So welcome to that 2015 NASA Ames summer series
Space exploration allows us to investigate the frontiers of space our future
it also allows us to make science fiction a reality and
In the process we learn about ourselves and our home planet Earth
One of the ways that
We study and investigate space and make sure that we survive that environment is to use model organisms
NASA Ames is the lead research center for conducting managing and building
Hardware to conduct rodent research in space
Today's seminar entitled flying through the ages rodent research for human health will be given by dr.
Ruth Globus
Ruth earned a BA degree in sociology in
1979 from the University of California at Santa Cruz
followed by another, BA degree in 1981 in biology from the same University
After that she
Worked at the lab of Emily Holton here at NASA Ames. Where she got introduced and got the bug of being at Ames Research Center
She worked for two years
And then she realized that her future lies in being a PI and doing space research and ground research with rodents
So she went on to get a PhD degree in endocrinology
From the University of California at San Francisco followed by a postdoc in cell biology
She became a principal investigator at NASA Ames in
1993 and then joined the civil servant staff in
1997
She has numerous awards and publications too many to go here at this moment
Please join me in welcoming - Ruth Globus
Thank you very much Jacob, thank you Ames for giving me the opportunity to share share
Our work, I won't say my work. I'll say our work, and I think as I proceed through this talk you'll see why?
We are have been actively engaged in
Developing capability to conduct long-duration rodent research on the space station
And it makes sense why do we want to do that what's our big goal? Where are we going?
So if we accept as our big goal we want to have long-duration human
habitation in space
Then let's set as a goal to stay healthy while we do that
Both during and after we come home to Earth
so ambitious goals
Call for ambitious questions, and here are some of the questions that came to mind as I thought about it
What are the biological changes that are relevant to human health?
What what changes occur and when do they occur how far do the adverse changes?
Progress some changes may or may not have an adverse effect
So what if anything do we need to do about those responses?
second big question
That you'll see emerging during this talk is really how do these changes come about?
What are the fundamental mechanisms at the molecular cellular and?
physiological levels that lead to observed responses
we want to do this both to better understand human biology and disease on earth and
Also, we hope that will lead to a better
ability to predict
Changes that occur and to identify interventions that may be needed in
Short these type of mechanistic studies that animal research and other
Other analog research makes possible is to take some of the guesswork
making decisions for our future in space
So general outline of what I want to talk to you about today is first to provide a background
What are some of the challenges of the space environment why do we study rodents?
I'll touch briefly on some of the past some of the what we've learned and then I'm going to go into some detail
Into what we're doing now with the rodent research project the challenges we face in accomplishing our objectives
What the capabilities are and some of our new and surprising findings that we've obtained?
So first what are the challenges that are posed by going into a space environment?
this
Should pose no surprise to people in this audience
And and thinking about the problem. We've all evolved on earth in 1g all species
This is a continuous except for very transient and short periods of acceleration
so ourselves our living systems are
The intact organism has evolved under that influence and in fact we already know quite
Well that we can adapt to changes in that
We haven't been in that environment for much more than two years at the most
So there's still many unanswered questions the second half important aspect of the space environment
That most are aware of his space radiation space radiation is is unique
Both in type and in exposure rates, and so it poses unique challenges
Potentially both short-term and long-term
to the health of astronaut crew
But that's not all those aren't the only challenges we respect we face when we go to go into space
Here are some of the others now these might
look somewhat familiar to you because these are challenges that we certainly face on earth as well and
In fact things like nutrition or demanding workload are we have a great deal of understanding of?
others
Somewhat less for example in the ISS environment. There is a low, but elevated
Level of carbon dioxide that the crew breathes in and that has a biological effect. We know some
something about that from Studies on
long-duration submarine errs, but when you combine all these challenges and these factors together you end up with an
Realization that the that it is not possible with reliability to predict the long-term
consequences of these environments especially
Especially as we seek to live in space
So what are those changes that occur now in microgravity? We have widespread
unloading or musculoskeletal Disqus
Also, because our circulatory system has evolved in 1g
The entire system is tuned to that and when we go into space
There is a fluid shift more an equalization of distribution of that fluid and many different sorghum systems in the body are affected
and yield a
adapt ation some successful some
Somewhat less successful and in fact as I've already mentioned. We understand a lot
We've been in we've been going to space for a while now. We know that there's muscle atrophy
We know that there's cardiovascular deconditioning and that there's very rapid vestibular responses i'm heightening
bone decrements here because this is my area of research and something I feel a lot of passion about so we will talk in a
Little more depth about that to illustrate some of the points. I'd like to make but these points equally pertain
Differing in detail to the some of the other systems that are affected by spaceflight and in bone decrements
What do we know about fracture repair in space in humans nothing it hasn't happened yet
What do we know about mechanisms?
