Somewhere tonight, someone 鈥� make that millions of someones 鈥� will wake up in desperate terror, reliving the horror of a traumatic event. The someones will range from combat veterans and abuse survivors to witnesses to mass-shootings and victims of natural disasters.
Right now, there鈥檚 nothing they can do except let the panic dissipate, like waiting out a summer thunderstorm. But in the near future, a remedy might be literally within reach, thanks to landmark memory research by Ed Meloni 鈥�91.
Picture this: Sitting on the bedstand of that someone is a xenon-gas inhaler. The sufferer breathes deeply from the inhaler. And poof: Not only is the traumatic memory gone, but so is the associated and sometimes debilitating condition known as post-traumatic stress disorder.
Ed Meloni ’91 speaks to students in Professor of Neuroscience Nancy Koven’s course on embodied cognition during his mid-March visit as the College Key Distinguished Alumnus in Residence. (Phyllis Graber Jensen/乐播传媒 College)
In any given year, more than eight million Americans suffer from PTSD, which develops in some people who have experienced a traumatic personal event. Most people probably know something about PTSD through its depiction in popular culture, particularly war movies. Early on, in 1946, there was the post-World War II movie Best Years of Their Lives, then movies like Coming Home, Born on the Fourth of July, and The Hurt Locker, all of which portray PTSD sufferers.
The nightmares and flashbacks 鈥� two 鈥� feel very real. In one way, they are, and that鈥檚 the key to Meloni鈥檚 research on xenon gas as a potential treatment.
at Harvard-affiliated McLean Hospital, where he works alongside , director of the hospital鈥檚 Behavioral Genetics Laboratory. During his visit to 乐播传媒 in March as the College Key鈥檚 Distinguished Alumnus in Residence, Meloni joined neuroscience classes, met with students, and delivered an evening lecture. He and I spoke for about an hour.
Researchers, Meloni explained, used to believe that 鈥渞ecalling a memory was like reading a file.鈥� It was read, then put back. 鈥淲e thought memories were immutable.鈥� Meloni and other scientists have shown that鈥檚 not the case. 鈥淥ur memories can be changed; new information can be integrated.鈥�
(In fact, Meloni says, 鈥渙ur memories are probably not faithful representations of what really happened,鈥� which has great implications for the reliability of crime eyewitnesses, a field of research by 乐播传媒 psychology professor Amy Douglass.)
This process of memory retrieval and updating is known as reconsolidation, and Meloni is an expert in the field. In 2014, he and colleagues at McLean showed that xenon gas can block the reconsolidation of fearful memories in lab rats, effectively eliminating the fear. The discovery garnered national attention for its promise to end PTSD suffering.
Now, the promise is getting close to reality.
PTSD can affect military service members who experience a traumatic event in combat. (U.S. Air Force photo/Tech. Sgt. Nadine Barclay)
For a discovery that could bear directly on human life, the route to finding it was 鈥渋ndirect,鈥� Meloni says. 鈥淚t was chance and serendipity.鈥� (And, we would add, also some creative thinking on his part.)
As the story goes, a colleague of Meloni’s was presenting research data at a conference, where he learned that a medical gas company was interested in providing a device that would allow scientists to use xenon gas in their rat-model experiments on neurodegenerative diseases.
“You can鈥檛 just get a rat to put a mask on.鈥�
The device was needed because “gases are hard to work with鈥� in research that uses a rat model, Meloni explains. 鈥淭here are a lot of intricacies with gas delivery. It鈥檚 not as simple as giving a drug. You can鈥檛 just get a rat to put a mask on.鈥�
So the medical gas company funded a research apparatus at McLean, the first of its kind in the world, to test the effects of xenon gas on a rat model.
In terms of its general medical use, xenon is hardly new; though expensive, it鈥檚 considered a superior anesthetic and is used in diagnostic imaging. And in recent years, new research indicated that xenon could be “neuroprotective” in the brain, Meloni says, a general term meaning that it might protect nerve cells from the kind of damage found in neurodegenerative diseases and traumatic brain injuries, such as concussion.
The unique research device in place, Meloni was initially part of an unrelated study that yielded 鈥渁 strong signal鈥� that xenon was indeed neuroprotective. Specifically, xenon is an 鈥淣MDA receptor antagonist鈥� that protects the brain from an insult, glutamate excitotoxicity.
