Astronauts, geese and realistic retinas

26 September 2019
Presented by Chris Smith.

BAR-HEADED GOOSE

A bar-headed goose

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This month, doctors doing U-turns: the medical practices without much evidence to prop them up, wind-tunnel experiments reveal how geese fly at extreme altitudes, why mating makes bees go blind, stress remodelling the brain's myelin, and what goes on during a stint aboard the International Space Station? Join Chris Smith for a look inside the latest papers in eLife...

In this episode

Gloved hand pushing plunger of filled syringe

00:33 - Clinical U-turns

When you go to see the doctor, do you ask them for the evidence behind their advice?

Clinical U-turns
Vinay Prasad, Oregon Health and Science University

When you go to see the doctor, and they advise a course of treatment, do you ask them for the evidence behind their advice? Or do you just swallow it, alongside the pills they prescribe? Most of us inherently trust the medical profession and assume that the therapy we receive has been rigorously evaluated. Sorry to burst that bubble, but that’s just not the case. The vast majority of medical treatments are not supported by high quality evidence at all, just a good story and a spattering of biological plausiblilty. Which is why this man managed to find nearly 400 examples of doctors doing U-turns when some routine and mainstream therapies were actually subjected to proper scrutiny...

SPEAKER: M1
When you go to see the doctor and they advise a course of treatment you ask them for the evidence behind their advice. Would you just swallow it alongside the pills they prescribe. Most of us inherently trust the medical profession and we assume that the therapy we receive has been rigorously evaluated. Well I'm sorry to burst that bubble but it's just not the case. The vast majority of medical treatments are not supported by high quality evidence at all. Just a good story and a smattering of biological plausibility which is why this man managed to find nearly 400 examples of doctors doing u turns when some routine and mainstream therapies were actually subjected to proper scrutiny.
SPEAKER: F1
Dr. Van I. I'm an associate professor of medicine here at the Oregon Health and Science University and in this paper I'm on a mission to identify low value and no value medical practices. Those are medical practices that offer no benefit to patients and only risks and costs.
SPEAKER: M2
So why would we dish out treatments like that for people.
SPEAKER: F1
I think doctors have long been seduced by medical practices that seem like they should help patients for which we don't have confirmatory studies documenting that they actually do help patients and some of the reason we're seduced by these practices is they make a whole heck of a lot of sense biologically. They have a strong plausibility for why they should help. And also we are motivated by our sense of optimism doctors want to be able to offer treatments to patients that benefit them. Finally I think one of the other incentives that drives this problem is the financial conflicts in biomedicine. Many people make a great deal of money from recommending practices that may or may not help patients and they might find it difficult to evaluate those practices rigorously or to abandon them when they fail.
SPEAKER: M2
So how did you go about finding these reversals where where people have done a U-turn on what appropriate therapy should be. And can you give us some examples of the sorts of things that you flushed out.
SPEAKER: F1
Yeah absolutely so we tackle this by a literature based review we picked three high impact medical journals and we surveyed 15 years of biomedical publications and we looked for randomized trials that tested and contradicted established medical practices or things we were doing but we didn't just stop there. We did a systematic review for every one of the topics that seemed like they might be reversals to make sure that the totality of the evidence really found that they didn't help patients. Some classic examples include the use of steroid injection for low back pain and spinal stenosis a number of randomized studies find that when you compare a steroid injection to a saltwater injection both groups get better. But the steroid injection group does not get additionally better it's a placebo effect. We found that using a popular catheter called a swan ganz catheter it can provide you information about the hormone dynamics in the heart. But that information doesn't leverage improved he alth outcomes for patients with shock. Another example that many listeners may be aware of is the use of stenting for chronic stable angina stenting for stable angina is a multi-billion dollar a year industry and it's often done with the hope or the expectation on the patient's side that will lower the risk of a heart attack and improve mortality. And we found randomised control trials contradict both of those claims.
SPEAKER: M2
Now is this physician led or actually is it pushy patients or is it both.
SPEAKER: F1
There's certainly a case in biomedicine that patients sometimes ask for medical practices that doctors may have ambivalence towards. But I think in the practices that we look at in this data set these were predominately developed curated recommended and extolled by physician bodies and physician groups. So it really is on the physician side. Doctors were optimistic that these were things that were gonna help our patients. Unfortunately in retrospect we turned out to be wrong.
SPEAKER: M2
