Welcome back to The Nature Podcast.
This week, the heated debate surrounding a tyrannosaur-like dinosaur.
And a breast cancer prevention therapy shows promise.
I'm Benjamin Thompson.
And I'm Sharmini Bundell.
First up, a debate 65 million years in the making.
Is a controversial Cretaceous dinosaur a young T-Rex, or is it a completely different species?
Paleontologists have been arguing about this for some time, but now new research in nature may finally end the debate.
The paper details a new examination of a fossil of a dinosaur dubbed Nanotyrannus.
This diminutive dinosaur was about five and a half metres long, about the same as a big car, and weighed about as much as a large cow almost 700 kilograms, so pretty hefty, but still about 10 times smaller than the enormous Tyrannosaurus rex.
For decades, paleontologists have suggested that the few nanotyrannous fossils that had been found were simply juvenile T rexes not yet fully grown.
Now the authors of this paper say that some newly examined nanotyrannous limb bones could reveal whether or not it would have grown up to become a T rex or simply stayed small as its own separate species.
I caught up with paleontologist Lawrence Whitmer, who's been writing a News & Views article about the new paper to dig into the details.
When he answered the video call, I was greeted by a room filled with dinosaur skulls.
In fact, Larry was already holding one.
So I asked him a clarifying question.
I think it'd be fair to say that you're a dinosaur fan.
Yeah, I've been a dinosaur fan since I was a little kid and had the opportunity to have my dreams come true that I'm actually a professor of dinosaurs as well.
So every little kid's dream, I was privileged enough to actually live out.
And paleontology, very serious science, but not without its controversies.
Would you say that paleontologists like a good argument?
I think people like a good argument.
And paleontologists are people too.
And when you care deeply about something, when you have deeply held views, you tend to hold on to them.
As scientists, one of the big difference though is we need evidence to support those views.
And as a result, that's sort of where we get into some of the controversies and the debate.
The idea is actually evaluating evidence.
And we sometimes get conflicting pieces of evidence.
And the sort of exciting thing about paleontology is that if we're willing to wait long enough, somebody's gonna find something.
Somebody's gonna find a new fossil that'll help us resolve the debate or send the debate off in a crazy new direction.
That happens too.
So the story we're going to be talking about today is certainly one that's been sort of a long time brewing.
Maybe you can take us right back to the start and tell us where did this story start?
So this debate about Tyrannosaurs really started with this specimen that I'm holding right now, which is a cast of a specimen that was found in the 1940s and published as a new species of an existing kind of tyrannosaur called Gorgosaurus.
But then in 1988 a new group of scientists came along and said wait a second, this actually is not Gorgosaurus.
It's actually its own thing.
And they renamed this Nanotyrannus, a whole different kind of dinosaur.
That really wasn't like anything else.
The kicker is that Nanotyrannus was found in the famous Hell Creek Mountains, formation just like Tyrannosaurus rex.
And so the question then became well, are these really a separate species Nanotyrannus, or are they actually juveniles, youngsters of T rex?
The kicker had been that we hadn't really any well-acknowledged specimens of baby T rex or young T rex.
And so folks were saying, well, how about these?
These are found in the same rocks.
Maybe these would have grown up to be T. rex.
What is this magical fossil that's been missing this whole time?
Sort of the game changer was a fossil that was found actually a number of years ago.
Was found by private collectors.
What's amazing about this one specimen is that it's beautiful and virtually complete.
And they were actually able to age this specimen.
They had limb bones that they could slice through and look at cross sections and actually age it based on the rings within the bone.
And what that showed was pretty, pretty exciting, because what it showed was that that specimen was basically an adult.
It wasn't quite done with growing.
So it was a young adult, but it was actually pretty close to stopping growth.
And so basically, that animal basically would never grow up to be the size of Tyrannosaurus rex.
Actually, the animal would grow up to be one tenth the size of Tyrannosaurus rex.
And you were pretty convinced by the evidence that was set forth in this new paper describing this new fossil.
What do you think some of the points of contention around that might be?
Yeah, I mean we published on this skull 15 years ago and we're criticize a little bit because we were a little wishy-washy about whether this was supported.
Nanotyrannus or juvenile T rex.
