now i am very excited to introduce tonight's speaker science journalist has used nearly every medium to produce award-winning journalism for pbs including documentaries, podcasts, short video series, interactive games and more. the articles on memory and addiction have been featured in

the "boston globe" magazine, the atlantic and a scientific american. this book in particular was supported by grant from the sloan foundation program andnd public understanding of science and technology. tonight we are joined by conversation the author of the poison squad, ghost hunters. the recipient of the pulitzer as the directors of the journalism program at mit. tonightl the two will be discussing the debut book held by science magazine as extensively researched, cinematic and accessible. joining us tonight, the book saying theh move with the roller coaster speed of the first race novel where simultaneously we offer a deeply compassionate and insightful look at the understanding oft what makes and

breaks human memory. we are so pleased to have them both with us for this event so without further ado, the digital podium is yours. >> thank you and i am so honored to be here in part because i am such a fan of the bookstore and such a fan of this book. when i first got a look at your book i felt deeply annoyed because most of the time i could go on to other things but i got sucked into the story that it actually interfered so this is me saying i'm happy to be talking about this book and i want to start by saying your book reminded me of this, sometimes there are scientists who will talk about the brain as

a black box, so mysterious and a and even more mysterious part your book reminded me of both of that mystery and the detective work that goes on to try to solve it so i am hoping we can start with you reading a brief excerpt that illustrates some of the detective parts of the sand then go on to the conversation. >> so, this is a scene from early on in the book. on the first friday of october, he leans forward in his chair and stares at the scam on his monitor looking at the brain of a young man admitted to the hospital and the image is so strange and beautiful that he knows something has to be wrong. whoa, he says out loud to his

empty office. this is weird. against the background of the rest are two structures on either side of the cavity. together they make up the hippocampus that holds the key to memory and the intense glow is a distress signal from many. some force has laid waste to just this tiny region leaving the rest of the brain unharmed. he looks out his door to the waiting room on the floor as the hospital and medical center in massachusetts just outside boston then he looks back atks e monitor. last night'sho phone call requestinges permission to transfer the patient suddenly makes more sense. the distraught 22-year-old had recently overdosed and was dragging one leg and askingpe hs mother if he was dying.

winchester is handling emergencies like a broken wrist or appendicitis but when patients with complex conditions or unexplained symptoms come in, the staff will often send them over to a facility that has hundreds of specialists and more equipment with a high quality image in front of him, he can see what the winchester staff could not and it explains why the patient was acting strangely. in ten years of medical training he's reviewed thousands of scams, brains shrunken from alzheimer's disease, tiny broken blood vessels, tubers in different sizes, shapes implications. in every case no matter what the damage looked like, it was pretty clear what was going on but it's strange and alien. it looks like someone took a

page out of the medical anatomy textbook and deliberately highlighted the memory center. he re-examines the mri scrolling up from the base of the school to this amazing structure until the hippocampus comes back into view. it seems certain that the patient will fail the memory test given today and the damage has triggered of these strange cases ofas brain disease. he believes more in chance then destiny but still he thinks it is almost as if the years of study and obsession guided him directly to this moment sitting in this office looking at this startling image.

to widen the lens a little i'm wondering if before we go any jfurther, you can just talk a little bit about who he is and explain some of the ways that he starts building this mystery detective part of the book. >> first i should say that he's a friend of mine and we sort of share the fascination because i have a somewhat weird brain. i suppose we all do. but i thought his opinion so he also happens to have trained as an epidemiologist so he looks for patterns and tries to

explain in addition to being a neurologist how do you make sense of it so for him when he saw this first patient i described, it was well, this is weird and this is what we know happened to him but there wasn't enough to say what caused that unusual damage. it wasn't until he saw the second case when he noticed the link and said there's a link with both of them but people have been using heroin for decades. what changed in 2012, sentinel started to w work its way into e drug supply in massachusetts so that was the new thing. the rest of the book he is setting out to find out if his hunch r is right.

