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Hello and welcome to Open Science.
I’m Dr. Marshall Porterfield, and today we will be discussing the impact of sex and
gender on adaptation to space.
Joining me today in this discussion, a distinguished panel: Dr. Graham Scott, to my left, from
the National Space Biomedical Research Institute; NASA’s senior medical advisor, Dr. Saralyn
Mark; and from the Human Exploration and Mission Operations Directorate, Dr. Bette Siegel.
Now that--together, as a team, you’ve been working with other investigators to study
and better understand the role of impact of sex and gender in space flight adaptation.
So, what are some of the key findings from your studies, just off the top?
Firstly, Marshall, let me say that both women and men do very well in space.
Having said that, we do see some differences--some of these are very subtle and others are more
pronounced.
For example, the majority of the astronauts are now having some visual impairment issues.
Most--in most cases, these are mild, really, just involving a change in the prescription
that an astronaut might need in her or his eyeglasses, you know, one to two months, let’s
say, into the mission.
But, in a minority of cases, maybe in about 20% of the cases, we’re seeing more significant
issues with the eyes, and these could involve changes in, actually, the shape of the eyes
that don’t even fully resolve when the astronauts return to Earth.
And we’re seeing these more pathological changes.
We’re seeing those only in the male astronauts.
The other area where there are some quite significant differences is in the ability
of our male and our female astronauts to spend time in space, and this is due to the radiation
limits that NASA imposes on the astronauts.
So, our female astronauts can spend significantly fewer days in space because, based on ground
studies and based on data that’s been collected over several decades, it’s been prognosticated
that the female astronauts are more susceptible to cancer.
And NASA has set a very strict limit of only having a 3% increased risk of cancer due to
time in space over the course of an astronaut’s lifetime.
So, there’s a couple of examples of where we do see some significant differences in
how our male and our female astronauts are adapted to space flight.
We also see interesting findings in the cardiovascular realm, generally, women who respond to stress
with an increase of heartrate.
Men tend to respond by clamping down their vessels primarily due to hormones such as
testosterone that causes that vasoconstriction, that closing down of the blood vessel to maintain
blood pressure.
We see with many of our women, female astronauts returning that they may experience what we
call orthostatic hypotension.
And what that means is a drop in blood pressure, which puts them at risk for fainting.
And it’s primarily due, we believe, to these changes in volume as well as how we respond
to stress.
Men and women respond differently in their vasculature.
What we did is we looked at things that we see here on Earth and tried to see if we would
see them in space.
So, we know, on Earth, we usually see women, especially as they get older, developing osteoporosis.
Their bones lose calcium.
But, when we looked at the data to see what we would see in space, we actually didn’t
see a gender effect.
We didn’t see a difference between the male and female.
It was all over the place, basically.
Yeah, and what Bette’s alluding to is that there are a lot of personal differences.
So, we’re now living in this era of precision medicine, and what we see is that there are
very individualized responses to the space flight environment.
To add onto what Bette’s saying, some people actually come back with increased muscle mass
relative to the muscle mass that they had when they left to go up onto the International
Space Station for six months, and others come back with somewhat less muscle mass or bone
mass.
So, there are real opportunities to tailor countermeasures to each astronaut and really
invoke this whole new approach of personalized medicine to really make everyone’s stay
in space as healthy and as productive as possible.
What we saw--and we had six work groups looking at how the human body adapts to space.
So, those work groups included cardiovascular, neurosensory, reproductive, immunological,
behavioral, and certainly, reproductive has been traditionally what we viewed, but we
went even well beyond that, and then, of course, musculoskeletal.
And we found difference throughout the body.
Now, the question is, is it statistically significant?
That may not be as much an issue in regard to how does that translate to what we see
clinically?
I think what’s exciting is, as we’re increasing our numbers of women flying, we’ll have
a better database.
We’ll be able to assess.
But, we have to keep in mind we’re not looking at who’s faster, who’s better, who’s
smarter, who’s better able to adapt.
What we’re doing is trying to understand what we’re seeing so that we can develop
the appropriate countermeasures, develop the appropriate equipment so that we can keep
both men and women healthy in space and when they return to Earth.
And that’s really a very important point because for our future exploration missions
are going to be men and women, and so we need to make sure.
We need to study it so that we know that the countermeasure to these changes that we see
in space are going to both protect men and women, both while they’re in space and when
they return to Earth.
Very good.
It’s a really fascinating area.
And I noticed, though, in the title of your primary publication that recently came out,
you made the distinction of sex and gender, using that term.
Can you explain to the audience why that’s important to make that distinction?
So, the institute of medicine has defined sex as your biology.
Are you male or are you female?
And gender is the way you respond in society, and so we don’t mean necessarily if someone’s
gay or not.
What we’re really looking at is, perhaps, because you might be a female, maybe you’re
getting the same medical care that you might get if you were male.
