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Sara Manning Peskin takes readers on a harrowing journey through the “hijacked brain.”

A Molecule Away From Madness: Tales of the Hijacked Brain
By Sarah Manning Peskin
W.W. Norton, $25.95

In A Molecule Away from Madness: Tales of the Hijacked Brain (W. W. Norton & Company), Sara Manning Peskin Gr’13 M’15 GM’19, an assistant professor of clinical neurology at Penn, unveils a series of medical mysteries. Writing at the intersection of medicine, public health, and molecular biology, she describes how missing, mutated, malformed, or toxic molecules can result in a panoply of neurological illnesses.

She begins with DNA mutations associated with Huntington’s disease, frontotemporal dementia, and early-onset Alzheimer’s—frightening degenerative diseases for which we still have no cure, though some treatments are in the pipeline. Then she discusses “rebel” proteins, whose malfunctioning can cause a range of ailments—often hard to diagnose but possible to cure. She ends with small molecules: both vitamins like thiamine and niacin that we need for health, and toxins like mercury that can destroy it.

Her debut book combines medical history and contemporary case studies: the Colombian clan plagued for two centuries with early-onset Alzheimer’s disease, the woman who hallucinates that she is in the TV show The Walking Dead, Abraham Lincoln’s spasms of temper that were possibly caused by mercury poisoning. 

“These are tales of havoc—wild personality changes, memory loss, death, and afflictions in between—that illustrate what any neurologist knows, and what the people in these accounts have come to understand intimately: we are each just a molecule away from madness,” Peskin writes.

She recently spoke about her book with frequent Gazette contributor Julia M. Klein.

Why neurology?

I was interested in diseases that changed people’s personalities and identities. Diseases of the body can change the way that people think or act, but it’s really only diseases of the brain that can fundamentally change someone’s identity.

How difficult was it to secure cooperation from the patients whose stories you told?

Most of the things I chose were relatively rare diseases, and people like telling their stories because it’s really lonely having these diseases. A lot of them had diseases that were undiagnosed for a long time, and there’s a feeling of wanting to publicize what happened so that other people in the future don’t suffer as long. It can be therapeutic for patients to tell their stories, and they don’t really get a chance to do that.

What was the thinking behind your title?

So much of cognitive neurology is trying to distill the macro to the micro. A patient comes in and they describe what’s going on in the real world. And our job is to distill that into what we think is going on in a molecular level in their brain. I wanted to capture that process, the trajectory of going from patient story to molecular diagnosis.

You suggest that we’re on a frontier when it comes to treating neurological diseases—that oncology is ahead, and maybe neurology will catch up.

They’re ahead of us in terms of figuring out what molecules are causing their diseases, but we’re getting there. Once they figured out some of the molecules that mark tumors, then they have treatments that target those molecules. And that’s what we’re trying in neurology. About 20 percent of people with frontotemporal dementia will have a genetic mutation causing it. And, for some of those mutations, we have [drug] trials.

In researching the book, what did you learn that was new or surprising to you?

I didn’t really know any of the medical history. When [Alois] Alzheimer first presented his description of Alzheimer’s disease, there was complete silence in the audience. Nobody cared at all. Later in the day, someone made a presentation about masturbation, and everyone was so excited to talk about it. Here Alzheimer had just defined this disease that’s going to change the world, but no one reacted at all. I just loved learning these stories.

The book has a hopeful tone.

That was very purposeful because earlier drafts did not. People felt it was too depressing. I actually feel that the field is in a hopeful place. We’re in this incredible time where we have tools that we never had before, and we can diagnose things that we could never diagnose before. A lot of the diseases I wrote about are now curable.

You call yourself a dementia doctor, and those diseases are the most intractable ones.

I’m part-time in the Penn Memory Center and then I’m part-time in the Penn Frontotemporal Degeneration Center. I also do some [work at] the Penn Neuro COVID Clinic, started this year, seeing folks who had COVID before and are noticing symptoms. So much of what we struggle with is the lack of tools to care for people, and the biggest thing we treat is really isolation. COVID has just been awful.

What impacts have you seen?

There have been some good things and some bad things. We certainly never did telemedicine before, [which] can be incredibly useful. On the other side, when we see new patients with prominent movement symptoms, telemedicine can be really frustrating because you sometimes can’t figure out what’s going on.

In terms of the social impact, it’s been tough. The way that we make life better for people who have cognitive symptoms is to keep them engaged and interactive, and that’s been so difficult with COVID. For partners and caregivers, it’s been particularly painful because being married to someone who has cognitive issues can be extraordinarily isolating. And then we’ve just taken away their face-to-face interactions.

What should happen?

If I could choose one thing that I wanted to do, I would have a lot more adult day centers. And then the other thing I would choose is better mental health support for caregivers, and for people with dementia.

What are some of the takeaways you’d like readers to draw from the book?

I would like people to feel an awe for the brain and an awe for how we function in everyday life with all of these molecular pathways that we have. We don’t even think about it, and then when one of them gets broken, it can have these dramatic effects. I wanted to impart a sense of awe for how we’re all living on the edge, and we don’t realize it.

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