Well, i just want to welcome you. We are still so thrilled tonight to be hosting doctor John Palfreman in conversation about his new book, brain storms the race to unlock the mysteries of parkinsons disease. His books are up for sale at the register. Also, a big thank you to the Parkinsons Institute in sunnyvale for helping us arrange this. And cspan is here filming tonight. I amim going to ask you to raise your hand if you have a question command i will bring the mic over. Professor emeritus of journalism at the university of oregon, and me, dupont, and peabody awardwinning journalist, nieman fellow, and recipient of the victor khan prize for excellence in medical science reporting. John palfreman is coauthor of the case of the frozen alex along with doctor jay william langston. The science fix director of the institute in sunnyvale, california. They coauthor, received numerous awards including the distinguished Achievement Award for modern medicine. Please help me give a warm welcome to the dr. Thank you. I learned we had parkinsons disease. Turning up in psych wards in prison cells unable to move or talk. Contracted the symptoms overnight. My colleague here cracked the case and realized there was a neurotoxin that led to a big revolution in parkinsons at the time. So i will say a few things. Thirty years. Northern california. Turned out to be a huge boon in research. Also started a whole renaissance and john read that and said this would make a great notebook. Awardwinning program. You think i would behave cigna in a sophisticated manner. After about a year i went to visit with bill in los altos. We talked about the developments in the last 25 years. I thought this was my duty as a parkinsons patient. And it has been a wonderful experience because i got to meet many neuroscientists instantly in common the share a lot with these other people and pretty sure tom isaacs walked around the coastline 4500 miles which is the equivalent of the Michael J Fox foundation and he is remarkable. Basically the exploration of parkinsons the journalist has to take care of the truth. There is always something coming around the horizon. Yes, and johns book and from my own personal view, 20 come almost 30 years really. And we had a lot of false leads. We can talk more about it later. I think we are on the threshold and can talk a little bit about issues regarding that an embedded. I think we have the corners. The jet was the talent on the size. A brilliant exercise this. And theres a lot of books that have been written on parkinsons disease. Some of them are about patients to talk about what its like to have the disease. And there really good books. And i dont want to preempt what you are going to say, but as a journalist people didnt no he had parkinsons but he basically interviewed the top 30 or 40 scientists in the world. When doctors no you have parkinsons there going to softball little bit. So he got straight information and put it together in a book where he goes between what its like to have the disease, change the thinking, pathways, dealing with it, but absolutely brilliant science and alternates more or less from chapter to chapter. My rationale for doing this was that i wanted the honest truth, no one holding back vital information. But i wasnt entirely convinced of my reasoning. Maybe i did it because i could get away with it. I told them up front i had parkinsons. On the other hand they usually avoided mentioning lab research. The truth is like many diagnose people and driven by an ever less practical desire to blend. I know the disease. But for now i think thei think the desire look normal is an important part of my therapy. Many patients would go through this sort of process. Under science parkinsons has been characterized for a long time as primarily a movement disorder. O ousi[uk it is difficult to talk about from a Patient Point of you. We have an idea of the bad actor. We think it is a mis folded protein that goes rogue which the stick hesticky comps go from cell to cell destroying them as we go. We have a model of pathology a bit like the zombie movements. The person touches they had another protein and it spread throughout the brain and that way which is given a lot of hope that disease modifying treatments to a lot of excitement. It has become kind of visit a pivotal piece entitled parkinsons disease, the tip of the iceberg. I felt when i wrote that that this can affect multiple areas in the body, the spinal cord. I thought i would get a a huge amount of lender letters from the editor, but i got accepted with them new revision and i never got one negative letter. And now we know that this disease does not affect many other areas. While it is in some ways not sounding so good, let me tell you a policy side. Before this neurologist, patients would come in and we put change their set up, but they have these other complaints. Its kind of like the waitress, its not my table. Constipation, urinary, bladder , we just didnt think that was part of our bailiwick. And now we know almost all of those are parkinsons. We are trying to develop what i call a circle of care are getting urinary bladder problems, experts in g. I. Problems, sleep disorders, and the doctors who are not just in their own specialty like a regular urologist but they really know the neurological. Parkinsons is doing