When you were looking at these studies was there any obvious way in which this dogma got established incorrectly in the first place. Was there a sort of common pathway through which something inappropriate or ineffectual treatment actually gets established. Because that would be the point of intervention wouldn't it. The way in which we can prevent this happening if we know how it tends to happen.
SPEAKER: F1
Yes. I mean I think the commonality here is that all of these practices got established based on weak low or quasi experimental evidence. By that I mean by traditional hierarchies of evidence we typically put randomized controlled trials at the pinnacle of evidence based pyramids and at the bottom we put case reports uncontrolled observational studies historically controlled studies or studies with poor control arms and in almost all of these cases. What drove a practice to prominence were those sorts of lesser evidence studies that are not adequately designed to test whether or not an intervention is better than the best available therapy of the time. I think this has been one of the major challenges in the movement of evidence based medicine which is that now 30 plus years into this movement many of us had felt that the standards of adoption of medical practice would have improved over time.
SPEAKER: M2
But some of us have been disappointed that they haven't improved that fast and we still have this enthusiasm for low levels of evidence for expensive though isn't it the kind of that you're seeking and that you feel comfortable with to accept a treatment works you're asking for spends in the millions in order to establish that evidence base very often aren't you. And that's just not feasible. When a treatment is just getting going so there's got to be a start somewhere.
SPEAKER: F1
I think that's a great question. One of the things is is that if you look at the average cost to enroll a patient on a randomized trial in the United States you might get a lofty figure like 20 to 30000 U.S. dollars at the same time. We have randomized registry trials that are done for as little as 50 dollars per participant. That's a randomized study called taste. I think it's interesting to me that randomization something that essentially is cheap and easy has a tremendous price tag largely because of the imposed bureaucracy of randomized trials. We hear a lot about innovation. One of the major things an innovator could do in the space of randomized trials is make them cheap and easy to deploy and that is something that's within our power we've done it before with this taste study and we can expand that model I think to other domains. And the other side of the question is some of these products for which we're not doing randomized trials. They're not cheap either. They often cost a hundred thousand dollars per year of therapy and they have cumulative health care spending in the billions of dollars. Sometimes it might make more sense to run a 20 million dollar randomized trial than spend 500 million dollars per annum on reimbursing a product that you don't know actually helps patients.
SPEAKER: M2
I mean that's a good point and I can't dispute that. But the fact is it's who spends that money because when the government spends it to establish evidence and then they find that the treatment doesn't work they'll say well that's money that we've wasted. But when patients and insurance companies spend money in an in an insurance led system like the US for example actually the loss is someone else's. It's not government money it's not public money. So actually that might bias the situation.
SPEAKER: F1
I 100 percent agree with you that many people in the health care space are thinking about their short term profits and revenues and there is sort of a tragedy of the commons going on here. But we have to remember that even in our system in the United States and of course in your system in United Kingdom the majority of health care expenditures are indirectly or directly borne by public payers. The largest payment the largest source of payments in this country is the Center for Medicare and Medicaid Services. And to a large degree private insurance in United States have been subsidized through governmental agencies through the subsidies we have for private health care insurance. And so to some degree we all pay for medical practices that are practiced and borne out of insufficient evidence.
SPEAKER: M1
Makes you think doesn't it. Van I preset that.

Bar-headed goslings

08:06 - How geese fly so high

From sea level to 8 kilometres up in hours: how do geese do it?

How geese fly so high
Jessica Meir, NASA

One of nature’s marvels is the annual migration of millions of birds. And among them are the bar-headed geese that routinely fly over the Himalayas. But how do they cope with an ascent from near sea level to extreme altitude and back down again in just a matter of hours? To find out, Jessica Mier, who’s both a physiologist and a NASA astronaut, developed a way to simulate their migration in a wind tunnel…

Jessica - These birds migrate annually over the Himalayas flying regularly between 5000 and 6000 metres through those passes. And of course the bar headed goose is quite famous for these early anecdotal reports where early explorers climbing the Himalayas say that they heard and saw a bar headed geese in the distance. So perhaps they're even flying as high as over the summits of the very highest mountains above 8000 metres. At these altitudes, the oxygen level is significantly lower than it is at sea level. So at these altitudes around 5000 6000 metres we're talking only half the amount of oxygen available when we start talking as high as the summits of the Himalayas. That is closer to only about one third of the levels that we have here at sea level.