Very we know something, but very little
We've also flown rodents
And I'll talk a little bit about some of that history in a moment we know things from research as well
And we're making progress in getting answers to some of these really important questions from that research already
in
Pointing to my example here in terms of the bone decrements
already to spaceflight experiments have looked at the ability of bone to repair from a fracture and
In fact have found that deficits do occur
We also have more detailed understanding of mechanisms than has we've been able to obtain from human flights
So when I talk about mechanisms, what do I mean here in fact?
there are a hierarchy of mechanisms that we could think about when we're trying to solve a problem and
Typically in biology we can start at the smaller level
From the molecular understanding, which specific molecules are responsible for a given outcome
the molecules organized into cells
into communities of cells into tissues
into organs and
into organ systems
And I'd like to pause here for a moment to point out as we all know one organ system or one tissue in our body
Communicates with many others they don't exist in and of themselves
To yield a healthy organism they work together
So in the end these together combine
to result in the observed behavior and
biological function of of the organism in this case the mammal
rodent
Now you might ask me. Why rodents why do we study rodents?
The simplest answer is because of the benefits that it can be accrued and have already been shown to be accrued
using those using rats and mice primarily
71 of the past Nobel prizes in medicine have been awarded to people who've used
Animals in their research and it's made possible discoveries that simply wouldn't have been possible otherwise such as the fracture healing
Studies that have been conducted
We don't embark lightly a plan to use to study rodents in long duration
Habitation in space and and develop the hardware and and and the plan and conduct the experiments
we do that under the advice of experts who who review what's needed and
In the National Research Council in
2011 produced a report on really looking carefully at what's needed in both the life and physical sciences
For
for Space Exploration and point out that the lack of a facility of
Rodent reefs for conducting long-term room research on the station is a major impediment
For important to to achieve important goals for
astronaut health and
And it's important to note here also that
We observe carefully the federal regulations and requirements to ensure the well-being of the animals so
Here's another interesting scientific reason why rodents and we can think about this together?
Aging the
typical life span of a human
depending on on
Many variables can be 70 to 90 years
Typical life span of a mouse is two years now despite this enormous difference in lifespan
rodents acquire age-related diseases that very closely resemble those of humans
osteoporosis the loss of bone cardiovascular deconditioning
Muscle wasting these are just several examples
So what that means is if you look at various stages during aging you have a compressed timeline
Here you see in humans age of twenty to thirty year old
Human in years corresponds to a three to six month old
Old animal in mice or and also approximately rats
Going on to two older and older ages, so what's the consequence of this for us?
Who are trying when we're trying to solve the problem of?
influence of long-duration habitation in space on human health
well, let's let's
Let's grab a hypothesis
Well, we'll look at the hypothesis. That's really been long-standing for many years. That's been based on the observation that
Age-related disease
Is such as bone loss and muscle loss is observed
And it's very similar in the spaceflight environment as I just mentioned the hypothesis is that living in space?
accelerates aging
Let me emphasize. This is a hypothesis. This is not a fact
What's going to take for us to test this hypothesis the age of our astronauts are?
38 in the approximately 38 to 47 year range
This is a one-year-old animal if you want to do a lifespan
Experiment let's just say design that experiment that would require roughly 40 years
For humans not very practical right now that same experiment could take about a year
much more doable
So now I'd like to describe to you in a little more detail the biology of the
Changes that occur in the microgravity environment. I just spoke to you about aging, but very similar
Changes can occur and have been shown to occur in various experiments with aging
with radiation exposures
disuse on earth
And hormonal changes in humans it takes months to decades
To go from a bone that looks like this to a bone that looks like this in response to these factors
This is a micro CT these are both micro
CT images Micro computed tomography images that throat that show the three-dimensional structure of
Cancellous bone which is the?
