The small-town Nobel Prize winner who wants to cure Alzheimer’s in 10 years

Prof Jennifer Doudna, the ‘Godmother of Crispr’, says ‘figuring out how to edit the brain is probably coming in the next decade’

Jennifer Doudna says she is an “unlikely success story” because she grew up in a small town with no scientists in her family to speak of.
But four years ago, she won a Nobel Prize for her discovery of the pioneering Crispr technology and now finds herself standing at the forefront of modern science.
The technology, known as “genetic scissors”, allows scientists to modify the DNA of living organisms and has the power to help future-proof crops against climate change, and create methane-free livestock.
Now, Prof Doudna, 60, hopes her breakthrough can find a cure for dementia in the next decade.
Prof Doudna, sometimes dubbed the “Godmother of Crispr”, invented a way to target a string of faulty DNA, cut it out and replace it with an alternative by repurposing a niche part of the bacterial immune system.
The bacterial process – when tinkered with in a lab – can replace any faulty and disease-causing genes in any stretch of DNA, including in people. It offers tantalising hope for those with genetic conditions ranging from sickle cell anaemia to Huntington’s Disease.
Her Nobel Prize win in 2020, just eight years after Crispr’s discovery, demonstrates the seismic impact this technology has had on biology and the potentially game-changing genetic medicines it could soon provide.
The Nobel Laureate is now based at the University of California, Berkeley, and founded the non-profit Innovative Genomic Institute in 2014 to help further develop Crispr and make it more accessible.
“There’s a lot of effort at our institute currently for neurodegenerative disease, so figuring out how to actually edit the brain, I think that’s probably coming in the next decade,” she told The Telegraph.
She said she wants Crispr to become a “standard of care in medicine for some diseases”.
The first Crispr medicine was authorised for use on the NHS this August. But the gene therapy treatment for the blood condition beta thalassemia, called Casgevy, requires an arduous hospitalisation process in which stem cells are taken out of a patient’s bone marrow, edited in a laboratory and then infused back into the patient at a cost of around $2 million each time.
But Prof Doudna wants to develop Crispr into an injection that can be given to patients like a vaccine in a GP surgery, making the therapy cheaper and more accessible. This, she says, could be just a couple of years away.
“Crispr injections are a milestone in showing how it can be used in the future by allowing patients to be treated in a doctor’s office rather than having to go through a hospitalisation type of process,” she told The Telegraph.
“We have felt real energy from the approval of Casgevy, but, at the same time, we recognise the challenges ahead for getting the technology into the public space where more people can access it.
“I think we’re going to see more Crispr treatments of blood disorders like sickle cell disease over the next few years, as well as other blood disorders and conditions affecting the liver.”
Prof Doudna’s team is now working on delivering Crispr deeper inside the body and hopes that alongside developing injections, an oral medication could be just a couple of decades away. It would mean being able to treat more conditions affecting a wider range of organs and body parts, she said.
“It’s a tall order, and we think we can figure it out,” she added.
“We’re working hard on strategies that will allow delivery of these editing molecules directly into the body. I’d say we’re making some headway in terms of the delivery strategies.”
The brain is a primary target for Prof Doudna and a challenging one but the genetic targets for Alzheimer’s are already known. For example, people with two copies of the faulty APOE-4 gene are 12 times as likely to develop the condition, some studies suggest.
“There definitely are some genetic susceptibilities that trigger neurodegeneration in certain classes of patients that are well documented,” she said. “We’ll focus initially on those kinds of genes, in particular for Alzheimer’s.”
Prof Doudna, who moved from Ann Arbor, Michigan, to Hilo in Hawaii when she was seven, acknowledges developing this technology will be a long-term project and states that she doesn’t want to give people false hope, but also believes it’s the right subject for non-profit groups like hers to focus on.
Some Crispr critics have cited ethical concerns over “playing God” with technology which allows a person’s genetic blueprint to be re-written in a lab, but others see it as a way to try to cure previously untreatable conditions and usher in a new era of medicine as transformational as the invention of the vaccine or the discovery of antibiotics.
Prof Doudna herself has called for an international prohibition of any germline gene editing – making edits to DNA in egg, sperm or embryo cells – and was appalled when He Jiankui, a rogue Chinese scientist, announced in 2018 that he had used Crispr on two unborn twin girls to try to protect them against HIV.
Using the technology in this way is riskier and the long-term impacts remain unknown. Prof Doudna led international condemnation of the blatant breach of scientific and ethical guidelines and is keen to prevent such transgressions in the future.
But she is bullish on the potential benefits of the technology outweighing any short-term regulatory and ethical teething problems.
And while she thinks Crispr may be able to cure diseases and treat Alzheimer’s in the next decade, she believes its largest benefit will be in farming, and saving the world from the damage caused by climate change.
“The biggest global impact of Crispr in the near term will certainly come from agricultural use,” she said.
“The need is so great, especially as we have a growing world population. We’re facing the challenges of the changing climate, and Crispr gives plant breeders technology for making precise changes in the genetics of plants that will introduce beneficial traits.”
Her team is working on making drought-resistant rice, for example, and is also altering the DNA of bacteria in cow guts to try to stop them from making methane and reduce their carbon hoofprint.
Cow flatulence is a notoriously large producer of the greenhouse gas, which is 80 times more potent than CO2, and a major reason why farming and meat consumption is so harmful to the environment.
“The thing we’re working on [in this project] harks back to what I said about the clinical use of Crispr – and that is how we actually deliver it into the rumen. We’re actually working with some of the viruses that infect these bacteria, and trying to use those as a delivery vehicle.”
The 2012 study and the subsequent Nobel Prize catapulted Prof Doudna and her work to the forefront of the public psyche as well as to the bleeding edge of science and her goal now is to elevate the work from the laboratory bench to tangible change in the real world.
This year’s Nobel prizes will be awarded in early October and Prof Doudna says her award during the pandemic, which she shared with co-discoverer Emmanuelle Charpentier, had a huge impact on her ability to pursue her ambitions of turning Crispr into medicines.
“I think in a perfect world, that’s what the Nobel does for any field,” she said.
“It really puts a spotlight on science, and it helps the next generation to think about and be inspired about what they might achieve in the future.”