Chris - And of course humans do go to those sorts of altitudes but they do it often with supplemental oxygen and they do it with enormous amounts of adaptation. First they don't just go straight to the top of Everest they go via base camp and so on and spend weeks acclimatising. And these animals are effectively doing this straight off the bat.

Jessica - That's exactly right. And to me that is one of the most interesting points. These birds cross from sea level in India over the Himalayas and only about seven to eight hours completely contrary to what you just mentioned as humans taking weeks in order to acclimatise.

Chris - So how did you explore how they're not just flying at these tremendous altitudes but doing it without this acclimatise Asian period, that if we were to do that we would be dead.

Jessica - We decided we needed a very controlled setting and we needed the birds to be very comfortable with the experimenters and comfortable with the equipment. So our idea was to fly these birds in a wind tunnel, measure things like heart rate things like how much oxygen they use how much carbon dioxide they produce and even measure the level of oxygen and the temperature in their blood vessels while they were flying. We wanted to do this not only in normal oxygen levels but also the reduced oxygen levels when they were at altitude flying over the Himalayas.

Jessica - We made a mask for the birds out of a thin sheet of plastic that we can form fit over the beat to collect exhaled air so we can know how much oxygen the birds use how much carbon dioxide they produce. The other thing that the mask allowed us to do would then allow us to reduce the overall amount of oxygen that the birds were breathing. We also had a little backpack recorder system that had heart rate electrodes so we could get EKG electrocardiogram. And then also in indwelling oxygen electrode that measured oxygen and also temperature in the arteries and the veins.

Chris - And when you do all this what actually emerged what was the pattern that you saw in these birds.

Jessica - Flying for birds is the most expensive form of locomotion for any vertebrate species. So we knew there was gonna be a big increase in metabolic rate and also there would be an increase in heart rate. So that of course makes sense it's extreme exercise. What we didn't know was how it would change between these normal oxygen levels and the reduced oxygen levels. And interestingly as we thought metabolic rate did increase during the flight it went up about 16 times compared to rest. And what we found was that increase was associated with an estimated amount in the amount of oxygen that was transported per each heartbeat with only a very modest increase in heart rate.

Jessica - So these geese appeared to have a lot of extra leeway in terms of their cardiac reserves what we think of as how much the heart can pump. The heart rate in those reduced oxygen conditions it was not any higher than in the normal exec the normal oxygen levels. So although there was an increase of course from a resting condition to a flying condition the heart rate was the same whether or not the oxygen level was normal or the reduced oxygen. The difference that we found between the two different conditions flight in the reduced oxygen level was achieved through a reduction in metabolic rate.

Jessica - So that means that the geese were actually using less oxygen in those flights and the lower oxygen conditions than they were in the flights with the normal oxygen conditions.

Chris - Have you any idea how they are doing this how are they registering this change and therefore knowing to keep their heart rate under control and how are they shifting their metabolism like that and doing it so quickly.

Jessica - We don't know for sure the answer to that question but we have some hypotheses. First of all the geese could be minimizing Oxygen required for other processes that are less essential during the flight. The gut of certain migratory species decreases in size a little bit before a long distance migration. This is also something that we see in diving animals. They will drastically change their blood flow, change what else is going on during a particularly long dive in order to preserve oxygen for critical organs like the heart and brain. Another thing that could be going on is that the birds are just simply adopting more efficient flight patterns and we did see some differences that basically made the geese fly a little bit more efficiently with the up stroke and the down stroke during flight.

Chris - Regardless though of behavioural changes and how the animals move, the tissues in the animals and specifically those really metabolically active tissues like the nervous system they're going to be seeing in these animals a sudden drop in oxygen, aren't they. Do we have any idea as to how the birds defend against that. Because if you did that to a person it would almost instantly result in a stroke?

