Episode 73: Michael Okun talks about the complexity and treatment of Parkinson’s disease

Nearly 60,000 Americans are diagnosed with Parkinson’s disease every year in the U.S. The disease is an incredibly complex disorder that affects more than 10 million people worldwide.

Our guest today is Dr. Michael Okun, who is considered the world’s foremost authority on the treatment of Parkinson’s.He is the Adelaide Lackner Professor and Chair of Neurology at the University of Florida Health College of Medicine as well as the co-director of the university’s Fixel Center for Neurological Diseases. The center is known for its interdisciplinary faculty that provides a one-stop, patient-centered clinical research experience that attracts patients from around the world.

Since 2006, Michael has been the National Medical Director for the Parkinson’s Foundation and works very closely with a wide range of organizations such as the Michael J. Fox Foundation. The American Society for Experimental Nuerotherapeutics recently awarded Michael the 2018 Presidential Award.  In 2015, he was recognized during a White House ceremony by the Obama administration as a “Champion for Parkinson’s Disease.”

Michael also is an accomplished writer with more than 400 peer-reviewed articles and even a book of poetry.

In today’s episode, we discuss:

• [00:17:56]What Parkinson’s disease is and the wide range of symptoms that can arise as a result of the disease.
• [00:29:19] How Parkinson’s disease is diagnosed since there is no specific test that can diagnose the disease.
• [00:32:11] The common risk factors associated with neurodegenerative disease.
• [00:38:20] The actor Alan Alda’s recent announcement that he has been living with Parkinson’s for more than a year.
• [00:41:04] A UCSF study that looked at the prevalence of Parkinson’s among veterans who had experienced traumatic brain injury.
• [00:46:32] Treatments that are available for Parkinson’s.
• [00:55:57] The cognitive, behavioral and mood effects of deep-brain stimulation.
• [01:17:11] The potential use of brain prosthetics or orthotics in patients with neurological disease.
• [01:29:26] Whether Parkinson’s therapy is moving toward local, systemic or a combination of the therapies.
• [01:31:48] The relationship between metabolism and nutrition and the progression of Parkinson’s disease.
• And much more. 

Show notes:

[00:02:53] Michael begins the interview taking about growing up in West Palm Beach, Florida, and his love of baseball and collecting baseball cards.

[00:03:39] After high school, Michael decided to attend Florida State University and focus on a liberal arts education. Dawn asks Michael if it’s safe to assume he wasn’t thinking about medical school when he started college.

[00:04:53] Dawn asks Michael how a history major ultimately decides to become an MD.

[00:06:18] Ken asks Michael to elaborate on a funny story about how he ended up going to the University of Florida for medical school.

[00:10:10] Michael talks about how went to med school thinking he wanted to be a black-back family practitioner, but became so interested in neurology that he changed his mind.

[00:13:06] Ken mentions that during Michael’s time at Florida, he became fascinated by what was going on in the brain of people who had tremors. Ken asks Michael if that is what led him to focus on Parkinson’s disease during his postdoc at Emory?

[00:17:56] Even though most people are familiar with images of people like Michael J. Fox and Mohammed Ali who have tremors, most people aren’t aware that Parkinson’s has a wide range of symptoms, which makes it an incredibly complex disease. Michael gives an overview of Parkinson’s and the various symptoms that can arise as result of the disease.

[00:22:29] Since Parkinson’s is such a remarkably complex and multi-system disease, Ken asks Michael how he integrates the different clinical disciplines that are required to treat someone with Parkinson’s.

[00:29:19] Ken mentions that there is no specific test to diagnose Parkinson’s, and asks Michael if the disease is primarily diagnosed by symptoms.

[00:32:11] Dawn mentions that when people are diagnosed with Parkinson’s, it means they don’t have Alzheimer’s or ALS. However, neurodegenerative diseases often have common risk factors such as type 2 diabetes or environmental exposures or trauma, as well as a neuroinflammatory or oxidative stress component. Ken asks what makes these diseases different beyond the specific areas of brain anatomy that they affect, and why might somebody with a given set of risk factors get one rather than the other?

[00:38:20] Dawn mentions that more than a million people in the U.S. have Parkinson’s, including actor Alan Alda, who announced in July that he has been living with the disease for more than a year. In announcing he had the disease, Alda stressed that he has been living a full and happy life. As the national medical director for the Parkinson’s Foundation, Michael often stresses that people with Parkinson’s can lead happy and healthy lives, and Dawn asks Michael to talk about that.

[00:41:04] Ken mentions a UCSF study in the online issue of Neurologythat looked at the prevalence of Parkinson’s among veterans who had experienced a traumatic brain injury. The study found that these veterans faced a 56 percent increased risk for Parkinson’s. Ken asks Michael to talk about the study and its implications behind a military population.

[00:44:35] With a growing understanding of repeat TBI and CTE, Dawn talks about how we are learning that there is a link between brain injury and neurodegenerative pathology. She asks Michael if we have any idea as to why there is a link between TBI and neurodegeneration?

[00:46:32] Michael gives an overview of the treatments that are available to treat Parkinson’s.

[00:52:39] Dawn asks Michael to talk about the current state of biomarkers for tracking the progression of Parkinson’s and tracking the response to a disease-modifying intervention.

[00:55:57] Dawn points out that Michael has had a prolific career as a researcher exploring non-motor basil ganglia brain functions. He also has helped pioneer studies exploring the cognitive, behavioral and mood effects of deep brain stimulation. She asks Michael to give listeners an overview of deep brain stimulation, also known as DBS.

[01:00:35] Ken asks Michael to talk about the primary mechanism of action of DBS.

[01:05:09] Michael discusses DBS’s dark past and how the intervention’s reputation has recently rebounded.

[01:10:53] Dawns asks what kind of patient is a good candidate for DBS.

[01:12:42] Michael talks about autonomic nervous system symptoms in Parkinson’s disease.

[01:14:40] Dawn wonders about other forms of non-invasive nervous system stimulation and asks if approaches such as transcutaneous vagal nerve stimulation have shown an impact on Parkinson’s disease or Parkinson’s symptoms.

[01:17:11] Ken points out that researchers at IHMC often work toward development of AI software systems intended as cognitive orthotics aimed at amplifying and extending human cognition. He asks Michael about the potential use of brain prosthetics or orthotics in patients with neurological diseases and what opportunities Michael sees to better understand the brain and brain networks. Ken also asks about the ethical challenges involved in such technology and who should be operated on.

[1:20:32] Dawn mentions that one arm of research for Parkinson’s treatment is developing vaccines or other approaches to aid in the removal of alpha-synuclein protein aggregation. Similar approaches have so far failed with the analogous approach to beta-amyloid in Alzheimer’s disease, where the amyloid burden also doesn’t directly correlate with disease progression or severity. Dawn asks if there is evidence that this might be a more successful approach in Parkinson’s.

[01:25:07] Ken brings up that stem cells are often mentioned in the context of Parkinson’s and asks Michael about the prospects.

[01:28:08] Dawns asks about editing certain genes in situ with a CRISPR-Cas9.

[01:29:26] Ken points out that PINK1 is involved with the ubiquitin pathway, and that LRRK2 is involved with the immune response. Ken asks if a systemic approach to treatment is more promising than a local treatment. He also asks if Parkinson’s disease therapy is moving toward local or systemic treatment or a combination of the therapies.

[01:31:48] Dawn asks if there are known relationships between metabolism and nutrition and the progression of Parkinson’s disease or its symptoms.

[01:33:21] Dawn talks about how the Obama administration recognized Michael during a White House ceremony in 2015 and how earlier this year the American Society for Experimental Neurotherapeutics honored Michael with its Presidential Award. Dawn asks Michael to share what that was like.

[01:34:40] Dawn ends the interview by asking Michael about his passion for writing. She points out that Michael received a scholarship for creative writing in school and that today he has more than 400 peer-reviewed articles and has also written a book of poetry. Dawn asks Michael to talk about the role that writing has played in his life.

Links

Michael’s UF Department of Neurology faculty page

Michael’s papers on PubMed

IHMC talk on “Parkinson’s Disease: The Latest Advances in Treatment and Research.”

IHMC talk on “Parkinson’s Treatment: 10 Secrets to a Happier Life”

UF’s Movement Disorders and Neurorestoration Program

“Parkinson’s Treatment: 10 Secrets to a Happier Life”

“10 Breakthrough Therapies for Parkinson’s Disease”

“Ask the Doctor About Parkinson’s Disease”

“Lessons From the Bedside”

Learn more about IHMC

STEM-Talk homepage

Episode 72: Peter Norvig talks about working at Google, digital privacy, fake news, killer robots and AI’s future

Today’s episode features a timely interview with Google’s Director of Research, Peter Norvig.  He is also the co-author of “Artificial Intelligence: A Modern Approach,” which is in its third edition and is a leading AI textbook.

In today’s interview, we talk to Peter about fake news, trolls, self-driving cars, killer robots, the future of artificial intelligence, and a lot more.

We also talk to Peter about digital privacy. Tech companies such as Google, Facebook, Twitter and others have been facing heavy criticism recently over the way they handle people’s digital data.

In May, Europe began enforcing a new law that restricts how people’s online data is obtained and used. In June, California passed a privacy law that requires tech and information companies to share how they’re collecting people’s data and how they’re sharing that information.  At the moment, Congress is considering a federal privacy law that also covers how personal digital data is handled.

Ken and Peter have a history that goes back to their days at the NASA Ames Research Center in Silicon Valley. Ken was the center’s associate director at the time and recruited Peter to become the center’s chief of the Computational Sciences Division.

In today’s episode, we discuss:

• How artificial intelligence has changed since the days when Peter first became a practicing AI professional. [00:19:20]
• How AI research is now increasingly driven by commercial interests rather than government grants. [00:23:39]
• What deep learning is and what the word “deep” means in this context. [00:27:48]
• The philosophical questions that surround AI, such as: “What does it mean to be intelligent?” and “Can a machine be conscious?” [00:36:58]
• Search function and privacy. [00:44:32]
• Google’s responsibility for the content posted on their platforms. [00:50:06]
• The problems that arise when tech companies police content. [00:51:17]
• Peter’s thoughts about a meeting Elon Musk had with U.S. governors where he urged them to adopt AI legislation before “robots start going down the street killing people.” [00:56:18]
• The meaning of “singularity” and whether Peter believes in it. [01:03:19]
• Peter’s advice for listeners who are interested in going to work for Google someday. [01:12:10]

Show notes:

[00:02:15] Dawn begins the interview asking Peter about an interview he did with FORBES magazine where he said, “I don’t care so much whether what we are building is real intelligence. We know how to build real intelligence. My wife and I did it twice, although she did a lot more of the work. We don’t need to duplicate humans, that’s why I focus on creating tools to help us rather than duplicating what we already know how to do. We want humans and machines to partner and do what humans and machines couldn’t do on their own.” Dawn asks Peter to expand on this belief and how it influenced his career.

[00:03:23] Dawn asks Peter about growing up in Boston and his habit of writing the local newspaper to complain about innumeracy and the sloppy language in its science stories.

[00:04:36] Ken mentions Peter’s father was a math professor and his mother an English literature professor. While in high school, even though teachers suggested a career in journalism, Peter decided to learn programming instead. Peter talks about how he also took a class in linguistics, which led him to start thinking about using computers to process natural language.

[00:05:54] Dawn asks Peter about classes he took at Brown University that led him to start thinking about artificial intelligence.

[00:07:00] Dawn mentions that Peter went to the University of California Berkeley for his Ph.D. and asks him what motivated him to enroll in the computer science department and research AI.

[00:08:03] Dawn asks Peter about the research he did after receiving his Ph.D. and becoming an assistant professor at University of Southern California as a research faculty member.

[00:08:36] Peter talks about the work he did in various labs during the early years of his career.

[00:09:45] Peter talks about how Ken, while on leave from IHMC, recruited Peter in 1998 to become the division chief of the Computational Sciences Division at NASA Ames.

[00:11:32] Ken and Peter recall a tag-team address they made at the 1999 conference of the Association for the Advancement of Artificial Intelligence. The talk was titled, “AI and Space Exploration: Where No Machine Has Gone Before”.

[00:14:07] Dawn mentions that in 1996 a couple of Stanford students developed a search algorithm that was originally known as “Back Rub,” which eventually led to the formation of Google in 1998. Peter joined Google in 2001 and Dawns asks how that came about.

[00:16:11] Dawn asks Peter to talk about the differences in the work cultures of Google and NASA.

[00:17:41] Ken mentions that the textbook Peter co-wrote with Stuart Russell is now in its third edition since its original publication in 1995, and that it is considered one of the leading textbooks on artificial intelligence. Ken asks if Peter is considering a new version of the textbook in the face of the fast evolution of the field.

[00:19:20] Dawn comments on how AI programming itself has changed over time with the iteration of new languages, tools, and communities. She asks how things are now different for the practicing AI professional, compared to when Peter was getting started.

[00:21:28] Ken asks if Peter has any thoughts on the relationship between reality and some of the inflated expectations that arise from the current overhyping of AI that has stoked fears as well as utopian dreams.

[00:23:39] Because AI is now increasingly being driven by commercial interests rather than government research grants, Dawn asks how the field will change.

[00:25:10] Dawn asks why the look and feel of Google web searches hasn’t changed that much over the past 10 years.

[00:26:09] Dawn mentions that Google’s search engine has flourished for 20 years because of its speed, relevance, coverage, and other such measures of performance. Given that Google is still the gold standard in search, she asks how Google tests for performance.

[00:27:48] Ken mentions that about a decade ago Google was slightly disparaging about the utility of AI, but then Google started to suddenly change its tune, at least that’s how it looked from the outside. Ken comments that this seems to be because of the sudden explosion of applications of deep learning which, when applied to very large data, yield numerous state-of-the-art results in domains such as speech recognition, image recognition and language translation. Ken asks Peter to explain what deep learning is, what it does well, and what the word “deep” means in this context.

[00:36:58] Ken comments on how, back in the day, good old-fashioned AI raised many big philosophical questions. Questions ranged from “What does it mean to be intelligent?” to “Can a machine be conscious?” Many of these questions were explored in famous films such as “Blade Runner,” and “Ex Machina.” Ken and Peter talk about whether there are new big questions being raised in the context of newer forms of AI.

[00:39:41] Ken brings up how he and Pat Hayes developed an award in the ‘90s that they called the Simon Newcomb Award that recognized the most wrong-headed arguments against the possibility of intelligent machines.

[00:41:25] Ken observes that the papers at the National AI Conference, while often technically excellent, are typically statistical in nature and narrowly cast. Ken goes on to propose that this could be a sign of the field maturing, or perhaps ducking the hard and interesting questions, or a bit of both. He asks Peter for his thoughts on this.

[00:44:32] Ken brings the conversation back to Google and asks about search function and privacy. He mentions that Google provides some of the web’s most used and appreciated software, including Gmail, Docs, Drive, Calendar, and more. But given Google’s access to vast amounts of data that has led to personalized searches and advertisements, Ken asks Peter for his thoughts about the concerns regarding loss of privacy and the use of personal information.

[00:47:45] Dawn asks Peter how Google recommends news articles based on people’s recent searches. Dawn says that some people argue that sending people news articles based on their history is not such a good thing.

[00:50:06] Dawn asks Peter if Google feels as if it has any kind of responsibility to weed out fake news and international trolling. She also asks if the controversies about fake news and trolls are beginning to muddle the definition of information itself.

[00:51:17] Ken mentions that problems are arising for platform providers not so much because of legal reasons but because of ideological reasons. Providers are now deciding to police content that comes onto their site and ban one group of ideological crazy people while not addressing another equally unhinged group.  Ken asks Peter how society will construe the role of Google, Facebook and others as they work to police the content that appears on their sites.

[00:55:31] Dawn asks Peter for his take on companies such as Powerset as well as others who see natural language search, which allows people to use sentences rather than keywords, as the future of search.

[00:56:18] Dawn mentions how last year she turned the tables on Ken and interviewed him for STEM-Talk on episodes 49 and 50. In one interview she asked Ken about a New York Times story that referenced the meeting Elon Musk had with governors where Musk said that they should adopt AI legislation before “robots start going down the street killing people.” She asks Peter if he ascribes to this killer AI theory.

[00:59:03] Ken comments on how interesting he finds the sudden change in the arguments, which has evolved from pundits saying AI was provably impossible to now saying that superhuman AI represents the greatest danger ever faced by the human race.

[00:59:49] Dawn mentions that the biggest question people asked Peter during a trip to Australia last year was the impact of self-driving cars on professions like truck drivers. She asks Peter to talk about the fear that algorithms and machine learning are replacing jobs.

[01:03:19] Ken mentions that earlier in this decade Peter spoke at the Singularity Summit where he remarked that he was not a believer in what some refer to as “the singularity.” He asks Peter to explain what is generally meant by that term, and also to talk about his views on it.

[01:07:44] Dawn comments on the coming “post app era” where a new type of human, computer, and smart-phone technology will replace the need for apps. She asks if this is something that Google is working on.

[01:10:25] Dawn mentions that Peter is widely quoted as saying that he has the best job in the world, and asks what it is that he does.

[01:12:10] Dawn asks Peter to share some advice for listeners who are still in school and are thinking about going to work for Google someday.

[01:12:55] Ken mentions that Peter and his wife enjoy cycling and ends the interview by asking Peter if he has picked up any other new hobbies over the years.

Peter’s Google AI page

Peter’s Wikipedia page

Peter’s web page

Peter’s CV

Peter’s Google Scholar page

Peter’s Amazon page

Peter’s Ted Talk

Lecture by Peter: “The Science and Engineering of Online Learning”

Lecture by Ken: “On Computational Wings: The Prospects & Putative Perils of AI”

Learn more about IHMC

STEM-Talk homepage

 

Episode 71: Elizabeth Nance talks about using nanotechnology to understand and treat brain diseases

Episode 71: Elizabeth Nance talks about using nanotechnology to understand and treat brain diseases

SEO: Elizabeth Nance, Nance Lab, University of Washington, nanotechnology, autism, traumatic brain injury, epilepsy, nanoparticles, blood-brain barrier,diffusion,dendrimer-NAC conjugates,Einstein’s brain, chemical engineering,Ken Ford,Dawn Kernagis,IHMC

Our guest today has been described by Forbes magazine as one of the “most disruptive, game-changing and innovating young personalities in science.”

Dr. Elizabeth Nance is known for her passionate search to find ways to more efficiently connect resources and information across multiple scientific and engineering disciplines. Her research focuses on using nanotechnology to understand the movement of molecules in the brain. She is particularly focused on better ways to treat brain diseases like autism, stroke, traumatic brain injury and epilepsy.

Elizabeth is the Clare Boothe Luce Assistant Professor of Chemical Engineering at the University of Washington. She also has an adjunct appointment in the school’s radiology department. Elizabeth and her lab, the Nance Lab, recently was awarded a $1.8-million-dollar grant from the National Institutes of Health to develop quantitative, high resolution imaging and analysis platforms to understand nanoparticle behavior, with a specific focus on the brain.

In today’s episode, we discuss:

• The pushback Elizabeth received in college when she tried to apply chemical engineering to neurological diseases. [00:11:33]
• How Elizabeth developed the first nanoparticles that could penetrate deep within the brain. [00:13:52]
• The many potential applications of nanoparticle technology in the treatment of neurological disorders, diseases and injuries. [00:17:10]
• The structure, and unique functions of the blood-brain barrier. [00:28:11]
• The dendrimer-NAC conjugates, and how they increase intracellular glutathione to reduce injury in the inflamed brain. [00:35:01]
• How “disease directing engineering” has the potential to allow for the leveraging of common hallmarks of neurological disease to better deliver therapies. [00:40:19]
• How change in brain metabolism affects targeted therapeutic deliveries to a specific region of the brain. [00:52:14]

Show notes:

[00:03:31] Elizabeth talks about growing up in North Carolina and how her family goes back nine generations to the original homesteaders of Charlotte.

[00:04:06] Dawn mentions that Elizabeth liked to spend a lot of time outdoors as a child and asks her if it is true that she was especially good at climbing trees.

[00:05:12] Dawn asks Elizabeth about her hectic schedule in high school, which, in addition to her studies, included soccer, track and volleyball.

[00:06:03] Ken asks Elizabeth when she became interested in science.

[00:08:22] Dawn mentions how in North Carolina a person has to decide early on if they are a Chapel Hill fan or a North Carolina State fan. Dawn asks if this culture contributed to Elizabeth going to NC State.

[00:09:28] Dawn asks Elizabeth about her decision to major in chemical engineering.