Highly metabolically active bone that's inside
the outside shell
This is looks like this in humans
It also looks like this in rodents, but we can see this depending on the stimulus even in a matter of days
Now how do we get to a structure that looks like this to one that looks like this?
It's a product of cells. We don't think about this in the context of bone
but just like the other tissues cells contribute to the
growth and maintenance of tissue function
And I'm going to talk more about that now in the context of what we've learned from spaceflight
we would like to understand at the
Cellular level as well as molecular level, which cells are responsible
responsible for the changes in bone structure that occur in the space environment
Two different lineages or derivations of cells are found in the bone marrow that give rise to
Excuse me the give rise to the most
differentiated or mature cells
the osteoclasts which break down bone and the
Osteoblasts which build or form bone together these cells define whether bone looks like this or this
These cells derive originally from stem cells two separate lineages
which divide and
mature
Sequentially to become the mature cells where in this process do we see defects and
We've acquired
Information from rodent experiments that the defect is not found only in
The mature cells that are responsible for breaking down
And forming new bone, but also in the earlier
Progenitors and precursors that are that supply a continuous
Source of cells throughout life
So now that I've introduced you to some of the concepts that we'll be talking about let's get into some details about
What we've learned for Space Flight experiments in the platforms, and I'll only have time to touch on those briefly
But there have been three different space
Platforms that have been used to date
the
the cosmos missions
Which have grown up until recently into continued into the by on missions are unmanned missions by the Russians and really
in these missions
performed
groundbreaking work in the midst of the Cold War
To determine. What are the basic physiological responses of rodents and mammals to the space flight environment?
many more experiments were conducted in the shuttle era and
And we're coming to the present in the ISS
so to summarize some of the most important features take-home features from this shuttle era of
Experimentation we really the input one of the key aspects of the shuttle program
Was it provided the opportunity to do multiple experiments?
gathering new information
And taking the next logical step
Which really formulates the basis of making progress in a race in research and?
in that that frequent access that was made possible in that program allowed us to both define responses and
test treatments
now what are some of the the gaps in knowledge that came be as a
consequence of of the structure of the shuttle program one was the duration
We never learned what what happens after three weeks. That was the longest flight
In that period we mostly not exclusively, but mostly studied growing rats
Not adult animals we know
Basic biology that the processes that control growth are very different than the processes that control
maintenance or
Aging, so what about adults?
All but two of the 27 run experiments that were conducted
using the shuttle platform entailed returning the animals to earth and
Recovering tissues and studying them now this entered is an additional variable of reentry
landing in a time delay which in the shuttle air was relatively brief only a few hours, but we know even that brief period
Can result in a change in
In outcome depending on what variable is being analyzed so these
findings really point to the science value
for doing on-orbit sample recovery
Now moving beyond the shuttle into long-duration missions the first one was
Was performed on the ISS using a mouse drawer system developed by the Italians
they
They achieved 91 days on station launched in 2009 via the shuttle
Male mice were flown and its
Samples were analyzed after after returned now. This flight resulted in a limited number of
Animals recovered nonetheless. There are some interesting new findings that invite further study and
Citations mentioned here along and and as of today we see more than five index papers
describing this study
More recently we've had an unmanned by an m1 mission
Which which is the Russian mission us investigators work closely with them in tissue sharing?
This is a 30 day mission that flew older male animals
Again, this is a sample recovery after landing in this case
13 hours a fairly long period of time and new results are still emerging from these studies more than 13
Papers have had been published to date
So learning from these examples. What are our main objectives going into the rodent research project here at Ames?
What kind of gaps in knowledge do we want to fill and and what do we need to do to fill those?
First
We know we wanted to provide reliable long door habitats for rodents on the ISS
We wanted a habitat that could support the animals in groups or individually
Rodents or social animals they like to live together, it's important to have that capability
We also wanted the hardware to have the potential for future modification so that we can support eventually multiple generations in space
it also needed to have relatively low maintenance to minimize crew time which is at a premium so
We could conduct daily health checks to monitor animal welfare
Without without taking up extra crew time
We wanted to perform multiple missions
Capture some of what the shuttle was able to do for us in that era the current plan for flying
these is to to conduct two flights per year and
Finally we wanted to make sure we had the science capability
To apply cutting-edge technologies to any samples that we recover on-orbit or after return should those experiments be conducted
What do I mean by technical advances well these here are a couple of examples?
One is genetically Anna modified animals these have already been applied in previous platforms
But there's a lot more work that needs to be done. What do I mean by genetically modified mice can be?
The the gene sequence can be modified so that a particular gene of interest is
Overexpressed or under expressed or knocked out and that allows us to derp de to determine
What the mechanism how important that particular gene and protein?
Product is for a given response and gain good example of that for a flight experiment is
The rodent research one cases some Novartis experiment, which I'll talk about in a moment
Second new technology that we wanted to make sure our samples were good for was to be able to apply really cutting-edge
Technologies that have expanded so that's so greatly in the last ten to ten to fifteen years
and those are loosely referred to as omics that is a character a chair duration of a large pool of
Molecules they may be
Genes
RNA transcripts
metabolites that allows us to have greater insight into structure and function and
An example here from a previous flight experiment where this
Technology was applied to learn something new and important is shown here
so
Talking about challenges. What were our challenges in getting something to work here and getting it up and running
So we decided to adapt legacy hardware taking advantage of the fact that we had 27 prior flights
that successfully flew
We needed to interface that hardware with new vehicles
We don't have the shuttle to take
anymore so we worked with SpaceX and
Developed the capability to use an unmanned Dragon capsule to deliver
to deliver the hardware
Finally we needed to take care of the animals provide
Husbandry that entails training of crew and monitoring the animal welfare every day, which I already alluded to
This all seems pretty straightforward doesn't it?
Well I'm going to delve into that for just a moment
This is the basic equipment that you need to conduct a rodent experiment on earth
This is a standard Mouse cage blown up here the scientists can sit in the chair and observe the animals
And one thing if you look at this you can see in fact that
You know this is pretty straightforward with gravity how this works the animals in the cage
and you know the water comes down and the waste falls into the bottom of the cage and you provide a
This orange thing in case you're curious is enrichment the animal plays and nests in this type of material
This is what you need to conduct an experiment on orbit
Not scaled to size
You need
habitats that will
manage the waste and provide the food and
In a way, that is not gravity dependent
You need to protect the cabin environment
and so you need systems and in which you handle the animals and transfer the animals in a controlled way and
You need a variety of kits and things to do all that in a safe
In a safe and productive way
So let's talk about the system that was developed
To accomplish that there are two hardware's that the animals live in the transport and the habitat
They look pretty similar on the outside, so I'm showing you this in a cutaway mode the animals live inside here
And this is a port that allows
It allows you to access two chambers both sides
To get into there's an airflow system through here that captures the waste
The there's also an animal access unit which is a simple
Glovebox type of arrangement that mates with either the transporter or the habitat
So that the crew can go in reach in and recover the animals
Placing them in a mouse transfer box because you can't take an animal and walk across you know walk across whoops all right
Walk across the room with it it needs always to be contained and it can be
Transferred in the mouse transfer box, and then we have too many kids to mention
this shows a view from the inside of
where the animals live
There are five mark the rim research one there are five animals per compartment to compartment
spur hardware system
you'll see grading on all sides that allows the animals to ambulate air float and trap the
To be collected in filters food. These are food bars
That are supplied continuously to the animal there's a water supply that is not gravity dependent for delivery
Which is you can't see from this picture?
Lighting we supply
Lights on lights off cycle the animals are most active in the dark cycle
as as you may already know and
And video cameras with infrared capability that allow us to monitor and observe the behavior of the animals so
Let's develop our concept of operations here, how are we going to get them up there and and and get our samples?
the animals are put in a transport Porter and delivered to Dragon or
Mounted in Dragon as a late load as a late payload
undergoes launch can be
In the case of rodent research one it was four days in transit before docking and the crew had
The it was scheduled and conducted the transfer operation
the animal access unit was attached the animals recovered and and
Placed into habitats where they lived for up to four as long as 33 days
making the longest stay in microgravity
37 days at the time at the termination of the experiment the animals were then transferred
into the microgravity science glovebox
Which had been prepared
And the animals were humanely euthanized and then tissues were retrieved and cover recovered
under specific conditions that made
sample analysis optimal
The samples were stowed and returned to earth
So that's the plan, but we don't get to the start yet
Because we have to make sure it all works before we go so we conducted extensive pre-flight testing
To show that the animals thrive in the hardware the operations work and the samples recovered as the crew would eventually do
Would be done so in a way that got the expected science outcome
So now all systems go we're in research one
There were two main aspects main objectives of read and research
one
one was validation this the goal of this was to demonstrate the capability to support the health of the animals in long duration of
Experiments this was achieved by evaluating all the key factors
Including animal health behavior and tissue results, which I'll be talking about in a moment
in addition
There were mice flown
For the national lab, which cases the Center for the Advancement of science and space manages
and a
Novartis
scientist
Planned this experiment where Murph one knockout mice. These again are mice that have a
Key, gene knocked out and are resistant to muscle wasting as well as control mice
were were flown
Here was our plan for sample retriever retrieval for validation we we were able to
Cases kindly shared samples with us, so we could work together to achieve our objectives
We recovered spleen liver also
preserved animals for measuring body weight after return to earth and also for conducting
post-flight tissue retrieval
So let me take a few minutes first now as we to start talking about how the experiment went to talk about behavioral
observations
Here are some qualitative observations that were made when animals first entered the habitat they very actively
Explored the compartments much like they would do they do routinely on earth when you transfer them from one cage to a novel cage
They are also observed eating drinking and grooming they groom both themselves and others while in the habitats and these are all again
considered normal behaviors of healthy mice
They were interesting to watch mice propelled themselves around the compartment in more than one way
Mostly by pulling along the cage with their four limbs although their hind limbs were used to a more limited extent
Also by floating from one location to another and remarkably
Resembling how crew ambulate around the cabin its time went on?
The mice move more more quickly around the compartment they train slated with ease through the open spaces, but they also
most often anchored themselves using their tails and paws a
Detailed behavioral analysis is now being in progress
So I'm going to talk to you about our initial results with the tissues first
I want to take a moment to explain the groups there were in fact four different groups to
To evaluate the responses that for a bit from the validation aspect of this flight
There was the space flight group and there were three controls, so as I pointed out to you
Changes occur rapidly over time with these animals because their lifespan is relatively short
So one independent variable in this design of a long-duration experiment is time
What are the changes that take place over time just due to aging and?
so for that we have what we call a basal group these animals were euthanized and tissues recovered at the time of launch from the
same group of animals that the flight animals came from
They were compared you can compare those results to though to those of animals that were
maintained in standard cages the way we normally do and we're an investigator in a lab in
Anywhere would do and and answer the question?
What is the effect of time as an independent variable on a given outcome?
What's the other variable here the other variable is cage
So the habitat is you can imagine nobody?
Does experiments in those habitats unless you're planning to go to space and in fact?
Changes in the environment of the animals can have very profound
consequences for
For basic physiological
And cellular responses and so we to facilitate future
investigators ability to evaluate whether the changes in their control groups could
Are due to the cage we include
We evaluate and compare this vivarium group in standard cages
The ground controls and the ground controls of the group of mice that are housed in
Identical cages to the flight they're also kept in an environmental chamber at Kennedy Space Center
that has the environment of
carbon dioxide
temperature and humidity matched to ambient conditions in the cabin on the space station
Because we want the main variable
In Khmer 'king the comparison between space flight and ground control animals to be space
and that is the final and
and
Key comparison
So this summarizes the results we've obtained to date. We have body weight and tissue weights from the
validation mice
The I'm not going to talk about the variable of time in cage in detail, but fortunately there were not
not huge differences which
yields a simpler
Analysis now we can in in the case of the spaceflight environment
We can simply compare the ground controls to the flight group and ask what were the direction of changes
Now one thing I've done. Here is I put in green
The changes or lack of changes that is new information
These are not changes that we observed in shorter duration Shuttle missions
they are different in direction from some of those experiments and
So going through them
sequentially
in
We saw no difference in body weights between the ground control and the flight nor compared to any of the other groups
There was an increase in liver mass there was no effect on
Adrenal gland now the adrenal gland is responsible for producing a principal stress hormone in the body in humans its cortisol in
mices corticosteroid and
previous short duration experiments on occasion observed
Hypertrophy or growth of the adrenal gland which can occur in response to a chronic stressor
So there was no effect of the space environment on the gland sighs
The thymus and the spleen are two glands that are involved in the immune response
We saw an increase
in mass shuttle missions have in mice have shown a decrease in short duration and
a decrease in spleen mass
Now what we did see that
It was consistent with previous missions is a decline in the salacious muscle mass and the soleus muscle is an antigravity
or postural muscle in the leg that atrophies in response to
Disuse or microgravity and that was a very consistent finding
What about the quality of our sample retrieved so?