Jessica - Right. So what we did see was that the arterial oxygen level was actually maintained throughout the flights. So overall there was a decrease when the animal had less oxygen on board but it was still maintained throughout the flight, so it didn't seem to be dropping to too critical of a level. The venous oxygen actually decreased during the initial portion of the flights.

Jessica - And that sort of shows us that the birds are continuing to extract more oxygen for those exercising tissues where they needed it.

Jessica - The other interesting finding that went along with this was that the temperature in the veins actually decreased during the flight. This is interesting because it can mean that there is significantly more oxygen in the blood hemoglobin, the protein that binds oxygen in the blood. When it's cooler the hemoglobin can actually hold on to more oxygen in the blood. So if you have a decrease in temperature there you can actually load and bind more oxygen at that site, meaning the bird could actually have more oxygen in their blood than they would otherwise if the temperatures were higher.

Chris - And it's not just the geese that are flying high you'll hopefully going to be doing this soon as well, aren't you?

Jessica - Yes that's right. In just less than three weeks I will be launching for a six month mission aboard the International Space Station. So the tables have turned. Now it is my turn to be the one poking and prodding for the Advancement of Science.

Mouse

15:33 - Stress and myelin structure

What role does the brain's white matter play in depression and anxiety?

Stress and myelin structure
Jia Liu, City University New York (CUNY)

Studies into depression and social anxiety have tended to dwell on what the neurones in the brain are doing. But that ignores over 75% of the cells in the nervous system! These are the glia, and they include cells called oligodendrocytes that make the brain’s white matter - or myelin - which invests and nourishes nerve fibres. And the structure of this myelin turns out to be critical to how the brain works and how it defends us against stress. By exposing mice to bullying from more dominant animals, City University New York (CUNY) scientist Jia Liu finds that 60% of them become socially withdrawn in the aftermath, and this is reflected in changes to the myelin pattern in discrete parts of the brain…

SPEAKER: M1
Studies into depression and social anxiety have tended to dwell on what the neurones in the brain are doing. But that ignores over 75 percent of the cells in the nervous system. These are the clear and they include cells called although dangerous sites that make the brain's white matter or myelin which invests and nourishes nerve fibres and the structure of this myelin turns out to be critical to how the brain works and how it defends us against stress. By exposing mice to bullying from more dominant animals Jill Lu finds that 60 percent of them become socially withdrawn in the aftermath. And this is reflected in changes to the myelin pattern in discrete parts of the brain.
SPEAKER: F1
We look at the brain particularly now neuronal cells and the reason is that the current literature has been heavily focused on the role of neurons and we're trying to tackle this problem from a different perspective. The other itself types in the brain we particularly look at one type of glial cells called the illegal gun site which produces a protective coating layer called the myelin. This myelin allows neurons to better and more efficiently communicate with each other. And although the undersized also provide nutrition and energy to maintain the house of this nerve fibers and what did you look throughout the brain or did you focus on any particular areas we particularly focused on two brain area and one is named medial prefrontal cortex and that is the area of the brain which plays a critical role in emotion and thinking and the other region. We also look at is the nucleus accumbens which is involved in the reward response and specifically where look at the number of other dangero us sites. In this two brain regions as well as the property of the Miley in this two brain regions the first thing we find is we see fewer number of mature older Denver sites and the thinner and shorter segments of Miley in the susceptible mouse that display the social avoidance but we only find this in the prefrontal cortex but not in the nucleus accumbens will be further investigated by inducing damage to Miley specifically in the prefrontal cortex. We find this damage was sufficient to impair the social behavior and also when the mailing was restored the social behavior was also restored. Therefore we think Miley is also contributing to why there are different behavior after particular social stress.
SPEAKER: M2
Why do you think that that hypo Miley nation in the prefrontal cortex causes or manifests as a change in social behavior. Why should it do that.
SPEAKER: F1
We don't directly know the answer to that. What we think is that although the Denver site is the cells that produce this myelin layer which is known to help the neurons to better and more efficiently communicating with each other a proper brain function or proper behavior output such as social interaction will rely on proper communication between multiple brain regions and such kind of communication can be manipulated or regulated depending on how the nerve signal propagate from one region to another and such kind of propagation especially for example in a medial perfect cortex which connects so many area of the brain can be regulated due to this different property of the myelin.
SPEAKER: M2
So how do you think then that the myelin gets changed in this way because your inputs are behavioral and social ones and it's manifest as a structural change not so much in the neurons but in the cells that support them.
SPEAKER: F1
So how do you think the message gets from the nerve circuits onto the audio to anthracite as a matter of fact although the donor side also expresses molecules which uses the same type of signal that neurons use to communicate therefore they're able to receive signals from the neurons to regulate their own molecular properties.
SPEAKER: M2
So do you think then and I'm speculating wildly I'm being highly provocative with my suggestion that if we look at humans who become depressed. Do you think that at least a fraction of those could well be that there is not so much a neurochemical imbalance in the brain but there might be a disruption albeit temporary in the myelin architecture of the brain and that perhaps some of the therapeutic effect of these drugs would give people is to help the brain actually to re myelin eight in a more healthy way.
SPEAKER: F1
I would be happily supporting that. Actually there has been association studies looking at post-mortem tissues from depressive disorder patients and showed that there are differences in the white matter content and what we're hoping to emphasize is that while the current treatment for depression or other psychiatric conditions will target neuronal cell function perhaps we should also look at other cell types in the brain as the potential cars for stress related mental disorders.
SPEAKER: M1
JetBlue from City University New York.

