Pharma & Healthcare
Roland Berger advises pharma, MedTech and insurance companies on how to master the challenges of the future.
by Fred Schulenburg
Photos by Winni Wintermeyer
Discovering the potential of gene editing made Jennifer Doudna literally laugh out loud. But the scientific breakthrough is no laughing matter. Besides winning her a Nobel Prize the new technology could, in the wake of a global pandemic, be poised to make giant leaps toward a new generation of health care. She talks to Think:Act about the opportunities and the risks it brings.
The dawn of a new scientific age – or of a nightmare of reengineered human beings? The ability to rewrite the "code of life" through gene editing has sparked strong, sometimes conflicting reactions. The technology that makes it possible – CRISPR associated protein 9 (or Cas9) – is the brainchild of the US biochemist Jennifer Doudna and her colleague, Emmanuelle Charpentier, a French microbiologist. Champions and sceptics alike believe that the ability to adapt and rewrite genes represents a milestone in scientific and human development, with consequences ranging across public health, agriculture and biomedicine. Business is also starting to grapple with the prospect of gene editing and the commercial possibilities CRISPR offers.
The advent of CRISPR comes at a time when, thanks to the worldwide pandemic, science and scientists have moved to the center of the global public square – and yet discussion around gene editing, perhaps one of the greatest life-changing innovations of all, remains relatively muted.
When did your CRISPR journey begin?
My involvement with CRISPR started with Dr. Jillian Banfield reaching out to me in 2006. We were both professors at UC Berkeley but had never met. We met for coffee and she started explaining these unusual repeats she was finding in microbial genomes called "CRISPR," and had an idea that they might be some sort of immune system against viruses. That was the first time I had heard of CRISPR, and it came at a moment when I was looking for some new projects for my lab. It was an interesting curiosity-driven science project at the time. Years later, I started collaborating with Dr. Emmanuelle Charpentier and we found that we could harness the CRISPR system to cut DNA at precise locations. It became clear that we had made a leap from fundamental science into something that could change the world. There was a moment that it all hit me and the first feeling was joy – I remember I started laughing while I was cooking dinner, and my son had to ask me, "Mom, why are you laughing?"
When her father handed her a copy of "The Double Helix", the young Jennifer Doudna dismissed the story of the discovery of DNA as a thriller. Yet it was the starting point in her journey to being awarded the 2020 Nobel Prize in Chemistry alongside Emmanuelle Charpentier for their pioneering work on developing CRISPR gene-editing technology. In 2014, Doudna, a biochemistry professor at UC Berkeley, co-founded the Innovative Genomics Institute which seeks to advance public understanding of genome engineering and guide the ethical use of CRISPR.
How, in simple terms, would you explain CRISPR technology?
I generally describe it as "molecular scissors." Scientists can program it to find and cut a specific place in any organism's DNA and then provide a new template to repair the DNA – making it possible to fix mutations in the genetic code, or to turn genes on and off. Before CRISPR, this had been quite challenging to do. What makes this so exciting is that this gives us a tool to potentially treat thousands of genetic diseases, like sickle cell disease, where we have known the cause for many years but have not been able to develop an effective treatment.
There have been some major concerns about CRISPR. To what extent do you think they are warranted?
People are right to be cautious with new, powerful technology, but CRISPR isn't fundamentally different from any other such technology. There are some concerns that are in front of us now, others that are years away but worth discussion, and others that are more the realm of science fiction. One concern of mine is that new technologies tend to benefit the few people that can afford them, and it's really critical that we work now to make sure that the benefits of genome editing reach everyone who needs them.
What do you see as the most realizable, practical benefits of CRISPR?
The practical benefits [are already here]. One that's often overlooked is how CRISPR has transformed life science research in just a short amount of time. It's now much easier to determine precisely what genes do and how different mutations affect their function. Just recently, there was a study that used CRISPR to determine why Romanesco cauliflower is shaped like a fractal.
