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Dr. Mark Shelhamer, Tuesday, 7-22-14 July 23, 2014

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Dr. Mark Shelhamer, Tuesday, 7-22-14

http://archived.thespaceshow.com/shows/2286-BWB-2014-07-22.mp3

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Guest:  Dr. Mark Shelhamer.  Topics:  A look at the risks associated with long duration human spaceflight.  Please direct all comments and questions regarding Space Show programs/guest(s) to the Space Show blog, https://thespaceshow.wordpress.com.  Comments and questions should be relevant to the specific Space Show program. Written Transcripts of Space Show programs are a violation of our copyright and are not permitted without prior written consent, even if for your own use. We do not permit the commercial use of Space Show programs or any part thereof, nor do we permit editing, YouTube clips, or clips placed on other private channels & websites. Space Show programs can be quoted, but the quote must be cited or referenced using the proper citation format. Contact The Space Show for further information. In addition, please remember that your Amazon purchases can help support The Space Show/OGLF. See http://www.onegiantleapfoundation.org/amazon.htm.  For those listening to archives using live365.com and rating the programs, please email me as to why you assign a specific rating to the show. This will help me bring better programming to the audience.

We welcomed Dr. Mark Shelhamer, Chief Scientist of the NASA Human Research Program to the show to discuss the critical risks associated with BLEO long duration HSP. You can hear his FISO talk on this topic from April 2, 2014 at http://spirit.as.utexas.edu/~fiso/telecon/Shelhamer_4-2-14/Shelhamer.mp3.  His associated Power Point can be downloaded at http://spirit.as.utexas.edu/~fiso/telecon/Shelhamer_4-2-14/Shelhamer_4-2-14.ppt.  During the first segment of our 95 minute discussion, Dr. Shelhamer started off saying  we would be talking about beyond low earth orbit only and that many of the risks are unknown since we have very little experience with BLEO.  Much of what we do know is extrapolated from our current knowledge base plus our Apollo experience.  Next, our guest defined three major areas/issues.  First he listed medical issues which he later described as onsite medical treatments for various complications, illnesses, surgical needs and such.  He classified physical deconditioning issues such as muscle and bone loss issues, cardio vascular issues in a different category.  The second group he identified had to do with radiation, and the third group included psychological-social issues.  I asked about Microgravity not being in the top three and he said because those issues are likely a constant for both LEO and BLEO missions.  He then talked at length about the challenges needing countermeasures/mitigation.  He did not say these were showstopper challenges but they do require effective countermeasures.  For example, he said humans could probably survive a trip to Mars today providing the hardware & life support was up to the job but their goal is to get the crew there in good condition, to be able to do effective work, and to return safely.  He did not think those goals could be obtained today.  I asked if money was a primary issue and it was not though he said more money is always helpful. He talked about the time needed for some human studies, team studies, and research, sometimes extending even longer than a year.  He then took us through the three categories to tell us what NASA was doing & how it was doing in that research area. You might be surprised by what you hear.  I certainly was.  Later, we talked about ocular/vision issues which are now getting front page attention.  He explained the latest theory causing the problem as possible fluid shifts.  Listen to this discussion.  Note that once we start with BLEO HSF, we may find other problems that do not now show up now.  Also, we may develop a countermeasure for one problem but that opens the door to lots of other problems currently unknown.  One tool he talked about that was being tested on the ISS Russian sector was lower body negative pressure.  Artificial gravity was a big part of our discussion.  While everyone is enthusiastic about it, he made the point of saying we don’t know the needed spin rate nor do we know what level of gravity is needed for humans or for how long. Just spinning a spacecraft without knowing this information is unlikely to be successful let alone cost effective or economic. He also pointed out that artificial gravity is costly, requires lots of energy, a huge spacecraft which means lots of mass to orbit, & to do it, it needs to be done in a way that maximizes the benefits for the crew.  Without knowing the precise spin rate and gravity needs for humans plus how long the crew needs to be in artificial gravity, it is likely it won’t be done just for cost and economic reasons alone.  Charles emailed in about bed rest analog studies.  Joe sent in a question about lower back pain & spine issues.  As the segment ended, I asked him if humans were lousy candidates for BLEO spaceflight.  Don’t miss his answer.

In the second segment, we took a call from Dave about nuclear submarines as an analog for HSF studies.  Our next topic was space radiation which our guest discussed in detail.  I then took two email questions from B John in Sweden.  He asked about the benefits of microgravity for disabled folks, then I read a longer email from him suggesting solutions for the microgravity, psychology, and radiation issues already existed and why was NASA not proposing and developing “these simple non-medical solutions to the problems you describe.”  Dr. Shelhamer responded to his email item by item. For the most part, he agreed with what B John was saying except that his information and perspective were limited and missing key components of the scenarios he was talking about.  Mark explained why our listener’s comments were way too simple and cited some scenarios to illustrate this.  It was a fascinating reply to what many of us believe are already effective countermeasures.  Unfortunately, while what many of us suggest is correct, what we suggest does not go far enough and does not contain the specifics and details of what is actually required to make a specific countermeasure work.  Otherwise, the countermeasures are far more complex than what B John asked about in his email which you will hear me read on the program.  I asked Mark about genetic modification and that took us to the subject of personalized countermeasures.  We talked about pioneering/space settlement, childbirth & children in the space environment, even gender differences for BELO HSF.  I asked about the differences from his perspective of doing HSF to the Moon, an asteroid, Mars, or Deimos.  There are differences, don’t miss his response.  As the program was ending, I asked if a commercial company without gov. funding could decide to do a BLEO mission without all the costs and safety concerns of NASA.  Mark said it might be possible though the costs of the missions and the technology needed would make it very hard for a commercial company to carry out.  He said a short cut bare bones mission might be achieved by a commercial company but the risks for the crew would be extreme.  If you were running a commercial company and funding such a mission, would you accept these risks, plus the risk the crew might not be able to do much or be effective once they got to their destination? As the commercial company CEO, would that be a good use of company money or would you dismiss what people like our guest today have to say about these issues.  Let me know your thoughts by posting them on the blog.

Please post comments/questions on TSS blog above. Mark can be reached through me or through his PPT presentation address.

Dr. Duane Graveline, Friday, 1-25-13 January 24, 2013

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Dr. Duane Graveline, Friday, 1-25-13

Co-Host Heather Archuletta

http://archived.thespaceshow.com/shows/1936-BWB-2013-01-25.mp3

Guests: Dr. Duane Graveline, Heather Archuletta.  Topics: Bed rest microgravity simulation studies. Dr. Graveline is the father of this research. Please direct all comments and questions regarding Space Show programs/guest(s) to the Space Show blog, https://thespaceshow.wordpress.com.  Comments and questions should be relevant to the specific Space Show program. Written Transcripts of Space Show programs are a violation of our copyright and are not permitted without prior written consent, even if for your own use. We do not permit the commercial use of Space Show programs or any part thereof, nor do we permit editing, YouTube clips, or clips placed on other private channels & websites. Space Show programs can be quoted, but the quote must be cited or referenced using the proper citation format. Contact The Space Show for further information.  We welcomed Dr. Duane Graveline to the program to discuss bed rest simulation microgravity studies, the early days of pioneering of his having pioneered this research, aerospace medicine and much more in our 1 hour 23 minute discussion. Dr. Graveline is the father of this research dating back to the late 1950s.  Please visit his website, www.spacedoc.com.  Heather Archuletta, the Pillownaut Astronaut, returned to co-host with me for this important discussion.  Check out Heather’s blog posts about Dr. Graveline and his work at http://pillownaut.blogspot.com/2013/01/the-bed-pilot-pioneer.html.  Dr. Graveline has allowed us to use two specific pictures referring to his pioneering work and both are on The Space Show blog per the above URL.  Picture 1 is Dr. Graveline’s water immersion tank and Picture 2 is the LBNP device. He discusses both of these in the program’s first segment.  Dr. Graveline started out with an overview of his early work, how he got into the field, his decision to join the Air Force and why this area of medicine interested him.  He explained his early bed rest tests and talked about the challenges with the test subjects. Heather and Dr. Graveline compared those early tests to those of today that Heather has participated in.  It was a fascinating compare and contrast, especially regarding the discipline of test subjects then and now. Dr. Graveline talked about water immersion, the aerospace lab he used, and his water immersion tank.  Don’t forget to check out the picture of it on the blog.  Dr. Graveline is looking through the window at the floating test subject.  Would you like to float as Dr. Graveline explained for one full week nonstop?  Throughout our discussion, Dr. Graveline told us many interesting and sometimes funny stories from his past like his visit to the Today Show and their wanting him to wear “flippers!”  Our guest described the low body negative pressure device (LBNP) which you can see in the second photo on the blog.  He talked about it, the old Soviet program, Mir and tilt table tests.  Dr. Graveline talked extensively about the Soviet program, how he was able to monitor much of their data, & he told us about Alexi Leonov when he had serious problems when caught outside his spaceship.  Many questions were asked about early animal studies, Laika, and more.  He told us how they were able to do blood pressure readings on dogs & the Soviets bragged about it since Dr. Graveline was able to figure out, copy, & improve the Soviet system.  Mice and centrifuge studies were discussed in some detail & Heather and Dr. Graveline had comprehensive discussions about exercise in the bed rest studies of today as compared to none in the early days of the studies. Dr. Graveline talked with Heather about his idea to abandon exercise in space so the astronauts could concentrate on their work, then return in a hydropod and rehab completely back on Earth for a few months.  You don’t want to miss this discussion or explanation from Dr. Graveline as to why this approach should be considered and tested by NASA.

     In the second segment, we talked about bone density issues and the applicability of space research and findings to terrestrial medical issues for people with this medical problem.  He was asked about a long duration HSF to Mars and he said the bigger problem was galactic radiation which he talked about in some detail.  He said that as of today, there are no mitigation tools for this problem.  The discussion went back and forth about water immersion and the use of the hydropod for returning astronauts & Heather talked about prohibitive costs & that immersion is not used today.  One of our UK listeners asked Dr. Graveline about his being part of Group 4 – The Scientists.  As this was the first astronaut group that was not composed of test pilots, our listener wanted to know about the selection process & getting more scientists to the Moon & on missions.  Dr. Graveline had much to say about this subject & shared with us some terrific & historical stories from the past.  He talked about Spacelab, astronaut Bill Pogue, & shared science stories with us.  During our program, Heather, with her bed rest study experience & her recruiting work (listen to her Space Show program on the studies she has recent completed at http://archived.thespaceshow.com/shows/1926-BWB-2013-01-08.mp3 from Jan. 8, 2013), contributed greatly to the discussion and Dr. Graveline was equally interested in talking with her about the program today as compared to the program he started decades ago.  Dr. Graveline’s book, “From Laika With Love: Secret Soviet Gifts to Apollo,” is still available. If you order it from Amazon using this link, Amazon will make a contribution to The Space Show/OGLF:  http://www.amazon.com/From-Laika-With-Duane-Graveline/dp/1424338700/ref=onegiantlea20.  Dr. Graveline was also asked about the use of his research today and if young scientists & researchers interested in the field still study his early work.  He said yes and talked about how much easier it was to do that today due to the internet.

     If you have questions/ comments for Dr. Duane Graveline or Heather Archuletta, post them on The Space Show blog per the URL above.  If you want to email Dr. Graveline or Heather, you can do so through me.  You can also comment and contact Heather through her blog which is mentioned earlier in this summary.

Here are Dr. Graveline’s photos discussed above:

Graveline Immersion Tank

Graveline Immersion Tank

 

Graveline LBNP Device

Graveline LBNP Device

 

Drs. Adrian LeBlanc, Thomas Lang & John Jurist, Sunday, 5-6-12 May 6, 2012

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Drs. Adrian LeBlanc, Thomas Lang & John Jurist, Sunday, 5-6-12