>> and he built a kind of network of people who were equally fascinated by this particular syndrome mostly in massachusetts. the story isn't always set in massachusetts but therere is ths mystery that begins here. it's an interesting story because it is on a shoestring budget because it is this weird syndrome that doesn't fall in anyone's particular area. it is and part of a research project that crosses two areas, addiction and opioids and memory. so you know, part of his job was roping in other people that had the expertise that he didn't have and the resources he didn't have so that was years of

late-night e-mails and cajoling and badgering until he was able to pull people together that could help him solve the mystery. >> that is one of the things i like to so much about it is you start seeing these different people and different parts of the puzzle trying to connect the dots essentially in making this work. let's back up a little bit though because one of the things that struck me again in looking at and reading your book is the understanding of memory, and i am not sure if this is a good thing or bad thing, but much of the understanding comes from injury and memory to the brain and if we do not seek that, a

lot of times this is what the fascination with these two cases to start with and i know that it gets to be more. a lot of times it is one case but too go backwards in historya little bit, to talk about the hippocampus itself and why it's so important, but a single case one of the moments in history that you've referenced is the case [inaudible] what was such a breakthrough moment if you could talk about that and also a little bit about how they lead us through this sort of group of detectives to recognize the role in memory. >> the famous story who was

later revealed, he had a terrible epilepsy and they couldn't treat it with medicine and finally in a last ditch effort to save him, sort of decided to remove both. there was good reason to think that might work because it is a very vulnerable region and it's very prone to seizures. if you think about removing the whole brain structure and it's t to do something, but they were hoping to save his life so it wasn't until he woke up in the hospital and kept asking his mother where the bathroom was that they realized they had a really hurt his memory so he was studied extensively by the rest of his life by others that were

able to tease out. we talk about what the hippocampus shapes and creates. it's the memory for the things you know or from episodes of your life that are stories that you can remember so, he lost the ability to create new memories of that sort but he had a some ngprocedural memory learning things like motor skills, but he would never recognize a new person. he didn't know despite having worked with her for decades, so it was a boom to science.

>> there's a number of kinds of memories but we do look at it as a kind of central structure, and it's not just -- it was not revealed so when you go through the papers there was a lot of recent decisions and a lot of times they will protect the identity by just using their initials, so to this day my hippocampus -- i've always felt so sorry for him and he it is part of a group of cases in

which damage to the brain this isn't the same thing but there was a famous case of a worker that had an iron bar that accidentally affect of the frontal cortex of his brain and that injury again allowed people to start recognizing what part of the brain help to deal with impulse control so he was usually influential but you follow a patient and he writes essays at the end of the book that you draw some parallels to in the way that his condition helps us understand memory and how the injury affects memory and i wondered if you would talk about him as a case study.

>> he overdosed after 18 months of sobriety on fentanyl and woke up in the hospital with this injury. because he studied memory in college, he understood immediately when the doctor said you endured your hippocampus what it meant for him and to this day, he still can't remember where he parked his car or that his best friend mightig have broken up with his girlfriend the day before. but because he was an incredibly organized person with executive

function he's managed to rebuild his life and has a job and takes classes at a community college, so he is a testament to, not to sound hallmark hardy but resilience and the ability to carry on. and he was also generous in agreeing to participate in this at the university of california san francisco aging center and a so there they learned they did to some very tailored scanning through a strange confluence and he had a scan just before his overdose so they knew what it looked like just before the overdose and then there was imaging done i at the time that showed that glowing image that i described before, then he came back and they measured the volume and it had a shrunken

write-in% which is as much is a 60-year-old would lose in a decade and they did this very detailed testing of his memory and other cognitive functions and his episodic memory for numbers or events he scored on par but the rest of his function is perfect so what his case showed is that it can zero in on this one structure in the brain and this was completely underrecognized. there was an anesthesiologist that did recognize that and handed done research for 20 years and gave up because no one wanted to fund it anymore, but it wasn't at all not well-known so now the question becomes now

we know that it can damage the hippocampus. can we turn that around and use that knowledge to find ways to protect the hippocampus? >> i want to zero in on that precise point for a moment and then open it back up to other emissues in memory moving even s you mentioned to the comparison between the memory affects that are comparable to alzheimer's. so, lots and lots of people had been prescribed in these versions of the same. we see this exposure and the

members even in your book. >> has the research been done because what causes the damage to memory, do people understand that? what is it about fentanyl? >> one is what causes the damage and why does it not happen to most people. the first one how does it cause the damage gets a little bit wonky but basically there's two main classes that we think about that get enough input and they sapass the message along. those represent the majority of