We evaluated RNA
quality
recovered from the liver and the spleen and
looked at the looked at the
quantitative value of
Quality and we found from the flight animals as well as the ground controls that the quality was
Acceptable for even the most demanding of analyses RNA seek is a method that allows it to
Sequence all all of the transcripts RNA transcripts in a sample and is demanding for high RNA quality in fact
We've achieved that the analysis hasn't been complete nor has the liver enzyme activity
Analyses that are still in progress
but we achieved our goal of
Obtaining samples of adequate quality for applying these very demanding
Techniques
Now how can we expand our sound science outcome from?
From our original goals one way. We do that
Is through biospecimen sharing so when when we got the samples back from the station?
the project recovered 32 tissues
From 40 validation mice, which yielded more than 3,000 vials of tissues that are now being stored in the life sciences data arc
these are destined for
distribution through the biospecimen sharing program of space biology which includes our Russian colleagues at
At AI MBP, who've requested tissues in addition some of the tissues will go to the NASA. Gene lab project
which I'll talk about in a moment I
Just want to take one moment to describe
Describe the biospecimen sharing because it's been so successful in the past
The images show a team that went
Traveled to Russia to recover samples from the bio M one mission, and you can see from
From the outcome from previous flights. This is only a select group of
scientific manuscripts that came
Out of a single Shuttle experiment, how insight into multiple?
Systems can be derived from this type of approach, so I'm very excited about
about the future
For the samples coming out of rodent research one in addition
We provided liver samples to the gene lab project who who are
Processing these samples to analyze the the RNA transcripts
DNA modifications and
Protein profile in the samples in some detail and these samples and datasets will be made available
to the scientific community
So I'm going to take a moment to summarize now where we are so far with rodent research
The hardware and operations were performed successfully on orbit
We got it all the way through to sample returned
The mice thrive through 37 days in my microgravity some Annelle important analyses are still in progress
it's important to note the common indicators of stress were not observed in the animals such as a loss of body weight an
Increase in adrenal gland weight they were the same in all the groups
Also the preliminary findings on wet tissue masses
Contrasted sharply to findings from shuttle experiments, which were shorter in duration
also had other variables but
duration may be one of the key variables in
Defining those differences and with biospecimen sharing much more to come
So I would suggest
from these findings and
This is a hypothesis
not a conclusion that there are at least two phases of
Physiological changes that occur after entry into the spaceflight environment of course. We don't know yet how far they will progress
So I'm addressing the audience to think about and invite you to pose your own hypotheses that might explain such a thing
But one thing I'd like you to keep in mind as you think about this in the future this sort of diagrammatically
represents
The problem that's being posed with the magnitude of the response on the y-axis and time in space on the x-axis
Each of the colors represents a different
organ system response so the green may represent the vestibular response which occur to
microgravity, which occurs very rapidly the red may be
cardiovascular adaptations which
Improve over time and the and the blue may be another system that takes a longer time
So these various time dependencies need to be taken into account as you think about whether or not
Duration and space is a key variable
And might explain our results and help us design new spaceflight experiments
Maybe we'll get some insight from rodent research to that mission all our on-orbit the on-orbit activities have been completed
Completed for a rodent research - that's a casus mission that lasted 60 days so perhaps. What gets insight into that
So I'd like to wrap up now
with a couple concluding comments
To live in space I
Hopefully I've effectively shared with you that there are multiple challenges
To the human body that are posed by that environment and that many different physiological systems can be affected
And I believe the resulting complexity is such the consequences of these
Challenges and these responses are such
That it's virtually impossible to predict with certainty
What those consequences will be for human health for human reproduction over very long periods of time?