That led Meloni to wonder: If xenon is an NMDA receptor antagonist, it should block learning and memory because that鈥檚 the outcome when animals are given drugs that block the NMDA receptor. 鈥淭hey don鈥檛 learn,鈥� he says. 鈥淥r, they stop fearing something they learned.鈥�
鈥淚 just wanted to test that,鈥� Meloni says. And among myriad tests involving xenon, rats, and fear, three results proved pivotal. First, they found that giving xenon gas to rats prevented them from developing a certain fear, in this case the fear of a mild shock. 鈥淲e blocked the learning of fear,鈥� Meloni recalls.
鈥淚 was floored,鈥� Meloni says. 鈥淭hat was the home run.鈥�
At this point, Meloni鈥檚 expertise in memory reconsolidation kicked in. He thought, 鈥淲hat if the animals are already afraid? Can xenon block a memory that was already there?鈥�
So Meloni decided to pair the administration of gas with the reactivation of a fearful memory (in this case, a mild shock) that the rats had learned by Pavlovian association. When the fear was reactivated, in this case by the sound of a tone previously paired with the shock, the rats were immediately exposed to xenon gas. Tested a few days later 鈥� even weeks later 鈥� 聽they did not show fear when the tone was presented.
鈥淚 was floored,鈥� Meloni says. 鈥淭hat was the home run.鈥�
Xenon gas fills a discharge tube shaped like the element鈥檚 atomic symbol. (Photograph by Pslawinski [CC BY-SA 2.5], via Wikimedia Commons)
Last summer, the U.S. Patent and Trademark Office gave Meloni and fellow researcher Marc Kaufman a 鈥� essentially a patent approval 鈥� for using xenon gas to treat PTSD. The biotech firm Nobilis Therapeutics has licensed the patent and seeks to develop a hand-held medical device for self-administration of xenon.
The hand-held device 鈥渋s absolutely critical,鈥� Meloni says. 鈥淚f a medical professional identifies that you might benefit from xenon therapy, you want to administer it as soon as the traumatic memory is reactivated, which happens 鈥渙rganically, out in the real world,鈥� Meloni notes, in nightmares, flashbacks, or by exposure to cues that remind the patient of the traumatic event, much like when the tone is presented to the fear-conditioned rats. 鈥淭hat鈥檚 when we think you鈥檙e going to get the most therapeutic effect.鈥�
Of course, FDA approval is still required. 鈥淯p until now, there鈥檚 been no FDA-approved way to administer xenon gas aside from an elaborate anesthesia machine鈥� in a medical setting, Meloni explains. At the moment, Meloni and colleagues are awaiting the go-ahead from the FDA to begin clinical human trials at McLean.
John Kelsey 鈥渁ctivated my brain,鈥� Meloni says.
If Meloni has shown smart and creative thinking in his xenon research, it鈥檚 safe to say those abilities were cultivated by his 乐播传媒 professors. A student in the days before 乐播传媒 developed its neuroscience program, Meloni designed his own interdisciplinary major to combine interests in biology and psychology.
Meloni wanted to study the brain, and 鈥減sychology alone didn鈥檛 quite fit the bill because the brain is a biological organism. Everything of the mind is derived from the biology of the brain 鈥� our cognition, how we feel 鈥� so I went with biology of the brain plus psychology: biopsychology.鈥�
On the bio side, mentors included Pam Baker 鈥�69, now retired, and Lee Abrahamsen. On the psych side, it was John Kelsey. (Also retired, Kelsey was recently honored with the creation of a new endowed professorship in his name, the John E. Kelsey Professorship in Neuroscience.)
As a faculty mentor, John Kelsey “activated my brain,” says Ed Meloni ’91. Here, at the 2014 Mount David Summit, Kelsey hugs friend and colleague Kathy Low, professor of psychology. (Phyllis Graber Jensen/乐播传媒 College)
Kelsey 鈥渁ctivated my brain,鈥� Meloni says. 鈥淗e forced you to think constructively and creatively and to problem-solve, to figure it out.鈥�
For Meloni, a common denominator among his professors was 鈥渇riendliness. 乐播传媒 professors take the time to get to know you personally and make sure you鈥檙e absorbing the material. They鈥檙e teachers, plus something more.鈥�
Those 乐播传媒 qualities are invoked a lot because they鈥檙e valuable. 聽鈥淔or an underclassman, that鈥檚 just so big. It鈥檚 so inspiring. It just resonates.鈥�
