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  • NATURE PODCAST

Podcast: Fake antibodies, cell diversity in tumours, and the devlopment of Earth's crust

This week, fake antibodies scupper research, the diversity of cells in a tumour, and what happened before tectonic plates?

In this episode:

01:18 Fake antibodies

Counterfeit antibodies are messing up some experiments in China. Feature: The secret war against counterfeit science

07:41 Creation of the crust

How the Earth turned from one big magma ocean to the planet we live on today. Research paper: Rozel et al.

13:02 Podcast survey

Help us improve the Nature Podcast by letting us know who you are. Podcast survey

13:24 Research Highlights

Printing without ink; and marijuana and memory. Research Highlight: Pictures printed without ink; Research Highlight: Marijuana memory boost for old mice

14:55 Dangerous science stats

An update on last week’s stories. Health and Safety in the Fieldwork of North American Anthropologists; Naturalists who died in the field

15:46 Cancerous complexity

The structure within tumours. Research paper: Tammela et al.; Research paper: Lim et al.; News & Views: Tumours build their niche

21:20 News Chat

The National Institutes of Health thinks about how it hands out its money; and testing the best violins. News: NIH grant limits rile biomedical research community; News: NIH to limit the amount of grant money a scientist can receive; News: Science can only tell us so much about Stradivarius violins

Never miss an episode: Subscribe to the Nature Podcast on Apple Podcasts, Google Podcasts, Spotify or your favourite podcast app. Head here for the Nature Podcast RSS feed.

doi: https://doi.org/10.1038/d41586-019-03095-1

Transcript

This week, fake antibodies scupper research, the diversity of cells in a tumour, and what happened before tectonic plates?

[Jingle]

Interviewer: Adam Levy

Hello listeners and welcome back to the Nature Podcast. As you might have noticed, we’ve had a little musical refresh. We reckon it reflects how we feel about science: multilayered but always exciting and fresh.

Interviewer: Kerri Smith

Don’t worry – the rest of the show is just how you like it: the best science from the last seven days.

Interviewer: Adam Levy

This week we’re taking a look at fake antibodies scuppering research in China. So, how do you spot a counterfeit reagent? And what’s China doing about the problem?

Interviewer: Kerri Smith

Cancers would be easier to treat if all their cells were the same, but that’s definitely not the case for lung cancers, at least.

Interviewer: Adam Levy

Plus, what happened before tectonic plates? A lot of swirling magma and spurting volcanoes, that’s what. This is the Nature Podcastfor May the 11th, 2017. I’m Adam Levy.

Interviewer: Kerri Smith

And I’m Kerri Smith.

[Jingle]

Interviewer: Kerri Smith

You name it, someone in China has faked it: Prada handbags; coffee from ‘Sunbucks’; Apple iPhones, even entire Apple stores.

Interviewee: David Cyranoski

I can walk out of my apartment and walk down my street and I can find watches, bags, DVDs.

Interviewer: Kerri Smith

This is David Cyranoski, Asia Pacific correspondent for Nature, based in Shanghai, China.

Interviewee: David Cyranoski

There’s not a lot of effort to crack down on this stuff.

Interviewer: Kerri Smith

The same is apparently true in science. Companies are selling counterfeit reagents: products for use in experiments like antibodies or serums, and scientists are finding out months, or even years later when their experiments keep failing or can’t be repeated. It figures that China would be a target for these fakes. There’s a lot of money going into research so plenty of scientists to sell them to. The real reagents have to be imported, which means a delay while they get through customs. And foreign companies rely on local distributors to sell their wares: a system where fakes can easily leak in. David Cyranoski has written a feature about the problem. I first asked him how common it is. It’s hard to get an estimate of how widespread it is. Partly because a lot of people don’t want to talk about it. For researchers – some reasons that I heard is that they are just embarrassed by it but also they’re afraid that if people knew they were using counterfeit products, they might start to doubt their previous results.

Interviewer: Kerri Smith

Are they good, these counterfeits? They must be if scientists can’t actually tell the difference between the ones they’re buying and real ones.