[00:11:33] Dawn asks Elizabeth to discuss the pushback she received in college when she tried to apply chemical engineering to neurological diseases.

[00:13:52] Ken mentions that Elizabeth developed the first nanoparticles that could penetrate deep within the brain. This was a major reason why Forbes named her one of its “30 Under 30 Disruptive Influencers in Science” back in 2015. He asks if she could talk about the work she did in developing that platform and how it changed the way we might think about delivering drugs in the brain.

[00:17:10]Ken mentions that there are many potential applications of nanoparticle technology in the treatment of neurological disorders, diseases and injuries. He asks Elizabeth to describe the structure of a nanoparticle in general, and how it can accomplish targeted delivery of a therapeutic.

[00:21:47] Ken comments on how after publishing her nanoparticle paper in “Science Translational Medicine” in 2012, one publication commented that they were worried about potential nefarious applications of such technology.

[00:25:23] Dawn asks why research and development for drugs used to treat people with injured or diseased brains take about 35% longer to develop than drugs for any other type of disease.

[00:28:11] Dawn asks Elizabeth to give some background on the structure, and unique functions of the blood-brain barrier.

[00:29:57] Ken discusses how a lot of Elizabeth’s work involves the use of nanotechnology and its potential applications in both understanding and treating the injured brain. He asks about the use of nanoparticles as probes, and how that helps us better understand the human brain microenvironment.

[00:32:11] Dawn comments on how much of Elizabeth’s post-doctoral work focused on the use of dendrimer-based nanoparticles in multiple different settings as a model for how to approach neurological disease treatment. Dawn asks Elizabeth how that has informed her current research.

[00:35:01] Dawn brings up how Elizabeth has published multiple papers on the dendrimer-NAC conjugates, and how it increases intracellular glutathione to reduce injury in the inflamed brain. Dawn goes on to say that some people have begun to take NAC to increase glutathione in the brain after a concussion or TBI. She asks Elizabeth to talk about the potential problems with giving NAC in the setting of excitotoxic brain injury, and why the use of a nanoparticle might be a potential solution to this problem.

[00:37:30] Ken comments on how Elizabeth is known to be fascinated by diffusion, to the point where she has said that it has kept her up at night. He asks why understanding diffusion is so critical to overcoming the barriers to investigating and treating the injured brain.

[00:40:19] Dawn mentions that a number of things that happen after brain injury can dramatically alter our ability to deliver a therapy. She points out that Elizabeth has coined the term “disease directing engineering” to describe an approach that has the potential to allow for leveraging of common hallmarks of neurological disease to better deliver therapies. She asks how that thought process informs the research in Elizabeth’s lab.

[00:43:37] Ken brings up one of Elizabeth’s review papers, where she summarized how nanoparticle properties affect movement within the brain, and from that she developed a formula with the highest likelihood of success. He asks what that formula is.

[00:46:16] Dawn comments on Elizabeth being very vocal about the drug delivery field’s movement toward increasingly complex delivery vehicles despite the limited translation of these approaches in the clinic. She goes on to ask why there is this gap.

[00:48:34] Dawn mentions that Elizabeth and her lab were recently awarded a $1.8 million grant from the NIH, and how she will be using the grant to develop quantitative high-resolution imaging and analysis platforms to understand nanoparticle behavior and compartmentalization on brain tissues.

[00:49:45] Dawn asks if Elizabeth could explain the idea behind her current work, which focuses on integrating biological data from the molecular level all the way up to animal behavior.

[00:52:14] Ken comments on how we know that in certain types of brain injury or disease, that metabolism and inflammation are significant components of the underlying pathophysiology. He asks if a change in brain metabolism affects targeted therapeutic delivery to a specific region of the brain.

[00:54:47] Ken asks if the leakiness of the blood brain barrier that occurs in certain forms of neurological injury and disease can be utilized in a targeted way to deliver a drug in the brain.

[00:56:54] Ken asks what Elizabeth sees as the most exciting up and coming areas of nanoparticle therapeutics research and development.

[00:58:20] Dawn asks Elizabeth about her decision to join the University of Washington.

[00:59:40] Dawn asks if Elizabeth’s adjunct position in the department of radiology helps her interact with clinicians or medical researchers who might wonder why a ChemE is working on the brain.

[01:00:49] Dawn asks if Elizabeth can expand on her idea that while interdisciplinary research is frequently talked about, that people are usually just giving it lip service.

[01:02:37] Dawn mentions that Elizabeth’s father was a minister, and her mother a nurse, and that one thing they instilled in her early on was that every person and conversation has value; and that a person has to be constantly willing to go outside their comfort zone in order to grow. She asks how these lessons shaped the philosophy behind Elizabeth’s lab.

[01:03:56] Dawn brings up a TED Talk that Elizabeth did where she stressed that we have made significant advancements in treating disease because of better prevention, better surgical intervention, and better diagnosis. But despite all this, we are still struggling to understand the majority of complex diseases, and that it is possible that we already have the tools we need to solve those problems but our approach to using them might be the issue, and that we might have the solutions already but we are just asking the wrong questions.

[01:05:06] Dawn mentions Elizabeth’s shift from ChemE to neuroscience and pediatrics after her Ph.D. led people to ask her on a regular basis, “What are you? What is your specialty?” Dawn asks if that is why Elizabeth often refers to herself as a glorified match maker?

[01:06:41] Dawn refers back to something Elizabeth said in her TED Talk about the idea of “specializing in not specializing”, and asks her to expand on that concept.

[01:08:28] Dawn asks Elizabeth about recently being named the European Union’s NanoMed Innovative Training Network’s Inspiring Young Investigator of 2018.

[01:10:08] Ken mentions that Elizabeth was recently on a podcast where she shared a remarkable story about how pathologist Thomas Harvey kept parts of Einstein’s brain after performing the autopsy on him in 1955. Some of the sections of the brain were recovered and analyzed decades later, showing that the structure and composition of his brain might have been slightly different from what we might normally expect to see. Ken asks if Elizabeth could discuss what those differences were and how this highlights the importance of probing.

[01:12:40] Dawn mentions that episodes 47 and 48 of STEM-Talk featured a two-part interview with Tommy Wood, a UK trained physician and Ph.D. who now also works at the University of Washington. When Dawn and Ken asked Tommy what brought him over to the U.S., he said “a girl.” Dawn asks Elizabeth if she knows something about that.

[01:13:31] Even though Forbes named Elizabeth one of its “30 under 30 in Science” in 2015, Dawn mentions that she understands Elizabeth was terrible at chemistry in high school. Dawn wraps up the interview by asking Elizabeth if that’s true.

Links:
Elizabeth’s University of Washington faculty page

Nance Lab website

Elizabeth’s TEDx Talk

Facebook page

Instagram

Elizabeth’s podcast interview where she talks about Einstein’s brain

A Dense Poly(Ethylene Glycol) Coating Improves Penetration of Large Polymeric Nanoparticles Within Brain Tissue

Systems-level thinking for nanoparticle-mediated therapeutic delivery to neurological diseases

Tommy Wood STEM-Talk interview, episode 47

Tommy Wood STEM-Talk interview, episode 48

Learn more about IHMC

Ken Ford Facebook page

Dawn Kernagis Facebook page

 

Episode 70: David Sabatini on the discovery of mTOR and its role in disease, longevity & healthspan

Peter Attia, who was our very first guest on STEM-Talk, describes David Sabatini’s discovery of mTOR as one of his two favorite science stories.

Today, Dr. David Sabatini joins us and gives us a first-hand account of how his research into rapamycin in 1994 as a graduate student led him to the discovery of mTOR, which we now know is a critical regulator of cellular growth.

Our interview with David delves into his continuing research into mTOR, which has led to promising opportunities for the development of new treatments for debilitating diseases such as cancer, diabetes and neurological disorders. He also discusses mTOR’s role in healthspan and lifespan.

David is a molecular cell biologist who, according to Reuters News Service, is on the short list for a Nobel Prize. David is on the faculty at MIT and heads up the Sabatini Lab at the Whitehead Institute.

In today’s episode, we discuss:

• Rapamycin, a macrolide antibiotic discovered in the soil of Easter Island
• David’s discovery of mTOR while a grad student at Johns Hopkins
• mTOR’s role as one of the major growth pathways in the body
• mTOR’s role as a nutrient sensor
• How mTOR inhibiton has become one of the hottest topics in longevity research
• mTOR’s role in diseases, especially its connection to cancer
• The role of RAG GTPases as key mTOR mediators
• Protein intake and downstream mTOR activation
• Research into ketogenic diets effect on longevity and healthspan
• Whether David would take rapamycin as a means to enhance his longevity
• And much, much more

Show notes:

[00:03:32] David talks about growing up in New York and having parents who immigrated to the United States from Argentina.

[00:04:00] Dawn asks what David was like as a kid.

[00:04:59] Dawn asks David about his decision to attend Brown University.

[00:05:56] David talks about his decision to become a scientist and the time he spent in the lab of Al Dahlberg

[00:06:53] Ken mentions that after his time at Brown, David headed off for Johns Hopkins to work in Sol Snyder’s lab, a professor known particularly for the work he and his colleagues did on the opioid receptor. Ken asks what drew David to Sol’s lab.

[00:08:25] David talks about how as graduate student at Johns Hopkins in the M.D./Ph.D. program, he began trying to understand the molecular mechanism of rapamycin, a macrolide antibiotic discovered in the soil of Easter Island. Rapamycin was known as a potent antifungal, immunosuppressive with anti-tumorigenic properties. That research led David to the major discovery in 1994 of the protein to which rapamycin binds, now referred to as the mechanistic target of rapamycin, or mTOR.

[00:11:46] Dawn asks David to give a high-level definition and overview of what mTOR does.

[00:13:44] Dawn asks why the “m” in mTOR went from standing for “mammalian” to “mechanistic.”

[00:14:11] Ken mentions that we now know mTOR is one of the major growth pathways in the body that is responsible for growth in both a positive sense and a pathologic sense. He goes on to mention that mTOR acts as a major switch between catabolism and anabolism, and asks David to explain why both of these processes are essential for survival.

[00:16:10] Dawn asks how the two different mTOR protein complexes, mTORC1 and mTORC2, differ with regards to their activation and downstream function.

[00:17:40] Dawn asks David about his decision to join the faculty atMIT and embark on a research-focused career there, starting his own lab at the Whitehead Institute rather than following the clinical path arising from his M.D.

[00:20:50] Ken asks about how nutrients and other inputs are sensed and integrated by the mTOR complexes, given how one of the most fascinating aspects about mTORC1 is its role as a nutrient sensor.

[00:23:46] Ken asks why both nutrients and growth factors are required to activate mTORC1.

[00:25:54] Dawn mentions her interest in the connection of mTOR to aging, mentioning that mTOR inhibition through rapamycin or its analogues is currently one of the hottest topics in longevity research. She asks why mTOR inhibition  appears to be life-extending?

[00:30:38] Ken asks what the risks are of excess catabolism, when inhibiting mTOR pharmacologically, in terms of both health and longevity.

[00:32:09] Dawn asks if there is data in humans suggesting that suppressing mTOR will extend longevity and healthspan, either pharmacologically, genetically or through diet and fasting.

[00:34:23] Dawn asks where mTOR is made, both in terms of the individual cell, as well as specific tissues in the body.

[00:35:02] Ken asks if there is a significant difference between the mTOR signaling in organs like the liver, skeletal muscle, and the brain.

[00:37:07] Ken asks if tissue specific inhibition of mTOR is possible.

[00:38:29] Dawnmentions how it is becoming clear that mTOR plays a role in a number of diseases, most notably is its connection to cancer. She goes on to say that in 2008, David’s team published a highly-cited paper in Science that described the role of Rag GTPases, key mTOR mediators, that sense the amino acid input of a cell. She asks David to discuss this discovery and about the importance of these enzymes in disease processes like cancer?

[00:42:27] Ken mentions that protein intake and downstream mTOR activation is often said to be associated with dysregulated cell growth (i.e. cancer). He goes on to ask if there is there sufficient evidence to suggest that high levels of protein or amino acid intake are necessary or sufficient to produce clinically-meaningful cancers?

[00:43:59] Dawn comments on the epidemic of type-2 diabetes in the United States, going on to say that the mTOR pathway is a known suppressor of the insulin-signaling pathway. She asks if mTOR modulators have the potential to make an impact in the diabetes world?

[00:45:28] Ken asks if the potential negative effects of protein intake on mTOR activation and longevity might be mitigated in the presence of lower-blood glucose or insulin signaling, given the overlap between the insulin and IGF-1 signaling pathways.

[00:46:31] Dawn opens the question by mentioning that late last year, the journal Cell Metabolism published two excellent papers related to ketogenic diets and the extension of healthspan and lifespan. She goes on to mention that the paper from Keith Baar’s group at UC Davis titled “A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice” was of particular interest to several people at IHMC. The findings showed that in mouse models, researchers have seen extended longevity, cognitive protection, cancer reduction, improved strength and coordination, and immune rejuvenation.  The paper from the team at UC Davis, showed a 13% increase in median life span for the mice on a high fat vs high carb diet. Ken jumps in and mentions that from his perspective the most important aspect is that those mice retained their quality of health well into later life. He mentions that it was particularly interesting that they found the ketogenic diet increasedprotein acetylation levels and regulated mTORC1signaling in a tissue-dependent manner. Specifically, the ketogenic diet increasedmTOR signaling in skeletal muscle and inhibited mTORC1 signaling in the liver.

[00:48:59] Ken mentions that an interesting paper from a year or two ago showed that ketones, particularly BHB, greatly increased IGF-1 sensitivity in the muscle.

[00:50:59] Dawn asks what the role of mTOR is in neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease.

[00:53:02] Dawn mentions that mTORC1 responds to intracellular and environmental stresses that are incompatible with growth, including hypoxia. She asks about the effect of hypoxia on mTORC1.

[00:53:51] Dawn mentions that the amino acid, methionine, is widely appreciated to have interesting effects on animal physiology, and that diets low in methionine increase longevity and overall health. She goes on to mention a paper David and a group of his colleagues published in “Science” that described a potential molecular link between the effects of methionine restriction and mTOR1. She asks David to give a summary of that paper and his findings.

[00:55:27] Ken mentions that several human pathologies are linked to mTOR hyperactivation such as TSC and epilepsy due to gene deletions.  He goes on to ask about the consequences of gene deletion-induced mTOR hypoactivation and if it would it confer a longevity benefit.

[00:57:02] Dawn comments on how a few years ago, David joined Peter Attia, our very first guests on STEM-Talk, and a few other friends to take a trip to Easter Island to explore the place where rapamycin was discovered. She asks if David could talk briefly about the story of the initial discovery and isolation of rapamycin on Easter Island, and how, at one point, it was only in Suren Sehgal’s hands and almost lost.

[00:59:17] Dawn mentions how David has previously written about how caloric restriction might produce the best balance of mTORC1 inhibition and overall organismal health, asking David to expand on that idea since caloric restriction does not consistently produce life extension in animal models.

[01:01:14] Dawn asks if rather than restricting nutrients in mass with caloric restriction, might it be possible to manipulate individual nutrients to extend human life.

[01:02:11] Ken mentions that in mammalian cells, inhibition of mTOR results in reduced cell size as a result of reduced protein synthesis. He goes on to ask what the downstream effects are of this, and if it results in a specific phenotype when mammals are exposed to mTOR inhibitors.

[01:03:40] Following up, Dawn comments that one might speculate that chronic inhibition of mTOR in humans would likely degrade a patient’s health and cause fragility due to immunosuppression and loss of muscle. She asks if intermittent use of low-dose rapamycin would help avoid these effects and some of the widely observed side effects such as mouth sores.

[01:05:11] Ken asks if David would hypothesize about intermittent use of low-dose rapamycin and its potential to activate autophagy in a meaningful way.

[01:06:04] Dawn mentions a story about David on the Whitehead Institute website that makes the point that rapamycin appears to have all the makings of a magic bullet for treating diseases involving the mTOR pathway. David, however, was quoted as saying “we’re not there yet”.

[01:07:08] Ken asks if we know how long mTOR inhibition takes with rapamycin before mTORC2 is inhibited.

[01:08:59] Ken mentions that one hears ofphysicians prescribing rapamycin off label for older patients. He goes on to say that there aren’t sufficient studies to justify this behavior, asking David’s for his thoughts on this.

[01:10:13] Ken comments on how the captive mouse studies, where the subjects are fed a bad diet, is not too far removed from human life in cities in many ways.

[01:11:06] Dawn asks David what evidence would have to be there to get him to consider taking rapamycin as a means for enhancing his own longevity.

[01:12:31] Dawn closes the interview by mentioning that Davidwrote a piece for the Proceedings of the National Academy of Sciences Journal titled, “Twenty-Five Years of mTOR.” Toward the end of that article David wrote that his friends in the field laugh at him whenever he says he’s done with mTOR, that there’s nothing left to discover. Dawn then quotes what David had to say about this: “Whenever I feel like calling it quits, the laboratory conveniently makes a great discovery that piques our interest in a new facet of the pathway.” And while, mTOR may not regulate everything, he went on to say, there are enough mysteries in how it senses everything to keep him and his lab occupied for the foreseeable future.

[01:13:07] Dawn closes the interview by asking David to describe some of these mysteries he and his colleagues are exploring.

Sabatini links:

David M. Sabatini MIT profile page

Sabatini Lab website

David M. Sabatini Wikipedia page

Sabatini Lab publications page

Peter Attia interview with David M. Sabatini

Twenty-Five Years of mTOR

RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion

Amino Acids and mTORC1

Growing Roles for the mTOR pathway

Rapalogs and mTOR inhibitors as anti-aging therapeutics

mTOR is a key modulator of ageing and age-related disease

Regulation of mTORC1 by amino acids

mTOR Signaling in Growth Control and Disease

The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span

Tim Ferris podcast about trip to Easter Island with David M. Sabatini and friends

 

Episode 69: David LeMay talks about countering inflammation with SPMs

Dr. David LeMay is a sports medicine and rehabilitation physician who is a consultant for the NBA’s Washington Wizards, the NFL’s Oakland Raiders and the National Hockey League’s Washington Capitals, which won the Stanley Cup this year, their first in the franchise history.

Dave is also a neighbor of ours in Pensacola who has a practice called Lifestyle and Performance Medicine that is located just a few blocks from IHMC.

Dave and his practice partner provide personalized preventative care that helps people reduce the effects of stress on the body and mind to maximize function and health. In his practice, Dave works with a lot of athletes as well as retired and active military members, particularly people in special-ops, who have inflammation as a result of persistent injuries and traumas.

Dave often recommends specialized pro-resolving mediators, also known as SPMs, which help promote the natural termination of the inflammation process and allow a person to avoid anti-inflammatory drugs. We will especially be talking with Dave about this rather new way of treatment in today’s interview.

Some other topics we cover in Dave’s interview:

• Neuroendocrine dysfunction, especially among military veterans.
• The role of inflammation in concussions and traumatic brain injuries.
• Dave’s work with the NFL Players Association Trust.
• The role of specialized pro-resolving mediators in an aging population.
• The proper dosage of SPMs for subacute inflammation.
• Dave’s efforts to improve the diets of former NFL players.
• The key components of keeping athletes healthy through an entire season.
• The correlation between heath-rate variability and athletic performance.
• Proper sideline protocols for players who sustain head injuries.
• Optimal treatment for people who suffer TBI and concussions.
• Establishing baselines for a person’s neuroendocrine function.
• The role of DHA and EPA consumption for maintaining optimal brain health.
• And much, much more.

Show notes:

[00:04:18] Dave begins the interview talking about growing up in Reno, Nevada, and playing sports non-stop as a kid.

[00:4:35] Dawn comments on how Dave’s love of sports lead to some injuries, including a few broken fingers and torn ligaments, and says she understands that this is how Dave first became interested in science.

[00:05:31] Dawn asks Dave about his decision to head to California after high school to attend Azusa Pacific University.

[00:06:37] Dawn asks what lead Dave back home to attend med school at the University of Reno.

[00:07:13] Ken asks Dave at what point he decided to specialize in physical medicine and rehabilitation.

[00:08:33] Dawn mentions that the University of Texas Health Science Center has one of the best physical medicine and rehab programs in the country. She asks Dave if this was the reason he decided to go there for his residency.

[00:09:21] Ken comments on how after Dave’s residency, he stayed in Austin for almost a year. But then Dave moved Pensacola and Ken asks how that came about.

[00:11:04] Dawn asks about Dave’s private practice, called Lifestyle and Performance Medicine, which he and his partner opened in 2013 after their time at the Andrews Institute.