neurons in the brain but there's also the inhibitory neurons, and those are to manage everything, like the balancers and they keep thingsgs under control so when they are out of commission, you have chaos and that's what happens with fentanyl, it locks onto these specific receptors on rsthe inhibitory and shuts them down so they are out of commission and then they are firing wildly and burning up more energy than they have and this is compounded by the people that use opioids so they are alsoso usually somewhat hypoxico that exacerbates the problem because they are not getting enough oxygen to this vulnerable structure so that's the idea of the mechanism of damage but why it doesn't happen to most people

is definitely still a mystery so it could be a genetic predisposition that's rare or a prior use for example owen had used drugs since age 11 but had been sober for a year and a half so was it the prolonged use followed by sobriety and a dramatic overdose that was the problem, is it vascular and how different people said in different ways, so they really don't know and that will be very hard to tease out because there are so few people and you are right there are more people thaa we realized but even so, there are few and i want to speak to the point about fentanyl is used in east asia every day and 80 to 90% of surgeries and clearly this doesn't happen to these

people but they are supported with oxygen and also it counteracts so it's protective. >> that is reassuring. >> i think a it's a question tht goes well beyond all of the different diseases and responses that we see and that lets the individual respond. so, still many mysteries that leads me to branch out into other issues of memory. let's talk about memory and then go and sort of expand this to something that's probably seen

as an epidemic which is alzheimer's and the more we understand memory and how it works or w what triggers injury and how we best treat that you can generalize from and that would certainly include the understanding of alzheimer's. i don't know myself if i would describe alzheimer's as an epidemic because it is always we are able to do better diagnostics so we are more aware of this specific condition and other dementias that affect memory. why does it matter so much, and it's not just about daily

function and if this gets back to the sort of core of the memory issue. to sort ofe navigate daily life but inf the more existential why doess, this matter so much? >> i will goo back briefly to i what i referenced in the beginning because what drew me to the story i had an episode whereor i lost my memory for a couple of minutes meaning i had no idea where i was or who i was. if you asked me my name i couldn't have told you so there was no connection to the past, present and future and that was deeply terrifying because yes without your memory you don't feel like anyone.

there's still even someone with severe memory problems feels loved and connection so it's not just as black-and-white as i described it but it's also about remembering the past and who we imagining the future and this is one of the more interesting experiments that i talked about in the book working with people with severe amnesia and damaging and people who were not damaged and so she asked all ofof them tell me about a day in the beach. what do you see? so they tell a whole story. there's a boat going by and i hear the same goals and lots of details. the people with the damage to

the i hippocampus, there's nothing. they know conceptually that there's light sand and a blue sky that that's all she can say. that's it, i'm kind of floating so they can't imagine, they can't create a new scene out of their mind. that's part of what makes us so human and what we are is imagining things that don't exist yet and projecting into the future so it is as much about having a future as having a past. >> that's such an interesting point. when we look at it, i am sort of making a huge leap over to the larger memory related to diseasesby opening up the alzhes

box. if we look at the complications and that affect alzheimer's, do you yourself see parallels and how alzheimer's affects the brain and most particularly condition or is it here is another issue in which we see central that we don't understand best how to protect ourls memories? >> there are some parallels i will send aware of in the opioid system and alzheimer's it wasn't clear very early on except for the fact they both target the hippocampus. in most forms it's where the damage first began so that's why in most cases, memory loss is

the first sign then the damage spreads out from there but from the inhibitory neurons and that and balance between them that can be damaging that is also known to be a feature both of aging and especially before alzheimer's disease so in the hippocampus there's this in balance and a little too much activity that makes it very difficult to encode memory so that is a new target for trade treatment is drugs that can kind of tamp down that hyperactivity. >> in the early test phase are they moving sort of towards the

clinical trial process that might be used? >> there's an off-the-shelf epilepsy drug, not too surprising but a tiny dose of it, and that is in a phase to be/3 it's the protocol of the trial, it's a smaller group but the result is good they could approve the drug and event what happened in late 22 so it's fairly far along when you start with a drug that is known and you don't have to go through all this testing to determine if it is safe or not. >> i want to come back at somee point and there might be interest in how the fda decides to improve treatment.