The expectation now is that people will actually really start to evaluate that evidence.
This new specimen that is reported part of the dueling dinosaurs, a very famous find that was found a number of years ago.
That specimen is now in a sense out in the open And other scientists can come study it and we can evaluate the evidence.
And we'll now look at these other specimens in new light.
And hopefully some of these other specimens that are out there may actually come out of the shadows.
There's lots of Tyrannosaur specimens that have actually been found by private collectors and commercial collectors.
And they're not really in museums.
And it's difficult for us scientists to actually study them or know too much about them.
They're not really sort of normal specimens, scientific specimens in museums that we can study.
So hopefully many more of those will come to light as well.
And that's been one of the impediments of this debate is that so many specimens that are relevant to this debate weren't really available to scientists.
They're important specimens, but we haven't been able to subject them to proper scientific study.
This new specimen was in that category too, except now it's in a museum and now we can study that specimen and let it speak, contribute and maybe even resolve this longstanding debate.
And can I ask you, sort of you personally, what did you feel when you saw that paper?
Yeah, when I saw the paper, I was, you know, sort of hoping and waiting for this study to come.
And what really struck me about the work they did was how careful they were, how conservative they were.
One of the things that's sort of a human subtext with their study is that they are not among the usual suspects.
These are not people that have been really vocal parts of this debate.
They had no access to ground.
They basically said, here's this fossil, let's see what it tells us.
But their study was outstanding, was very meticulous.
They knew that people were going to be very concerned about their new specimen and whether it was really a near adult or was it really a juvenile that could have maybe grown 10 times larger, to be as big as T rex.
And so All of their work was very careful.
They looked at the evolutionary relationships and really made some interesting hypotheses about what that means for the broader evolution of the group as well.
And so for a relatively short study, they actually covered a lot of ground, which is going to give the scientific community a lot to chew on.
That was Lawrence Whitmer from the Ohio University College of Osteopathic Medicine in the US.
And you can head over to the show notes to find a link to Lawrence's news and views article and a short video I made.
Coming up, how blocking a specific hormone could play an important role in preventing breast cancer.
Right now, though, it's time for the research highlights with Dan Fox.
A new hormone, artificial neuron, could help scientists to build computers inspired by the human brain.
Computing systems that mimic biological neural networks are the basis for many AI applications.
But these synthetic neural networks typically consume a lot more energy than their biological counterparts, because conventional electronics are less efficient than nerve cells.
One solution could be to construct artificial neurons using electronic devices known as diffusive memristors.
To demonstrate this approach, the team behind this research built an artificial neuron from a diffusive memristor, a resistor and a transistor.
This artificial neuron shared characteristics with biological neurons, and future versions could be more energy efficient than a neuron from a human brain.
A simulated neural network based on these devices reached a computational accuracy of 91, comparable with that of the current leading artificial neural networks.
Read that paper in full in Nature Electronics.
Large predators typically seek large prey while, by contrast, small predators usually graze on small animals that are abundant and easy to catch like insects.
But some bat species this trend instead going after vertebrates closer to their own size, such as frogs or birds.
To understand how these bats were hunting such big prey, given the limited amount of energy they can store in their small bodies, researchers fitted 20 wild fringe-lipped bats with tags that recorded sound and movement to spy on their hunts.
They found that the bats are incredibly efficient hunters.
Spending just 11 of the night on the wing.
They typically hang and wait, locate prey with sound, then ambush them with a fatal swoop, succeeding half the time.
But this strategy works best in areas where small vertebrates are abundant, suggesting the expert hunters might not fare well in the disturbed habitats of a world reshaped by human activity.
Swoop on that research in Current Biology.
Next up, a preventative treatment for breast cancer shows promise in a small trial.
Reporter Nick Petridge-Howe has the story.
Breast cancer is the leading cause of death by cancer in women globally.
And for women aged 35 to 64 in the UK, it's the most common cause of death altogether.
Prevention of this devastating disease is key.
For those particularly at risk, if they have a genetic predisposition or family history, for example, there are some preventative measures available.
But they're pretty invasive.
At the moment, they would need to either have two options, either surgery, mastectomy, or long-term hormone therapy with anti-estrogens.