[00:11:27] Ken points out that veterans, and some active-duty folks, particularly those with special operations backgrounds, comprise about half of Dave’s practice. Ken says he understands Dave has seen a great deal of neuroendocrine dysfunction in this group, and asks Dave for his observations.

[00:12:56] Ken mentions that Dave is the medical director for a program that is run through the NFL Players Association Trust. He asks Dave to describe the type of rehab that this program provides the former NFL players.

[00:14:54] Dawn comments on the concept of inflammation being a unifying component of many diseases that afflict Western Civilization, and how it is also a major contributor to the magnitude and persistence of different sports injuries and traumas. She asks Dave to talk about inflammation, and specifically its role in concussion and TBI, as well as give a brief overview of what inflammation is.

[00:17:51] Dawn mentions how Dave has been looking at how targeting inflammation may serve as a therapeutic way to also treat fear- and anxiety-based disorders.

[00:20:34] Ken asks if the process of EPA and DHA conversion into SPM’s through an enzymatic process diminishes in its efficiency as one ages.

[00:21:18] Ken asks if Dave thinks there is a role for exogenous SPM’s for the aging population.

[00:22:13] Ken asks if there is a particular SPM brand, or collection of brands, that Dave finds to be the most interesting or efficacious.

[00:23:01] Ken asks what dosage would Dave suggest for subacute inflammation, and what would be proper for an acute inflammation stage. He goes on to ask about those people who experience a constant, mildly inflamed state.

[00:24:52] Ken asks how Dave wound up working as a consultant for the NBA’s Washington Wizards, the NFL’s Oakland Raiders, and the National Hockey League’s Washington Capitals, who won the Stanley cup this year.

[00:26:35] Dawn mentions that Dave has been on the Performance Nutrition Advisory Board for EXOS for several years. She points out that one of the things Dave does when working with former NFL players is to walk them through ways to improve their diet.

[00:28:19] Dawn asks what are the key components to keep athletes healthy, playing at a peak level throughout an entire season.

[00:30:48] Ken asks if Dave ever looks at heart rate variability (HRV) as a way to measure the extent to which people are in a balanced state.

[00:31:23] Ken mentions that the Ohio State wrestling team looked at HRV very closely, and that there has been found to be a direct correlation between the performance of the athletes and their HRV. He goes on to mention that in his own life, as well as with the wrestlers at Ohio State, the thing that seems to be the most effective in improving HRV is float tank experience.

[00:32:55] Ken asks what the immediate and delayed symptoms of concussion and mild traumatic brain injury are that players experience, and what are the types of treatment that they typically go through?

[00:35:15] Ken asks if, after an injury, coaches are still asking players on the sidelines questions like, “Who is the President?”

[00:39:12] Ken mentions how he often wonders how much of the benefit of the float tank is from the transdermal magnesium.

[00:40:01] Dawn asks if there are any efforts to track TBI in professional hockey, given that concussion is a concern in that sport with its high-speed pace and consequent impacts sustained by players during the game.

[00:42:00] Dawn mentions how she appreciates Dave’s approach to TBI and concussion, which is to try to fix the issue from the inside out by getting at the core of the injury. She goes on to mention that Dave has discussed the need for individuals who have been diagnosed with TBI to see someone who practices something along the lines of integrated medicine to have a full system approach to their treatment. She inquires as to what an optimal care plan would look like for someone diagnosed with TBI

[00:46:16] Ken mentions that in the Special Ops community, there is a lot of talk about establishing an individual baseline for each person’s neuroendocrine function since these men, prior to service, must have had robust levels of hormones such as testosterone, leading to their exceptional attributes and abilities. Thus the idea of determining their health by comparing their levels to what is considered “normal” for the general population doesn’t seem appropriate for this cohort group.

[00:50:42] Dawn asks if Dave thinks that increasing DHA and EPA consumption would be beneficial for TBI patients.

[00:52:06] Ken mentions how he once had the opportunity to suggest to a representative of the NFL that they should look at the APOE status for every player, and make the findings known to them. He went on to state that this suggestion was not warmly received.

[00:55:13] Dawn comments on how there has been a potential link, suggested by the recent literature, between the uptake of DHA, an SPE precursor, and Alzheimer’s disease or dementia development. She goes on to mention a study done in 2017 that showed grey matter uptake in young adult APOE4 carriers is significantly higher than age-matched APOE4 non-carriers. APOE genotype has been shown to be a significant risk factor for development of Alzheimer’s.  The thought is that increased uptake may be related to increased regional brain activation and higher cognitive abilities observed in young adult APOE4 carriers. As these young adults age, the hypothesis is that this greater uptake of DHA, which yields cognitive benefits at a younger age, also increases susceptibility to greater brain DHA loss due to increased metabolic demands and ultimately brain exhaustion and memory failure with age. Based on these and other recent findings, it has been suggested that APOE4 carriers should increase DHA consumption in order to meet the greater metabolic demand for DHA in the brain, and other clinical trials have reported cognitive benefits from increasing DHA consumption in cognitively healthy APOE4 carriers. Dawns asks Dave for his thoughts on the role of DHA or EPA consumption for maintaining or optimizing brain health?   Or, she adds, would SPMs be more efficacious?

[01:01:30] Dawn asks Dave what the role of genotyping will be in optimizing our nutrition, fitness, and overall wellness.

[01:07:50] Ken asks what some of the common deficiencies and recommendations are for people who have trouble falling asleep, and also for those who have trouble staying asleep.

[01:11:09] Dawn ends the interview asking Dave how he goes about taking care of himself, given his busy schedule, in terms of his diet and fitness routine.

Links:

Regenesis Performance website

Concussion presentation by David LeMay

Sports Nutrition presentation by David LeMay

DHA brain uptake and APOE4 status

Resolution of inflammation is altered in Alzheimer’s disease

Infection regulates pro-resolving mediators that lower antibiotic requirements

Resolvins, specialized pro-resolving lipid mediators and their potential roles in metabolic diseases

Pro-resolving lipid mediators are leads for resolution physiology

Specialized pro-resolving mediators from omega-3 fatty acids improve amyloid-b phagocytosis & regulate inflammation in patients with minor cognitive impairment

Pro-resolving lipid mediators and mechanisms in the resolution of acute inflammation

Episode 68: Steve Anton talks about diet, exercise, intermittent fasting and lifestyle interventions to improve health

What’s the best way to eat and the right way to exercise to ensure a healthy lifespan? Our guest today is Dr. Stephen Anton, a psychologist who has spent his career researching how lifestyle factors can influence not only obesity, but also cardiovascular disease and other metabolic conditions.

Steve is an associate professor and the chief of the Clinical Research Division in the Department of Aging and Geriatric Research at the University of Florida. In today’s episode, we talk to Steve about his work in developing lifestyle interventions designed to modify people’s eating and exercise behaviors in an effort to improve their healthspan and lifespan.

One of Steve’s best-known papers appeared in the Obesity Journal titled “Flipping the Metabolic Switch.” The study looked at intermittent fasting and suggested that the metabolic switch into ketosis represents an evolutionary conserved trigger point that has the potential to improve body composition in overweight individuals.

Topics we cover in today’s interview include:

• The increasing prevalence of metabolic syndrome associated with aging.
• Why so many hospital health and wellness programs fail.
• How fasting and intermittent energy restriction promote autophagy.
• The relationship between muscle quality, body fat and health.
• How age-related loss of muscle function and mass leads to sarcopenia.
• Effects, risks and benefits of testosterone supplementation in older men.
• Optimal exercise methods for long-term health.
• Therapeutic approaches that potentially can help avert systemic inflammation associated with aging.
• Steve’s study that looked at the effects of popular diets on weight loss.
• Controversies surrounded calorie restriction as a strategy to enhance longevity.

Show notes:

2:30: Steve talks about growing up in Tampa and playing sports as a kid.

3:53: Dawn asks Steve about his decision to attend Florida State after high school.

4:17: Dawn comments on how Steve bounced between medicine, business, and psychology before finally deciding to major in psychology. She asks if having two parents who were also psychologists played a role in his decision.

5:24: Ken asks about Steven’s experience pursuing his Ph.D. at the University of Florida.

6:28: Dawn brings up that Steve became a fellow of behavioral medicine at the Pennington Biomedical Research Center in Baton Rouge, La. She mentions that Pennington has one of the nation’s premier programs in obesity metabolism and diabetes. She asks if that was the reason he decided on Pennington.

9:33: Dawn asks what prompted Steve to return to the University of Florida.

10:08: Ken asks what is driving the increased prevalence of metabolic syndrome that’s associated with advanced age.

11:19: Dawn brings up how hospitals have tried to promote health and wellness programs for decades, but notes how hospitals are designed to treat people who are sick and injured rather than delivering lifestyle interventions. She asks if Steve can give a summary of what he has learned in looking at ways to deliver interventions.

13:23: Dawn mentions that the traditional treatment and management approaches for type 2 diabetes are relatively ineffective and only reverse the disease in about one percent of the cases.

15:02: Ken mentions that Jeff Volek, STEM-Talk Guest on episode 43, has been a pioneer in researching type 2 diabetes.

16:49: Dawn points out that she and Ken had an in-depth conversation with Dr. Mark Matson about autophagy on episode seven of STEM-Talk. Matson also discussed fasting, and intermittent energy restriction and how it promotes autophagy, which is often described as the body’s innate recycling system. Dawn asks if Steve can elaborate a little on this process.

18:02: Dawn mentions that Steve has written about muscle quality and body composition and the risk of metabolic diseases and functional decline. She asks about the relationship between muscle quality, body fat and health.

19:17: Dawn asks if Steve can talk about how the age-related loss of muscle function and mass often lead to sarcopenia, and how this condition effects the individual and society.

20:31: Ken asks for Steve’s thoughts on the group of people who could be classified as having “pre-sarcopenia.” Ken mentions his interest in this group given that dietary and exercise intervention can still make a huge difference in their lives.

21:35: Dawn brings up the point of how testosterone tends to decline as men age, which is associated with a number of adverse health problems, including: cardiovascular and metabolic disease, sexual dysfunction, and mood disorders. Dawn asks about Steve’s study on the effects of testosterone supplementation in older men, and about the risks and benefits of supplementation.

24:12: Dawn asks if Steve can describe the difference between muscle quality and quantity, and if there is an easy way we can track and measure muscle quality.

25:28: Ken asks how we should be thinking about pharmaceutical therapies in these conditions as the field goes forward; given that so many new pharmaceuticals are in various stages of development, and that many of the currently available pharmaceutical approaches to age-related muscle loss have, to date, been effective at increasing muscle mass but not necessarily function.

26:30: Dawn asks what exercise methods Steve recommends for optimal, long-term health.

27:57: Dawn mentions that in 2016 a team of Spanish and Italian researchers published an article in the prestigious journal, Nature, showing that autophagy is a critical regulator of stem-cell fate and has implications for fostering muscle regeneration and sarcopenia as well as other disorders. She goes on to mention that autophagy typically declines with age, and this may be because stem cells start to lose their “steminess,” and become senescent (the loss of a cell’s power of division and growth). She goes on to ask about fasting and ketogenic diets, and how both interventions increase autophagy and could account for the common benefits we see in both of those interventions.

29:51: Dawn asks about the emerging concept of normal-weight obesity.

31:07: Ken asks about the consequences and challenges of sarcopenic obesity.

33:20: Dawn mentions that a growing body of evidence strongly indicates that chronic systemic low-grade inflammation plays a significant role in contributing to sarcopenia and associated functional decline. She goes on to say that preserving muscle and mobility is essential to maintaining a high quality of life as we age. She asks Steve what promising therapeutic approaches are out there that can potentially help avert systemic inflammation that’s associated with aging.

34:41: Dawn asks what the connection is between body fat and inflammation.

35:52: Dawn asks about the phenomenon that inflammation seems to be central to many lifestyle-related chronic diseases.

36:40: Dawn mentions that exercise has anti-inflammatory effects and asks if we should be considering anti-inflammatory intervention strategies as a starting point.

37:08: Ken mentions that Steve has a paper published in the obesity journal titled “Flipping the Metabolic Switch,” a study which looked at intermittent fasting and suggested that the metabolic switch into ketosis represents an evolutionary conserved trigger point that shifts metabolism to the mobilization of fat through fatty-acid oxidation and fatty-acid derived ketones. This mobilization shows that intermittent fasting regimes that induce ketosis have the potential to improve body composition in overweight individuals. He asks how the review was designed and what was learned.

39:17: Ken comments on how this whole discussion of intermittent fasting and the resulting elevated level of ketone bodies leads one to wonder whether exogenous ketones such as esters would recapitulate some of the effects of fasting or the ketogenic diet.

41:05: Dawn mentions that from religious to medical practices, fasting has been performed for thousands of years, dating back to the Greeks, Romans, and Chinese. She asks if Steve could give an overview of the history of fasting and also why so many researchers and scientists today are taking a renewed interest in episodic caloric restriction.

42:30: Ken asks if Steve could talk about the role of resistance training in maintaining muscle mass, function and quality as we age. Ken also asks what Steve has learned in examining exercise-based interventions as well as the combination of exercise and dietary interventions.

45:45: Ken mentions that poor muscle quality and functional decline are associated with the loss of type-two muscle fibers, and increased intramuscular fat. Going on to mention that these same changes are regularly seen in endurance athletes. He asks if these adaptations might become maladaptive as these athletes age.

47:15: Dawn asks if there is an upper limit of benefit, in terms of muscle gain, and a lower limit in terms of optimal body fat, when it comes to longevity. Inquiring as to whether there is a point of diminishing returns or increasing harm when it comes to gaining muscle or losing fat.

49:18: Dawn mentions another one of Steve’s major review studies that looked at the effects of popular diets on weight loss. Steve examined the evidence for the diets that were listed in the 2016 U.S. News & World Report’s rankings of the best weight-loss diets, which ranged from the Mediterranean to Atkins to Ornish to the Paleo diets. She goes on to say that the review found the Atkins diet to have the most evidence in producing meaningful short-term and long-term weight loss.

53:00: Dawn asks what Steve’s diet and exercise routine look like.

54:24: Dawn mentions how it is not the lack of knowledge on the biology of disease, and what interventions will be effective for different individuals, but rather the implementation and adherence at a population level. Given his background in psychology, Dawn asks Steve what his thoughts are on ways to help people implement these interventions into their lives.

59:59: Ken mentions how calorie restriction is a controversial strategy to enhance longevity. Some say that it is the only strategy that has worked consistently, across species, to extend lifespan. Ken mentions that there is also evidence from multiple meta-analysis that shows only about 50% of rodent studies result in a longevity benefit. When one accounts for the quality of the food given to primates, the situation becomes even more unclear as to whether or not calorie restriction has a longevity benefit. Ken asks Steve if the same could apply to humans.

1:03:49: Dawn mentions that she understands Steve persuaded his 72-year-old father to try intermittent fasting, and that his father has become a great testimonial for Steve.

Links:

Dr. Stephen Anton faculty page:

http://aging.ufl.edu/profile/anton-steve-phd/

STEM-Talk episode 43, Dr. Jeff Volek:

https://www.ihmc.us/stemtalk/episode-43/

STEM-Talk episode 7, Dr. Mark Mattson:

https://www.ihmc.us/stemtalk/episode007/

Molecular Inflammation: Underpinnings of Aging and Age-related Diseases:

Molecular Inflammation – FINAL Paper

Effects of Popular Diets:

Popular Diets – Published Article

Flipping the Metabolic Switch:

Anton_et_al-2017-Obesity

 

Episode 67: Doug Wallace talks about mitochondria, our human origins and the possibility of mitochondria-targeted therapies

Today’s guest is Dr. Douglas Wallace, the director of the Center for Mitochondrial and Epigenomic Medicine at Children’s Hospital of Philadelphia.

He is internationally known as the founder of mitochondrial genetics. Mitochondria are tiny structures within cells that produce 90 percent of a person’s energy and play an essential role in health and disease.

Dr. Wallace’s groundbreaking research in the 1970s defined the genetics of DNA within the mitochondria, as distinct from DNA in a cell’s nucleus. His research has shown that mitochondrial DNA is inherited exclusively from the mother and that genetic alterations in the mitochondrial DNA can result in a wide range of metabolic and degenerative diseases.

One of Dr. Wallace’s seminal contributions has been to use a mitochondrial DNA variation to reconstruct human origins and the ancient migrations of women. These studies revealed that humans arose in Africa approximately 200,000 years ago, and that women as well as men left Africa about 65,000 years ago to colonize Eurasia.

Dr. Wallace was inducted last year into the Italian Academy of Sciences during the academy’s 234th annual meeting in Rome. Founded in 1782, membership in the academy is limited to 40 Italian scientists and 25 foreign members. Over the years, the academy has seen such notable members as Albert Einstein, Benjamin Franklin, Louis Pasteur and Rita Levi-Montalcini.

Links:

Dr. Wallace’s Children’s Hospital of Philadelphia bio:

https://www.chop.edu/doctors/wallace-douglas-c

 Mitochondrial DNA Variation in Human Radiation and Disease

Wallace Cell Perspective 9-26-15

Mitochondrial DNA Mutation Associated with Leber’s Hereditary Optic Neuropathy

Wallace LHON 11778 Science 1988

A Mitochondrial Bioenergetic Etiology of Disease

Wallace JCI Wallace JAMA Psychiatry2017

Association Between Mitochondrial DNA Haplogroup Variation and Autism Disorders

Chalkia_jamapsychiatry_2017

Maternal Inheritance of Human Mitochondrial DNA

Giles Maternal Inheritance 1980

Show notes:

 3:32: Dawn opens the interview by mentioning that Doug grew up exploring the woods outside his neighborhood in the suburbs of Annapolis, Maryland. Dawn asks if his time outdoors sparked his interest in science when he was young.

4:14: Dawn asks Doug what led him to attend Cornell University after graduating from high school.

5:15: Doug talks about his decision to focus on genetics in school.

6:21: Dawn asks Doug how he selected Yale for his graduate studies.

7:49: Ken mentions that mitochondria can be considered bacterial “power-pack” organelles that generate the majority of a cell’s energy, as well as much else. He goes on to say that mitochondria account for about 30 percent of our bodyweight, and that there are roughly 500 trillion of them. He finally points out that despite all this that they are surprisingly under attended to and asks Doug to give listeners a brief mitochondria 101.

13:37: Ken mentions how he’s glad Doug answered the question of how mitochondria ended up losing 99 percent of their original genes, considering that mitochondria used to be free living bacteria with roughly 1,500 genes.

15:25: Dawn points out that Doug and his colleagues are credited with founding the field of human mitochondrial genetics more than 40 years ago.  She then asks if anyone else was doing similar research when Doug started working on human mitochondrial genetics during his post-doc.

17:55: Following his post-doc at Yale, Doug spent seven years at Stanford University School of Medicine. Dawn asks Doug about his work during this time.

22:01: Dawn mentions that in 1983 Doug became the professor of biochemistry, anthropology and pediatrics at Emory University in Atlanta. During this time, he also was chairperson and senior editor of the Mitochondrial DNA Locus-Specific Database for the Human Genome Organization. Dawn asks what that work entailed.

24:11: Ken asks Doug about accepting a professorship of molecular genetics at the University of California, Irvine where he founded the Center for Molecular and Mitochondrial Medicine and Genetics.

26:25: Dawn mentions that in 2010 Doug moved to Philadelphia to become professor of pathology and laboratory medicine at the University of Pennsylvania. Going on to mention that he also became the founding director of the Center for Mitochondrial and Epigenomic Medicine at the Children’s Hospital of Philadelphia (CHOP). She asks what took Doug to CHOP what sort of work goes on at the center.

28:07: Dawn asks Doug to expand on the work he and his colleagues have done that shows that mitochondrial DNA is inherited exclusively from maternal linage, and that genetic alterations to mitochondrial DNA can result in a wide range of metabolic and degenerative diseases.

31:34: Ken brings up that Doug often talks about how Western medicine has generally approached most diseases from a primarily anatomical and Mendelian perspective, and how it seems that our bioenergetics inheritance has been largely ignored. He asks if this is beginning to change, given the recent attention Doug’s work has gained.

33:53: Ken discusses things from a systems perspective, saying that it stands to reason that as energy availability declinesone would expect to see organ specific symptoms of a systemic defect, asking for Doug to elaborateon this rather sensible perspective when viewed through the lens of energetics.

37:10: Dawn asks Doug to discuss his research into the mutation referred to as, “mtDNA ND6 P25L,” which results in elevated reactive oxygen species production and neurological disease.

45:21: Ken asks Doug to further discuss his work in using mitochondrial DNA variation to trace human migrations and origins.