let me ask you at this point, i don't think even though we can look at structures like this and play a central role i wouldn't say we've written a book on how memory works it's what causes were triggers the memory loss either. every finding comes with

asterisks and understanding the full picture but it's always incomplete. those that recognize the importance the different case studies that remind us i think this one case really tells us something. we've got the individual varied response and universals about how the brain works so going back to alzheimer's for a minute, when you think about the way that it affects memory, what is your best understanding of the mechanisms and we have a few

questions andle i want to encourage people if they have questions about anything in the book this is a great moment to add them into the q-and-a. talk about alzheimer's a little bit, and i'm curious as to whether working on this book madede you think about alzheimes in a different way or sort of impacts in a way that you hadn't thought about before? this u is true for many of us because by the time someone has alzheimer's, usually you don't see them. they don't go around, they are visible unless you know someone who has it or you know someone who is taking care of someone with alzheimer's.

but we know a lot about alzheimer's, but we don't know what causes it so that makes it hard to treat so it's known a lot of features or what they call biomarkers like these toxic proteins that build up in the brain and hyperactivity and inflammation and where the damage is but it's believed to have happened way early year and it's not clear why it begins and there may be multiple causes were on ramps to the disease, so it's very hard to figure out because it is a diseasee of aging. many people with alzheimer's

disease might have some other disease as well. they might have some a cerebral vascular disease, so it can be sorto of hard to see the part. >> the more i think about e'alzheimer's if there is a there's apersonal connection, ms hope to go throughgh our lives with no connection i think. i'm going m to briefly mention mine and that is going to allow me to segue into personal stories. it's the one person who was diagnosed with alzheimer's. i was shocked actually.

of all the people i would have predicted would have ended up with an alzheimer's memory disorder was the last person on that list and i will add this also comes up in your book anyway that has been disruptive in some ways the things that are not focused onon infectious disease she ended up in a memory care unit that was knocked down due to covid so i have strong feelings about alzheimer's and i have a question here but is related to something that you raised in the book and also personal. can you say more about your own experience and what caused it

did your memory simply return? now we talk about the personal experiences again. >> what happened is it turned out it was a type of seizure that was caused by a brain lesion, so i went through a lot of the testing after his injury and i was advised by the chief ofto neurosurgery and i didn't like that idea, so i got a lot of second opinions and i was told by neurologists to hang tight and take some medicine and i would be fine. that has been the case. i've had a tons of mris and the lesion is still there. fortunately for me it was a one time event and i consider myself

extremely lucky. >> didn't that add some depth of understanding in the book? >> definitely both in terms of the period of not knowing what was happening was so scary and even if you get a bad diagnosis that's what people with this opioid syndrome were missing is what happened to me and why and emi the only person out there. >> that makes perfect sense. this is a question from pat

related suddenly there were other chemicals that affect the memory suddenly or slowly i suppose, especially after the lifestyle chemical? >> anot lifestyle chemicals tht i'm aware of but there is another toxin that can damage adjust the hippocampus, and it's called shellfish poisoning and it's a toxin that accumulates in shellfish during algae blooms. so, similarly, it's just zeroes zerosin on the hippocampus and y damages it very severely. ..

>> ended turn over their text messages. which were fascinating because they show the kind of back-and-forth in the evolution of ideas over the years as they tried to sort out what does this mean? what can we learn from owen rivers? what are thefo implications? could this form the basis of the new model for alzheimer's?

so actually i am a little surprise he let me do this because he doesn't like the limelight. but he was very much motivated by wanting to get the word out because there are undated undoubtedly more people out there who don't know what happened to them. it is possible that now more people will be aware of it. >> that makes perfect sense. and those personal main characters. how do you choose the material to include and why would you want to include those personal snapshots? >> it sounds silly but science

is done by people and i think how science advances depends is depend so much on people'ss personalities and how they think about problems and who they talk to. so those text messages and e-mails really revealed people's personalities and their persistence and how they thought about things that would be boring for me to just describe in the omniscient voice it is interesting to hear directly from those people. of course there were tens of boring e-mails i sifted through. but you have toe, choose. but the ones that tell the story, you will not sit down and tell everyone oseverything that happened. you will choose the highlights. so that's what i did see that that's good writing. related to that, was there

anything that was fascinating you learned in your research that ended up on the cutting room floor or story you did not tell? >> it was some interesting science which i just could not working because it derailed the story. but again at uc san francisco that with those opioid respect —- receptors and found out that we have our own opioids like sentinel and those behave differently and go inside neurons and they activate other receptors.