But both of these options have an impact both, of course, on their physical well-being if they go for surgery, or also cancer side effects that are associated with anti-estrogens that are given to prevent breast cancer.
This is Bruno Simoes, a researcher who has been looking for alternative ways to counter breast cancer.
One avenue that has shown promise is looking at a hormone involved in pregnancy and the menstrual cycle progesterone.
We know that progesterone, which is a natural hormone, can drive the growth of certain breast cells that have the potential to turn into cancer.
So basically, we wanted to see if blocking progesterone signaling could reduce the risk of breast cancer.
Previous research has shown that progesterone is linked to the growth of cells that can become cancerous, in both mice and humans.
Synthetic progesterone progestin, which is given as a contraceptive, has also been associated with a higher risk of breast cancer.
So Bruno and his colleagues wondered if they could block it.
What we did was to use an anti-progestin called olipristal acetate, which is already approved for other conditions.
And we gave it then to the women that were at increased risk of breast cancer.
In a trial with 24 premenopausal women, Bruno and the team administered an antiprogestin known as elicitil acetate over 12 weeks.
And in this week's Nature, they described the results.
Now, they didn't look at breast cancer incidence itself, but instead assessed the breast tissue for the telltale signs that the risk of cancer had changed.
For instance, they assessed the tissue density, which is a measure of how much fibrous and glandular tissue there is compared to fat, and the stiffness of the breast tissue, as denser and stiffer tissue is associated with a higher risk of cancer.
And we saw that their breast tissue became less dense and less stiff.
And also the number of cells that could give rise to cancer decreased with this treatment.
So overall, these were all signs that breast was becoming a less favorable environment for the cancer to develop.
The team also looked at the specific proteins involved to try and discern how this therapy was having its effects.
So we did observe this reduction on these cells that are normally the ones that give rise to breast cancer, but we also observed dramatic changes in the breast tissue.
So we found that this antiprocessing treatment was reducing the number and the function of certain collagen proteins that normally help support the breast tissue.
And one of the proteins in particular was collagen six, and this was the one that was most decreased after treatment.
So we are now exploring if this protein can directly influence the behaviour of these cells that normally give rise to breast cancer, called luminal progenitor cells.
Collagen 6 has previously been associated with the aggressiveness of other kinds of cancer, but in breast cancer not much is known about its role.
Bruno believes though, that these results showed that this protein could be a promising avenue for research.
Kalinda Schreiler, a breast cancer researcher who wasn't involved in this new study, thinks that this work shows the promise of such anti-progestin treatments.
It's really the first proof of concept that this could potentially also have a role or have an effect in female population.
To her.
One of the strengths of the study was that it showed a link between changes to the cells and the breast density.
This is something that could be relatively easily measured to help assess the effectiveness of the treatment.
Such measures have been quite difficult to find.
However, she does caution that we're still some way from being able to know if this could prevent breast cancer altogether.
Now to really show that this anti-progestin treatment could indeed prevent cancer, you need bigger trials and also the duration needs to be much, much longer than just 12 weeks.
But this takes time and also it takes a lot of money, of course, to be able to set this up, but I definitely think this study is really promising and I hope there will be follow-ups.
Bruno and the team are keen to work towards larger trials, as they think this work opens the door to an effective way to reduce breast cancer risk without having to surgically remove breast tissue.
Ulipristal acetate.
The treatment they used is already approved for use as an emergency contraceptive and as a medicine for fibrous growths on the uterus, so it could be rolled out quicker than a brand new drug.
However, more needs to be done to understand how best to administer this anti-progestin.
We would need further studies to analyse this on the long term.
So, for the moment, what we can say is that, because we know that progesterone plays a key role in stimulating these breast cells that can become cancerous cells, we know that by blocking its action we can target the root biological processes that drive breast cancer, rather than just treating it after it appears.
But we don't know for how long.
So we get this drug for three months and we don't know for how long we will need to keep the treatment to maintain the reduction of their risk.
So we would need to do further studies in the future to test that.
Ultimately, Bruno is excited about the potential of this treatment and what it could mean for people at risk of breast cancer.
Overall, it was exciting. incredibly rewarding to see these results.
So we've been studying how hormones influence breast cancer for many years.
