Ivar Giaever, Nobel Winner in Quantum Physics, Dies at 96
It was 1956, and he was applying for a position at the General Electric Research Laboratory in Schenectady, N.Y. The interviewer looked at his grades, from the Norwegian Institute of Technology in Trondheim, where Dr. Giaever (pronounced JAY-ver) had studied mechanical engineering, and was impressed: The young applicant had scored 4.0 marks in math and physics. The recruiter congratulated him.
But what the recruiter didn't know was that in Norway, the best grade was a 1.0, not a 4.0, the top grade in American schools. In fact, a 4.0 in Norway was barely passing — something like a D on American report cards. In reality, his academic record in Norway had been anything but impressive.
He did not want to be dishonest, Dr. Giaever would say in recounting the episode with some amusement over the years, but he also did not correct the interviewer. He got the job.
He proceeded to spend the next 32 years at the laboratory, along the way developing an experiment using superconductors that provided proof of a central idea in quantum physics — that subatomic particles can behave like powerful waves — confirming a game-changing theory about superconductivity. For his work, Dr. Giaever shared the Nobel Prize in 1973.
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KJ was born at the Children's Hospital of Philadelphia with a rare genetic disease that prevents him from breaking down proteins properly. The therapy, called base-editing, replaced a faulty letter in KJ's DNA with the correct one that now lets him eat some protein. KJ's treatment represents the next phase of CRISPR-based therapies. While CRISPR treatments have been approved by the FDA to treat sickle cell disease and certain types of beta thalassemia, those therapies involve removing cells from patients, editing them with CRISPR to correct the genetic defect, and then infusing those cells back to the patients. In KJ's case, the CRISPR editing occurred in his own body, via three injections of a therapy developed just for him. That's the same model that the new center will use. 'With that story, there was a lot of momentum within our teams about whether we could do that again, and how we could learn from this to create a pipeline to reduce cost and make this therapy much more widely available,' Doudna says. Doudna thought of Chan, whose initiative has the mission of curing, preventing, or treating all diseases by the end of the century. It was an ideal match, since Chan had trained as a pediatrician at the University of California San Francisco and spent eight years treating children with rare genetic diseases after finishing medical school. 'When Jennifer called me, I thought, 'This is perfect,'' Chan tells TIME. She recalls encountering families whose babies were affected by diseases so rare that there was often little, if any, information about them. 'I have seared in my mind the image of a parent handing me a PDF that they carried around to explain to each resident that this is what we have, and this is all that we know about it. I carry that around daily.' The experience inspired her to create the Rare As One program at the Chan Zuckerberg Initiative, a network of patients, researchers, and scientists from different disciplines that highlights the need for basic research needed to better understand these conditions in order to develop more effective treatments for them. Read More: The Surprising Reason Rural Hospitals Are Closing CRISPR, with its ability to target specific genetic mutations, holds the most promise for changing the course of such diseases. But time is of the essence. In KJ's case, the entire process of identifying his mutation, developing the treatment, testing it, and receiving FDA clearance took nine months. KJ was just six months old when he received his first CRISPR treatment. Acting that quickly is critical for conditions like these, since once cells or organs are damaged by disease-causing mutations, they can't always be rescued. The idea is to intervene with a CRISPR therapy to minimize the effects that the mutations could have. Currently, about 6,000 rare diseases affect 300 million people worldwide, and 72% of them are linked to genetic aberrations. A similar proportion primarily affect children. The new center will focus on identifying disease-causing mutations that can easily be targeted—such as in the liver, as in KJ's case. 'Jennifer and her team, and the team at UCSF, will be very careful in choosing mutations that are amenable to this treatment,' says Chan. 'Not all mutations will work well with this version of there will be a delicate balance in choosing patients who stand to benefit the most in this situation.' Patients will join a clinical trial to receive the treatment, and the research team will study them to learn from their experiences and continue to improve the treatment and the process. Read More: Why It's So Hard to Have Your Fertility Tested In the first cases that the center will try to treat, the FDA will consider each treatment on its own and decide whether to approve the customized therapy for that particular patient. But, says Doudna, 'as we continue to get more information on the safety and potential risks of CRISPR for different indications, what is emerging is the potential to designate CRISPR as a platform technology.' That means that if regulators approve the framework of the CRISPR gene-editing process, doctors would not need to conduct animal tests for each new CRISPR therapy designed for a patient. The only thing that would change would be the guide RNA, Doudna says, which carries the genetic instructions for finding the specific mutation that needs to be addressed. 'Even there, most of the guide RNA stays the same, and it's just the piece at the end providing the molecular zip code that changes.' Key to making that happen will be advances in other scientific areas, including using AI to predict how changing specific genes will affect a cell's function and what potential health outcomes a CRISPR-based treatment might have. That work is ongoing separately at places like Chan Zuckerberg Initiative and elsewhere, says Chan. Eventually, says Doudna, 'we hope as the process moves forward, it will be possible to both predict clinical outcomes of CRISPR therapies accurately and ensure that by changing just a little part of the guide RNA, everything else will remain the same, so you don't have to do full-blown animal testing for every single iteration of CRISPR. If that becomes possible, then it will make CRISPR a lot cheaper and a lot faster to test these kinds of therapies.' That would make it available for many more patients as well. Contact us at letters@