49:03: Ken mentions how some of his friends submitting genetic material to “23 and Me” and seeing the haplogroups they have inherited from their mother has led to some confusion.

52:23: Dawn asks about the aspect of Doug’s research that suggests that there might have been an ancient European migration to the Americas, a conclusion extrapolated from studying a Native American Tribe in Central North America.

55:49: Dawn mentions the molecular clock, which is essentially the concept that mutations accumulate in a piece of DNA at a roughly constant rate because they occur by chance. She asks about the role of the molecular clock in mapping a population’s history?

58:05: Ken asks if Doug has looked at manipulating cells (when there are some cells with mitochondrial DNA mutations, and some without), to enhance autophagy and thereby get rid of the cells with the mutant mitochondria, and if so, would such interventions like intermittent fasting and the ketogenic diet have any benefit in patients.

1:01:23: Ken mentions that interventions such as intermittent fasting inhibit mTOR, asking if this inhibition is sufficient to have a substantial benefit.

1:03:36: Ken asks Doug to dive deeper into the phenomenon of how the high susceptibility of the mitochondrial DNA to mutations, alongside the fact that it is passed only along the maternal lineage, allows for the rapid adaptation to environmental stimuli while also eliminating the majority of detrimental mutations. Ken asks Doug to also talk about how these changes in mitochondrial genes enable animals to adapt swiftly to changing diets and climates.

1:07:18: Shifting gears, Ken asks for Doug’s thoughts on the possibility of life on other planets, and the bacterial basis for mitochondria on earth that allowed for the explosion of complex life on our planet.

1:09:30: Dawn asks Doug to expand on the concept of mitochondrial DNA variations permitting our migrating ancestors to adapt to new environments, and the idea that these adaptations can predispose certain individuals to disease in environments that their mitochondrial DNA isn’t adapted to.

1:12:21: Dawn mentions that Doug and his colleagues at the center are exploring how mitochondrial genes influence adaptation to extremes in our environment, such as artic cold, tropical heat and high altitude. Mentioning thatIHMC does a great deal of work on human performance in extreme conditions, Dawn asks Doug to talk his work in this area.

1:15:00: Ken asks — if it is even possible — if we should attempt to change how coupled we are, given that mitochondrial coupling can affect disease risk.

1:18:05: Dawn asks which haplogroups are at the highest risk for common diseases such as type 2 diabetes, Alzheimer’s, and cancer.

1:20:02: Dawn asks if people should be testing their haplogroups to see their susceptibility to certain diseases.

1:21:00: Dawn asks if Doug could talk a bit about his research into the association between mitochondrial DNA haplogroups and Autism Spectrum Disorder (ASD).

1:23:18: Dawn asks about Doug’s thoughts on the use of pro-nuclease transfer through three-person IVF, which is a very new and somewhat controversial technique designed to allow mothers with mitochondrial disease to have a baby without passing on that mitochondrial defect.

1:28:49: Ken discusses how mitochondria can no longer be viewed only through the lens of bioenergetics but also as platforms for intracellular signaling, regulators of innate immunity, and modulators of stem cell activity. Each of these properties provides clues as to how mitochondria might regulate aging and age-related diseases. Ken asks Doug to discuss how mitochondria participate in aging and whether a new era of mitochondrial-targeted therapies to potentially slow or reverse the aging process might be in prospect?

1:32:44: Dawn asks if there are any common environmental exposures that are negatively affecting mitochondrial function.

1:34:28: Ken asks Doug if, in addition to exercise, there are any other interventions that he thinks are broadly helpful in regards to improving mitochondrial function.

1:35:49: Dawn discusses how mitochondria produce local electromagnetic fields bymoving electrons as part of their normal function. She asks Doug if he has any thoughts on how external electromagnetic fields, such as those generated by electronics or communication devices, might interfere with mitochondrial function?

1:37:33: Ken mentions that Doug has hypothesized that the Qi and energy fields mentioned and targeted in Chinese medicine may actually be a proxy for mitochondrial phenotype and function. Asking how one might measure these in a human, and how could that affect disease treatment?

1:40:54: Dawn mentions how she is looking forward to seeing what comes out of the institute Doug is working on in China, which is bringing together Western, anatomical perspectives with the concepts found in Chinese Medicine.

1:41:09: Dawn comments on how Doug wasinducted into the Italian Academy of Sciences during the Academy’s 234th annual meeting in Rome. The Academy, founded in 1782, has a mission of encouraging scientific research. With a membership limited to 40 Italian scientists and 25 foreign members, the Academy’s long history, has seen such notable members as Albert Einstein, Benjamin Franklin, Louis Pasteur and Rita Levi-Montalcini. She closes the interview by mentioning how rewarding that must have been for Doug.

 

 

 

 

 

 

 

 

 

 

 

Episode 66: Peter Neuhaus talks about exoskeletons, robotics, and the development of exercise technologies for space and Earth

In today’s episode, Ken and Dawn interview their colleague Dr. Peter Neuhaus, a senior research scientist here at IHMC. Peter is an engineer well-known for his work on wearable robotic devices. In particular, Peter has focused on lower extremity exoskeleton devices and their applications for mobility assistance for paraplegics and other people with disabilities or partial paralysis.

In 2016, Peter lead an IHMC team that won a silver medal in the international Cybathlon, a competition conducted in Zurich in which people with disabilities used advanced assistive devices, including robotic technologies, to compete against each other.

In today’s interview, Peter talks about IHMC’s humanoid robotic efforts as well as his work with NASA designing an exercise machine for a human mission to Mars or other missions beyond low earth orbit.

Peter also describes the work he is doing with IHMC High-Performance Director Joe Gomes, the former Oakland Raiders strength and conditioning coach. Peter and Joe as well as others at IHMC are designing exercise technologies to extend the resilience of high-performing humans, such as astronauts and elite warfighters. Many of these technologies will eventually be able to be utilized by the general public.

Links:

 Peter Neuhaus IHMC page:

https://www.ihmc.us/groups/pneuhaus/

 DARPA Robotics Challenge videos:

http://robots.ihmc.us/drc/

 Cybathlon videos:

http://robots.ihmc.us/cybathlon/

 IEEE Robotics and Automation Magazine article about Cybathlon:

https://arxiv.org/pdf/1702.08656.pdf

 IHMC newsletter article about Cybathlon:

https://www.ihmc.us/wp-content/uploads/2015/08/IHMCNewslettervol10iss3.pdf

 IHMC newsletter article about DARPA Robotics Challenge:

https://www.ihmc.us/wp-content/uploads/2017/07/IHMCnewslettervol13iss1.pdf

 Show notes:

3:03: Dawn asks Peter about growing up in New York City.

3:33: Ken mentions that after high-school, Peter enrolled at MIT. Ken asks Peter what led him there.

4:04: Ken asks why Peter decided to major in mechanical engineering.

4:35: Dawn asks Peter what led him to travel across the country to attend the University of California, Berkeley for graduate school after he graduated from MIT.

5:10: Dawn asks what it was like for Peter to teach science to 5^th– and 6^th-graders as well as high-schoolers in Brooklyn after he received his master’s degree from Berkeley.

6:23: Peter talks about how after two years of teaching, he decided his window of opportunity to get a doctorate was shrinking and that it was essentially “now or never,” which led him back to Berkeley.

7:02: Dawn mentions that once Peter finished his doctorate, he went to work for a startup as a mechanical engineer. She asks what sort of work he did there.

7:47: Dawn talks about how a year and a half after getting his doctorate Peter met his future wife, who eventually led him to Pensacola, and in a roundabout way, to IHMC. She asks if he could share how that all came about.

9:22: Ken comments on how since joining IHMC in 2003, Peter has focused on wearable robotics systems and legged robots. Ken further mentions that Peter was one of the lead IHMC researchers participating in the DARPA Learning Locomotion project, where he helped develop quadrupedal locomotion algorithms for the Little Dog robot. Ken asks if Peter could talk about his work on this project?

11:08: Dawn, continuing with the discussion about DARPA projects, mentions that Peter played an important role in both the development of technology and in the management of IHMC’s humanoid robotics effort for the DARPA Robotics Challenge that was held between 2013 and 2015. IHMC placed second and brought home $1 million in prize money. Dawn asks what that experience was like.

12:10: Ken mentions there were three competitions that were part of the robotics challenge, and asks Peter to talk about IHMC’s performance in each of the competitions.

12:57: Dawn mentions that for more than a decade, Peter has been working on exoskeletons, wearable robotic devices that assist people with paralysis and other disabilities. She asks Peter how he got interested in this, and if he could give an overview of what is involved in the development of exoskeletons.

14:39: Ken comments on how wearables are a challenging application for robotics. He asks if Peter could elaborate on some of the specific technical challenges that go along with it.

15:27: Dawn changes the topic to the Cybathlon, a competition, held in Zurich, Switzerland for people with disabilities who are supported by modern assistive technology. IHMC won another silver medal in that competition and Dawn asks about the IHMC team’s preparation for the Cybathlon.

18:18: Ken mentions that a key factor that set IHMC’s exoskeleton apart from the rest at the Cybathlon was the incorporation of powered ankles, which improved mobility. Ken asks Peter to talk about the importance of this feature that the team added to the exoskeleton.

20:05: Dawn asks whether the balancing algorithms that are used in humanoid robots could also be used for ekoskeletons.

22:25: Dawn reads something that Peter once said: “Humans are great at perception. We can look around an area and see where we should go, and what we should step on. But communicating that information to a computer is pretty challenging.” Dawn asks Peter what those challenges are, and if he could speculate about the features that might be incorporated into a state-of-the-art exoskeleton 10 years from now.

24:41: Dawn asks about Peter’s involvement in the X1 exoskeleton that was developed in collaboration with NASA Johnson Space Center.

25:32: Continuing the discussion about NASA, Ken mentions that Peter and his team are also working with NASA on an exercise machine for long duration deep-space missions, such as a Mars mission. Ken talks about how astronauts are so susceptible to bone density and muscle loss while in space that exercise is very important. He asks Peter about the challenges of building exercise devices specifically designed for microgravity.

27:22: Dawn quotes the director of exercise physiology of the Johnson Space Center, Dan Hagen, who said, “Exercise is the number one health priority for astronauts when they are in space. No other activity, except eating and sleeping, is given that much priority. Two and a half hours each day are devoted to fitness.” Dawn asks if a computerized exercise machine could reduce the amount of time someone needs to train, which would free them up to be more productive.

28:33: Ken asks about Peter’s thoughts on how his work with NASA on exercise technology could have applications here on earth.

29:21: Dawn mentions that IHMC recently hired Joe Gomes as the institute’s high-performance director. She goes on to mention that Ken is in the process of building a team to search for ways to extend the resilience of high-performing humans operating in extreme environments and conditions. The team multi-disciplinary team is comprised of engineers and software developers, physicians, pathologists, social scientists, and human-performance specialists to improve training and maximize a person’s physical and cognitive performance. In light of that, Dawns asks Peter to give an overview of how he is teaming up Joe to develop an exercise machine.

30:18: Dawn comments on how health and fitness wearables and apps have, up to this point, merely tracked activity and reported it after the fact. She goes on to ask if it’s correct that the device Peter and his team are developing will enable both the trainee and trainer to receive immediate feedback and prompts during a workout.

31:14: Ken asks Peter whether the technology he is developing with Joe and the rest of the team will get away from a one-size-fits-all model and lead to a more personalized-training model.

32:26: Dawn asks Peter about rehabilitation, and if the exercise machine, or some version of it, will help track and quantify someone’s rehab from injury.

33:37: Dawn asks about the potential commercial uses for the exercise device.

34:21: Dawn asks if computer-controlled motorized resistance also makes exercise safer.

34:55: Ken asks Peter to discuss how the exercise device could potentially help the aging population given that muscle mass begins to decrease substantially after age 60 and leads to falls, frailty and insulin resistance, among much else.

36:49: Dawn asks Peter about the Mobility Unlimited Challenge, sponsored by the Toyota Mobility Foundation. She asks about IHMC’s role and why Toyota is interested in exoskeleton technology.

37:34: Dawn mentions that recently IHMC hosted the 13th annual Dynamic Walking Conference, where students, professors and engineers from around the world gathered in Pensacola for five days of presentations and demonstrations. She asked Peter to explain what the conference was about and what were some of the highlights from the meeting.

38:57: Ken mentions that 2020 is shaping up to be a big year for Peter and the entire IHMC Robotics group. In addition to the Toyota Mobility Challenge, the next Cybathlon is also scheduled for 2020. Ken asks if Peter could discuss his plans for that event.

39:45: Dawn brings up how Peter likes to participate in triathlons, and that he’s been quite active in the triathlon club in Pensacola. She says she understands that Peter recently had to give up running and asks about if that’s true.

41:01: Dawn closes by asking Peter if there is any chance that one day some of the technology Peter is developing could help him get back into running.

 

 

Episode 65: Dr. Brendan Egan talks about the importance of muscle and his research into exogenous ketones

Dr. Brendan Egan is an Associate Professor of Sport and  Exercise Physiology at Dublin City University who is well known for research that shows resistance training can improve strength, muscle mass, reduce falls in older people, and perhaps even extend lifespans.

In addition to being a first-class researcher, Brendan is also a stand-out player in Ireland’s national sport, Gaelic football.

His current research is exploring the synergy between nutrition and exercise interventions to optimize performance in athletes and the elderly.

Current projects also involve protein hydrolysates in recovery and glycemic management; leucine and n-3 PUFAs in the elderly; and exogenous ketones and athletic performance.

Links:

 Brendan Egan’s faculty page: 

https://dcu.academic.ie/live/!W_VALOCAL_DCU_PORTAL.PROFILE?WPBPRSN=1631629

Brendan Egan’s Researchgate profile

https://www.researchgate.net/profile/Brendan_Egan2/contributions

Brendan Egan’s TEDx talk:

https://youtu.be/LkXwfTsqQgQ

Exercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation

https://www.sciencedirect.com/science/article/pii/S1550413112005037

Metabolism of ketone bodies during exercise and training:

https://physoc.onlinelibrary.wiley.com/doi/epdf/10.1113/JP273185

Fueling performance: Ketones Enter the Mix:

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(16)30438-7

Does Strength-Promoting Exercise Confer Unique Health Benefits?

https://academic.oup.com/aje/article-abstract/187/5/1102/4582884?redirectedFrom=fulltext

Does Strength-Promoting Exercise Confer Unique Health Benefits?

https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP275938

Show notes:

2:46: Dawn opens by mentioning that Brendan was born in Detroit, and that his Irish father moved the family to Ireland when Brendan was 3 years old. Dawn asks if Brendan’s mother was American.

4:09: Dawn comments on how Brendan was very athletic as a child and played Gaelic football, which is Ireland’s national sport, and asks if he could explain how this game is played.

6:02: Ken, following up on the last question, asks what Brendan’s training is like for this sport, and how he manages to fit it into his busy schedule as a professor.

7:41: Dawn asks if it is true that even though Brendan’s best grades were in math and physics, he never considered a career in science while he was in high school.

8:37: Dawn mentions that Brendan ended up at the University of Limerick after graduating, asking what made him decide to attend Limerick as well as what prompted him to major in sports and exercise science.

9:46: Dawn asks about two people, Phil Jakeman and John Kirwan, who played a big role in shaping Brendan’s education at Limerick.

11:58: Dawn comments on how after completing his bachelor’s of science degree, Brendan went to work on his master’s, heading to the UK and attending Loughborough University where he graduated with distinction in sports exercise and nutrition. Dawn asks what made him decide to attend Loughborough, and what stood out about his time there.

13:33: Dawn mentions that Brendan returned to Ireland in 2004 to start his doctoral studies under the supervision of Dr. Donal J O’Gorman at Dublin City University. Dawn asks what that experience was like.

15:06: Ken asks what Brendan learned from his research with Dr. O’Gorman, which focused on skeletal muscle adaptation to exercise and, in particular, continuity between acute molecular responses to individual bouts of exercise and the adaptations in skeletal muscle induced by exercise training.

18:30: Dawn asks what took Brendan to Karolinska Institute in Stockholm.

19:51: Brendan talks about his work at Karolinska using animal intravenous cell systems, and his research into transcriptional regulation of skeletal muscle insulin resistance and type 2 diabetes utilizing small non-coding RNA’s.

23:39: Ken mentions that Brendan’s first faculty position was at the University College Dublin in 2011, where he spent five years establishing his own independent research group. He then moved to Dublin City University in 2016. Ken asks how Brendan developed his research group, and what kind of work the group does now.

25:44: Dawn asks Brendan to discuss the prevalence of the age-related loss of muscle function and mass, which often leads to sarcopenia. She also asks about its effects on individuals as well as its impact on society.

27:45: Ken mentions that the heavy use of Prednisone, which a lot of older people are put on for long periods of time, rapidly diminishes their muscle mass.

29:35: Ken mentions that falls are a huge issue, seemingly associated with the loss of fast-twitch muscle as we age, and that falls are more a result of loss of power than loss of strength and mass. He proposes that this is a major, yet overlooked, driver of the prevalence of falling in the older population.

31:11: Ken comments on how there are complex and interacting causes of this loss of mass, strength and power which are not completely understood yet. He lists off certain drivers such as: insulin resistance; decreased availability of anabolic hormones coupled with increased anabolic resistance; the need for more protein as we age; decreased motor neuron function; elevated intercellular oxidative stress; reduction in satellite cell numbers and regenerative capacity; elevated myostatin signaling; reduced physical activity; increased chronic inflammation; changes in autophagy; and mitochondrial abnormalities. Ken asks Brendan to share his thoughts on what he considers the primary drivers of muscle loss.

33:06: Dawn mentions that one of Brendan’s most recent research studies is centered on the optimal way to exercise in terms of time efficiency. She inquires as to what the best combination of exercise would be for someone with a limited amount of time per week.

35:53: Dawn asks Brendan to talk about the importance of leg strength.

37:05: Dawn mentions that it has been well established for many years that resistance training can improve strength and muscle mass, and reduce the incidence of falls and fractures. She asks Brendan to talk about a recent study, done over the course of 15 years with more than 30,000 participants 65 years and older. The study showed that people who did strength training twice a week lowered their risk of dying by almost half.

38:33: Dawn asks what Brendan found in a follow-up study he did where he looked at a nutrition intervention that featured a high protein diet in combination with exercise versus a high protein diet alone. Unlike most similar studies, Brendan’s follow-up study used whole foods rather than protein supplements.

40:47: Dawn mentions that Brendan and other scientists at UCD are currently investigating a dairy-based protein which has been predigested from hydrolysate to see if it will enhance the insulin response and lead to a faster recover compared to other protein and carbohydrate drinks.

42:06: Ken comments on how optimal recovery post-exercise is more and more appreciated, and it’s obviously desired across athletic populations. He asks what happens at the cellular and molecular level during recovery that Brendan finds most relevant and interesting.

43:50: Dawn mentions that Brendan has been looking at exogenous ketone supplementation, particularly in the area of sport science, and how it might relate to athletic performance, and asks what this research is specifically focused on at the moment.

44:41: Ken asks Brendan for his thoughts on increasing the circulating availability of BHB by consumption of exogenous ketones and wonders if it would recapitulate the many positive effects of decreasing carbohydrate intake, which manifests itself in those engaged in a keto-adapted phenotype.

46:20: Dawn mentions that in some circles there is concern that one might overload the mitochondria by providing both high levels of glucose and ketones, asking what Brendan’s thoughts are on this.

47:23: Dawn asks what we know about the impact of exogenous ketones in athletic performance.

51:36: Dawn asks about exogenous ketone esters, particularly the HVMN monoester. She also asks about the AcAc diester developed by Dominic D’Agostino. She supposes that the two different compounds would have distinct pharmacokinetics and somewhat different effects. She asks Brendan to discuss this.

54:39: Dawn mentions that Brendan has given ketone salts and esters to athletes, and that there’s talk in the community about the tolerability of these different compounds. She asks about his experience with them and how he has improved the tolerability in his studies.

56:02: Ken asks about the effects of exogenous ketones on carbohydrate metabolism in high intensity sport, and what he thinks of the glycogen sparing versus glycogen impairing debate around exogenous ketones.

1:00:39: Dawn mentions that exogenous ketones lower blood glucose, asking what the role of the hepatic glucose output is, versus the change in peripheral uptake, and asks Brendan if he thinks BHB could be altering peripheral glucose uptake.

1:02:24: Ken asks about Brendan’s thoughts on studies concluding that exogenous ketone esters helped blood ketone concentrations reach greater than 2 millimolar and is likely a key mediator of any potential ergogenic effect.