Interviewee: David Cyranoski

There are different kinds and some of them – sometimes they might just take a real product and then dilute it and scientists would normally dilute some of these products anyway, so, instead of diluting it in one in five hundred times, they’re diluting it one in a thousand times without knowing it. And that might not affect the experiment but if the dilution gets to a level where you don’t have any of the reagent left, or you don’t have enough to pass a critical threshold, then you would get no response and your experiment wouldn’t go well. There are other things like there’s a lot of counterfeit antibodies, and if you have a counterfeit antibody and it’s targeting the wrong protein, your experiment is not going to work, and not only is it not going to work, it might give you a false positive result. You might end up finding that you’ve targeted something, thinking that it’s the thing you were looking for and neither you nor anyone else can reproduce your results.

Interviewer: Kerri Smith

It did cross my mind that even though reproducibility and not being able to replicate other people’s results is a global problem in science – that there are certain high profile papers that have come out in recent months and years from China that haven’t been able to be reproduced. I supposed we’d be speculating if we tried to work out whether those were subject to this problem.

Interviewee: David Cyranoski

Yeah, I have heard sometimes, people whose papers are being questioned, or their papers are being challenged now on the grounds of reproducibility and in a few cases they’ve taken the defence that, well maybe it’s just bad reagents. It could be a convenient excuse for people. It could also be the real reason people are having trouble because there were people that I talked to that published a paper and then couldn’t reproduce it. They found out that it was just a bad reagent, a counterfeit reagent that was to blame.

Interviewer: Kerri Smith

Are the companies themselves trying to do anything about this?

Interviewee: David Cyranoski

The companies themselves, yeah, they’re very aware of the problem and they do different things. One is to get online or to have seminars, manuals, how to differentiate between a good product and a bad product. Something else they do is to make specialised bottles, or make specialised labels that are hard to replicate. That was one of the stories that caught my attention for this actually because they had a cleaning woman that was going through the trash cans at this institute in Beijing and she was taking out these bottles and one of the researchers said ‘what are you doing?’ and he was afraid that she was going to take them home to drink from them or mix juice in or something and she said there was someone outside who comes here and pays me 40rmb, so about 5 or 6 dollars or something like that, to give them these bottles. So the company’s measure was working but the counterfeiters were finding a way around it.

Interviewer: Kerri Smith

Do you have any reason to believe this could be happening outside of China?

Interviewee: David Cyranoski

No, some people that used Chinese products outside of China have been affected. They bought products from a Chinese company and have expected.

Interviewer: Kerri Smith

For scientists listening to this who might be affected, because we do have quite a lot of downloads in China, and perhaps some of our listeners are practising scientists, what would be your advice to them? How do they get around this problem if they think they’ve been affected or they want to avoid being affected?

Interviewee: David Cyranoski

I guess the biggest thing is to go to reputable sources for your reagents and validate all your biological reagents before you start your experiments to know that it’s really testing for what they want it to test for and to note to go back to these reagents you’re using. When an experiment doesn’t work, know that that’s one possibility. I guess what surprised me the most was that there wasn’t more push back using legal measures by some of the people who had been duped. If I were a researcher and I had wasted 6 months or a year using something that someone sold me just so they could make a hundred dollars or something like that, I would be angry. I would be pissed off so I would probably go and try to find the police and get them shut down. There wasn’t much of that.

Interviewer: Kerri Smith

That was our Asia Pacific correspondent David Cyranoski. To find out more about the counterfeit reagent market in Asia, I highly recommend his feature which is online now at nature.com/news. Stay tuned for the Research Highlights featuring inkless printing and elderly mice on marijuana, that’s after a look at the earth in its infancy.

Interviewer: Adam Levy

Pretty much every school kid has a mental picture of the structure of the earth. At its centre is the core, made mostly of molten iron. On top of this is a wide band of rock called the mantle. On the surface of the mantle is the crust. That’s where we all live. Plate tectonics keep things moving: creating and destroying crusts where two plates meet. But the earth hasn’t always looked like this. When it first formed about 4 and a half billion years ago the earth would probably have been one big magma ocean. So how did the earth transform from this liquid fireball to a planet with a cool crust and plate tectonics? A study out this week has built a model to help search for an answer. I called Antoine Rozel who led the study to find out why it’s proven such a tricky question to answer.