Queen bee fitted with an RFID tracker

21:39 - Mating makes queen bees blind

Male bees resort to chemicals to blind females and reduce sexual competition...

Mating makes queen bees blind
Joanito Liberti, University of Lausanne

In nature, when a female mates with multiple males, this introduces competition between the sperm and a conflict between the sexes: the males “want” to transmit their genes to the greatest number of offspring, while the females “want” to maximise the genetic diversity - and hence fitness - of their brood. And among insects, a range of tricks and techniques are used to load the odds in favour of one sex over the other. But honey bees have taken this to a whole new level, as Joanito Liberti has been finding…

SPEAKER: M1
In nature when a female meets with multiple males this introduces competition between the sperm and a conflict between the sexes. The males want to transmit their genes to the greatest number of offspring while the females want to maximize the genetic diversity and hence the fitness of their brood about insects. A range of tricks and techniques are used to lower the odds in favor of one sex over the other but honeybees have taken this to a whole new level as UNESCO liberty has been finding when a honeybee Queen meets chemicals found in the Seminole fleet of males affect the vision of the Queen.
SPEAKER: M2
And this is potentially a manipulation that the males are imposing on the female to reduce possibility of meeting with other males because only b queens have to fly out of their hive and find congregations where the males are waiting for her to mate. So the vision is very important.
SPEAKER: M1
Tell us how the story began then. How did you actually embark on this journey.
SPEAKER: M2
During my P H D I was interested in the effects of the reproductive secretions of the sexes and how they regulate the conflicts incorporation within and between the sexes. As part of these we looked at what are the specific effects of seminal fluid on the female vision. So we set out to do an experiment in which we artificially inseminated the queens and specifically looked at what happened in the brain after these insemination.
SPEAKER: M3
When a B actually mate tell us a bit about that process about how the queen finds a mate or mates and what happens during that all social insects have a very special meeting biology in which the Queens fly out to mate only on a single day early in adult life they meet with males in the air and then they come back to their hive or they find they have found a new nest and after that they will never ever have sex in their life. And sometimes the life of a social insect can extend for one or two decades and they use the sperm that they collected on the single day to fertilize all the eggs throughout their lifetime. So they have to keep this sperm alive for many many years. Now the honeybee is special in all of these because she conducts potentially multiple mating flights over a few days and that's where the potential for sexual conflict arises because older populations up and one after the other because she flies on multiple consecutive days the sperm that have already inseminated the q ueen may not want the Queen to fly out again and dilute the chances that this sperm will actually end up being stored.
SPEAKER: M1
How did you hit on the visual system as being the key to this then. How did you realise that that was what was potentially going on.
SPEAKER: M2
He analysed gene expression data where we compared quints that were inseminated with a saline solution as a control and other queens were given seminal fluid and what I realized is that there were some genes related to vision that were different in their expression.
SPEAKER: M1
How did you pursue that and how did you resolve that difference and work out that it is something in the seminal fluid that then affects the visual system of the female and how do you know it actually affects the visual system. In other words renders her less visually able.
SPEAKER: M2
So from these gene expression data we predicted that there would be effects on vision because genes were altered but of course gene expression is not enough to demonstrate that something is actually happening to the vision. So we performed an other experiment where we put little electrodes on top of the eyes of the queens and then we stimulated the vision with flashes of light and recorded the electrical signal and basically found that Queens that had received seminal fluid from male could respond less to stimuli which showed that something was truly happening to the visual perception of Queens.
SPEAKER: M1
How do you know though that that change translates into a reduction in inclination on the part of that Queen to go mate with more males.
SPEAKER: M2
We could measure the cost of these effects right. We put little tags on the Queens and then monitor their flight activity after we again used the same artificial insemination the queens that had received seminal fluid compared to the Queens that only received a saline solution. We're more likely to get lost so we assume that impaired visual perception will reduce the possibility of the Queen to actually find throne congregations and meet with them India.
SPEAKER: M1
Do you know yet what the chemicals are in the seminal fluid that are doing this or do you just know that seminal fluid as a whole does this.
SPEAKER: M3
We know what the composition of the seminal fluid of the honeybee is. So we know what proteins are present in the fluid but we do not know yet which ones are responsible and it will be exciting in the future to try to identify the specific compounds mediating these effects.
SPEAKER: M1
It will indeed. You only told about Berti that he's at the University of Lausanne.