this. And in outreach urologist wont even think about this. And it is different. Now we are starting to grapple with them. 80 percent of my practice now im dealing with all these other issues. Sometimes more bothersome to get sleep, up all night because there having to urinate frequently, constipation, horrible. We are dealing with that which is the good news. One of my colleagues at ucla said you know, the gps. We now know we have to deal with these things. The 2nd thing on the policy side is, many of these start before parkinsons in fact we now know a huge number of them can. Ranging from the ones john mentioned, rem sleep behavior, anxiety, depression, parkinsons my five or ten years. Now, that is a clue. If we can get early for this reckless devastation, every system needs what is called secondary prevention. So we do these words gives us a handle. In 06, so i start with a little vignette. And he said he lost his sense of smell for ten years. About five years ago hes having problems with constipation. Now he comes in because having violent behavior, the acting behavior, this part of parkinsons. See people, see doctors. And parkinsons is the 1st diagnosis. We all know that is different. It gives you a chance to get in there and do something early. The other thing is dealing with the whole disease. Any drug that helps you got to deal with the whole thing. Those things you mentioned, risk factors, what you need is a biomarker. If you had a biomarker ten years before your parkinsons is a kind of Skeptical Science journalists, i dont expect them to work totally straight off the bat, but there is good grounds for hope. The other side of it, that is what we call disease modifying therapy. The other thing that is important, help us with the symptoms, some to modifying. Extremely fortunate to have this chart levodopa although i have to say that it has been known for over 50 years and in that 5050 years we have been to the moon, sequence the human genome and invented the internet. As a patient i see this and say more should have been done. Do you agree . Fifty years and what have we cured . A better way of delivering levodopa. There is good news on that front. And i want to come back to this in a minute. Number one, one of the big problems is, it is still the best drug after 50 or 60 years, when you take a pill it peaks in about an hour and a half. And so their all these problems. It wears off, its inconsistent. And now we think upanddown, it actually works, i think, almost forever. It is just doing the ups and downs. And when the side effects it you have to cut the dose when you want more. A couple of exciting developments. What is out there, and it just came out on the market about three months ago. In this drug, we help them for ten years withten years with it. It is a castle with many little castles inside and each one dissolves a different rate. So we take it and keeps releasing levodopa. Instead of bouncing all over the place you get these nice spots and there isnow evidence if you can get that some side effects go away. That is out there right now. A lot of the companies are not covering it yet. We can work on the insurance, but you can get that right now. Now. Secondly, really interesting is inhaled levodopa. To starting the trial on that. A form now, like an inhaler and within minutes he turned on. There just talk, frozen. This could. This could be a wonderful rescue therapy, even in the best circumstances. Just start rolling patients without trial about two years ago which is another one right now. The 3rd one that i think will be the big winner, the company has a form of levodopa , you have a little box in there are tons of little needles, epidermis into the dermis. And when you put it on the measure. Straight into the bloodstream. No, no down. Side effects, therapy, if you can get that kind of continuous stimulation it goes away. Already in phase i trials in israel. I said, look, we want to be the 1st place. I think thats about a year away. That is going to be huge. They already on the trail with it. Some of these other compounds. It is a big deal. One area. The 2nd is to do with deep brain stimulation. Seems to me so far it has been a bit hit and miss. Miss. Spectacular results with some patients but not very good with others. There is wonderful closed loop systems. Instead of putting in an electrode and turning on and leaving it you have a system which weights. Membranemembrane tells me know about to termer and it kicks on and interferes with the circuit that is causing the tremor. Those kind of Adaptive Systems are coming out, and i think they are pretty interesting. The 3rd area which seems to me to be an absolute nobrainer is the important of exercise. Data and exercises so compelling that if you are a parkinsons patient you really need to do as much exercises you can. There is a concept called forced exercise. I do walks every day command she is a pacemaker, important. The speed at which you walk is incredibly productive for mortality and morbidity. If you can push yourself it is an advantage. The data always. I can tell you an interesting story. I believe that for 25 years and tell my patients exercises every bit as important as the medicines. A mile a day keeps the doctor away. And a couple years ago they came in from the university of maryland which i championed. The 1st