1:03:32: Ken mentions the topic of recovery, pointing out that there have been several papers in recent years that look at the BHB monoester and recovery. Ken asks Brendan to discuss these studies and their implications for future research.

1:07:10: Dawn asks if exogenous BHB might have the same effect as exercise, which has long been known to increase brain derived neurotrophic factor (BDNF) which enhances mental abilities, reduces anxiety, and increases neuroplasticity, considering that BDNF has been shown to be inhibited by histone deacetylases (HDACs), and that BHB inhibits HDACs.

1:08:21: Ken mentions that there have been a few ingestibles that have had effects that act as exercise mimetics. He inquires as to Brendan’s thoughts on these compounds.

1:10:14: Dawn asks Brendan about how Ireland is projected to become the fattest nation in Europe in the next 10 to 15 years.

1:11:07: To wrap things up, Dawn asks Brendan to give three to five pieces of advice for living a longer and healthier life, no matter the age.

Episode 64: Valter Longo talks about the fasting-mimicking diet and the keys to longevity

Today’s episode features Dr. Valter Longo, director of the Longevity Institute at the University of Southern California.

Valter is best known for his research on stem cells and aging as well as his fasting-mimicking diet. Often referred to as FMD, the diet is intended to avoid the downsides of fasting while reaping the health benefits of a calorie-restrictive diet.

Over a 25-year career, Valter has published numerous papers about the ways specific diets can activate stem cells and promote regeneration and rejuvenation in multiple organs to reduce the risk for diabetes, cancer, Alzheimer’s and heart disease.

He writes about this research and diet in a book that was released earlier this year, “The Longevity Diet: Discover the New Science Behind Stem Cell Activation and Regeneration to Slow Aging, Fight Disease and Optimizer Weight.” The book details an easy-to-follow everyday diet that is combined with short periods of the fasting-mimicking diet. Valter says the diet has the potential to help people live healthier and longer lives.

Valter is a native of Genoa, Italy and moved Chicago when he was 16. He received his bachelor’s of science degree at the University of North Texas in 1992 and his Ph.D. at UCLA in 1997.

Links:

Longevity Center website:
http://longevityinstitute.usc.edu

Longo’s USC faculty page:
http://gero.usc.edu/faculty/longo/

“The Longevity Diet”:
https://amzn.to/2s1fcky

A periodic diet that mimics fasting promotes multi-system regeneration:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509734/

Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration:
https://www.cell.com/cell/fulltext/S0092-8674(17)30130-7

Fasting-mimicking diet and markers/risk factors for aging:
http://stm.sciencemag.org/content/9/377/eaai8700

Prolon FMD website:
https://prolonfmd.com/fasting-mimicking-diet/?doing_wp_cron=1526216346.5062971115112304687500

Show notes:

2:24: Dawn opens the interview by mentioning that Valter was born and raised in Genoa, Italy, the hometown of Christopher Columbus. She asks if reports of him driving his neighbors mad playing Dire Straits, Jimmy Hendricks and Pink Floyd on his electric guitar as a youth are accurate.

2:43: Dawn asks Valter what his parents said when he tried to talk them into letting him go to London to be a rock star when he was 12 years old?

3:10: Valter left home when he was 16 to go visit an aunt in Chicago, but ended up staying in Chicago to go to school and play music. Dawn asks what that was like?

3:49: Dawn comments on how in addition to being exposed to some of the best blues music in the world, Valter also was exposed to some of the unhealthiest food in the world. Valter then talks about what he refers to as “the heart-attack diet.”

4:48: Dawn asks what lead Valter to attend the University of North Texas College of Music.

5:30: Valter joined the Army Reserve to help pay for college and ended up assigned to a battalion of Army tankers. Ken asks Valter what that was like.

6:15: Dawn asks if it’s true that the idea of directing a marching band lead Valter to switch majors as a sophomore.

7:07: Dawn comments on how not many jazz performance majors, who have never taken a biology course, decide to switch their major to biochemistry. She asks Valter what the people in the biochemistry department had to say about that.

8:04: Dawn mentions that when Valter was five years old, he saw his ailing grandfather pass away. She asks him to talk about that experience and the role it played in his decision to study aging.

9:14: Dawn mentions that after switching over to biochemistry and graduating from college in 1992, Valter headed to UCLA, which at the time was one of the world’s leading centers of longevity research. She asks Valter how that opportunity came about.

10:22: Ken brings up Valter’s work at UCLA in the lab of the pathologist, Roy Walford. Valter studied the effects of caloric restriction in the lab and Ken asks Valter to talk about what he learned.

11:25: Dawn comments that while in Walford’s lab, Valter made two important discoveries using a method that he invented. Dawns asks him to describe the discoveries.

13:20: Dawn asks Valter what led him to do his post-doc work at the University of Southern California, and what the focus of his research was at USC.

14:04: Dawn asks what it was like to study in a community of dwarves in Ecuador, a group of people who lack the receptor for the growth hormone, which is known as Laron syndrome. Valter talks what he learned from that experience.

16:08: Ken notes that these dwarves seem to be nearly immune to cancer and diabetes. Accidents, convulsive disorders and alcohol deaths, however, account for 50 percent of their mortality. Among non-dwarf relatives, these same causes of mortality account for just three percent of deaths. Ken asks Valter what causes this big disparity.

17:54: Dawn recounts that Valter went on to become a professor of gerontology and biological sciences at USC, and that in 2011 he became the director of the Longevity Institute. She goes on to say that the institute is not just interested in the idea of people living longer, but also understanding how people can live healthier longer. She asks if Valter could give some background on the institute and the type of research it does.

19:27: Ken notes that Valter believes it is smarter to intervene on aging itself, rather than try to prevent and treat diseases one by one as they come up. Ken asks Valter to talk about that.

21:04: Dawn mentions that Valter has traveled the world studying people in “blue zones,” areas of the world with the longest-lived populations. She goes on to mention that because of his time with centenarians, Valter concluded that in order to understand how people can live healthy lives, one needs to go beyond the scientific, epidemiological, and clinical studies, and investigate actual populations that age successfully.

23:11: Ken mentions that Valter had the opportunity to know Emma Romano, who lived to 117 and was reportedly the oldest person in the world. He goes on to mention that Emma’s sisters also lived into their 90s and some of the sisters made it to 100. These women, it would seem, were rare individuals who could eat and do just about anything they wanted and still age successfully. Ken asks how much of a role genetics played in their lifespan.

24:30: Dawn shifts gears to talk about Valter’s book “The Longevity Diet,” which is the outgrowth of Valter’s 30 years of research on aging. The book describes a daily nutritional regiment that is combined with the “fasting mimicking diet.” Dawn asks if Valter could define the fasting-mimicking diet.

27:02: Ken asks Valter what it is about the fasting-mimicking diet that actually mimics fasting.

28:38: Dawn asks if one should measure markers such as glucose, ketones, insulin, and IGF-1 while undergoing the fasting mimicking diet.

29:42: Dawn asks if the implementation of the diet requires a doctor’s supervision.

30:46: Dawn inquires as to what a typical fasting-mimicking diet meal looks like.

31:13: Dawn asks how Valter arrived at the 5-day period as the necessary time to experience the benefits of the fasting-mimicking diet.

32:22: Dawn asks if there are populations that Valter wouldn’t recommend the diet to.

33:33: Shifting gears, Ken asks if one can have coffee on the fasting-mimicking diet, mentioning that Valter’s grandfather and Emma Romano likely enjoyed espresso.

35:01: Ken mentions that Valter has said that skipping breakfast increases overall morality and asks him to explain this.

36:42: Dawn mentions that Valter has published a number of papers that indicate that cycles of fasting and refeeding can cause multisystem regeneration and rejuvenation that lead to extended health spans and effects ranging from those on the immune system to the nervous system to muscles. She asks Valter to talk about this.

38:27: Ken asks if Valter could share what he calls the “five pillars of longevity.”

41:31: Dawn asks about the mechanism by which fasting causes an unfavorable environment for cancer cells.

44:24: Ken brings up metformin as an example of a compound that can artificially induce some of the benefits of fasting in the body.

45:45: Ken returns to IGF-1, asking what role it plays in both health and disease.

46:31: Ken brings up the epidemiology research done in the 2011 meta-analysis by Burgers Atoll which showed that both low and high IGF-1 concentrations are associated with increased mortality, essentially showing that the hazard ratio appears U shaped in that both ends of the spectrum are hazardous to a person’s health. Ken asks if there is a sweet spot, or if Valter considers it to be a case of the lower the better, or if it somewhat depends on a person’s age?

48:42: Ken mentions that something that tends to be overlooked in discussing IGF-1 is that fasting, the ketogenic diet, and other such things increase the receptor sensitivity for IGF-1. Thus, even at a relatively low level, the effects would not be the same for someone not in a state of ketosis.

49:52: Dawn asks if protein intake is the only dietary factor involved in regulating IGF-1 levels.

50:21: Ken mentions that Valter’s 2014 cell metabolism paper leveled the risk firmly at the door of IGF-1 concentrations. Ken brings up that IGF-1 regulation of metabolism, however, is more about the interactions of IGF-1 with binding proteins. Ken asks how much IGF binding proteins play a role in IGF.

51:42: Dawn brings up that in 2014 Valter published a study with Levine Addal that said, “We provide convincing evidence that a high-protein diet, particularly if the proteins are derived from animals, is nearly as bad as smoking for your health.” She asks Valter to explain the process of coming to that conclusion.

52:33: Following up on that question, Ken mentions that the risks purported in the paper were relative risks, not absolute risks. In other words, the relative risk of dying from cancer in the high-protein group was roughly four times that of the low-protein group, but the absolute change in risk was maybe half of one percent. Ken points out that depending on how one presents the risk, it could lead to different headlines.

53:26: Ken comments on how he believes the presentation of risk to be misleading, because the change in absolute risk was so negligible as to be noise.

53:58: Ken, returning to protein, mentions that protein intake is complex and multifactorial. Ken asks Valter if the epidemiological research that has been discussed in the interview is able to tease out the important nuances and variables.

56:43: Dawn mentions that Valter often receives emails from people diagnosed with cancer, autoimmune disorders and neurodegenerative diseases who are seeking options beyond the standard treatments offered by their doctors. Valter says this was a key reason he established the Create Cures Foundation, and goes on to give an overview of the foundation and how it is funded.

58:01: Interview ends.

Episode 63: Keith Baar talks about collagen synthesis, ketogenic diet, mTORC1 signaling, autophagy, post strength training nutrition, and more…

Dr. Keith Baar joins Ken and Dawn today for the second of his two-part interview for STEM-Talk. Keith is a renowned scientist in the emerging field of molecular exercise physiology who has made fundamental discoveries on how muscles grow bigger, stronger, and more fatigue resistant.

He is the head of the Functional Molecular Biology Laboratory in the Department of Neurobiology, Physiology, and Behavior at the University of California, Davis. In his lab, he leads a team of researchers attempting to develop ways to improve muscle, tendon and ligament function.

Part one of our interview, episode 62, covered Keith’s childhood in Canada and his undergrad years at the University of Michigan as well as his time at the University of California, Berkeley, where he earned a master’s degree in human biophysics. We talked about Keith’s work at the University of Illinois, where he received a doctorate in physiology and biophysics. We also covered Keith’s time in the lab of John Holloszy, who is known as the father of exercise research in the United States, as well as the five years Keith spent at the University of Dundee in Scotland.

Episode 63 picks up with Keith explaining his decision to return to the states and join the faculty at the University of California, Davis.  Ken and Dawn then talk to Keith about his most recent research, some of which is looking at how to determine the best way to train, as well as what types of foods compliment training to decrease tendon and ligament injury and accelerate return to play. This work has the potential to improve muscle function not only in athletes, but also improve people’s quality of life as they age. Another key topic covered in part two of our interview is the research Keith is doing on a ketogenic diet and its potential to reduce cancer rates and improve cognition. Keith also provides his thoughts on what optimal workouts and nutrition should look like.

Links:

Baar’s UC Davis physiology department bio:

https://www.ucdmc.ucdavis.edu/physiology/faculty/baar.html

Baar’s UC Davis biology department bio:

https://biology.ucdavis.edu/people/keith-baar

Functional Molecular Biology Lab website:

http://www.fmblab.com/ 

Molecular brakes regulating mTORC1 activation in skeletal muscle paper:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137116/

Age-related Differences in Dystrophin article:

https://www.ncbi.nlm.nih.gov/pubmed/27382038

Show notes:

2:54: Dawn begins part 2 of our interview by mentioning that for the past eight years, Keith has been working at the University of California Davis. She asks Keith what prompted him to return to the U.S. from Scotland and join the faculty at UC Davis.

3:37: Dawn points out that Keith’s Functional Molecular Biology Lab conducts research across a range of related topics, including musculoskeletal development and adaptation as well as methods for engineering functional musculoskeletal tissues in vitro. She asks Keith to give a high-level overview of some of that research.

4:16: Dawn comments that some of Keith’s recent work has shown that we can use specific nutrition and training strategies to optimize injury recovery and prevention. She goes on to say that musculoskeletal injuries are among the most common problems that active people have.

8:45: Ken talks about how Keith has noted that tendon stiffness is dependent upon collagen content, and the amount of crosslinks within. He goes on to mention that Keith has developed various training modalities, as well as nutritional protocols, that can increase and decrease tendon stiffness. Ken begins this line of inquiry by asking about the training methods for this purpose.

12:04: Following up on the previous question, Ken asks whether anyone has looked at how blood flow restriction training, which is increasing in popularity, affects tendon stiffness.

13:32: Dawn moves on to asking about nutrition. She mentions that Keith’s lab has done a great deal of groundbreaking work on the use of gelatin and a small amount of vitamin C to augment collagen synthesis in tendons, ligaments, cartilage, and bone. She asks if he could talk about this nutrition protocol and its effects, particularly when combined with jumping rope.

17:52: Ken mentions that this work is not only interesting scientifically, but it has an immediate, practical application that people can use in their life. Ken goes on to say that those suffering from stress fractures or a variety of other ailments could benefit from this.

21:09: Ken mentions that there are several different forms of collagen, asking if there is any particularly efficacious form, or if they function equally.

22:40: Ken comments that it is not just lower body weakness and injuries in tendons, but also tendonitis that is found in the shoulders and elbows. He asks if there is a variant of Keith’s protocol that is suited for this sort of tendonitis as well.

24:37: Ken asks a question submitted by friends in the special ops community. He mentions that one of their biggest issues is force absorption, due to the repeated, substantial, damage accrued in both training and in operations. He goes on to ask if a focus on eccentric training would lengthen fascicles to allow for greater absorption, and how does it influence the ability to contract concentrically.

26:13: Dawn mentions that she has heard Keith discuss “sugar cross-linking” in the context of aging and diabetes. She asks if this explains why diabetics suffer an increased incidence of tendon and ligament ruptures and injuries.

28:22: Ken, coming back to tendon stiffness, mentions that in addition to fast exercise, inactivity also leads to increased tendon stiffness, counterintuitive as that is. He asks if Keith could discuss this, somewhat surprising, fact.

30:20: Ken comments that ligament engineering is another fascinating area of Keith’s research; he goes on to say that Keith and his colleagues recently engineered the first in vitro ligaments. He goes on to inquire as to how these ligaments are created, what insights can be gleaned from them, and how Keith sees them being used in the future.

34:23: Ken states that mTOR inhibition by rapamycin is arguably the only strategy that has reliably resulted in lifespan extension across a multitude of different species. He goes on to say that we know that mTORC1 activation increases muscle mass and strength, which is critical for optimizing health span into old age. He goes on to bring up a recent paper Keith co-authored with Megan Roberts that showed the ketogenic diet had tissue-specific effects on mTORC1 signaling; decreasing signaling in the liver, while increasing it in the muscle. Ken postulates that perhaps researchers should focus their attention on tissue-specific mTOR activity, to further elucidate the issue of balancing mTOR for longevity with the maintenance of muscle for strength quality. Ken asks Keith if he had unlimited resources, how would Keith design a study to explore this.

43:32: Ken asks if Keith is familiar with a class of drugs that one could characterize as PPAR-delta agonists, sometimes called exercise mimetics, given the overlap between the effects of the ketogenic diet and this class of drugs.

45:10: In regards to longevity, Dawn mentions that few would argue that many elite athletes train for performance at the expense of health. She asks what would be Keith’s overall training recommendation for someone who wants to maximize healthspan and lifespan, and if that is possible while also striving for top levels of performance.

49:24: Ken comments on a belief in the world of “bro science,” that post-exercise carbohydrate ingestion is absolutely necessary for maximizing the anabolic response of resistance training. Ken asks if this is true, and if not, if Keith would educate us as to why and what optimal nutrition and workouts should look like.

51:18: Ken asks what Keith sees as the role of autophagy in the maintenance of muscle mass in aging adults.

53:48: Ken comments on the phenomenon of older people developing anabolic resistance, much like insulin resistance; mentioning a paper that recently looked at the ketogenic diet in that context and found it increased IGF-1 receptor sensitivity.

54:46: Dawn asks to what extent does Keith think a person’s baseline body composition can impact the response to an exercise stimulus.

55:44: Ken points out that Keith has been a scientific advisor for a number of different athletic teams and organizations, pointing out that Keith works to maximize the effects of training for both endurance and strength as well as ways to minimize injury. Ken asks Keith what that experience has been like.

58:27: Ken mentions his intrigue with the mission statement of Keith’s Functional Molecular Biology Lab: “To perform world class musculoskeletal research in a family environment.” Ken asks Keith to explain the story behind including “a family environment” in his mission statement.

1:01:08: Interview ends.

Episode 62: Keith Baar talks about muscle and explains mTOR, PGC-1a, dystrophin, and the benefits of chocolate

Today’s episode is the first of a two-part interview with Dr. Keith Baar, the head of the Functional Molecular Biology Laboratory in the Department of Neurobiology, Physiology, and Behavior at the University of California, Davis.

In his capacity as a researcher, Keith has made fundamental discoveries on how muscle grows bigger, stronger, and more fatigue resistant. He is a renowned scientist in the emerging field of molecular exercise physiology, and is leading a team of researchers attempting to develop ways to improve muscle, tendon and ligament function.

Part one of our interview features our conversation with Keith about his background and his time time in the lab of John Holloszy, who is known as the father of exercise research in the United States.

Episode 63 of STEM-Talk has Dawn and Ken talking to Keith about his most recent research, which is looking at how to determine the best way to train, as well as what types of foods compliment training to decrease tendon and ligament injury and accelerate return to play. This work has the potential to improve muscle function and people’s quality of life, especially as they age. Ken and Dawn also have a conversation with Keith about the research he is doing on a ketogenic diet and its potential to reduce cancer rates and improve cognition.

Links:

UC Davis physiology department bio:

https://www.ucdmc.ucdavis.edu/physiology/faculty/baar.html

UC Davis biology department bio”

https://biology.ucdavis.edu/people/keith-baar

Functional Molecular Biology Lab website:

http://www.fmblab.com

Molecular brakes regulating mTORC1 activation in skeletal muscle paper:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137116/

Age-related Differences in Dystrophin article:

https://www.ncbi.nlm.nih.gov/pubmed/27382038

 Show notes:

3:14: Dawn opens the interview by mentioning that Keith grew up in Canada, and asks what he was like as a child.

4:02: Dawn asks if Keith was interested in science as a kid.

4:53: Dawn comments that after high school, Keith came to the U.S. to attend the University of Michigan, where he earned a bachelor’s degree in kinesiology. She Keith if Michigan was where he first became interested in the science of how muscles work.

7:54: Dawn asks Keith if he played any sports at Michigan.

8:34: Dawn asks what lead Keith to attend the University of California, Berkeley to pursue a master’s degree in human biophysics.

9:39: Dawn mentions that after his time at Berkeley, Keith returned to the Midwest to attend the University of Illinois where he received his doctorate in physiology and biophysics. She asks why he decided on Illinois for his doctoral work.

11:12: Ken mentions that Keith’s Ph.D. work focused on the effect of resistance exercise on specific molecular markers that are related to muscle growth. He goes on to say that Keith identified that mTOR complex 1 was activated in response to resistance exercise and that the activation was proportional to the load across the muscle. He asks Keith to talk about this work and its significance.

16:20: Ken comments how surprising that discovery must have been.

17:33: Ken asks Keith to explain the two basic ways of activating mTORC1 in skeletal muscle. Ken also asks whether these two are merely additive, or if together they elicit a greater muscle protein response than either would independently.