In the world of medicine, it looks like we are well on our way to a cure for sickle cell disease, caused by a single letter mutation in one gene. There are a number of people from the first CRISPR-based clinical trials who are symptom-free. That trial used CRISPR to reactivate fetal hemoglobin, which isn't affected by the mutation that causes sickle cell disease. Others, including work at the Innovative Genomics Institute, are taking a different approach and attempting to directly repair the mutation using CRISPR. All of the momentum on sickle cell disease is exciting, and I'm optimistic that it will result in a cure, and one that's affordable and accessible by everyone who needs it.
Get acquainted with the technology that is expected to be at the forefront of significant breakthroughs in medicine and agriculture for years to come.
CRISPR was lauded by the Nobel Committee for Chemistry as a technology that has "revolutionized basic science" and will deliver groundbreaking new medical treatments and produce innovative new crops. Its origins, however, are perhaps more humble. For hundreds of millions of years bacteria have fought off viruses through a system of basic gene editing by which bits of invasive DNA are identified and remembered so that they can be targeted and "snipped off." This part of bacteria's immune system is known as "clustered regularly interspaced short palindromic repeats" – or CRISPR for short.
But it was only recently that the wider potential of such "genetic scissors" was realized by scientists such as Jennifer Doudna and Emmanuelle Charpentier. They saw how it could be reengineered and repurposed to a more general, immensely powerful tool that could be deployed in any living organism. In 2012 they published their findings in a paper in Science magazine. In 2019 the first patients were treated with CRISPR-based technology in clinical trials.
The advent of CRISPR has taken life sciences into a new epoch, one that Doudna's biographer Walter Isaacson likens to the third great revolution of modern times, following earlier breakthroughs in atomic physics and information technology. It brings with it the prospect of combating existing diseases, improving crop yields or providing mechanisms for tackling future pandemics. It has already been enlisted in the fight against Covid-19.
The ease of ability to manipulate genes in human cells through CRISPR has also fueled concerns about the potential for abuse. The 2018 announcement by the Chinese scientist He Jiankui of the world's first gene-edited twin babies prompted widespread condemnation of experimentation with human embryos and calls for greater regulation. The US director of national intelligence added CRISPR to the list of potential weapons of mass destruction.
Chinese scientist He Jiankui infamously engineered the birth of "CRISPR twins" – babies with modified DNA, supposedly to thwart a disease passed on from their parents. How did you react when you heard of his experiment?
I was totally shocked and appalled.
The He case obviously raised an ethical question around CRISPR's application and of how one can regulate technology that is relatively easy to deploy. Do you think that it is even possible?
There is no one-size-fits-all solution to regulating the use of genome editing, but I'm optimistic about international cooperation [working to develop] governance frameworks for genome editing that can be applied around the world. What's key is that we establish clear guardrails while not stifling innovation.
$4.2 billion: The estimated global market for CRISPR gene editing by 2024.
12%: The respondents to a 2020 poll who saw CRISPR as the most impactful technology for health care.
80%: The increase in overall survival in a study on two deadly cancers that used gene editing on tumor cells in mice.
Source: Statista, Harvard
The Covid pandemic has put science at the center of public life, sometimes with unedifying consequences. Given that we can't seem to agree on something as straightforward as face masks, how confident are you that we can have a proper debate about CRISPR?
The pandemic has been a terrible tragedy for the world, but it has resulted in the greatest moment of science that I've ever experienced. We developed highly effective mRNA vaccines, filled gaps in diagnostics and developed new ways to test on a massive scale. At the Innovative Genomics Institute, we pivoted our work to a diagnostic testing lab for the UC Berkeley Campus and the surrounding community and supported dozens of rapid research projects.
Misinformation is rampant, trust in expertise is at a low, but science has stepped up and delivered. We're going to have debates about CRISPR, and they may not all be rational, but as scientists we have to be transparent in our work and keep delivering practical results.
Observers say we are living through another great age of science, but worry the subject is still too male dominated. Have you witnessed or experienced any gender bias in your career?
I was told in high school that women didn't go into science and that I should think of a different career. I didn't listen. This is still an issue, though much has improved. We're losing potentially great scientists when we drive people of any background away from science. I've found that working with a diverse group that comes with different perspectives, different life experiences, leads to fresh thinking and better science.