really Scientific Study on exercise in parkinsons. You know, the others did video games, etc. 3 million. Exercise, particularly walking is the only thing that has been scientifically proven to help gate and balance which is a huge issue of parkinsons. And so the person who did it, you know, been telling my patients this for 25 years. She said,said, i wish you had told me in the 1st place. It is nice to have it. So in that study normal walking, just normal walking. Go out,. Go out, leave your front door, walk for 30 minutes and come home. It also reduces the incidence of stroke in fatal Heart Disease by 20 percent. So its a good thing to do. Do you want to talk more . So many neurodegenerative diseases, one of the big problems is it doesnt make new neurons. There is some evidence it can do that, but mostly they dont regenerate will. If all your memories are stored and neurons get kicked out with new ones there goes the memory. Its a huge handicap and treating disease. All these are due to ms. Folding proteins. And if you think of it like a towel, proteins are kind of like that, except they are folded in all different ways. As they get misfoldedmis folded the body cannot get rid of them, so they pile up. Think of it like you cannot take your garbage out of the house anymore. So that is what happens with ourselves. These proteins fold and can cause cell damage and eventually maybe cell death and for the 1st time we have approaching in parkinsons. Its called huntington approaching. A betaamyloid. Discovered through a rare family that had a mutation gene. All these and other symptoms we are talking about. When you do that, if at isnt where it is, it can be huge. Not only do i think we could stop the process of parkinsons disease but it turns out there are some areas of the brain those cells actually die. In many areas they dont. The cells are just not working. You look at the processes, they are not working, but they are still alive, still death is so overrated because a lot of times is piling up, the cells are still bare so if you can find a way to get in there, not only stopped progressing, this protein reporter we might be able to stop symptoms but sold death no. These neurons can better transport. If we get rid of that a lot of the come back. It is a social problem. The body has its own means to deal with the garbage, it gets overwhelmed. There are these Little Things there are many of them in each cell. They actually look like garbage disposals. They outlived their usefulness, kicks out of me know as since the start over and make new proteins, anybody here put artichokes than a garbage disposal, it doesnt work. That is what happens in these cells, they choke on it and cant do it. And before it hits these did garbage disposals is find a way to get rid of it. Hearken back to this, these antibodies studies, it is an exciting time. Within five years would never have said that before. The first time he announced he had parkinsons disease, it was myself, and 200 advocates and the agency the head of that, i couldnt believe, with enough money you could solve this disease in five years and i was shocked. 10 or 15 years from now. I do think with what we have now we might be able to do it. When this hearing ended it was the first time, in people magazine, parkinson, there were so many cameras in the balcony and when the hearing ended i actually got to remember the beginning of this, george bush was president , it hit the scene. They said michael, what do you think of stem cells for parkinsons and i will never forget the response, this president said stem cells, you are asking me about stem cells, i didnt even graduate from high school. I wonder if we can take a few questions. We have a microphone. Can you tell the name . Just like it sounds. Rypier rypierre. It came on the market two weeks ago. Parkinsons, we have to have the laws about it and maybe start it is really doesnt work for everybody. Number one, switching is tricky. We only get it to rise half the time so then you have to adjust and there are only four doses. You dont have a lot of them there and it doesnt work all the time but if time, youll learn how to switch, in these tassels, were going to get better. But it is terrific. There are problems and we will work with those. Talking about solving rather than curing. Very careful about using the word cure. I say dont use it. Because clearly unless we get to the point we stop it before it gets into the brain, it never is going to be but actually curing, once it is not in the brain, the cells have died, truth cure is a long way away. Stem cells are not going to do it anytime soon. Feels sells under Ronald Reagan which he put a moratorium on, they didnt work. Sunday i think there will be an answer but most people early on are not really disabled. If we could stop it right there, and doing it before my idea is how they dont know what the symptoms are for that. And cell testing. And maybe this room suite, two of those when you go into age 50, snail testing, the doctor is in the waiting room, wont take any time, we can track the heart for earlier symptoms. As far as the annual physical. And imaging test now. Trying to find imaging agents it binds protein so you can actually see the pathology. We would have an absolute people are working very hard. I want to know, i dont know if this is folklore