient safety and speedy innovation are not exactly aligned. Maybe we need speedier approvals, but this necessarily means less time to understand Adverse Events. Is it worth it?
If you’re going to be a utilitarian about it, then provide us an argument.
Not sure why this is surprising. More than half of the postdocs in the US that are working in this field are from the referenced countries.
Comments are closed.