29:49: Dawn mentions that after Illinois, Keith went to work in the lab of John Holloszy at Washington University in St. Louis, a professor of medicine who is known as the father of exercise research in the United States. Dawn asks if is Holloszy is the one who discovered that when people do endurance exercise that their muscles accumulate more mitochondria.

32:24: Ken asks about the role of PGC-1a.

38:43: Ken comments that we know most sports require a combination of strength and endurance for optimal performance, bringing up the topic of concurrent training.

48:02: Ken asks if we know which form of AMPK is activated by things such as Metformin or the ketogenic diet.

49:24: Dawn comments that Keith eventually accepted a position at Michigan where he worked with Bob Denis, who figured out how to engineer muscles as well as ligaments. She asks Keith to share some things about the research they did together.

50:41: Dawn mentions that after Michigan, Keith accepted a position at the University of Dundee in Scotland, where he worked for 5 years. Dawn asks what that experience was like.

55:20: Ken mentions that from looking at the literature, it seems as though Keith discovered that the non-contractile portion of the muscle plays a key role in the transfer of force, and that this is nearly as important as the size of the muscle fiber itself. He asks Keith to elaborate on this finding.

58:45: Ken asks if Keith’s work has elucidated a potential countermeasure to the loss of dystrophin, for both the aging population and cancer patients. Keith then talks about research at the University of California, San Diego, that has shown the beneficial effects epicatechin, a flavanol in dark chocolate.

1:00:37: Ken mentions that some athletes are using Transdermal Epicatechin, and asks about the efficacy of such practice.

1:01:54: Interview ends.

Episode 61: Chris McCurdy discusses kratom and the opioid crisis

More than 90 Americans a day are dying from opioid abuse. Today’s guest, Dr. Christopher McCurdy, is at the forefront of research designed to help the U.S. deal with this drug overdose crisis.

Chris is a medicinal chemist and behavioral pharmacologist at the University of Florida who is internationally known as an expert on kratom, a botanical mixture that has been shown to help people struggling with addiction. He recently became president of the American Association of Pharmaceutical Scientists, and has spent his career focusing on the design, synthesis and development of drugs to treat pain and drug abuse.

Chris earned his bachelor of science degree in pharmacy from Ohio Northern University, and a Ph.D. in medicinal chemistry from the University of Georgia College of Pharmacy in 1998.

He did his postdoctoral work at the University of Minnesota where he focused on opiate chemistry in relation to drug abuse and drug addiction. He joined the faculty at the University of Mississippi in 2001 where much of his research was successful in discovering unique and selective tools for sigma receptors, NPFF receptors and opioid receptors.

Dr. McCurdy accepted a post as a professor of medicinal chemistry at Florida in 2017 and became the director of the university’s Translational Drug Development Core.

 Links:

 Christopher McCurdy UF faculty page:

http://pharmacy.ufl.edu/faculty/christopher-mccurdy/

American Association of Pharmaceutical Scientists:

https://www.aaps.org/home

Translational Drug Development Core:

https://www.ctsi.ufl.edu/research/laboratory-services/translational-drug-development-core/

 Suspected Adulteration of Commercial Kratom Products with Hydroxymitragyine:

https://www.ncbi.nlm.nih.gov/pubmed/27752985

Self-treatment of Opioid Withdrawal Using Kratom:

https://www.ncbi.nlm.nih.gov/pubmed/18482427

Herbal Medicines for the Management of Opioid Addiction:

https://www.ncbi.nlm.nih.gov/pubmed/22133323

Show notes:

 2:58: Ken opens by asking Chris if he ever dreamed of becoming a professional athlete as a result of growing up in Pittsburg during the hay-day of the Stealers and the Pirates.

3:28: Dawn mentions that Chris’s father was a pharmacist, and his mother, a science teacher. She further mentions that in addition to being interested in sports, that Chris also was interested in science, and she asks what role his parents played in that.

4:45: Dawn mentions that Chris moved to a suburb of Youngstown Ohio just as he was starting high school. Chris talks about playing basketball, being part of a competitive swim team, and his reputation as a fairly straight-laced kid.

5:27: Ken mentions that Chris headed to Ohio Northern University after he graduated from high-school and initially pursued a double major in pharmacy and music. Ken asks what prompted that particular combination.

6:39: Ken talks about how at Ohio Northern, Chris’s first real mentor in science noted his talent for research, and suggested that Chris should head to the University of Georgia for the summer to get acquainted with research. Chris talks about how that eventually led to him attend Georgia for his doctorate.

10:39: Ken asks Chris to talk about his doctoral research into Native American Tobacco.

13:28: Dawn comments on how there weren’t too many post-doc opportunities available at the time he finished his studies at Georgia, but that she understands there is an apparent pattern in his life of being at the right place at the right time. She asks if it was this pattern that lead him to the University of Minnesota.

17:05: Dawn inquires as to what got Chris interested in working on the natural product called Salvinorin A (Magic Mint), and what became of that research.

20:40: Dawn mentions that because of his work on salvia divinorum, Chris was invited by the National Institute of Drug Abuse to give a talk in 2004, which is where he first learned about kratom.

23:08: As context, Ken asks if Chris could expound upon kratom’s history, the different types of kratom, and the varying effects they have on users.

32:10: Ken brings up the debate surrounding whether kratom is properly construed as an opioid. Chris goes on to talk about the differences between kratom and classic opioids.

37:33: Following up on the previous question, Ken mentions that the distinction between opioid and opiate is quite important, given that when people talk of opioids they are generally thinking of opiates specifically. Given that respiratory depression is a major issue for those on opiates, Ken asks how many lives could be saved by moving people off opiates.

40:32: Shifting the conversation, Ken asks about the use of kratom among athletes.

43:10: Ken, following up on the last question, mentions that the primary use of kratom among athletes is not for performance enhancement, but rather recovery, and coping with the pain.  One frequently hears of kratom use among athletes, especially those engaged in sports such as wrestling, mix martial arts, bodybuilding, and football to help manage the pain associated with their sport-related injuries.

47:08: Ken comments on the importance of Chris’s endeavor to perform clinical trials with kratom, and asks about the resistance he has faced in doing trials.

50:17: Dawn asks if there are any documented side effects of chronic use of kratom, and if there is the potential to overdose.

53:49: Dawn, shifting gears, mentions that while at the University of Mississippi he met Bonnie Avery, an analytical chemist, and that he began to collaborate with her. Dawn goes on to mention that Bonnie became known as the bearer of bad news, asking how she ended up with that reputation, and also how Chris ended up marrying Bonnie.

57:10: Dawn says that in 2013 the Florida Legislature announced that it was going to create a preeminence program that would provide state universities millions of dollars to attract top level faculty members and scientists. She mentions that because of this program Chris was approached, and that he and Bonnie eventually joined the Florida faculty. Dawn asks how that all came about.

59:39: Dawn asks Chris about a mentor who once advised him, “Always focus on the science, and be true to the science.” Dawn asks Chris if that is advice he, too, shares with people.

1:01:55: Interview ends.

Episode 60: Marie Jackson talks about the amazing endurance of Roman concrete

Why is it that modern marine concrete structures crumble and corrode within decades, but 2,000-year-old Roman piers and breakwaters endure to this day?

Episode 60 of STEM-Talk features Dr. Marie Jackson, a scientist who has spent the past two decades figuring out the answer to that and other questions about the durability of ancient Roman mortars and concretes.

Marie is a research associate professor in the department of geology and geophysics at the University of Utah. She is known for her investigations in pyroclastic volcanism, mineralogy, materials science, and archaeological science that are breaking new ground in understanding the durability and specialty properties in ancient Roman mortars and concretes.

She is particularly focused on deciphering Roman methods and materials in the hope of producing innovative, environmentally friendly cementitious masonry products and nuclear waste storage materials that would benefit the modern world. She was the lead principal investigator of a drilling project in the summer of 2017 on the Surtsey Volcano, which is on a small isolated island off the coast of Iceland. The volcano is growing the same mineral cements as Roman marine cement and the drilling project is helping provide extraordinary insights into the materials and processes the Romans used.

She is particularly focused on deciphering Roman methods and materials in the hope of producing innovative, environmentally friendly cementitious masonry products and nuclear waste storage materials that would benefit the modern world. She was the lead principle investigator of a drilling project in the summer of 2017 on the Surtsey Volcano, which is on a small isolated island off the coast of Iceland. The volcano is growing the same mineral cements as Roman marine cement and the drilling project is helping provide extraordinary insights into the materials and processes the Romans used.

After receiving her bachelor of science in earth sciences from the University of California Santa Cruz, Marie traveled overseas and received a doctorate from the Universite de Nantes in France. She returned stateside and received a doctor of philosophy from John Hopkins University as well as a Ph.D. in earth and planetary sciences.

Marie then went to work as a research geoscientist for the U.S. Geological Survey. After taking time off to raise a family, Marie joined the department of civil and environmental engineering at the University of California, Berkeley, as a project scientist. She stepped into her current position at the University of Utah in 2016.

Links:

Mechanical resilience and cementitious processes in Imperial Roman architectural mortar:

https://www.researchgate.net/publication/270161645_Mechanical_resilience_and_cementitious_processes_in_Imperial_Roman_architectural_mortar

Marie Jackson ResearchGate profile:

https://www.researchgate.net/profile/Marie_Jackson

Surtsey blogspace:

https://surtsey50years.utah.edu

 Show notes:

 4:06: Dawn begins interview by mentioning Marie’s love of the outdoors as a child and asks her to talk about those days.

4:38: Dawn asks if Marie’s father, who was a geologist, contributed to her love of the outdoors.

5:11: Dawn asks what topics Marie was interested in while in high school.

5:44: Dawn mentions that when Marie went to college, she never envisioned herself as a scientist, but this changed in her junior year, when her interest in earth sciences took root. Dawn asks Marie to elaborate on how that happened.

6:27: Ken asks Marie what role, if any, her family’s ranch played in motivating her interest in geology.

7:22: Dawn mentions that after college Marie worked for a mining company for a few years, which enabled her to save enough money to travel to France, where she worked on a doctorate. She asks if this is how Marie ended up in northern Corsica, in the Italian Alps.

9:39: Ken asks about her transition back to the United States, where she attended John Hopkins University after spending 3 years in France.

10:23: Ken mentions Marie’s reputation at John Hopkins for being a “desert rat” in Utah’s Henry mountains. He asks her to elaborate on her experiences in that area.

12:06: Dawn comments on how after Marie got her PhD in 1987, she went to work for the U.S. Geological Survey, and that she ended up doing a structural study of the seismically active Kaoiki fault zone on the southeast flank of the Mauna Loa Volcano in Hawaii. Dawn asks Marie to talk about that.

13:44: Dawn comments on how Marie didn’t know much about Rome until she spent a year there in 1995. Marie talks about her experience.

14:17: Ken mentions that Marie’s priority for many years was to raise her children, but Ken asks what else she did in those days.

15:05: Dawn comments on how during this period, Marie was writing papers and working with scientists who were nearing retirement.  Dawn asks what that was like.

17:55: Dawn asks about the work Marie did after she started, in 2011, working at UC Berkley’s Department of Civil and Environmental Engineering as a project scientist.

19:55: Ken mentions that after a couple of years at Berkley, Marie accepted a position at the University of Utah. He comments on how that must have been an interesting transition to come full circle back to Utah.

20:44: Dawn asks for Marie to explain exactly how the Romans made concrete, and what made it so unique.

22:11: Ken mentions that while modern maritime concrete structures typically degrade significantly within a matter of decades, the Romans built piers and breakwaters 2,000 years ago that endure to this very day. He inquires as to what prevents Roman maritime concrete from degrading.

26:42: Ken comments on how the Romans are often said to be very deliberative people. He asks how much of the invention of their concrete does Marie think was deliberate, and how much a happy accident.

28:51: Ken asks about a comment that Pliny the Elder made in the first century about how the best maritime concrete was made from volcanic ash found in the regions along the Gulf of Naples. Ken asks Marie what is so particularly special about the ash at that particular region.

31:24: Ken mentions the Romacons project, and the book that came out of it, “Building for Eternity,” which was published in 2014. Marie is one of the authors, and the book explains how the Romans built these lasting structures in the sea. He asks if Marie could elaborate on the story the book tells.

35:14: Dawn asks Marie what the cementing characteristics are that have made Roman concrete so unique.

37:23: Ken mentions the demonstrated durability and longevity of Roman maritime concrete. He asks if lessons learned from the Romans could be of relevance to engineers currently working on devising containment for long term storage of hazardous waste substances.

41:11: Marie talks about her current project as the lead principle investigator on the Surtsey Volcano.

44:48: Dawn asks how Marie is disseminating the knowledge and information about the work that she and her team are doing at Surtsey.

46:20: Dawn asks Marie what life and career advice she would give to an up and coming scientist.

47:11: Ken inquires as to what Marie enjoys doing in her time away from research.

48:31: Interview ends.

Episode 59: Stephen Cunnane discusses the role of ketones in human evolution and Alzheimer’s

Nearly five million people in the United States have Alzheimer’s disease. In 30 years, that number is estimated to be 16 million

In today’s episode, Ken and Dawn interview Dr. Stephen Cunnane, a Canadian physiologist whose extensive research into Alzheimer’s disease is showing how ketones can be used as part of a prevention approach that helps delay or slow down the onset of Alzheimer’s.

Cunnane is a metabolic physiologist at the University of Sherbrooke in Sherbrooke, Quebec. He is the author of five books, including” Survival of the Fattest: The Key to Human Brain Evolution,” which was published in 2005, and “Human Brain Evolution: Influence of Fresh and Coastal Food Resources,” which was published in 2010.

He earned his Ph.D. in Physiology at McGill University in 1980 and did post-doctoral research on nutrition and brain development in Aberdeen, Scotland, London, and Nova Scotia. From 1986 to 2003, he was a faculty member in the Department of Nutritional Sciences at the University of Toronto where his research focused on the role of omega-3 fatty acids in brain development and human health. He also did research on the relation between ketones and a high-fat ketogenic diet on brain development.

In 2003, Dr. Cunnane was awarded a senior Canada Research Chair at the Research Center on Aging and became a full professor at the University of Sherbrooke. He has published more than 280 peer-reviewed research papers and was elected to the French National Academy of Medicine in 2009.

Links:

Castellano et al AD dPET J Alz Dis 2015

Nugent et al dPET YE Neurobiol Aging 2014

Cunnane & Crawford J Human Evol 2014

Courchesne-Loyer et al PET KD JCBFM 2016

Croteau et al. AD MCI CMR Exper Gerontol 2017

Show notes:

3:33: Dawn mentions that Stephen was born in London but that his family emigrated to Canada when he was an infant. She asks him about growing up in a suburb of Montreal.

4:02: Ken mentions that he has been told by a reliable source that as soon as Stephen got into high school he spent a lot of time in the chemistry lab, where sometimes created mischief.

4:58: Dawn asks if it is true that Stephen nearly flunked out of college when he first started.

5:16: Dawn comments that Stephen got his PHD in physiology at McGill University which is when his interest in science really caught on and asks how that came about.

5:55: Stephen talks about communicating with Desmond Morris while Stephen was working on his post-doc.

8:03: Dawn asks about Stephen’s post-doctoral research, for which he traveled to Aberdeen London and Nova Scotia; as well as what prompted his interest in nutrition in the brain.

9:01: Dawn mentions that in 1986 Stephen became a faculty member in the department of nutritional sciences at the University of Toronto. She asks how he ended up teaching nutrition when he didn’t have a degree in nutrition.

10:33: Stephen talks about accepting a senior Canada Research Chair at the Research Center of Aging and a full professorship at the University of Sherbrooke.

11:57: Ken talks about Stephen’s interest in human evolution how it eventually led him to research the nutritional importance of shore-based foods and omega-3 fatty acid in particular in the development of human’s brains. He asks Stephen to talk about his work leading up to the hypothesis that humans evolved near the water.

16:32: Dawn asks which of the various forms and sources of omega-3 are optimal for overall wellness and brain health, and what are the differences between them.

18:50: Dawn asks Stephen if there was any pushback against his research into the importance of ketones and fat in the brain development of infants? Dawn points out that Stephen was working on this during the middle of the low-fat craze in the U.S. and Canada.

20:33: Dawn mentions that there is evidence that intermittent fasting improves cognition, and asks if there is any evolutionary basis for that?

21:49: Dawn asks if it was Stephen’s research into the metabolism of omega-3 fatty acids and the importance of ketones that lead him to write his book Survival of the Fattest?

23:04: Dawn notes that it seems as if ketones are at the core of Stephen’s way of thinking about infant brain development. She asks him to elaborate on this.

24:15: Dawn asks Stephen to talk about what it’s going to take to transition to the therapeutic use of ketones.

26:06: Ken mentions how Stephen has noted the importance of ketosis in postnatal life for a number of reasons, including brain development and survival and early breast milk availability. Ken asks about the effect of women consuming a ketogenic diet while breastfeeding children, and if this inadvertently lowers ketone levels in the infant due to lower medium chain triglyceride (MCT) levels in the breast milk, a phenomenon found in rodents fed a ketogenic diet during lactation.

28:36: Dawn comments how Stephen has said that certain brain-selective nutrients — such as DHA, iodine, iron, selenium, zinc and copper — would be best supplied by a shore-based diet. She asks which shores humans would have evolved close to and which types of food made up this diet during human evolution?

32:29: Dawn mentions that at Sherbrooke, Stephen’s research has been focused on the use of brain imaging techniques to study changing brain fuel metabolism and cognitive function during aging. She asks if he can give an overview of what he is finding.

34:08: Dawn comments on the increasing interest in exogenous ketones for treatment of neurological disease. She further mentions that these ketone esters can elevate Beta-hydroxybutyrate (BHB) levels far beyond what is normally attained during the ketogenic diet. She asks Stephen for his thoughts on the initiation of ketosis through MCTs versus exogenous ketones (salts or esters) versus carbohydrate restriction versus fasting. She asks about mechanistic differences between each of these methods of initiating ketosis.

35:39: Ken mentions that Stephen’s tracer work has used 11c acetoacetate in the setting of endogenous ketones and neurological disease. He asks if there are any key differences in brain ketone metabolism between endogenous and exogenesis ketosis after mentioning how BHB and acetoacetate appear in a relatively predictable 1:1 ratio when ketosis is induced through diet.

37:28: Ken mentions that it has been noted that ketones are 10% more efficient than glucose as a brain fuel. He asks Stephen about his understanding of cerebral fuel selection given ample availability of both glucose and ketones.

38:25: Dawn asks if there are areas of the brain that are particularly high users of ketone bodies, and if so, could that have any link to some of the functional or behavioral changes, such as mood, that are seen in some cases of animals or people adhering to a ketogenic diet.

39:16: Dawn asks Stephen to talk about his research into how and why omega-3 fatty acid homeostasis changes during aging.

40:21: Dawn asks for Stephen’s opinion on what are the primary challenges that our brains face as we age.

41:12: Dawn mentions how that Stephen is currently focused on Alzheimer’s research and ketones. She asks for an overview of his research that’s looking into how ketones can be used to the advantage of a person suffering from Alzheimer’s disease.

43:21: Dawn comments on how we know that APOE4 carriers have an increased risk of development of late onset familial Alzheimer’s disease. She asks if there is a link between the genotype and a change in brain metabolism.

44:42: Ken asks if substrate utilization differs between healthy subjects and those with neurological conditions, such as mild cognitive impairment or Alzheimer’s disease.

45:18: Dawn asks Stephen what other metabolic interventions he thinks have promise for a neurodegenerative disease.

46:01: Dawn mentions that exercise helps to get more ketones into the brain. She inquires as to how much exercise is needed to do this effectively.

46:49: Dawn asks Stephen to elaborate on his recommendation that older people who might not be able to exercise effectively should consider consuming a ketone drink made from MCTs that people can make in their kitchen.

48:31: Ken comments how he envisions it not being too long before studies can be done with powerful ketone ester drinks, and that exogenous ketones will become more readily available and more potent, giving people more effective options to elevate their level of circulating ketones.

50:09: Dawn asks Stephen if chronically high systemic inflammations contribute to neuroinflammation and cognitive decline. She also asks if targeting systemic inflammation with nutritional ketosis would be an acceptable strategy to enhance and also preserve cognitive function and brain longevity.

51:15: Dawn mentions that we know ketones increase brain blood flow and metabolism. She goes on to ask if Stephen thinks that some of the beneficial effects might be working through the newly discovered brain lymphatic system or glymphatic system.