but i can tell you parkinsons was mainly genetic, and starting to wonder, so many people are getting it. Is it an environmental, they would have died of other things, why does it seem to be more maybe that is your question is from the heart it is now if you go back in history, it started in the 1800s. The pioneers, muscular dystrophy and parkinsons, both have opposing views, the great pandemic of 1918 came along, killed 20 million people. They got parkinsons after that so we thought was environmental. And we discovered this, molecule, a lot of things, oil tankers, you name it. Way back toward environmental. In 1997 the first true genetic form of parkinsons was discovered. Something we thought we found the cause. Of few families on earth, with parkinsons, it is a classic where rare genetic forms, where are we now . The biggest respect would be aged. Genetic environment, we have one example if we are exposed to a certain chemical, lets take another one. Head trauma, parkinsons, not that clear. A mutation in our genes causing morea risk, kind of soft. If you had the genetic change which increased and one episode of head trauma, loss of consciousness for head trauma, increased 11fold. We have not found something similar used by dry cleaners and play to that now. I think it is going to be both, genetic or environmental, you still have to have something kick it out. Theres no clear answer. 20 years ago. What is the purpose of properly foldouts in a clean in the body. Focus, first described it, you will love this. Is very important when bird starts to learn how to it goes back up, being discovered by environmental biologists, and in alzheimers disease, some of the facts, it wasnt until the genetic form came out, and parkinsons, parkinsons, we know when it is damaged, chemical or mutation in the genes, making what we do parkinsons early, two months of it. What its normal function is we still dont know. Still dont know. One of the worries about these drugs to knock it down is does it do much . We may find out for the first time when it is important for. We knew having too much is a bad thing but we dont know about how little so the answer to the question is after 20 years is still a mystery. This ray of evils you talk about. Is that what some people are referring to as a stomach pump . Subcutaneous. And we are not doing that as well. You have to make an incision and put a tube right into the small intestine. This is a gel and it has a little pump that pumps it in constantly. We are just starting we have wonderful g i dr. Parkinsons on the west coast, he will do surgery for us, the same concept, you pump in consistently, it slowly dissolves. Not as far as the stomach at all. Almost instantaneously. That is another way to do what we are talking about. The problem is the surgery, someone told the the first thing you have to be a little bit of a plumber. It is quite user friendly. We still take insulin pumps and use it. And the new one is narrow dome, the epidermal, really coming. More often than that one. Hi have a friend who has parkinsons, one of the questions my husband and i have as we continue our friendship and parkinsons continues to progress and things are more difficult, what would be the best way to be supportive and encouraging this combination of being supported and tough, the easiest thing with parkinsons is to give up, stay home, lose your selfconfidence and you are not sure what you can do that you used to be able to do and since we have this new model, every possible malady is parkinsons, you can blame anything on it. That is not a very helpful strategy. You have got to push the envelope. You should be able tough on the people as well as supportive. It is tough but i see a lot of people, when you go to these patients, some people are doing really well, some people go downhill incredibly fast. I totally agree with that. I always compared to the tin man in the wizard of oz, you dont use it you are going to lose it. Sometimes that takes a push, not being overly supportive. He spoke at the Institute Two years ago and it was a volunteer 15 years old, my grandmother has parkinsons, this and that, what should i do . I dont think that is right. It will make her feel dependent, maybe she needs to do that. I thought that was an interesting answer. You got to take a balanced approach, we need to be chairs that push you out. Really push you up and out of the chair. We got to get this, no. It is a balanced approach. It is not good. The other thing is there is an enormous variation in the attacks parkinson people get, enormous range and some people, you get the parkinsons patient, good days and bad days and it is mysterious, you dont know why. You may be anxious one day and another day you might be fatigued and you dont bet an explanation. You see a neurologist couple times a year and they have 500 patients and they get a snapshot of this so it is difficult to get a sense. I dont think we understand much about the phenomenology of parkinsons and patients need one thing that is encouraging, sharing a lot of tricks, all kinds of tricks to get around the tremors. How do we need something with a spoon without spilling it . Also some tricks about changing your mood when you feel too down . The easiest thing, the problem with all these nonvoters symptoms is if you end up with too many