Human eye

26:55 - Realistic retina in a dish

Microfluidic culture and a retinal pigment epithelium produce a retinal organoid

Realistic retina in a dish
Christopher Probst, Fraunhofer Institute, Stuttgart; Kevin Achberger, Neuroanatomy Institute, Tubingen

The human retina contains hundreds of millions of cells organised in very specific ways and with intimate three dimensional relationships with other cells and structures in the eye. This complexity has made studying the retina - and retinal diseases - a major challenge in the past. But now Christopher Probst, from the Fraunhofer Institute, Stuttgart, and Kevin Achberger, at the Neuroanatomy Institute, Tubingen, think they’ve cracked it. They’ve developed a microfluidic three-dimensional system that - critically - also incorporates the retinal pigment epithelium layer present at the back of the eye. The result is mini-retina “organoids” in dishes that much more closely resemble the real thing. Kevin Achberger first...

SPEAKER: M1
The human retina contains hundreds of millions of cells organized in very specific ways and with intimate three dimensional relationships with other cells and structures in the eye. This complexity has made studying the retina and retinal diseases a major challenge in the past. But now Christopher Probst from the front of four institutes took God and Kevin Berger at the neuro anatomy Institute chimp again. Think they've cracked it. They've developed a micro fluid Dick three dimensional system which critically also incorporates the retinal pigment epithelium layer present at the back of the eye. The result is Mini Retina organize in dishes that much more close to resemble the real thing. Kevin.
SPEAKER: M2
In the past people were mainly using animals and there are a lot of ethical concerns around them and it can just not really reflect the human biology and that's why you need new human models. And the only way you can do that is using in vitro experiments. So with cell culture and have really astonishing model which you can use are organize tissues which can be derived from stem cells and on the retina they are the so-called retina overnights which are beautiful preform tissues which can be used for analyzing drugs and diseases.
SPEAKER: M1
But do they faithfully represent what the Retina looks like as the retina is pretty complicated in terms of its structure it's got lots of layers.
SPEAKER: M2
Yeah that's actually the amazing part about these organizers that can really structure in layers. They can form the cells which are the light sensitive cells. And what we found in experiments that there are even light sensitive you put on light and they will react to it.
SPEAKER: M1
Sir Christopher if we can already make these organized IDs what was left to be done. What did you do that added value here.
SPEAKER: M3
So what added while you're here was we added further cell type into basically a polymer based ship with channels where you can flush in cells and cultured them so keep them alive. And by combining is organized and these further cell type India we got better functionality what has not been possible in these conventional organized models and what was the additional cell type that you were able to bring to the party. So these are the so-called retinal pigmented epithelium cells which interactive these light sensitive cells to photo receptors to keep them alive and to really have these functionality between these two because in a real retina in an animal and even in a human that retinal pigment epithelium layer would be at the back of the eye and the photo receptors the rods and cones would nuzzle up against it wouldn't it.
SPEAKER: M1
And the two have an important conversation because the retinal pigment epithelium keeps the retina healthy and it recycles various components and cleans up debris. Exactly yes. And so why was that not included in previous attempts to recreate retina in dishes.
SPEAKER: M4
So maybe I can come in. So the thing is that in the normal retina organize the pigment the themes cells are present however they are not coming into the natural state of interaction so they are not in the right positioning just due to the culture method itself. And what we did is we really positioned them in in this architecture of the organ on a chip in a way that they can face each other and they can interact with each other.