51:41: Dawn points out there are about five million people with Alzheimer’s disease in the U.S., and that the number of Americans with AD is estimated to swell to 16 million in the next 30 years. She asks if Stephen thinks this dramatic increase in the prevalence of Alzheimer’s is related to the Western diet which has created an epidemic of type-2 diabetes and other chronic diseases.

52:42: Ken mentions that a number of recent papers show dramatic improvements in both health span and life span of rodents that are fed a ketogenic diet. While humans are not rats, he asks Stephen for his thoughts on the effects of prolonged ketosis as a promoter of human healthspan and perhaps even longevity.

53:51: Dawn concludes the interview by asking Stephen’s about his interests outside of work.

Episode 58: Flora Hammond discusses traumatic brain injuries and how treatments are evolving

Today’s episode features one of the nation’s leading physicians and researchers who has spent years studying and treating traumatic brain injuries.

Dr. Flora Hammond is a professor and chair of the Department of Physical Medicine and Rehabilitation at Indiana University School of Medicine. She also is the Chief of Medical Affairs and Medical Director at the Rehabilitation Hospital of Indiana. She has been a project director for the Traumatic Brain Injury Model System since 1998.

Shortly before we conducted this interview with Dr. Hammond, she and a team of physicians and scientists at Indiana University received a $2.1 million grant to continue research into people who suffer traumatic brain injuries and how these injuries affect the lives of patients as well as their families.

Dr. Hammond is a Pensacola, Florida, native who graduated from the Tulane University School of Medicine in 1990 and completed her residency in Physical Medicine and Rehabilitation at the Baylor College of Medicine in Houston. She also completed a brain injury medicine fellowship at Wayne State University School of Medicine in Detroit. Her research in the area of brain injury includes studying the prediction of outcome, aging with brain injury, causes of and treatments for irritability, and quality of relationships.

In 2016 she received the Robert L. Moody Prize, which is the nation’s highest honor reserved for individuals who had made exceptional and sustained contributions to the lives of individuals with brain injuries.

Prior to the 2016 Robert L. Moody Prize, Dr. Hammond received local and national awards for her teaching, clinical care and research, including the 2001 Association of Academic Physiatrists Young Academician Award, the 2011 Brain Injury Association of America William Caveness Award, and the 2013 Baylor College of Medicine Distinguished Alumnus Award.

In 2011, 2012, and 2013, Dr. Hammond led the Galveston Brain Injury Conferences which focused on changing the view of brain injury as an incident with limited short-term treatment to a chronic condition that must be proactively managed over the course of life.

She co-chairs the American Congress of Rehabilitation Medicine Chronic Brain Injury Task Force, and serves on Journal of Head Trauma Rehabilitation editorial board. She has authored more than 140 peer-reviewed publications.

Links:

Flora Hamond faculty profile:
https://medicine.iu.edu/faculty/20302/hammond-flora/

“Potential Impact of Amantadine on Aggression” study
https://www.ncbi.nlm.nih.gov/pubmed/28891908

Show notes:

4:08: Interview begins.

4:38: Dawn says it’s her understanding that Flora dreamed of becoming a physician ever since middle school. Dawn asks what inspired her at such an early age to become a doctor.

5:02: Flora talks about also wanting to become a teacher, but worried that she would have to give up teaching to become a doctor.

5:40: Continuing with Flora’s history, Dawn mentions that after high school Flora traveled to New Orleans to attend Tulane University. Dawn asks if it’s true that Flora’s grandmother was her landlord while she was in college and med school.

6:20: Ken mentions that Flora’s mother was a dietician and that her father was a pathologist. He asks Flora what specifically inspired her to specialize in brain injury rehabilitation and research.

8:36: Dawn comments on how before Flora accepted a positon at Indiana, she was in the Carolinas, and asks about her work there.

9:30: Dawn asks how Flora ended up at the Indiana University School of Medicine.

10:23: Ken mentions that Flora’s lecture at IHMC attracted a lot of interest and a full-house. He follows up by asking Flora what she thinks is driving the interest in brain injuries.

11:34: Dawn talks about how Flora and a team of physicians and scientists at Indiana have spent years studying and treating TBI (Traumatic Brain Injury) and the effects of TBI on the lives of patients and their families. She goes on to mention that Indiana recently was awarded a $2.1 million grant to continue those studies for the next five years. Dawns asks Flora to talk about the scope of the work she will be doing as a result of the grant.

12:57: Ken mentions that Flora has pushed to have a national approach to the treatment of TBI, where patients and physicians continuously track the injury and continue treatments. He asks her to expand on her thoughts on such a program and how more people and organizations can start working toward an integrated approach.

13:48: Dawn asks for Flora to explain the different types of brain injury, and to clarify that TBI is not merely one singular disease or type of injury process.  Flora goes on to explain the difference between mild, moderate and severe injuries, and then describes how the treatments differ.

14:50: Dawn asks Flora how she diagnoses the severity of TBI, and if there are any biomarkers that are currently in use.

16:01: Dawn asks what common issues patients struggle with after a traumatic brain injury.

17:08: Dawn proposes the hypothetical scenario of a patient coming into Flora’s rehabilitation clinic, and asks Flora to walk us through an example of how they would treat that person and what program they would go through.

19:21: Ken mentions that there are a number of TBI centers that focus on integrative medicine, and rather than just treating the brain injury they are now treating the patient as a whole human being. He talks about optimizing sleep, proper nutrition, and ways to manage aggression and anxiety in addition to specific treatment of the brain. He asks Flora how much does it seem that physicians are currently integrating these approaches into TBI treatment around the country.

20:17: Dawn asks what we know about the triggers of irritability and aggression in TBI patients, and if there is a biochemical component to these triggers or if it is something else.

22:21: Dawn inquires as to the different ways that Flora uses to track a patient’s condition on the cognitive or emotional level.

22:45: Flora talks about research on aging after TBI, and that interestingly enough, it’s not always about worsened outcomes. Some people actually get better over time, while others stay the same or their condition even worsens over time. Dawn asks if there are ways to differentiate who will improve and who will worsen with time.

23:50: Ken comments on how in the past it was thought that brain plasticity, and thereby recovery, was more plausible for a child with TBI, but that recovery would plateau at some point. He points out, however, that much of Flora’s work has shown that recovery can occur in older individuals and they can continue to improve long after the initial injury. He asks Flora if she could talk about that work.

24:44: Dawn asks if there is a difference in treatment for a child with TBI compared to an adult with a similar injury.

25:17: Ken mentions that ApoE 4/4, and even 3/4 status, has been shown to be a genotype that is associated with worsened patient outcomes after TBI, and that there are other genetic variables beyond ApoE that are relevant. He asks, in regards to the era of precision medicine, are we looking at these genetic variables with respect to a personalized patient treatment program?

26:21: Ken asks if we are able to accurately predict outcomes in the early hours and days following the injury.

27:00: Dawn asks if a severe brain injury typically implies a poorer outcome.

27:36: Mentioning that she has several people close to her with various types of TBI, Dawn talks about how she loves the idea of a participatory research system that Flora has proposed and implemented. Dawn asks Flora to expand on this approach to TBI research.

28:31: Ken talks about how Flora has focused a lot of her research on non-pharmacological interventions for TBI. He asks for some examples of approaches that she has studied, and if those approaches are being harnessed by the general TBI treatment community.

29:33: Ken mentions that Flora recently published a study on the promising ability of the drug Amantadine to curb aggression in TBI patients. He asks if she could elaborate on that.

33:27: Dawn comments on how in most treatment modalities for brain injury, the focus is on the acute phase. She asks how can treatment be extended after the initial management, and what else does Flora think long-term treatments for TBI patients should include.

34:13: Dawn asks if it is true that all of the recovery from a brain injury happens within the first year.

35:08: Dawn asks if medication in the early recovery phase has a downside in the long term.

36:01: Ken mentions that a number of therapies for TBI that showed great promise in animal studies, failed to yield the hoped-for results in human trials. He asks what are the current barriers to developing new acute therapies that reduce morbidity and mortality in TBI patients are.

37:09: Ken comments on how TBI is an injury to the brain, but it also affects a variety of other systems and pathways in the body. He mentions that the Hypothalamic Pituitary Adrenal access can often be impacted in TBI patients. He asks for a brief explanation of the HP access and how damage to it can affect the patient.

38:38: Ken asks if there would ever be a case where a person with HPA access as their dysfunction could be misdiagnosed with TBI and vice versa?

39:24: Dawn mentions that it seems as though the HPA axis  has been widely ignored, comparatively speaking, to other metrics in TBI patients. She asks if we are starting to include its assessment and status in patients, as far as tracking is concerned.

39:52: Dawn comments on how Flora has coined the term CBI (Chronic Brain Injury). Dawn asks if CBI has been incorporated into a public health and societal approach, in addition to traditional medicine.

40:37: Ken asks Flora to elaborate on how she would scope and define CBI as opposed to TBI.

41:17: Dawn asks for Flora to talk about how brain injury rehab has evolved over her career.

42:21: Dawn congratulates Flora on receiving the Robert L. Moody Prize last year, which is the nation’s highest honor for individuals who have made exceptional and sustained contributions to the lives of people with brain injuries. She follows up by asking for some background on the award itself.

42:48: Dawn asks where Flora sees the field of TBI research and rehabilitation heading in the next 10 years.

43:48: Dawn closes by asking Flora how she likes to spend her free time.

Episode 57: Lauren Jackson discusses radiation exposure, including the effects of a nuclear strike

Today’s interview features Dr. Lauren Jackson, a nationally known expert in the field of tumor and normal-tissue radiobiology. She is especially recognized for her expertise in medical countermeasure development for acute radiation sickness and delayed effects of acute radiation exposure.

Lauren is the deputy director of the Division of Translational Radiation Sciences within the Department of Radiation Oncology at the University of Maryland School of Medicine.

Lauren, who also goes by Isabel, received her bachelors in science in microbiology from North Carolina State University in 2006, and her PhD in pathology from Duke University in 2012.

She currently is a principal or collaborating investigator on a number of industry and federally sponsored contracts and research grants. She has published extensively on the characterization and refinement of animal models of radiation-induced normal tissue injury that recapitulate the response in humans. Models developed in Lauren’s laboratory have gone on to receive FDA concurrence as appropriate for use in medical countermeasure screens.

Lauren is a senior associate editor for Advances in Radiation Oncology, a journal of the American Society of Therapeutic Radiation Oncology, and serves as an ad hoc reviewer for several peer-reviewed journals. She also is the author of several book chapters on normal tissue tolerance to radiation, mechanisms of injury, and potential therapeutic interventions.

Links:

Jackson’s University of Maryland web page: http://www.medschool.umaryland.edu/profiles/Jackson-Isabel/

Radiation Emergency Medical Management website: https://www.remm.nlm.gov

Centers for Disease Control website: https://www.emergency.cdc.gov/radiation/index.asp

BARDA website: https://www.phe.gov/about/BARDA/Pages/default.aspx

NIAID website: https://www.niaid.nih.gov

Show notes:

5:06: Dawn begins interview by asking Lauren about her childhood and if it’s true that she was one of those children who was always asking questions?

5:39: Lauren talks about how she was more interested in history and the humanities in high school and wanted nothing to do with science.

5:59: Dawn asks Lauren about her decision to attend the University of Georgia to major in journalism and political science.

6:28: Ken comments on how even though Lauren was just 18 at the time, she was one of two students picked to represent the University of Georgia at the Center for the Presidency in Washington, D.C. Lauren then talks about how thanks to that experience, she decided journalism and political science weren’t the right majors for her.

7:38: Dawn points out that when Lauren first went to college, she took the minimum number of science classes.  Lauren goes on to talk about how after spending time in D.C., she ended up applying to North Carolina State University and switching her major to microbiology.

8:52: While at N.C. State, Lauren worked for Dr. Hosni Hassan, an expert on Oxidative Stress. Dawn asks Lauren about the focus of her research with Dr. Hassan.

9:58 Dawn talks about how when Lauren was an undergrad at N.C. State, she became interested in tumors and cancer treatment, and found a professor down the road at Duke University who was doing interesting work in that area. Dawn asks Lauren if that’s why she ended up going to Duke for her doctorate.

10:52 Dawn asks Lauren to elaborate on how her background in journalism and political science connected her towards the path of radiation countermeasure research.

 11:42 Dawn points out that as a graduate student at Duke, Lauren took part in projects that looked at radiation injury. Dawn asks Lauren to give an overview of what sort of work was involved in the projects.

 12:46 Ken asks Lauren to explain the difference between clinical radiation exposure and radiation that someone would experience as a consequence of a nuclear attack.

13:59: Ken shifts the conversation to human space flight, asking Lauren to discuss the radiation astronauts will experience outside the protection of the Earth’s magnetosphere, such as galactic cosmic radiation and solar particle events. He also asks how they relate to the other previously mentioned clinical- and weapons-based radiation.

14:52: Ken asks Lauren to describe what the lifetime limits are for radiation exposure, how they are produced, and what is the biggest source of radiation exposure for the average person.

16:06: Dawn asks if it’s possible to translate the findings in clinical radiation to these other types of radiation exposures, such as nuclear weapons and space radiation.

16:40: Dawn asks if clinical radiation research is playing a role in the work that’s being done in space research as well as research into the effects of nuclear-weapons attack.

17:27: Ken asks Lauren to explain how radiation doses are defined.

18:28: Ken mentions that Lauren’s work has focused on both the acute and chronic effects of radiation exposure, then asks her to give an overview on how the body would respond at the cellular and physiological levels to an acute exposure.

19:56: Dawn mentions how proximity to the event, in the event of a nuclear attack, would be a variable factor as to the level of exposure, then asking what else determines the degree of an acute response.

22:35: Dawn asks if the impact of radiation exposure is different based on different systems in the body, further asking which systems are more or less susceptible and what the different responses are.

24:06: Dawn mentions how Lauren has focused a large part of her research on the effects of radiation exposure to the pulmonary system, then asking her to talk about those chronic and lifetime affects following initial exposure.

25:38: Ken remarks how oxidative stress is a major focus on Lauren’s research, and follows up by asking about the impact of oxidative stress on the tissue, surrounding tissue, and its role in the overall injury response.

26:54: Ken remarks on the evidence that shows that animals fed a diet high in blueberries have some degree of resistance to the inflammatory response due to the blueberry’s antioxidant activity. He asks if antioxidants, more broadly, could play a role in the prevention of radiation injury.

27:46: Dawn asks about genetic susceptibility to radiation injury, and if we know of any individuals who are more or less susceptible to injury based on their genetic makeup.

28:48: Ken wonders if the genetic screening for radiation tolerance were developed adequately, that perhaps it could have an application in the selection process for long-duration missions into deep space.

29:25: Ken inquiries about the counterintuitive fact that smokers have a reduced incidence of radiation-induced lung cancer.

30:07: Dawn asks if gender or age play a role in a person’s susceptibility to radiation injury.

31:13: Dawn mentions how we know that epigenetic modifications (changes with respect to how a gene is expressed) can occur in response to a wide variety of different stressors or environmental influences. She then asks if we are seeing modifications that occur as a result of radiation exposure at the epigenetic level.

31:47: Dawn mentions that Randy Gerald was at Duke at the same time that she and Lauren were at Duke, and that he was the founder of epigenetic modifications.

32:15: Ken asks that in regards to a point-of-care test that could identify individuals who have been exposed to radiation and injured, what are the potential markers that Lauren would look for.

34:01: Dawn asks if markers of tissue injury, such as lung-radiation injury, are found in the blood.

35:44 Ken mentions the importance of timing from the point of injury as being critical with most biomarkers. He then asks that given the temporal nature of radiation injury, is there a time effect on biomarkers of radiation injury.

36:37: Ken asks about the effects of radon.

37:30: Ken notes that some areas are inherently much higher in radon levels than others, such as New England, and parts of Florida. He asks if there is a level that Lauren would consider safe for basements.

38:42: Dawn asks about the current position Lauren holds at the University of Maryland School of Medicine as the Deputy Director of the Division of Translational Research Sciences, and the Department of Radiation Oncology, and her research team that she has there.

40:32: Dawn asks about the different categories of potential countermeasures for radiation injury that Lauren has been looking at.

41:28: Dawn mentions how Lauren also works alongside the FDA, where she serves as a subject-matter expert for the review committees. She asks Lauren to describe her work with the FDA and in particular the FDA animal rule and the role that plays in countermeasure approval for humans.

44:03: Lauren explains the role that the NIAID (National Institute for Allergy and Infectious Disease) plays in countermeasure development.

45:56: Ken asks if countermeasures that we might develop to limit the damage from a nuclear attack might potentially be used for applications such as clinical radiation or space radiation exposure.

47:12: Dawn asks about a countermeasure drug called Bio300 that Lauren worked on with a company called Humanetics Corporation, asking where it stands with respect to research and potential clinical applications in humans.

48:37: Dawn asks Lauren to talk about the approval process and the specifics of Neupogen and Neulasta, (the first two drugs ever approved as potential countermeasures for acute radiation syndrome) that were approved on the basis of data generated at Lauren’s laboratory.

49:58: Ken notes that Neupogen has demonstrated improved survival in people exposed to lethal radiation doses on Earth, then asks if Neupogen, Neulasta, or some other bone-marrow active medical countermeasures have applications in human space flight.

50:54: Dawn asks if there is a one-size-fits-all drug to target all the physiological systems in response to radiation exposure, or if a patient would need to take an array of countermeasures to cover each of the different systems.

52:22: Dawn notes that after Fukushima, potassium iodine pills were flying off the shelves, and asks if that is a viable option for protection against acute radiation syndrome.

53:32: Ken asks if there are any prophylactic treatments approved or in development for radiation exposure.

54:46: Ken asks Lauren to talk a little more about BARDA (Biomedical Advanced Research and Development Authority) and the role it plays in radiation injury research and countermeasure development.

56:44: Dawn notes that Lauren has served as the program director for the BARDA Radiological and Nuclear Model Development Program, asking her to talk about that position and what that work entails.

57:25: Lauren talks about how it seemed that no one was interested in radiation after the Cold War, but that recent interest in radiation research has grown significantly.

59:48: Dawn mentions that four or five years ago you couldn’t get any companies interested in looking at ways to improve survival in case of a nuclear attack, but that in just the last two weeks of November that Lauren has had 22 companies reach out to her.

1:01:48: Dawn asks what the current threats of nuclear or radiological terrorism or nuclear attack are.

1:02:18: Ken asks how much protection to radiation exposure, arising from a weapon’s detonation, does a basement offer.

1:03:05: Ken remarks how, in regards to basements, those that do not have windows would be preferable in the context of protecting against radiation exposure.

1:04:13: Ken asks if any of the countermeasures developed thus far could be effective against space radiation, and thereby offer NASA an ability to leverage the BARDA investment.

1:05:26: Ken remarks how he is glad to hear that the federal agencies are wisely leveraging each other’s investments, rather than independently pursuing them.

1:06:31: Ken talks about long-duration missions in deep space and the possibility that astronauts might experience serious cognitive deficits caused by radiation exposure. He also points out the need for a countermeasure against cognitive decline as a result of radiation is not yet met here on Earth, citing that workers who cleaned up the Chernobyl nuclear disaster experienced serious cognitive decline close to ten years after the incident.

1:08:22: Ken asks if potential neurocognitive medical countermeasures exist today or if they may be available in the near future, and would a single agent be effective for both terrestrial exposures and the galactic cosmic radiation found in space.

1:09:18: Dawn wraps up the interview by asking Lauren if she is an N.C. State fan or a Duke fan when it comes to basketball.

Episode 56: Jon Clark talks about NASA, supersonic jumps from the edge of space, and humans in extreme environments

Today’s episode is the second of a two-part interview with IHMC Senior Scientist Dr. Jonathan Clark, a six-time Space Shuttle crew surgeon who has served in numerous roles for both NASA and the Navy.

Part one of our interview, episode 55, ended with Jon talking about the tragic death of his wife, astronaut Laurel Clark. She died along with six fellow crew members in the Space Shuttle Columbia disaster in 2003. February marks the 15^th anniversary of the disaster. Today’s episode picks up with Jon talking about becoming part of a NASA team that investigated the Columbia disaster.

Ken and Dawn also talk to Jon about the extensive research he has been doing on the neurologic effects of extreme environments, and also about the instrumental work he has been doing in developing new protocols to benefit future aviators and astronauts.

Jon received his Bachelor of Science from Texas A&M University, and medical degree from the Uniformed Services University of the Health Sciences in Bethesda, Maryland. He is board certified in neurology and aerospace medicine. Jon headed the Spatial Orientation Systems Department at the Naval Aerospace Medical Research Laboratory in Pensacola. He also held other top positions in the Navy and qualified as a Naval flight officer, Naval flight surgeon, Navy diver and Special Forces freefall parachutist.