Interviewee: Antoine Rozel

Strictly because, the oldest rocks we see are about 3.7 or 3.8 billion years old. There are very few pf these rocks. That’s the big problem we have: how to go from this early stage to the present day picture we have.

Interviewer: Adam Levy

So what’s the suggestion of what could have been happening to the early earth before we get to the stage of plate tectonics?

Interviewee: Antoine Rozel

There is no clear consensus what was happening because there is very little data. But the alternative to global plate tectionics in the early earth is you have a lot of volcanism and magma in general, so in the top of the mantle in general we have very big temperatures. Some magma forms and then ther’s two things that can happen. You can have volcanism. The magnma cools down very quickly at the surface. So then you end up with a very cold surface and you can also take the magma but it’s possible that it doesn’;t make it to the surface, doesn’t make it to the volcanoes but it stays in the cruist, at the base of the crust. And then the magma cannot really cool don at the base of the surface, so basically you have 2 choices. If you generate a lot of magma you can either erupt everything and make it very cold. And if it doesn’t make it to the surface then it satays in the crust and it’s insulated from the atmosphere and then I t stays warm.

Interviewer: Adam Levy

And in your study you simulate lots of different earths with different mixtures of magma being kept in the crust or spewing out as volcanoes. What did these simulations tell you about how we got to the earth we have today.

Interviewee: Antoine Rozel

So they main finding of this study is that we absolutely need to leave the magma warm in the crust. If we don’t, we generate very, very cold resulting crust and this crust cannot melt again – at least in good conditions to generate continental crust. But if you erupt a little bit, generate some volcanoes but not only volcanoes, and if you also keep it warm inside the crust then you are in good conditions to form continental crust.

Interviewer: Adam Levy

So you need a bit of a mixture between these two processes in order to explain what we see today.

Interviewee: Antoine Rozel

Exactly. We need a bit of volcanism but we need a lot of intrusion – this process where you keep the magma inside the crust.

Interviewer: Adam Levy

Were you surprised that you needed a mixture between these two processes or was it kind of what you were expecting in the first place?

Interviewee: Antoine Rozel

It was exactly what we were expecting in the first place because in the present day there is volcanism, there is intrusion and there is also magma being stored in the crust itself. So basically what we’re saying is the same conditions might have occurred in the early earth.

Interviewer: Adam Levy

In simulating the conditions of the early earth, you also spotted a behaviour where a large part of the crush, or even the whole crust, can sometimes sink and get swallowed up by the mantle. Is there any evidence that this kind of behaviour actually takes place?

Interviewee: Antoine Rozel

So the interesting idea of this study can also apply to other plants. So I’m thinking in particular about Venus. So, Venus is about 470 degrees warmer than the earth; it’s extremely warm. And it somehow looks like the early years, probably, which was probably about 300 degrees warmer at least in the mantle. So, one interesting observation is when people look at the surface of Venus there are a few craters but not so many, and that means that quite recently – which means 500 million years ago – the whole surface of Venus actually destabilised and sank in the mantle. Our models actually show similar behaviours. So if we put too much crust in the surface, then the surface can actually sink in the mantle. So we believe that it’s what happened in Venus and we see it happening in a simulation for the early earth, so it seems like Venus and the early earth had similar behaviours.

Interviewer: Adam Levy

That was Antoine Rozel who’s at ETHC Zurich in Switzerland. Give his study a read at nature.com/nature.

Interviewer: Kerri Smith

Thanks again to everyone who’s taken the time to respond to our survey. We’re going to leave it up on our website as well as Twitter: @naturepodcast. And the survey shouldn’t take longer than 2 minutes.

Interviewer: Adam Levy

In the news just around the corner, DC reporter Sara Reardon joins us with stories of sublime strings and how the National Institutes of Health is dividing up its dosh. Now though, it’s time for the Research Highlights read by Charlotte Stoddart.