NASA Bone Loss & Bisphosphonate Study

http://archived.thespaceshow.com/shows/1769-BWB-2012-05-06.mp3

Guests:  CLASSROOM:  Dr. Adrian LeBlanc, Dr. Tom Lang, Dr. John Jurist.  Topics:  Bone loss issues for human spaceflight & the use of bisphosphonates for mitigation.  You are invited to comment, ask questions, and discuss the Space Show program/guest(s) on the Space Show blog, https://thespaceshow.wordpress.com and The Space Show Classroom blog, http://spaceshowclassroom.wordpress.com.  Comments, questions, and any discussion must be relevant and applicable to Space Show programming. Transcripts of Space Show programs are not permitted without prior written consent from The Space Show (even if for personal use) & are a violation of the Space Show copyright.  In addition, at the end of this summary, you will find links to relevant papers for our discussion as provided us by Dr. Lang.  We welcomed Dr. Adrian LeBlanc, Dr. Tom Lang and Dr. John Jurist as co-host to discuss the NASA bisphosphonate and bone loss study in progress.  Dr. LeBlanc along with his associate in Japan, Dr. Toshio Matsumoto, are leading this study and Dr. Lang is part of the team.  We started our discussion with Dr. LeBlanc providing us with a brief historical overview of bone loss issues of concern to NASA since the early days of the space program.  We talked about Skylab, Mir, the use of the DEXA scan, the use of quantitative computer tomography (QTC) and CT scans through to the ISS, Space Shuttle, and current research projects.  Our discussion was technical at times so if you need to look up or Google a technical term, please do so. In addition, we had some audio issues with the phone line used by Dr. LeBlanc as he faded in and out from time to time.  We apologize for any inconvenience this might have caused.  The first segment went through the bone loss issues, problems, consequences, & the methodologies involved in analyzing the conditions encountered by the astronauts participating in these studies.  Issues we discussed included the use of prescription drugs in space, long term use of bisphosphonates, risk factors for spontaneous hip fractures, exercise programs, bone strength, bone mass, the impact of radiation, skeletal recovery back on Earth after spaceflight to something different than before the spaceflight took place as well as the implications for astronauts as they age.  We talked about using artificial gravity to mitigate bone loss.  You might be surprised to learn that using partial gravity may not help matters.  Bisphosphonates do seem to help and will possibly play a role with exercise as we move to long duration spaceflight but we are in the very early stages of fact finding on these issues.  We also discussed informed consent with the astronauts regarding their participation in these and other experiments.

In the second segment, a listener asked about the relevance of this type of space research to the taxpayer who funds it and to the general population.  Our three guests responded to this question, explaining why the research is relevant and important. Don’t miss their answers.  We then talked about following the astronauts here on Earth to see the continued impact of having been in space on their bones as they age.  We learned that bone changes after being in space for four weeks or more and it is important to follow these changes as part of the aging process.  Our guests talked about calcium excretion issues in space and the risk this causes for a renal stones.  Bisphosphonates may inhibit calcium excretion which would help mitigate this risk.  Near the end of our discussion, we learned about new medications being developed that are more advanced than the bisphosphonates we have today.  We also talked about the competition with astronauts for different scientific experiments.  As Dr. Jurist pointed out, we really do need lots more human spaceflight!  At the end a listener asked about bed rest studies and our guests provided us with the basics.  If you are interested, visit https://bedreststudy.jsc.nasa.gov.  Our guests made important closing comments and take away points.

Please post comments/questions on The Space Show and Classroom blogs.

Dr. Lang provided us with these links that will be of interest to us all.  These documents can be accessed without a subscription to the journals. These papers provide some background to the problem of bone loss in spaceflight, the recovery of bone after spaceflight and use of CT and the use of CT-based finite element modeling to assess bone loss.

Cortical and Trabecular Bone Mineral Loss From the Spine and Hip in Long-Duration Spaceflight http://onlinelibrary.wiley.com/doi/10.1359/JBMR.040307/full

Adaptation of the Proximal Femur to Skeletal Reloading After Long-Duration Spaceflight http://onlinelibrary.wiley.com/doi/10.1359/jbmr.060509/full

Reduction in proximal femoral strength due to long-duration spaceflight http://scholar.google.com/citations?view_op=view_citation&hl=en&user=0zFSO9sAAAAJ&cstart=20&citation_for_view=0zFSO9sAAAAJ:4DMP91E08xMC

Click on link on right “[PDF] from http://cof.org.cn ” for free pdf copy of the report.