So to finally be able to see that there was clear evidence that blocking progesterone could actually make the breast less likely to develop big cancers, it feels amazing.
Also, of course, knowing that this could one day help women avoid going through the trauma of breast cancer.
You know, that's also amazing.
And that's what really drives us and our work.
That was Bruno Simois from Manchester University here in the UK.
You also heard from Kalinda Scheler from KU Leuven in Belgium.
For more on that story, check out the show notes for some links.
Finally on the show, it's time for the briefing chat where we discuss a couple of articles from the Nature Briefing.
And I'm going to go first this week.
And it's some really exciting news about using CRISPR to treat genetic conditions.
And this is a clinical trial that's been described in the American Journal of Human Genetics that is hoping to begin next year and change the way that people are using gene editing therapy to treat certain conditions.
Right, which has long been the hope for this technology.
And there's been a lot of progress in this area, but still more to come.
Yeah, and this is kind of off the back of a really big development in this area, which was a baby that was born with a really severe genetic condition that was treated very successfully using this gene editing.
And this was last year, and it was this big Almost collaboration because they needed so many people around the world, different scientists,
They needed support from US government funders and regulatory agencies.
There was a lot of people coming together and that baby is doing really well.
They were able to do a few rounds of this gene therapy and reduce the number of medicines that this baby has to take for a very serious liver condition.
And now the same sort of team behind that say we want to do it again faster.
So what they did last year was basically a record-breaking six months to get this personalized gene therapy for this one baby, and now they want to open this up to other babies, other people with these conditions, and get that time down so that they could make personalized treatments in maybe three or four months, because i imagine that speed is of the essence for many of these conditions, and getting it down would make a big difference.
I mean, how are they going about then?
What halving the time that it took previously?
Well, having done it for the first time, they now can see all the steps involved, all the problems, all the potential barriers.
And so they're working off that to improve the whole system.
So a key thing about this is that, of course, it's personalised, right?
So you've got a treatment that is specifically designed for one individual.
So this individual might have a specific genetic mutation and then you're making a sort of CRISPR treatment that is really specific to that individual particular mutation.
So this isn't something that we're looking at.
Hey, here's a treatment, we're going to get this signed off and it can treat a whole bunch of people, and it seems like there's the making it, the creating of the therapy, but there's also the sign off, because thus far you have to get different, separate approval for each separate treatment, And the US Food and Drug Administration, the FDA, would usually require separate clinical trials, separate safety tests.
But in this case the doctors and researchers have been talking to the FDA, have been going back and forth with them.
And now they think that it's possible that the FDA could accept some of the safety data from this treatment and apply that to future treatments, so that you don't have to go through completely separate trials processes for each possible treatment.
Which clearly, as you're saying, there then does a up a lot of the time from drawing board to putting this treatment in someone's arm.
What are folks saying about all this then?
So one of the researchers working on this said that personalised treatments are definitely the direction we need to steer towards.
And they said this technology could be more than a game changer.
It could be revolutionary.
Another researcher said that this is a textbook example of a rising tide that lifts all boats, because this team are also sharing their correspondence with the FDA to serve as a model for other researchers, so that people can see how they did it and then again hopefully, do it again.
So a lot of discussions of what the framework might be.
How long until this comes? sort of thing is put into practice?
Well, they've got plans for a clinical trial that will start next year, and even to have reached this point of this clinical trial, they've actually already spent months negotiating with US regulators on ways to simplify the usual convoluted path that a gene editing therapy would normally take before it can even enter trials.
So they're at a good place and hopefully next year they will be able to put into practice developing therapies for some children with rare diseases.
Well, it's rare that we talk about regulatory stuff.
But of course, here we are with CRISPR moving forward.
And these are conversations that need to be had in terms of the best way to develop treatments and, as I say, get them into the folk that need them.
So we'll keep an eye on that one, of course, Sharmilee.
But let's move on to my story this week, Sharmilee.
Now, we, of course, do a lot of talking as part of our job.
Vocal cords are very important to us.
I try and do a warm-up before each show.
I often get teased about it by members of the team.
He does.
And of course, we try and avoid them getting damaged.
But for a lot of people, damage to their vocal cords does happen, maybe after undergoing surgery to remove cysts or growths from their vocal cords, for example.