[Jingle]

Interviewer: Charlotte Stoddart

Words and pictures printed in ink can fade over time as the chemicals break down, so scientists in Denmark have developed an ink free technique that relies on the shape of the surface to reflect light of different colours. They took a thin film made of tiny disks and used laser beams to bend the disks into different shapes. Spheres for example, reflected red light. The authors made a pretty convincing, if slightly grainy picture of Niels Bohr and suggest using the new material on plastic packaging, posters, even cars, to reduce the need for chemical dyes. Find the paper in Science Advances.

[Jingle]

Elderly mice given a low dose of marijuana’s active ingredient did better on memory tests but the performance of young mice suffered when they were given the same compound. The brain’s endocannabinoid system, which has roles in mood and memory is less active with age. It also responds to the active compound in cannabis: THC. So scientists put two and two together and tried boosting THC to improve memory. Afeter a month on a low dose, old mice did as well on memory and learning tests as young, untreated mice. Nature medicine has the full report.

[Jingle]

Cancers form when a random mutation causes a random cell to start dividing out of control: a simple genetic mistake. But the outcome can be impressively complicated, as Shamini Bundell found out.

Interviewer: Shamini Bundell

There are two papers out this week, looking at how certain lung cancer tumours survive and thrive. One important factor is the internal complexity of the tumours. Different cell types seem to form different rolls and can even help create a micro-environment where specific local conditions help the tumour thrive. Meritxell Huchhas co-authored a News & Views article on both papers and I asked her why a cancer cell’s environment is so important.

The tumour cells by themselves, it’s not that they can self-sustain themselves; they cannot do that unless there is this micro-environment which nourishes them. And the interesting thing is that they produce their own micro-environment.

Interviewer: Shamini Bundell

The micro-environment has to provide everything the tumour needs: things like food and oxygen have to be transported from elsewhere but there are some things a tumour needs like certain signalling molecules that it can produce for itself.

What they are producing is actually two signalling cells called Wnt and Notch ligands which both are very important during development and during growth and repair and surprisingly the cancer cells themselves produce their own Wnt producing cells and their own Notch producing cells.

Interviewer: Shamini Bundell

So, rather than relying on other parts of the body for these signalling molecules, certain cells within the tumour are specialising to provide Wnt and Notch to the rest of the tumour.

And what is more interesting is the cells that do that are derived from the tumour cells themselves, so you would have a mother tumour cell that produces a daughter tumour cell that is the one that will produce the Wnt and Notch to nourish the mother tumour.

This is interesting because you might assume that a cancer causing mutation could only give rise to a tumour made of identical cells all doing the same thing.

But actually this is starting to be quite well understood, that this is not the case, that there is a lot of cellular heterogeneity within a tumour.

Interviewer: Shamini Bundell

This cell heterogeneity is sort of like a division of labour where different cells are performing different jobs within the tumour.

For instance the cell that produces the Wnt ligand does not produce the Wnt receptor but helps the cell that is next to it to divide.

Interviewer: Shamini Bundell

Meritxell Huch, there. As she mentioned, one of the papers looked at Wnt signalling and found some cells producing Wnt ligands and others receiving them. The author of that paper, Tuomas Tammela, explained what Wnt ligands do in normal tissue.

Wnt ligands are secreted proteins that are made by cells and typically provided to a neighbouring cell. And these Wnt grow-factors, play a very important role in the maintenance of adult stem cells.

Interviewer: Shamini Bundell

We all have adult stem cells in our bodies that can divide and give rise to different types of daughter cells and the fact that Wnt signalling is involved with normal stem cells, turned out to be quite important in Tuomas’s work on Wnt signalling in lung cancer.

My experiments show that Wnt is produced by one cancer cell population to another cancer cell population that receives the Wnt ligand and these cells that receive the Wnt ligand behave like normal tissue stem cells in the sense that they have a lot more capacity to give rise to other cancer cells.