but that was interesting. >> i went to go to an interesting question from cindy which has to deal with exceptionally good attention and as describing an 80 -year-old who has an incredible memory counting backwards seven from 100 i'm not sure i could do. she totally nails that and in another cognitive test or memory test, she is all over it. i actually think about this myself but when you get to be middle aged but with memory

and longevity he start to lose some of your memory for names as we get older. and i certainly see some of that and myself sadly enough i don't remember names as well as i did. but not only does it with diseases but do we understand any of the biology behind an exceptional memory? but that is a great question i don't know the answer. i don't know if that has been studied. is that something i looked into i met someone on a research trip that every day of her life she could go back and tell me what was happening

and remember conversations but it was wild. some people those who have those exceptional memories are not a great thing but for her it just seems that it was fine that she enjoyed it. >> that should be your next book. [laughter] >> memory geniuses. i don't know if it will be is as good as this one but related to that in the pinpoint way is there any evidence that memory exercises or games or crosswords or whatever actually havee any effect from the any memory enhancing spirit there is a concept called cognitive reserve the ability for your brain to still keep functioning well even in the

face of damage that is happening. there is evidence that cognitive exercise is helpful to stave off every loss in dementia but not the kind of things like the crossword puzzle you do every day like sidhu go on —- it has to be hard whether learning a new language or challenging yourself and to be socially engaged. and having experiences. your brain needs input also why having hearing loss is problematic because you are not interacting with the world is much. anything you can do to basically work your brain is a good idea.

>> that reminds me of the many times people say to me with some work related questions which i hopee we can get to and then i expect you have got ando these before that have been approved but let's look to these quickly. so other books about memory or amnesia or related have you read the new book about the sackler family and do you have any results? >> i have not read that book. one of the books i read is the old —- an oldie but a goodie

talking about memory and what it is for and how it fails us and still holds true today. there are two recent books with the problem of alzheimer's if you want to dig into and how we should be caring for people. that is good. there is a new book out called rememberingsa that is more focused on the science of memory. if that is your interest and then one of the books i read about addiction that i found interesting is called the biology of desire. that takes the position that it is as much a disorder of learning and memory as it is the disease. >> i like alice and the points

of memory. i should look at that. the fda, and this has been with the science writer approved the drug and then the approval process actually has three sciences from the fda on the board because they were so unhappy how it turned out. but yet there is a lot of people lose hope it would be helpful. so talking a little bit about that would be wonderful. >> so the advisory panel recommended against approval. that is not to say they know

it doesn't work but the evidences and their in their opinion to show that it does. so many people were surprised it was approved because they were 25 previous clinical trials targeting the amyloid data w so similar purchase did not work so why this was finally approved, there are a lot of ideas why it was approved and of course everyone once a drug to work so it's harder b to develop other drugs because there is already a shortage of people for clinical trials. now that will be made worse because there are so many people taking this drug that they are not available. that is a concern but is also possible because the fda approved this drug people will feel more confidence to come up with other strategies.

so before this decision was made i spoke with a lot of researchers this at this is a great time in the field so talk about finding a treatment it is a renaissance and we can see that three or five or ten years. so despite all of the concerns with the bill and the optimism in the field is not what the answers are. >> so as we close, are there other points you would like to

say about memory or potential investigation are the secrets or the points you would like to leave our audience with? so the case study is scorned those comforters were low-level and one-off. but for me and those are the opportunity to say what did they miss? when something doesn't m make sense is either the observation was't incorrect or we didn't know something that is important. you are seeing it for the first time. what does it mean?

the way in the back of your mind and movee on or are you in a position to say i want to figure out what this means? sometimes it unlocks adi holy way of understanding human health that is very valuable. so sometimes it is the opposing ideas of the things that make sense to make sense and the open-minded but also skeptical and check yourself before you jump to conclusions i'll be both critical and be open at the same time so to be a great scientist that is what you have to do. >> that such a wonderful way to close this discussion. i wish we could the questions

have been so smart and then to talk about a great book like this thank you to everyone. >> think it's a great conversation great to be here. >> i will echo you both. once again tremendously and with the recent fda decision as well. and thank you everyone out there all overin the country. for spending your evening with us. have a great night and please keep reading and be well. take care.