Jon’s service as a Space Shuttle crew surgeon was part of an eight-year tenure at NASA, where he was also chief of the Medical Operations Branch and an FAA senior aviation medical examiner for the NASA Johnson Space Center Flight Medicine Clinic. He additionally served as a Department of Defense Space Shuttle Support flight surgeon covering two shuttle missions.

In addition to his new role as a senior research scientist at IHMC, Jon is an associate professor of Neurology and Space Medicine at Baylor College of Medicine and teaches operation space medicine at Baylor’s Center for Space Medicine. He also is the space medicine advisor for the National Space Biomedical Research Institute, and is a clinical assistant professor at the University of Texas Medical Branch in Galveston where he teaches at the Aerospace Medicine Residency.

Links:

Jon Clark’s NASA bio:

https://www.nasa.gov/offices/nesc/academy/Clark-Jonathan-Bio.html

Jon Clark You Tube Channel:

https://www.youtube.com/playlist?list=PLZLZ5yKgXJR0L1xZzhdTY_dUzo5ZLILxS

Jon Clark Red Bull Stratos page:

http://www.redbullstratos.com/the-team/jonathan-clark/index.html

Part one of Jon Clark STEM-Talk interview:

https://www.ihmc.us/stemtalk/episode-55/

Show Notes:

4:07: Ken comments that Jon was part of the NASA team that studied every detail of the Columbia disaster. When the team’s report came out, Jon said, “You have to find ways to turn badness into goodness. You have to. It’s the only way you get through this.” Ken then asks Jon to talk about some of the lessons NASA learned.

7:27: Dawn says that on October 14, 2012, Jon was part of a team that successfully accomplished the highest stratospheric free fall jump from 128,100 feet. Dawn asks Jon how he became involved in this record-breaking jump.

9:37: Dawn asks Jon what his support team looked like for the jump.

11:15: Ken asks Jon what kind of preparation he and the team went through for the jump, and how long the preparatory period was.

12:46: Dawn asks Jon what the medical concerns for the jump were.

16:54 Dawn comments that when Jon discusses the medical team, he talks a lot about continuous physiological monitoring in the research world. She then asks Jon what kind of monitoring he was doing before, during, and after the jump.

22:58: Dawn asks Jon to discuss research he has done around neurological issues, specifically when it comes to space exposure.

23:31: Ken comments that intermittent artificial gravity has been discussed over the years, as a way to potentially mitigate some of the medical risk factors associated with long duration space missions. Ken then asks Jon how this may be accomplished in space and what we know about the effects of intermittent gravity.

30:30: Dawn says that NASA recently released a report describing an increased incidence of white matter hyper intensities in astronauts. She then asks Jon why we are seeing these lesions now and not in earlier crew.

34:01: Dawn comments that the DOD communities are also interested in the issue of white matter hyper intensities. Dawn then says that she and Jon are on a NASA Translational Research Institute project that is looking at the effect of simulated microgravity on brain lymphatic outflow. She then asks Jon to talk more about this study.

38:24: Dawn says that trying to perform effective aeromedical research with either aviators or astronauts can be difficult due to a fear of participating in studies whose findings might affect their flight status. She then asks Jon how he addresses these concerns.

41:02: Ken says that Jon has been extensively involved in previous investigations focused on physiological episodes in the aviation community. He then asks Jon to discuss what is meant by the term physiological episode and to give a few examples.

46:09: Dawn asks Jon what he sees as some of the most exciting areas of research for extreme environmental medicine in human performance.

48:42: Ken comments that Jon was instrumental in having EEG recordings removed from the standard flight physical. Ken asks Jon what led to his concerns on this measurement.

51:15: Dawn says that Jon has done research with hyperbaric oxygen and that right now we are seeing a push to bring hyperbaric oxygen therapy in as treatment for things like traumatic brain injury and PTSD. She then asks Jon what his thoughts are on this.

56:00: Dawn says that Jon has been extensively involved in suit testing for NASA and other commercial entities. She then asks what this testing involves and what the future space suits will look like.

1:00: 19:Ken says that there was a meeting at IHMC years ago where NASA displayed each of the generations of NASA space suits.

1:03:41: Dawn asks Jon to expand on his comments about how to get a deliverable from research.

1:05:05: Dawn says that William Fife was a key mentor of Jon’s and that now Jon works with William’s daughter. Dawn asks Jon to discuss the time he spends mentoring young students and what advice he has for them.

1:08:03: Ken says that NASA has been formulating plans for a crew tended cislunar space station concept, known as the Deep Space Gateway. This station could be used as a staging ground for robotic and human lunar surface missions as well as eventual travel to Mars. Ken then asks Jon to talk more about the Deep Space Gateway.

1:11:41: Dawn asks Jon to discuss his recent sailing expedition off the California coast.

1:15:27: Ken mentions that Jon participated in the National Outdoor Leadership School executive expedition that went into the Wind River Range of Wyoming.  Ken points out the Roger Smith, who was featured on episode 51 of STEM-Talk, and his wife Margaret Creel were longtime instructors at NOLS, and asks Jon for his thoughts about NOLS and the work it does.

1:19:20: Ken and Dawn thank Jon for joining them.

 

Episode 55: Jon Clark looks back at his Naval and NASA careers and the Space Shuttle Columbia disaster

Today’s episode is the first of two-part interview with IHMC Senior Scientist Dr. Jonathan Clark, a six-time Space Shuttle crew surgeon who has served in numerous roles for both NASA and the Navy.

In a wide-ranging conversation with Ken and Dawn, Jon talks about his 26-year career in the Navy, his extensive research on the neurologic effects of extreme environments on humans, and the tragic death of his wife, astronaut Laurel Clark, who died along with six fellow crew members in the Space Shuttle Columbia disaster in 2003.

Jon received his Bachelor of Science from Texas A&M University, and medical degree from the Uniformed Services University of the Health Sciences in Bethesda, Maryland. He is board certified in neurology and aerospace medicine. Jon headed the Spatial Orientation Systems Department at the Naval Aerospace Medical Research Laboratory in Pensacola. He also held other top positions in the Navy and qualified as a Naval flight officer, Naval flight surgeon, Navy diver and Special Forces freefall parachutist.

Jon’s service as a Space Shuttle crew surgeon was part of an eight-year tenure at NASA, where he was also chief of the Medical Operations Branch and an FAA senior aviation medical examiner for the NASA Johnson Space Center Flight Medicine Clinic. He additionally served as a Department of Defense Space Shuttle Support flight surgeon covering two shuttle missions.

In addition to his new role as a senior research scientist at IHMC, Jon is an associate professor of Neurology and Space Medicine at Baylor College of Medicine and teaches operation space medicine at Baylor’s Center for Space Medicine. He also is the space medicine advisor for the National Space Biomedical Research Institute, and is a clinical assistant professor at the University of Texas Medical Branch in Galveston where he teaches at the Aerospace Medicine Residency.

Links:

Jon Clark’s NASA bio: https://www.nasa.gov/offices/nesc/academy/Clark-Jonathan-Bio.html

4:32: Ken and Dawn welcome Jon to the show.

4:47: Dawn comments that Jon was the son of an army officer, and as a result, he grew up all over the world. Dawn then asks Jon what it was like to move so frequently to different army bases as a youth.

5:24: Dawn says that Jon is known as a fairly frugal person and asks him to tell the story of a piece of burnt toast in Germany that contributed to his frugality.

6:39: Ken asks Jon to share the story of how he learned how to fly planes in Germany as a teen-ager.

9:43: Dawn comments that Jon had aquariums in his bedroom as a child. She then asks Jon what drew him to marine biology.

13:53: Dawn asks why Jon chose Texas A&M for college after leaving Germany.

15:36: Jon talks about how he was accepted into medical school during his senior year of college, and how he was disappointed that the Navy sent him to flight school instead.

18:46: Ken says that after flight school, Jon ended up going to medical school after all. Ken asks Jon to talk about what happened.

20:09: Dawn asks Jon what it was like transitioning from being an officer in the Navy to a student in medical school.

21:24: Dawn comments that Jon was three years into his neurosurgery residency when his plans shifted. She asks Jon what happened.

24:52: Dawn says that Jon spent 26 years on active duty with the Navy, qualifying as a Naval Flight Officer, Naval Flight Surgeon, Navy Diver, U.S. Army Parachutist, and Special Forces Military Free Fall Parachutist. She asks Jon if it is fair to say that he has an appetite to try new things.

26:35: Ken comments that he and Jon met in Bruce Dunn’s lab at the University of West Florida in the late 1980s while Jon was in Pensacola working at the Naval Aerospace Medical Institute. Ken says that he recalls Jon working with Bruce on electrophysiology studies. Ken then asks Jon how he and Bruce met.

30:36: Ken says that Jon met his wife, Laurel, while he was in the Navy Dive School in Panama City.

35:34: STEM-TALK BLURB

36:00: Dawn asks Jon to share his experiences with the Marines in Desert Storm.

38:44 Dawn comments that Jon ended up back in Pensacola in the mid-1990s as the department head of the Naval Aerospace Medical Research Laboratory. During this time, Jon looked into the low-frequency active sonar, which was injuring both marine life and divers. Dawn then asks Jon to discuss this project.

41:14: Dawn asks Jon to discuss the Bug Springs project.

44:32: Ken comments that in 1996, Laurel was selected as a NASA astronaut, and she moved to Houston to begin astronaut candidate training. During this time, Jon was still in the Navy. Ken then asks Jon how he ended up working at NASA in Houston.

50:07: Ken asks Jon to discuss the transition at NASA.

53:02: Dawn asks Jon what his responsibilities were as a NASA flight surgeon.

55:00: Ken comments that it must have been an extremely tough experience when Laurel was aboard the space shuttle Columbia, that disintegrated upon reentering Earth in 2003.

1:00:40: Dawn comments that Jon’s son Ian asked why his mother did not bail out during the accident. Ian also told Jon that he was going to become a scientist and invent a time machine in order to go back in time and warn everyone. This was when Jon realized he had to focus the rest of his career on making it safe for those following in Laurel’s footsteps.

1:02:00: Part one of the interview ends.

 

 

Episode 54: Brianna Stubbs talks about ketone esters and their application in sport

Late in 2017, a San Francisco startup company brought one of the commercial ketone esters to market. Today’s episode features an interview with a scientist and world-class athlete who has spent the past year helping develop and rollout HVMN Ketone, an FDA-approved drink that promises increased athletic ability as well as heightened focus and energy.

Dr. Brianna Stubbs earned her PhD in biochemical physiology from Oxford University in 2016 where she researched the effects of ketone drinks on elite athletes. During Brianna’s collegiate athletic career, she won two gold medals while representing Great Britain at the World Rowing Championships. She first made international news when as a 12-year-old she became the youngest person ever to row across the British Channel.

Brianna graduated from Oxford’s Pembroke College with a BA in preclinical sciences with the idea of becoming an MD.  But after spending a year working as a research assistant helping to investigate the effect of exogenous ketones on human performance, she decided instead to pursue her doctorate in biochemical physiology and investigate how ketone compounds might be applied in a sporting and healthcare setting in the future.

While at Oxford, she worked alongside Dr. Kieran Clarke to develop a novel ketone monoester that has been shown to improve exercise performance in endurance athletes. She also was a member of the Great Britain Rowing Team and in 2016 become the World Champion in the lightweight guadruple sculls. Brianna’s time at Oxford gave her a unique opportunity to combine her scientific interest in sports physiology and metabolism while also competing at an international level.

Brianna moved to the United States in June of 2017 to work at HVMN and help bring the company’s ketone ester to market.

Links:

HVMN website: https://hvmn.com/ketone

Mark Mattson STEM-Talk: https://www.ihmc.us/stemtalk/episode007/

Wikipedia: https://www.youtube.com/watch?v=hNhuJ4JiK40

Mice and ketones cognition: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102124/#!po=10.1064

Owen and Cahill: https://www.ncbi.nlm.nih.gov/pubmed/6061736

Oxford ketone study: https://www.ncbi.nlm.nih.gov/pubmed/27475046

Glycogen re-synthesi and ketones: https://www.ncbi.nlm.nih.gov/pubmed/28398950

Ketones, glycogen and mTOR: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440563/

Caryn Zinn: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506682/

Ketone esters vs ketone salts: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670148/

Acetoacetate paper:            https://www.frontiersin.org/articles/10.3389/fphys.2017.00806/full

HVMN online fasting community: https://www.facebook.com/groups/136348456816447/

Show notes:

3:52: Ken and Dawn welcome Brianna to the show.

4:07: Dawn congratulates Brianna on bringing one of the first ketone esters to the commercial market, and asks Brianna to provide some background that led to the ketone ester launch.

5:31: Ken comments that the HBMN ester has been approved by the FDA as “generally recognized as safe,” or GRAS. He then asks her to expand on what this means in terms of human use and to expand on the value of the GRAS status.

6:31: Dawn asks Brianna what sparked her interest in science.

7:18: Ken comments that he heard Brianna was seven years old when she ran her first race, and that she ran so hard, she made herself sick. He asks if this is true.

8:16: Ken says that Brianna’s father was the one who got her interested in rowing, and when she was six years old, he signed her up for the first rowing race across the Atlantic Ocean. Ken asks if it’s true that he had never rowed before.

10:21: Dawn comments that Brianna used to run and row with her father as he trained for these races, and then when she was 12 years old she rowed across the English Channel, becoming the youngest person to ever do so. Dawn asks how this came about.

11:59: Dawn asks what Brianna’s mother was doing while she and her father were off rowing across the English Channel.

12:41: Dawn says that Brianna won her first international rowing event when she was 16, and then at 18 she won a silver medal at the junior world championships. She then asks Brianna’s to describe her training schedule as a teenager.

13:44: Ken asks Brianna what it feels like to be the best in the world at something after winning a gold medal in rowing at the 2013 and 2016 world championships.

16:32: Ken says that as a rower, Brianna mainly competed as a lightweight. He then asks what this meant in terms of preparing for competition from both a nutritional and training standpoint.

18:18: Dawn comments that the problems associated with excess training stress and inappropriate energy balance in female athletes were previously called the female athlete triad, but it has now been renamed relative energy deficiency in sport (RED-S). She then asks if Brianna experienced any physiological issues associated with competing as a lightweight athlete and if she saw this in any of her male colleagues.

20:35: Dawn asks Brianna if she has any thoughts on how coaches, nutritionists, and sports scientists could better support their athletes to prevent these issues.

22:39: Ken says that it was during this time, when Brianna was at Oxford, that there was a study being done on the effects of ketone esters on rowers. He then asks how Brianna became directly involved in the study.

23:51: Dawn asks why Brianna chose to postpone her medical school training to devote more time to researching ketones.

25:04: Dawn says that she understands that the CEO and a team from HVMN visited Oxford and that Brianna sort of invited herself to dinner and convinced them that they needed to hire her to roll out the ketone ester. She then asks if that is how Brianna ended up in San Francisco.

26:52: Dawn asks what Brianna’s first year in the states has been like.

27:40: Dawn says that a bottle of the ketone ester provides 25 grams of beta-hydroxybutyrate, one of the ketone bodies that the body naturally produces during a fast or period of starvation. She then asks Brianna what happens after someone consumes a bottle.

29:32: Ken asks Brianna if she has given any thought to possible consequences of supplementing with only beta-hydroxybutyrate. He then says that it has occurred to him that there might be a reason why the liver produces roughly equal amounts of acetoacetate and beta-hydroxybutyrate.

31:34: Ken says that looking back on the Cahill study, he can’t imagine proposing a study like that to an IRB now.

32:01: Dawn comments that the work Brianna was doing with Dr. Clark suggests that drinking ketones alongside a high-carb meal deliver a powerful performance boost. She then asks Brianna if the carbs are necessary to get the full performance boost of the supplement.

32:56: Ken says that state, where there is high carbohydrate availability and high ketones, does not seem like something that would naturally occur and asks if Brianna has any thoughts on this.

33:47: Ken says that you can imagine sparing the glycogen stores for when you really need them would be a great advantage in many sports, as most sports are both aerobic and anaerobic.

34:18: Dawn asks if ketone esters are best utilized as a training aid, as opposed to being acutely administered before an event.

36:03: Ken says that there is evidence that the HVMN ketone ester improves athletic performance. He then asks Brianna about its effects on cognitive performance.

37:10: Dawn asks Brianna to talk about some of the animal studies that are being conducted on ketone esters and their impact on physical and cognitive performance.

38:37: Dawn asks Brianna to explain the difference between ketone salts and ketone esters, and to also give an overview of what the advantages and disadvantages are for each.

41:56: Ken asks how Brianna envisions people using the ketone esters as part of their nutrition plan for a multi-day race.

42:55: Ken asks Brianna if there has been a study to look at the effects of chronic ketone ester administration on performance.

44:27: Dawn asks Brianna to discuss the study in cell metabolism that was published last year that looked at ketone metabolism in elite athletes.

47:15: Dawn asks how Brianna blinded people to which was the ester and which was not during these studies, since the ester tastes bitter.

48:57: Ken asks if it would be feasible to put the agents into capsules to avert the possible confounding effects of distinguishing the rather unique taste.

49:55:  Brianna believes there are important factors in running a successful and accurate sports science study.

53:00: Brianna discusses where ketones fit in the hierarchy of fuel selection during exercise.

55:53: Ken says that the terminology, ketone and ketone esters, are not synonymous, and asks Brianna to give an overview.

57:06: STEMTALK BLURB

57:31: Dawn asks Brianna if administration of ketone esters in the context of moderate carb intake overcomes the alleged problem of reduced PDH activity associated with ketogenic diets. She then asks Brianna if she has measured PDH activity.

58:06: Ken asks Brianna if you could, by use of the ester for an athlete that was in ketosis, have the best of both worlds.

1:00:07: Dawn says that ketone supplementation has a lot of potential to improve the performance of elite athletes. She then asks Brianna if weekend warriors or average recreational athletes can benefit from ketone supplementation.

1:01:21: Ken discusses a study recently conducted in Australia which reported that an acetoacetate diester slightly decreased performance in elite cyclists.

1:04:16: Ken comments that the authors’ speculated that the observed performance decrement was the result of elevated acetoacetate levels, which he noted, does not make sense.  He also noted that all of the study participants experienced GI distress which could easily have accounted for the performance decrement.

1:06:29: Dawn asks Brianna if she thinks this study will further confuse the topic of ketone supplementation.

1:07:37: Ken says that science and religion are two different things, and that particularly in nutrition science and topics related to nutrition, it is an emotional hot button, and people get all spun up about it.

1:08:54: Ken discusses again how many sports are a mixture of aerobic and anaerobic work. He then asks Brianna how athletes will use exogenous ketones in sports with varying degrees of intensity.

1:12:39: Ken comments that it is where the ketogenic diet will have the largest effect for the aging population, both in terms of general wellness and signaling effects, with respect to avoidance of sarcopenia.

1:12:51: Brianna talks about how athletes who are already on a ketogenic diet will use ketone esters.

1:13:47: Ken discusses the increase in BDNF after exercise and a study by Sleiman et al. that showed that HDACs inhibit the production of BDNF. Also, that beta-hydroxybutyrate inhibits HDACS, which would likely increase the production of BDNF. He then asks Brianna if she has any thoughts on whether exogenous ketone ester, such as the HVMN product, might also elevate BDNF.

1:16:00: Ken says that we know that the endogenous ketones have powerful signaling functions, but one of the most fascinating questions is about which of those the ketone ester will provide equivalent or better.

1:17:50: Ken says that it is possible to have high ketone elevations with the ketogenic diet, but it makes it difficult for the people doing the study.

1:22:41: Dawn says that it was noted in a recent paper from a group at UC Davis that ketones, and specifically beta-hydroxybutyrate, potentiated mTOR-1 signaling in skeletal muscle. She then asks Brianna if there is reason to believe this occurs in other tissues or organs of the body, where a potentiating mTOR might not be welcome.

1:23:20: Ken says that they found that it was tissue specific, so the level in the liver was not elevated in that study.

1:24:55: Brianna talks about the public’s response to the launch of the HVMN ketone ester, and gives a rundown of common questions people have been asking.

1:27:51: Brianna shares what her diet is like now that she has retired from competitive rowing.

1:30:42: Ken comments that Mark Mattson discussed intermittent fasting on STEM-Talk on an earlier episode.

1:31:13: Dawn comments that it seems as though most researchers also have a social media presence today, allowing people to collaborate more. She then asks Brianna if she is active on social media.

1:34:02: Ken and Dawn thank Brianna for the interview.