Interviewer: Shamini Bundell

And these Wnt receiving cells even have the capacity to give rise to Wnt reducing cells. This stem cell-like flexibility has beig implications for treatment of the cancer, for example, current therapies may focus on killing the Wnt producing cells, but getting rid of only these cells might not work if the stem cell like Wnt receiving cells can then turn back into Wnt producing cells and thus keep the tumour going. Tuomas and his team tested whether destructing the Wnt pathway could be used to treat tumours.

So, targeting Wnt made the tumours lose this stem cell activity that we had shown was very important in driving the growth and proliferation in these tumours and when we took out cancer cells from a tumour that was treated with this Wnt inhibitor and transplanted them into a recipient, they were no longer able to form tumours.

Interviewer: Shamini Bundell

This result reveals just how complex the internal workings of tumours are, and, as Meritxell Huchexplained, these lessons could change the way we treat cancer.

It is clear that it is not enough to target the cell that divides, but you also have to targets the cells that nourish the tumour because tumours can change the fate of other cells that would not be producing the tumour into tumour producing cells. I think that’s what is remarkable: the tumour cells really are independent; they don’t need a host in a sense because they produce their own environment, their own nourishment.

Interviewer: Shamini Bundell

That was Meritxell Huchodf Cambridge University talking to Shamini Bundell. Before that you heard from Tuomas Tammela of MIT in Cambridghe, Massuchussets. Both papers and the nesws article are available on nature.com/nature. For those who want to know more about Wnt and Notch and those clever cancer cells.

Interviewer: Adam Levy

Time now for out weekly peep into the News section of Nature and Sara Reardon joins me on the line from Washington DC. Hi Sara.

Interviewee: Sara Reardon

Hi Adam.

Interviewer: Adam Levy

So, first up, the National Institutes of Health is implementing a new approach to grants. Before we get into the impacts of it, what are they actually planning on doing.

Interviewee: Sara Reardon

There’’s been a problem in recent years which I’m sure we’ve talked about many times before on the podcast where younger researchers have had trouble getting their first grants sometiomes, because there are so many people in the field and the competition is stiff. And so what the NIH is trying to do is to see if there’s a way to see if they can limit the number of grants that any one scientist can have and then make those other ones available to more researchers so ultimately more people would have grants rather than having sorts of weath concentrated on a few labs. And, as you can imagine, this is going to be very controversial, especially given a lot of outcry form a lot of people who have a lot of grants and, see, there’s a reason they have a lot of grants which is that they’re doing they best research. So, NIH is going to have a lot of work to do to figure out a way to implement this fairly.

Interviewer: Adam Levy

So what is actually the approach that they’re implementing?

Interviewee: Sara Reardon

So it’s actually very difficult to assess how much grant support someone has because if you’re running a huge clinical trial with a thousand people, it’s going to be much much more expensive than if you’re trying to run, say, an experiment in yeast in your lab, so you can’t just say, everyone should have a maximum amount of money because then that’s a ridiculous amount of yeast research compared to cancer research. And so what the NIH decided to do was to implement a points system. Every type of grant is worth a different number of points. The maximum number that someone can have going forward will be 21 points. That’s the equivalent of three R01s.

Interviewer: Adam Levy

How well do they expect that this should be able to redistribute the money from these effectively wealthy researchers to poorer researchers?

Interviewee: Sara Reardon

Well, according to the NIH’s statistics, they don’t think that that many researchers are going to be affected. They said that it’s only 6% of investigators but they said that redistributing those will free up another 1600 grants. That’s a lot more people who could get one or two grants.

Interviewer: Adam Levy

Now, I’ve spoken in the past with younger researchers who’ve been frustrated at how difficult it is to get grants. I’m sure some of them are welcoming this, but across the spectrum, what’s the reaction been from people who might seek to get grants from the NIH?