SPEAKER: M1
And when you do this Christopher what difference does it make to the function of the retina that you grow in the dish.
SPEAKER: M3
So basically we see the photoreceptors growing towards this RPE retinal pigment a perfume layer which are on the bottom of this organized chip system and which is really astonishing you just see that when underside would organize faces to these retinal pigment and the feel themselves and not to the other side. So we already see that we have an attraction after photo receptors to the IP and what we can also see which is really a stunning thing is that photoreceptors segments are taken up so recycled by the retinal pigmented Buffett himself.
SPEAKER: M5
And Kevin does this mean we've actually got something that much more faithfully reproduces what you would see a knife now then yeah I think so because we have really some aspects of the retinal biology which we're not yet possible. What Chris mentioned the father site tells us of parts of the photoreceptors which is an extremely important process and this will actually be also one of our future targets to really look in detail how this process is going on.
SPEAKER: M6
Obviously one very powerful opportunity offered by this is that one could not just study health but also disease an arguably understanding how to put a disease right is understanding why that disease occurs in the first place so could you take this model and actually make it unwell.
SPEAKER: M4
Yeah exactly we can do this and this is actually one of the next steps we want take the beauty about the model is that these organizers can be generated virtually from every person saw of a healthy person or a disease affected person.
SPEAKER: M5
So the next step will be to take also cells from a person suffering for example from retinitis pigmentosa and just see what will be the differences in our model and this really might help us to find out what was really going on in these patients.
SPEAKER: M1
Presumably Chris that means you can accelerate the process of drug development.
SPEAKER: M3
Yes exactly. And this is one of the great possibilities of organ on a chip technology that we shrink these models to really small scale and integrate human cells human tissue in. And that could potentially affect how we can better transfer data from preclinical research into clinic and also speeding up the process of drug development and seeing maybe things which might get lost in a standard animal model.
SPEAKER: M6
What we have seen in the past obviously preventing disease is one major priorities. It's it's easier probably to do that than to let someone become unwell and then fix things later. But there are a significant number of people who have retinal diseases where they've already got significant pathology so Kevin one therapeutic strategy is to put new cells into a disease retina so they can repair and replace what's been lost. Could you use your model to investigate whether that's feasible.
SPEAKER: M5
In principle yes. I mean there's not only cell replacement therapies but there are also gene replacement therapies for example. So the model itself is really versatile and can be applied for any kind of clinical question.
SPEAKER: M1
Very exciting development Kevin burger and Christopher Propst their.

Astronaut and physiologist Jessica Meir

Life on the International Space Station
Jessica Meir, NASA

On 25th September, Jessica Meir blasted into space and she’s now in orbit 400 kilometres above us, and travelling about 27,000 kilometres per hour. So why’s she up there…?

Jessica - We are participating in a wide variety of experiments so everything from how microgravity and the spaceflight environment affect the human body. There are some specific hard issues that we're looking at right now in terms of the health of astronauts' eyes. We're seeing some vision changes in astronauts that are coming back that we need to make sure we have a good understanding for, when we start thinking about the future of space exploration. We have some evidence now that the arteries of astronauts are actually thickening in spaceflight. Even in a six month mission we have about the equivalent of 20 to 30 years of aging here on the ground. So a pretty significant increase and we need to understand more about that mechanism as well.