consultants, psychiatrists, neurologists, cardiologists you could become a fulltime patient. That is the key to what were going to do. We will have our own entrance but we have specialists in every one of these areas, and we are all on the same medical records so every one of those, you dont have to go to San Francisco or somewhere else. All those things will be right there. If you get that they are all communicating the same funds, the diagnostic community is here but right now you wind up going to all of this full time stuff. Deep brain stimulation doesnt work for everyone. Why does it work for anyone . When you talk to people like the experts, they are not sure, basically the way i understand it is deprived of dopamine these circuits are downstream, start misbehaving, and if you get the electrode in the right place to block it you can interfere, you can shutdown something, better to shut down something that is behaving badly than to let it go. They say it is real estate, location location location, the way they the operations are very long and last six hours, most of them still do it by listing, they drop the contact and listen to the sound of the neurons and when it makes a crackling sound, that is going from spanish to fringe and english, sells have different languages. They adjust the voltage on this device, put it to four volts and a persons face goes like that and they turn it down to two. It is hit and miss. But when it works is amazing. It is magic. Synthetic heroin, that gave us the first really good model in animals with the disease and they use that model to trace out when the game does and it turns out the actual when it goes down is inhibiting and stimulating another place which is another place on and on and it is crazy and able to match the animal model. With the nucleus which once this Rube Goldberg apparatus, this area was no longer inhabited. And the model of parkinsons, it went away and started to be nobody is really. It is almost as significant and new imaging techniques, probably the best guy in the country, they dont have to do this. Damaging is so good. Under general anesthetic. Trying on the patient but it is all the same. We will do three more questions if that is okay. You talked about medication to treat the symptoms. What is the status of medication to slow the progression of the disease . That is what i am talking about. There is one drug, trying to slow the disease down, theres a lot of evidence i think it is the safest drugs, something we start on. The gold ring in this, the drug that clearly stops that is where we are. There have been some setbacks, factors, hoped that they would reside neurons that havent worked. They dont mention neural grafting that was done to replace a lot of things that looks like they were going to work 20 years ago that failed in double blind placebo trials. It is very robust with parkinsons, particularly in surgical trials. That is something we can use as well. That was a great disappointment. Science is a process of going up alleys to see if they are blind. One Board Members said once why dont you do experiences that you know are going to work . No, no, no. We had disappointments and a lot of them. I have been through all of them. I was a cheerleader for narrow transplantation but it didnt work and we still dont know why. It completely corrects a pets can. The scan of the brain there is mild inflammatory response to it this, we still dont know. That is why maybe you just answered my question. I thought i heard an investigator six months or a year ago talking about new stem cell therapies putting them right in still quite positive. Did i miss a trial way will let oversold stem cells and i think scientists, doctors stated this as much as low media. Stem cells are starting to kick in, things like rental disease, macular degeneration, we have already done it with fetal tissue, the same thing basically. It didnt work. People who are trying to do that with them sells oil down to repeated. And we have the measure, all of those and more are reasons. It is inspired and they sent 3300 million developing this indeed is only used for child could, 73 cases in the United States says theyre sitting on a 300 Million Investment that could change the way we diagnose parkinsons so we are working closely, we have gone to the level of the guy who writes the check is and we get it and start doing this scan and particularly if youre going to clinical trials, one genetic form which 1. 5 , half of those get the other half dont. They get the generation and child pass college. You got to know. Anybody who knows anybody, scientists all want to do this. They will cannibalize that scanning if they already got it. Now trying to convince the business people, we will be most. Thank you so much. We dont have time for any more questions that they will be happy to chat in the signing wine. Give them. Give them aline. Give them a. Give them a warm thank you. [applause] let me get them up to the table and then you can come with your books, thank you. [inaudible conversations] you are watching booktv on cspan2 with top nonfiction books and authors every weekend. Television for serious readers. This weekend on booktv we discuss race in america with National UrbanLeague President on after words. Edward lucas looks at cybersecurity and narrow scientist peter highbrow examines human behavior. And a look at the early presidency of george washington, the creation of d. C. As the Nations Capital and the Brookings Institution explains the president ial primary process. For a complete Television Schedule go to booktv. Org. Booktv 48 hours of nonfiction books and authors. Television for serious readers. Tom gjelten is a correspondent with npr news. He offered a new book a nation of nations a Great American immigration story. Why did your book start and end in fairfax, virginia . Fairfax county, virginia is one of the best examples of the community that has been totally transformed by immigration over the last 50 years. How america has changed during these 50 years is what is interesting to me and i wanted to set is in a particular community. Fairfax county in 1970, 0. 