Interviewee: Sara Reardon

I’ve seen really mixed reactions, both with people I’ve talked with and on social media. Ity’s been getting a lot of play on social media. As you probably would expect, young researchers are thrilled and think that its time that things get made a little bit easier for them. Older researchers, some of them are saying that this is redistribution of wealth and that they’;ve earnt these grants. The reason that the NIH though has decioded that this is a good idea is based on a number of studies and outside researchers have done a number of studies too, they find that the more money a lab has, the better research, typically. But that only is true to a certain point. Once a lab gets too many grants it’s essentially spread too thin. The quality of the research flattens out or even goes down because the scientists no longer have the time to spend on any given project. So that’s their rationale: even if you’re doing really good science, you’ve only got 24 hours in a day and maybe someone else would be able to be more productive with that amount of money.

Interviewer: Adam Levy

Assuming that they can et everyone on board and this goes ahead, when can we actually expect this to come into play?

Interviewee: Sara Reardon

Well, they don’t necessarily need to get everybody on board. They’re going to get feedback and people will see what they decide to do and this is going to be an NIH wide policy that’s just going to be their rules going forward. They said that it could be as soon as this fall but that, as are many other aspects of this policy, are still up in the air.

Interviewer: Adam Levy

Well, we’ll have to see how that plays out and how it ends up shaking up the research world, but in the meantime there’s been a new piece of research which looks like it might shake up the music world.

Interviewee: Sara Reardon

Yeah, this is kind of a neat study out of the Proceedings of the National Academy of Sciencesjournal this week. It has to do with Stradivarius violins which are widely considered among violinists, the best instruments ever. They were created from the 1800s and no-one is quite sure why they sound so good. There have been a lot of studies trying to figure out whether it’s a special varnish of wood or whether it’s the way they’ve been carved. But this study that’s out isn’t trying to look at that question. What it’s trying to look at is, is this kind of legend about them being the best instruments ever, really justified, and so what they did was have violinists play Stradivariuses on modern violins in concert halls for audiences and as it turned out the Stradivariuses did not seem to be better. Rather, people judged that the modern violins were just as good, if not better themselves. And they weren’t able to tell either whether each violinist was playing a Stradivarius or a modern instrument.

Interviewer: Adam Levy

We’ve actually got some of the recordings, so here’s one of the violins, and here’s another. [violin sounds] and here’s another. [Violin sounds]. So, for the record, the first one was a Stradivarius. Now, I couldn’t tell the difference either, but is this the first time this kind of comparison has been made between a Stradivarius and a very good modern violin.

Interviewee: Sara Reardon

No there’s been some blind tests before but those have been done in labs or in tudios and the critique, the criticism that the musicians have given back to the researchers is that it’s not a realistios scenario. The Stradivarius is – their whole legend comes from how good they sound in a concert hall.

Interviewer: Adam Levy

How is this news being received by people in the classical music industry – either by people who play or listen to music?

Interviewee: Sara Reardon

Well there’s some questions about the study that are valid. Forst of all, that the person who’s actually playing is going to know what kind of instrument they’re playing even if the audience doesn’t. and they might be more skilled if they’ve been playing th Stradivarius their whole life. So they might be playing one a little bit better than the other, or even their own preconceptions of ‘Stradivarius is the best, so it’s going to sound the best’ and then they play it better. That could be possibly having an influence as well. So I thought that that was a pretty valid question. As far as musicians go, it might not really matter for the music world. The whole impetus for trying to figure out why Stradivarius have these qualities is so you could imrove other violins and if these other violins sound good and Stradivariuses sound good, there is no real reason to say, well, science says we should use this one, or science says we should use this other one.

Interviewer: Adam Levy

So, if you have a Stradivarius at home, don’t throw it away yet I suppose.

Interviewee: Sara Reardon

I think that is generally good advice.

Interviewer: Adam Levy

Thank you Sara for joining us. And, for more on those News stories and, of course, other, head to nature.com/news.

Interviewer: Kerri Smith

That’s all for this week. A big thank you to the composer of our new music: the uber talented James Bulley. Find him on Twitter @JJBulley. That’s JJBulley.

Interviewer: Adam Levy

Tune in next week to hear how robots can help humans work together. I’m Adam Levy.

Interviewer: Kerri Smith

And I’m Kerri Smith.

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