Dr. John Jurist, Tuesday, 3-27-12 March 27, 2012

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Dr. John Jurist, Tuesday, 3-27-12

http://archived.thespaceshow.com/shows/1744-BWB-2012-03-27.mp3

Part 1, Bisphosphonate Usage in Microgravity

Guest:  Dr. John Jurist.  Topics:  This is the first in a series of programs focused on the use of bisphosphonates to mitigate bone loss in long duration spaceflight.  You are invited to comment, ask questions, & discuss the Space Show program/guest(s) on the Space Show blog, https://thespaceshow.wordpress.com. Comments, questions, & any discussion must be relevant & applicable to Space Show programming. Transcripts of Space Show programs are not permitted without prior written consent from The Space Show (even if for personal use) & are a violation of the Space Show copyright.  We welcomed back Dr. John Jurist for the first of several programs devoted to understanding bone loss in microgravity & the use of prescription the bisphosphonate family of drugs to mitigate the problem.  Dr. Jurist provided talking points which you can find below this summary on The Space Show blog.  A significant portion of the second segment is devoted to understanding these talking points so follow along.  We started our discussion with an explanation of the bone loss problem facing those in microgravity.  Following this brief overview, Dr. Jurist told us about bisphosphonates, the origins of this drug, how it was developed, how its usage, what some of the side effects are, some of the trials that have been associated with the drug, & space/NASA studies.  Later in this nearly hour long segment, we talked about the human population & what happens to our bone mass at various stages in our life. We talked about gender, racial, & ethnic differences in human bone mass issues.  As you will hear, there are gender & other differences among our diverse population.  This led us to asking about using targeted genetics in selecting crews for longer spaceflight missions.  Genetic modification was mentioned, especially for the long term, but for the near term, looking for better exercise routines & pharmaceutical modification/treatment seem to hold the most promise.  Dr. Jurist then talked about bisphosphonate side effects.  Fast transit time to Mars or a long duration mission destination came up. As you will hear, even if you get to Mars faster, you still have the problem on the surface of Mars.  The big problem is we have no credible information on what the gravity prescription for humans needs to be so we do not know if Martian gravity is sufficient to mitigate the problem.  Next, we focused on the need for an orbiting centrifuge, we talked about the size & spin rate of the centrifuge, & what to actually test for in experiments.  Dr. Jurist suggested that starting with 1/6th lunar gravity made sense because if it was sufficient, we would know that anything stronger than 1/6th would work.  If not, we should probably next experiment with Martian gravity which is about 1/3rd Earth gravity.

In our second segment, Dr. Jurist referred to his talking points which you will find on The Space Show blog. We went line by line so follow along with us.  Despite interruptions, John stayed on topic with the talking points.  Listener questions asked about how gravity & having a load on bones works & what happens in space when that load is no longer present.  We talked about the time prescription as well as the load factor (G force).  Toward the end, John told us about a reviewed radiation article from 2010 showing that radiation impacted bone loss so the issue in space is more complex than just microgravity.  Near the end, John got a question asking about ETs & their thin, pencil like shape making them perfectly designed for microgravity.  This was both an interesting & fun discussion, bordering on science fiction.  Another question asked about fish, reptilian, sea mammal, & bird bones.  Our final topic dealt with the release of personal astronaut medical information & others & the ways for private information to be legally released to the public.

Please post your comments/questions on The Space Show blog URL above.  Email for Dr. Jurist can be sent to me for forwarding.

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Dr. John Jurist Bisphosphonate Talking Points:

Bisphosphonate show Tues 8:00-9:30 MDT Talking Points

Introduction:             Bone is incredibly complex with many inter-related factorsGoal:                          Brief outline of cellular, structural, and functional aspects of bone metabolism in order to help listeners better understand and appreciate the potential role of bisphosphonates (which is the subject of a future show)

Bone Function:          Two types of bone – compact and trabecular: Compact is outer shell, very dense, and fairly strong

Trabecular – also called spongy, contains spicules, plates, and struts of bone tissue with lots of vascular and fatty marrow, called trabecular

Remodeling:             Bone is constantly being turned over or remodeled with portions being torn down and constituents dumped into bloodstream and other portions being built up from nutrients supplied by blood