5 of the population was born outside the country. Today close to one out of three president s of Fairfax County board outside the country said the influx of immigrants from all over the world has completely changed Fairfax County from a whirl largely white county into the that any of multicultural america. Why do you believe that is . All of america has been transformed by immigration during this time. The population is three times what it was 50 years ago and immigrants are coming from places where they didnt come from before. 1960, and nine of ten and the grits were from europe. In 1960s seven of eight immigrants were from europe, nine of ten immigrants are from outside europe so that is represented in Fairfax County. In 1865, when we did away with the discrimintory coasts we became a nation of immigrants from all over the world. The truth is that is the traumatic event to go through. We had gotten aaccustomed to considering ourselves a nation of immigrants. In the last six years, we have been bringing people from countrys who have different backgrounds. It has been challenging and controversial and we are still dealing with it. For me, bottom line, the incorporation of immigrants has been a successful experience but there are lots of troubled people. Fairfax county in fairfax, virginia was a conservative area and now is considered to be a liberal enclave. What happened there . What happened in Fairfax County is three things. In 1960 it it was rule and segregated. In the 60s and 70s Fairfax County went through urbanization and segregation. As washington, d. C. Expanded to incorporate Fairfax County, they became an exurban suburb in an almost urban part of washington, d. C. The third thing was immigration. So as i said, we have this huge influx of immigrants into the fairfax. Any of those three things is traumatic and the combination of the three in quick secession really changed the character of the county. And now with these new residents and sort of new character of the county it has changed politically as well as sociologically. Immigration will probably be part of the president ial primaries and comes up every four years. Do we follow through with it after the primaries and elections are over . What is interesting about this primary season is that for the first time the issue on immigration is not just what do we do about undocumented people which has been an issue we debated for years. For the first time we are now hearing people saying didnt we have too many immigrants period. Legal or illegal. Candidates were not saying that before. Maybe we are getting the immigrants from cultures that are not like our own. Too many muslim immigrants, you hear that from some of the candidates. There is a different character. I think it is really forcing americans to think about the definition of our country. Is this the idea where you can get a fresh start and if you believe in in the American Dream you can become american. We told ourselves that but now we are putting it to the test. And there are a lot of politicians fanning the fears of people unlike us and it seems to be coming back. See saw it in the 20th century and with immigrants becoming a big share of the population we are seeing it again. The author of nation of nations, thank you so much for join ug. Here is a look at authors featured on booktvs after words. Tom daschle and trent loft offered their solution to resolve the current state effects in washington. And we talked about the recently discontinued onechild policy in china. And james rosen looked ad former Vice President dick cheneys time in the bush administration. And matt lewis will explain the Republican Party must reembrace conservative principles to remain relevant. Derrick lancer will explain his research on Violent Crime in america. Also coming up, senator corey booker will recount his upbringing and his choice to pursue public service. And this weekend, eddy glad argues america continues to suffer from racial inequalities. The presumption of full civil rights happened in a substitive way but we know integration isnt a reality i talk about the value gap and i think that is fundamental. And that is the reason why some People Matter more in this country than others you can watch all previous after wards programs on website. Booktv. Organize. Now we discuss the plot to assassinate roosevelt, churchill, and stalin in 1943. Good evening, and thank you for coming. I am susan from portfolio books and. We are thrilled to have bill yenne here tonight. He is the author of more than three dozen