And so, for example, on Earth, when people have a heart attack, we know these symptoms.
You might have crushing pain in your chest and shooting down your arms, but that’s
really what men experience.
Women, very often, experience fatigue, or they may experience feeling an upset stomach,
nauseous, or something.
And so, when they go to the doctor, someone may not check them out that see if they’re
having a heart attack.
So, in our papers, that’s how we use the word gender.
And, actually, after a while, the definitions started to blend together more.
And then, I just want to follow up on that.
When the Institute of Medicine released the report in 2001 entitled Does Sex Matter?
looking at the biological contributions to health, they were very clear on how they define
sex and gender--again, the psychosocial construct implying gender, the biological chromosomal
implying sex--as we’ve evolved into the world of precision medicine, as we’ve evolved
into a world where we understand the influence in genetics or human genome on our health,
we’ve come into a space that we call epigenetics, and that certainly influences how we live
our lives.
So, in a sense, as Bette has alluded to, the definition, the delineation between sex and
gender has become more of a continuum.
But, we felt, for the nature of this paper, we wanted to be a little more clear-cut, acknowledging
that the environment influences the genome, and the genome influences the environment.
Very good.
So, the data--the body of data that you used for your study included both ground-based
and space flight-based research.
How does your study benefit us back on Earth in terms of our medical technologies?
I think space is a fantastic platform to study how the body adapts.
I’m a geriatrician endocrinologist, so I see it as a model for, in a sense, accelerated
aging.
The body adapts to space, and it adapts in a way that is appropriate.
The question is can the body readapt back to Earth, and can we reverse some of the findings
so that we can keep people healthy in space and, certainly, when they return to Earth?
I think what we have seen is that, as we just alluded to, that there are changes in every
system of the body.
So, for example, we mentioned osteoporosis.
Osteoporosis is a state of low bone mineral density as well as what we call microarchitectural
deterioration meaning that the structure of the bone can be impaired, and that puts you
at risk for developing fractures.
On Earth, 80% of those afflicted tend to be women, and they’re at high risk, certainly,
for developing fractures, and men tend to develop osteoporosis and fractures later on
in life.
So, as we study how the body adapts, how bones adapt, how muscles adapt to space, we can
learn appropriately how to prevent bone loss and how to mitigate against that, and we can
take those lessons and imply what we need to keep people healthy on Earth.
We see it, really, in every system of the body.
One of my other particular interesting favorites to study is how the body adapts from an immunological
perspective.
We know, on Earth, women are more resistant to infection.
But, when they do get infected, they amount very robust responses.
When women are pregnant, they lose that resistance, of course, so that they don’t reject their
fetus.
In space, we know we have changes in the immune system.
There’s an altered immune expression to microbes, to bacteria, to, really, everything
that you’re experiencing in your environment.
And we want to see.
Are we going to find those same findings in space as we do on Earth?
And, if so, how can we change that so people can stay healthy in space?
Again, every system of the body changes and it has significant relevance to how we age
and stay healthy here on this planet.
I think space medicine can also be translated to Earth in a couple of other contexts.
So, one is in the radiation area, so increasingly now, the leading cancer hospitals are using
particle therapy - proton therapy, and in some parts of the world, using carbon ions.
And these are the types of particles, actually, that are impacting our astronauts, that are
potentially causing damage in their cells and to their chromosomes.
And so, by studying the effect of space radiation on our astronauts, we may, actually, also,
in parallel, gain some insights to the effect of this particle therapy that is now being
therapeutically applied to patients here on Earth.
The other thing that I think is interesting is that space--the space environment is the
ultimate stressful environment in terms of the human body.
The human body has not evolved to, necessarily, to live in space, but yet, we can live there
very nicely.
So, given that this is a stressful environment, I think that the way the body adjusts both
at a molecular level and also at a physiological level can actually give us some really deep
insights into how much stress we can actually endure as a species and what actually happens
as we go through those stressful situations, again, in terms of our molecular responses
and our physiological responses.
So, just so that we have a better idea of the scope of the work that you’ve accomplished
in this study, over what time period was the data that you used collected, and what are
we talking about in terms of population of subjects, astronauts?
So, we looked at the data from 1998 to about 2013 because that’s when we finished our
study, but actually, there were studies and reports done that were even prior to 1998.
So, we were looking at the shuttle astronauts and the astronauts that were on space station.
This included the U.S. astronauts as well as the astronauts of the partners.
And, at that time, during that time period, when you looked at the total number of astronauts,
women were about 20% of the astronaut core.
The good thing is we’re moving in the right direction as the last astronaut selection
was eight astronauts - four men and four women.
And the reason that’s important to us is, as a scientist, I want to see things that
are statistically significant.
