The woman who never forgets.
Text: Angelika Jacobs
There are only about 60 people in the world who can remember everything they have ever experienced. For many of them, this is a source of considerable suffering. Researchers are now scouring their DNA for an answer to the question of why we are able to forget.
"I’m having problems with my memory,” it read. James McGaugh had received numerous emails of this sort back in the summer of 2000. In response to the message from 34-year-old Jill Price from Southern California, he wrote that he was a research scientist, not a doctor, and suggested she turn to a medical institute instead. But her reply grabbed his attention immediately: “I run my entire life through my head every day and it drives me crazy!!!”
Two weeks later, the researcher was meeting Price in person on the campus of the University of California in Irvine. McGaugh tested her memory using a book of 20th century historical events and other sources. She could remember each event clearly and tell him where she was when she first heard about it. She knew who she was with, whether or not it was sunny out and what else had happened to her that day. Price merely had to think of a specific date, and the scene would unfurl in her mind’s eye.
Memory as a burden
Today, Jill Price is recognized as the first person to be diagnosed with something called hyperthymestic syndrome. She shares this diagnosis, which is also known as Highly Superior Autobiographical Memory (HSAM) with some 60 other people in the entire world. Similarly scarce is any hard data about the condition. Minute differences have been pinpointed in certain brain structures. “However, they don’t explain why some people go on to develop HSAM,” says Andreas Papassotiropoulos, Professor of Molecular Neuroscience at the University of Basel. Papassotiropoulos has spent long nights discussing the syndrome with his colleague, Dominique de Quervain.
“A couple of years ago, we initiated a search within the German-speaking countries and received thousands of replies,” explains the researcher. But they were not able to isolate a single case of HSAM. The vanishingly small number of people diagnosed with the syndrome further complicates this puzzle.
However, one approach seems promising: People like Jill Price learn new information just as efficiently as those without the condition. The difference is that the brains of people affected by HSAM do not delete experiences or impressions. That means that while they are able to lead relatively normal lives, they are dogged by the persistent presence of their memories – and forced to relive every sad or unpleasant moment they’ve ever experienced. Jill Price views her memory as a burden, and many others diagnosed with HSAM suffer from psychiatric problems. “In order to function properly, your memory needs to be able to disregard trivial information,” explains Papassotiropoulos.
A gene for forgetting
This is an active process of tidying up the memory archives, not the gradual degradation of unused archival materials. In 2014, the research team headed up by Papassotiropoulos, de Quervain and Attila Stetak was able to prove this fact by identifying a gene in roundworms that is key to the process of forgetting. The “musashi gene,” as it is called, is present in humans, too.
A stack of magazines sits atop the sofa table in Papassotiropoulos’ office; the memory researcher has amassed a small collection of the scientific journal Cell, which published the team’s highly regarded study. Beside it lie an orderly collection of other journals bearing his publications.
The professor has a fondness for order, not just when it comes to memory, but in his office, too, and the space reflects that fact: His large, clearly organized desk is set against a shelf lined with punctiliously labeled files and crowned by the framed certificate proclaiming him the winner of the 2013 Cloëtta Prize. “We started by looking at the musashi gene in people affected by HSAM, but in this respect they’re no different from other people,” admits the neuroscientist. His voice almost seems to catch in a pang of regret.
Irvine-based researcher James McGaugh – “Jim” to his friends – offered to collect DNA samples from 21 people with HSAM and some of their blood relatives back in the early 2000s. “We went ahead with it even though we didn’t know what to do with that information at the time,” he recalls. That all changed just a few years later with the advent of the gene sequencing revolution. It had finally become both technically and financially feasible to analyze in detail the wealth of hereditary data.
A risky venture
At the Transfaculty Research Platform in Basel, researchers have been looking for gems in this data source. They can detect the tiniest deviations in the genes of those with HSAM, unique sequences that do not occur in the same place in 100,000 other people. “We are concentrating solely on the sections of DNA that actually code for proteins, and we sequence them down to the smallest detail. If there’s something that can be traced back to a single gene, we’ll find it,” underlines Papassotiropoulos.
But it is a risky bet. HSAM could just as easily result from interactions between multiple genetic anomalies that produce the syndrome only when one specific combination occurs. It might also be caused by a mutation in a gene that does not code for a protein at all, but instead carries out a regulatory function in cellular processes. Papassotiropoulos admits that their probability of success is slim compared with other projects. Their study was made possible thanks to financing from the FreeNovation Award granted by the Novartis Research Foundation; the award is designed to fund speculative ideas just like this one.
Risk aside, if Papassotiropoulos’ team were to pinpoint a genetic cause for hyperthymestic syndrome, it would be a revolutionary discovery. A finding like that could completely transform our understanding about how we forget. Not only would it shed light on the cause of the extraordinary abilities of people like Jill Price, it would also boost research into more common phenomena in which the brain forgets too much or too little. This includes conditions such as Alzheimer’s or post-traumatic stress disorder, in which sufferers experience persistent memories of traumatic events.
Papassotiropoulos concedes that he is trying to rein in his expectations. The data often seems to suggest an imminent breakthrough, but that initial promise is frequently thwarted upon closer scrutiny: “I always think I’ve finally got the answer, but then it slips through my fingers again.”
Should his team strike upon a discovery capable of bearing up to the most rigorous testing, it would be a dream come true for Papassotiropoulos. If and when that day finally comes, he would like to travel to the United States to meet Jill Price and others with HSAM – and finally give them the answers they are hoping for.
Andreas Papassotiropoulos has been Professor of Molecular Neuroscience at the University of Basel since 2007. He heads up the Transfaculty Research Platform Molecular and Cognitive Neurosciences together with his colleague Dominique de Quervain.
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