And folk can have trouble speaking because they're scarring to the folds in these vocal cords or they can become stiff, that sort of thing.
Now studies have shown that using hydrogels, these networks of polymers containing lots of liquid can help heal people vocal cords right.
They can be shaped to mimic their natural structure and support tissue growth, right?
They can really help the healing process.
But getting them into the right place can be tough for surgeons, of course, because there's not a huge amount of room right?
Like it's quite a restricted area.
And that's where my story comes in this week.
Researchers have developed a new device, a 3D bioprinter that they call the world's smallest, that can get into vocal cords, and they've got a paper about it in the journal Device.
Wow, okay.
So I've got to admit, when you say vocal cords, my mind goes to those cartoons where the vocal cords are basically like a harp and possibly there's some sort of cartoon animal strumming them and they're in your throat somewhere.
But can you give me a quick anatomy catch-up?
Where are we talking about here?
So our vocal cords are in our larynx, sort of the top of our airway, and they're quite a complex structure right, lots of layers of different tissue, we've got muscle, we've got ligaments, all that sort of stuff and, as i say, it's not the biggest space to work in, and so the folk behind this work then have turned to 3d printing technology.
Now bioprinters can be used to layer up things like cells, or also things like polymers and ceramics that are biocompatible.
And there's a quote in this article that says bioprinting typically addresses skin defects from the outside.
Reaching a defect internally has been a challenge in the field.
So what's happened here is they've developed this bioprinter that can get into the larynx and print things onto the vocal cords.
So they want to put a printer down someone's throat and have it fix your vocal cords from the inside.
Whereabouts are they on doing this?
Well, this is early work, but i think it shows promise, and the team behind it actually shall we.
They took inspiration from the animal world when they made their little machine, specifically elephants trunks.
Okay, now they've designed a soft, robotic arm that moves like a trunk and can get into the tight spaces without blocking a surgeon's view, which is, of course really, really important.
Now, they first made a prototype that was eight millimeters in diameter and That was too big.
So they shrunk it down to make it fit more easily through the one centimeter wide scope that surgeons use looking down the throat.
And apparently this miniaturization is what's taken all the time.
So their current version is 2.7 millimeters wide, and it has this tiny, tiny printhead at the end.
And they've shown that it could be used to deliver dollops of a type of hydrogel very accurately into gaps in artificial vocal cords.
Now, these are used in surgical training.
That's like a surgical dummy.
And what's brilliant is this little robot on the printer is controlled by a PlayStation controller.
Is it actually?
Yeah, apparently.
And you asked, you know, how far along is it?
The team are hoping to move towards clinical trials.
And they would like to program it, they say, with images of the surgical site so they can maybe get it to independently go where it needs to go, follow a specific pathway and say, squirt this hydrogel into the place that can do the most damage, healing.
And they're also interested in whether it could be used in other processes too, not necessarily just for vocal cord repair.
Could they attach things like scalpels to the end or maybe forceps?
Because the idea of this system is that it can kind of reach into places that are difficult to work.
And of course, scalpels are quite large things.
So if they could shrink it all down and get it in there, it could allow for more precision work.
So that's super tiny.
And I guess the precision is then really key, because this little device is is able to be really precisely controlled with this PlayStation controller.
That's certainly the hope, but there is a ways to go yet.
Someone quoted in the article says, you know, there are questions about testing, of course.
Now, typically, before human trials take place, animal trials are done.
And working out how to shrink this device even smaller so it could fit into an animal is going to be difficult challenge, but it's one of those interesting stories where researchers have looked at the animal kingdom and said okay, this is cool, we've got a problem, how can we solve it?
And and have come up with this rather interesting device.
Well, i always love it when there's some animal inspiration for things, especially some interesting soft robotics and medical applications like this.
That's great.
Thank you ben, and listeners for more on those stories.
We're going to put a link where you can sign up to the nature briefing and you can get stories like those straight into your inbox.
And that's all we've got time for this week.
If you'd like to get in touch with us, you can do so on X or Blue Sky.
We're at Nature Podcast.
Or you can send an email to podcast at nature.com.
I'm Benjamin Thompson.
And I'm Sharmini Bundel.
Thanks for listening.