Chris - So what you're saying is you're going to come back looking 30 years older, with the arterial tree of someone in their 70s - and possibly in need of new eyes - but other than that, it's going to be fine!

Jessica - [Laughs] - Hopefully it won't be quite that extreme, but of course the benefit of researching these things is to make things better for the future. And those are just a few examples of those physiology studies of course. My interest really lies there. But we are doing things like combustion experiments - even flames burn differently in space. As you can imagine, if we can eliminate any of these gravity driven effects that we would have here on earth constantly when we're doing any experiment, we might expose a whole new world of other factors that might otherwise be masked. So everything from human physiology to combustion experiments, to protein crystal growth, we can we can grow more pure and bigger protein crystals on the space station. So that has actually led to the development of drugs for things like Duchenne muscular dystrophy; and more recently we are looking at Alzheimer's and Parkinson's. The Japanese space agency even has a drug in development in clinical trials for Duchenne's muscular dystrophy, based on that space station protein crystal growth research.  Some of the other work in the combustion facility will help us hopefully improve fuel economy processes here on earth, and also we'll look toward engines and fuel systems for future spacecraft.

And when we're on the space station we're also doing a lot of routine and maintenance and repair: the space station's actually getting a little bit old now - it's about 20 years old. So as you can imagine, if a light bulb needs to be changed or we have to fix the toilet, we can't just call a plumber or electrician. We have to do all that ourselves. So it's part of the routine operations that we're doing up there. We go for spacewalks as well. Any time we need to upgrade a system or if we need to conduct some kind of unanticipated repair that has to be done on the outside of the space station we put the spacesuit on and have to go work out there for the day. So one of the things that I really like about the job as an astronaut is that it is very active and very diverse doing something different every day.

Chris - Was this always an aspiration of yours: I'm very good at doing this on Earth, but, actually, there are some questions I can answer even better in space...?

Jessica - So I just applied to become an astronaut since it was a dream of mine since I was five years old. And, luckily, I think some of my experiences working with the physiology of organisms in extreme environments like the Antarctic or with these bar-headed geese helped them see that perhaps my background - my diversity as a human - would be pretty useful in the space environment as well.

Chris - And given that you've alluded to the fact that we are aware of all these health impacts of periods in space, are you concerned about that?

Jessica - Personally no... I... It is really just part of the job. You know I think the way that I've approached my research in the past, as well, without risk you truly don't have a reward. And I know safety is always the number one concern. So the protocols that we have in place at NASA and even the health and medical requirements are really designed to make sure that we stay safe that we still maintain our health and come back as healthy individuals with with a lot more lifetime to live. So no, I don't really think about that part.

Chris -  And how is your Russian, because that was the thing that many people are quite surprised to learn that you have to become extremely good at Russia because it isn't a lot of the control materials only written in Russian?

Jessica -  Yes, so the International Space Station is not just American NASA astronauts; we are up there with the Russian cosmonauts and then also the European, Japanese and Canadian astronauts. Those are all the international partners for the space station programme. There are two official languages on the space station and those are English and Russian. So everybody up there has to be competent in both languages. We like to describe it as a little bit of "Runglish" that really gets used most of the time. For over the past year and a half I've been over here off and on in Star City, the cosmonaut training centre outside of Moscow, and I've been learning to be the co-pilot of the Soyuz spacecraft. That's what I'll be launching in. And all of that training is actually in Russian. Pretty interesting to learn how to not only be a co-pilot, given my background, certainly not in that field, but learn how to be a co-pilot in Russian! It has been an absolutely incredible experience.

Chris - And would you like to sign off for us now. With a little bit of Russian just to prove that you've really mastered it?

Jessica -  Sure. I might need a second though of thinking about what would be a good way...

Chris - Can you say "live long and prosper!"

Jessica - [Laughs] - Not without looking that up... I can say [speaks in Russian]... So I basically said "be happy and until the space station!"

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