Very rapid bone loss can lead to kidney stone formation from calcium dumped into blood

Turnover rate and the volume of total skeleton undergoing remodeling at any given time tends to go down with increasing age (remember this – important)

Balance between formation and resorption (tearing down) also tends to be lost after about age 30, lack of activity, certain hormonal imbalances, diseases, etc. with resorption predominating – one rationale for estrogen replacement therapy after menopause

Coordination between formation and resorption partly controlled by mechanical strains on bone tissue (called Wolff’s Law and issue in microgravity) – some evidence that mechanism is electrical in nature – rationale for electric and electromagnetic bone growth stimulators used to treat problematic fractures and improve incorporation of bone grafts

Cells:                          Stem cells differentiate (or specialize) into osteoprogenitor cells which differentiate into osteoblasts which are the bone formers

Osteoblasts create and secrete a protein and polysaccharide matrix called osteoid which is then calcified later to form the stuff we call bone

Interference in that calcification leads to rickets in children and osteomalacia (Greek for soft bones) in adults

Osteomalacia is often a result of interference in Vitamin D metabolism or dietary deficiencies

During bone formation, some osteoblasts “paint” themselves into a corner and get surrounded by bone – they are then called osteocytes and somehow maintain bone tissue

If osteocytes die in a volume of bone, that devitalized bone no longer undergoes remodeling but can eventually be replaced by a process called creeping substitution (remember comment about remodeling volume going down with age)

Devitalized bone can accumulate fatigue defects and eventually suffer fatigue fractures (called stress fractures – common in military recruits and deconditioned people who recondition too rapidly) if the defects are not replaced by new bone during creeping substitution

Other cells, with multiple nuclei and called osteoclasts, differentiate from marrow cells (monocytes and macrophages) which in turn differentiate from stem cells

Osteoclasts are the bone resorbers and destroyers

Autoradiographic studies show that their nuclei also came from osteocytes as well – presumably as they are resorbed during bone destruction process

Osteoclasts are related to multinucleated “giant cells” which are associated with inflammation in ways I do not understand

Bisphosphonates:      Used over past 20-30 years in clinical medicine – brands include Actonel, Boniva, Fosamax, Aredia, etc.

Multiple mechanisms with different dose-response properties results in clinicians juggling doses and brands to get effects they want without effects they do not want

Bind to hydroxyapatite – the mineralized  portion of bone tissue (calcified osteoid)

Inhibit bone resorption by inhibiting osteoclastic activity

Inhibition of resorption signals osteoblasts to slow down formation rates after a delay (but increases their lifetimes (anti-apotosis)

Bisphosphonates also inhibit mineralization of osteoid – especially at higher doses

That eventually reduces turnover rate and can lead to fatigue fractures with prolonged treatment (remember to call 1-800-BAD-DRUG)

Orthopedic surgeon (Frost atHenryFordHospital) figured out that cyclic therapy exploits delay in osteoblast inhibition relative to osteoclast activity and results in better bone mass gains

Bisphosphonates used in oncology to preserve bone and reduce pathological fractures with osteolytic tumors such as breast and prostate cancers.  Also to counter hormonal blocking therapy used for prostate and breast cancers, but side effects increase with duration of treatment

Interesting sidelight with oncology is some evidence that bisphosphonates reduce risk of tumor metastasis to bone and other sites (somehow involving same signaling pathway as giant cells?)

Oral bisphosphonates cause stomach upset – advise staying upright for an hour or two after taking pill – how does this affect microgravity exposure?

Intravenous bisphosphonates get around oral gastric upset, but placing line or port has risks too (most oncology patients have ports during active treatment)

Also cause osteonecrosis – especially jaw which I believe is septic or infective – and atrial fibrillation (talk to Bill Rowe on this one since he is interested in heart physiology in space)

Bone quality:             Turnover rates and percent of skeleton not devitalized important factors in determining bone strength – measuring bone mass by DEXA or other means is not the be all and end all in evaluating bone strength and risk of fracture.

My Goal:                   General background on bone physiology and function to aid in appreciating upcoming show(s) on bisphosphonates in space medicine