And, in order to do that, you have to increase the N. And so, if we fly more women, we can
study more women, and then we can make sure that the countermeasures we’re developing
will protect their health and the men’s health as well.
And I think what makes this program, what we develop, this study exciting is that it
was a collaborative effort.
We had six work groups.
We had over 50 scientists working across the country.
Not only did we develop the manuscripts, but we also had a virtual workshop so that we
could share our information with the general public.
And it was very much a collaborative effort and, hopefully, an ongoing effort.
As Bette has alluded to, we are, every day, gathering new data both from our academic
partners and, certainly, within NASA and our other agencies that we work with so that we
can better ascertain sex and gender differences so, again, that we can develop the appropriate
products, and policies, and programs to take care of our astronauts on Earth and when they
return to space.
Obviously, this is an important new study.
It has importance and significance in terms of how we plan and operate the Human Research
Program in the future.
How have you been working with the Human Research Program and conducting this study, and what
are your recommendations?
Yeah.
So, the Human Research Program has taken a really strong interest in this study.
And, as Dr. Mark just mentioned, a number of the investigators that were authors on
the various paper that were published, they’re actually funded, in many cases, by the Human
Research Program.
So, there are a lot of touch points.
A number of the aspects, in fact, the majority of the aspects that were looked at in terms
of musculoskeletal health or cardiovascular health, these impinged directly on some of
the major risks that the Human Research Program is seeking to mitigate, to close technology
gaps, and to develop countermeasures for.
So, I mentioned earlier in the conversation this visual impairment issue.
This is the number one risk to human health in lieu with all that.
And so the Human Research Program is keenly interested in better understanding this visual
impairment issue - how to fix women, how to fix men, why there appear to be some differences.
That could actually really give us a clue to what’s going on at a molecular or at
a physiological level.
Why are no women currently having these more clinically significant symptoms?
That could actually be a big clue in terms of solving the underlying mechanism of what’s
causing this visual impairment, and then, ultimately, leading to a countermeasure.
So, absolutely, the Human Research Program and the organization that I work for, the
National Space Biomedical Research Institute, we’re very much involved in architecting
and participating in the study.
And now, the flow on effect is that there’s an increasing impetus to involve roughly equal
numbers of males and females in Human Research Program and NSBRI funded studies.
Now, it isn’t possible in every single case, but there’s a real ground swell, if you
will.
And this has been seen in solicitation documents as well to really try to get, as Dr. Siegel
said, enough female and enough male subjects that you can really start to look for these
trends.
And then, ultimately, the goal is to build countermeasures for our females and for our
male astronauts, and also to develop these again, going back to what I said earlier,
for--on a personalized basis and on an individualized basis.
So we had--oh, I’m sorry.
We had six teams, basically, and I just wanted to say, in each team had a chair and a co-chair.
And the chair usually was a NASA expert meaning they’re NASA or NSBRI.
So, there were people from HRP, and then the co-chair would be someone who had an expertise
in sex and gender research.
And then, the team members were about six to ten people, and they were, again, divided
up like that.
I just want to follow up when we talk about how do we assess the data?
Traditionally, we have used statistical significance as being the ultimate goal, the gold standard.
What we have learned from the national institutes of health who’ve implemented a policy since
1993 through their NIH revitalization act, that they needed to include male and female
subjects in their studies unless there is a particular reason why they should not be,
that you don’t actually need statistical significance to determine value.
They’ve moved into a space that we call valid analysis.
Dr. Scott has mentioned trends, and we can learn a lot from that.
I think it helps our researchers to know that they don’t have to have exorbitant numbers.
It doesn’t have to be financially draining, but they do have to have sufficient numbers
so that we can do the valid analysis.
We’re also moving into a time where we’re looking at preclinical, so meaning we can
study what happens in the cell culture as well as animal studies to give us insight.
We look at ground-based studies, what happens here on Earth.
We also have flight-based studies.
We work with animals.
We work, of course, with humans.
And, I think, when you look at the compendium data from both those environments and all
the various study subjects, you can make a best assessment of how the human body and
the animal body adapts and what we need to do to keep people healthy.
So, it’s well aware the agency has a goal of performing a human mission to Mars at some
point.
What are your recommendations from your study with regards to Mars architecture for human
exploration?
We had five robust recommendations, and if you were to drill down, the bottom line is
we need to include more women and more men to fly and to conduct experiments both on
Earth and in space, and that sex and gender is incorporated into all our experiments and
what we do.
And that will certainly influence, again, the policies that we draw up, the products
that we need to have so people can live in space, the educational programs that we need
to provide to our astronauts and to the people that work with them to ensure that everyone
has the best opportunity to live and work safely and with quality in space and on Earth.
I want to take the opportunity to thank you all for joining me today.
This is really a fascinating topic, and it’s very important to the agency and to the future
goals of the agency.
So, thank you very much for your hard work, and good day.
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