We believe that insight into those responses and mechanisms will improve our ability to predict and
Potentially mitigate make decisions about what we need to do to protect humans in space
Living in space and also that rodent research on the ISS
Will help us get there
I'll finish
Finish up with some acknowledgments this shows a very happy group of people after staying up all night
Talking the astronaut crew through some
Some difficult on-orbit operations in rodent research one, but of course there
They are a very small sample of the number of people who actually
Had a hand in in making have a hand in making rodent research work on station
It would vie with the number of people that showed up to break the Guinness Book of World
Records for dancing at the same place at the same time in Mexico City, but
but still
There are many important people who who can't be named here
And also I want to mention the inspiration that comes from the research lab that I work in the bone in signaling a lab
And I'm going to finish up here and leave up during the Q&A period first
Thank you very very much for listening so patiently
And also I'm going to leave this up in case you have interest in in
Following up on summit with some of these links and some aspects of what I've talked about today
So, thank you Ruth, we have a few minutes for questions if you have a question
Please line up on the microphone in the center of the aisle
Please be brief and no follow-up questions
Thank You
Ruth is this the first time that
mice have been in space for that 30-day duration that the longest one of the longest periods
One question sorry, I'll ask is what you're basically I'm just
Fascinated about what would happen with adaptation of those animals over that long period of time term it's a behavior interacting with feed systems
interacting with each other that kind of thing right well, so
There were two other flight experiments that
130 days the bayan mission was a 30 day mission and the mouse drawer system experiment was a 90 day mission that was flown once
The
You pose a good question about interacting over time and that is one of the reasons why we are performing a very careful
And quantitative behavioral analysis of the video collected from that mission
But I think we need more
Longer duration missions so we can capture a larger
Fraction of that total time in space
I
Was wondering if there were any plans to do partial gravity
simulations in space or on the ground like one-third
so so
JAXA the Japanese Space Agency is
Going to be is working on flying an experiment run an experiment now. Well where I do believe the plan is to
Completely replace the gravity vector, but the ability once the capability is developed for first centrifugation
Then it's possible to do partial gravity experiments, and there's there's a lot of interest in doing that in thinking about going to other planets
Would it be helpful to have a centrifuge too different, so you could tease out the effects of weightlessness versus radiation
Absolutely it would be great
Rufe there's more data on humans in space in terms of duration than there are in mice
Have you done anything to compare the mice results to data that you've gotten from humans?
That's a really good question because fundamentally if we want to extrapolate from the result the assumption of these studies is that they will?
Yield insight into humans, so that's a word as you can imagine the answer to that question is a work in progress
We there are limits to every model system
And as the you know in terms of going forward with the the new capability we have
that's going to be important be an important aspect to look at so a
Work in progress wouldn't follow on question and that is
Do you have a data that suggests where an end point would be I mean we know the endocrine system is damaged the muscles are
Problematic the skeleton has issues at what point would we decide well gee we can't do space. It's going to be too difficult
We're never going to be able to colonize space do you have a feeling after?
40 years of data collection
Well, I am not sure that I would answer that question that is a question. That's going to take more than rodent experiments to answer
It's an excellent question without a single end point, and I'm sorry I don't have a better answer for you
But I think that the answer to that question needs to take into consideration
Both our ability to extrapolate from the rodent experiments also
An understanding of when the changes that we observe
pass the bar from subclinical into clinical significance
And that's very important the human research program at NASA spends a lot of time
Reviewing that and and they've compiled
evidence books in all
related to all of the major identified risks to human health and
Part of that process the goal of that process is really to identify
When do you see a change?
That's acceptable and when do you pass into the paths into significant versus?
Very severe risk and so I would say there's a whole program devoted to answering that question
All right, please join me in thanking dr. Ruth Globus for an excellent seminar
You
