Podcast: Starting up in science

Host: Kerri Smith

Alison Twelvetrees has come to London to give the most important presentation of her career.

Alison Twelvetrees

I woke up at half-past five this morning with like a massive anxiety dream about the minus 80 freezer door being open. Just like such a stereotypical scientist’s nightmare to have.

Host: Kerri Smith

It’s spring 2020, a very rainy day, and Ali has travelled from the north of England, where she’s a neuroscientist at the University of Sheffield. Less than an hour from now, she will walk in front of a panel of 30 experts and give a five minute talk. This talk will determine whether her new lab succeeds or fails. She’s pitching for over a million pounds.

Kerri Smith

Are you the kind of person who memorises your presentation given that it's only short? Or are you hoping to wing aspects of it?

Alison Twelvetrees

No I think you have to memorise it, it's five minutes, right? And it's a million pounds.

[Music]

Host: Kerri Smith

Labs in the UK don’t generally come with funding – new lab heads have to first get a job, and then go out and get their own money. So there’s a lot riding on this for Ali. It’s a million pounds. £1.11 million, to be exact. That’s enough to run her fledgling lab for at least five years – paying her own salary, recruiting and paying staff, and buying a microscope that she can’t do her work without. Right now she and a handful of students get by on stipends, small start-up grants, and a shared microscope.

As if that wasn’t enough pressure, her husband Dan is in the same boat – new job, needs money.

Daniel Bose

It’s like you’re at the starting blocks you want to run the race and you’re waiting for the funding come in so you can start.

Host: Kerri Smith

It’s also the second time that Ali has applied for this big chunk of cash. Time is running out. Her small start up grants are running out. She needs this.

For the last three years, four reporters from Nature have been following Ali and Dan, as they try to get their labs off the ground. Then there’s a global pandemic. And then something even more traumatic happens for Ali and Dan. From Nature, this is Starting up in science.

There were four of us working on this story, and here on the podcast we’re telling it in four parts. So you’ll hear from a different reporter in each episode. And in this episode, we’re talking money.

Producer Benjamin Thompson takes it from here.

Host: Benjamin Thompson

Every year, thousands of scientists around the world open the door to their very own labs. And what they all want is, broadly, the same. They want answers to burning questions – about exoplanets, or dinosaurs, or cancer.

At Nature, we most often talk to scientists when they’ve started to answer those big questions, by which point they’ve usually already set themselves up – big lab, great kit, new discovery.

But for this show we wanted to tell a different story. An origin story – the tale of neuroscientist Ali...

Alison Twelvetrees

I’m Alison Twelvetrees.

Host: Benjamin Thompson

...and her geneticist husband Dan...

Daniel Bose

So my name is Dan Bose.

Host: Benjamin Thompson

...as they set up their labs from scratch.

Daniel Bose

You push really, really hard to get to where we are and you want to keep pushing, you want to be doing great science.

Host: Benjamin Thompson

Ali and Dan have been scientists for over 10 years, married for nine, and they have a six-year-old daughter, Ada. They both managed to get positions at the University of Sheffield and started in 2017. Even getting those jobs in the same place has been a slog, but we’ll get to that in the next episode.

The story we want to tell you in these podcasts spans more than a decade, but we’re going to start about two-thirds of the way through, right when Dan and Ali landed in Sheffield, in the spring of 2017.[Walking sound effects]

Host: Benjamin Thompson

One April morning, Dan walks into the grand red-brick entrance hall of the university and through the courtyard with its neatly mown grass. He goes up an ornate but scruffy staircase in the biology department, and then down a windowless corridor. The walls of this corridor are covered with large posters that have been presented at conferences; doors lead off to several labs. He stops in front of one of them.

It’s his.

Daniel Bose

It’s first day at school, I think. You come in, you don’t really know what to expect.

Host: Benjamin Thompson

He looked at the door for a bit longer, and then he got stage fright.

Daniel Bose

I didn’t go in for the first couple of days. I was in the office to start. And then I knew lab space was there – there was quite a big barrier before going into lab space and discovering what was there and you had to work with.

Host: Benjamin Thompson

Dan knew that, in time, this lab was where he would grow his ideas, mentor a group of his own, and search for answers to all his most pressing scientific questions. But the reality of day one was quite different.

Daniel Bose

I think the first time I went in… So I walked in and looked at it, and thought, ‘OK what do I do now?’. I maybe tidied, I think I sprayed down and wiped off a bit of dust, and then walked out again. And I did this solidly for about two weeks every day, walked in and ‘OK, where do I start? What do I do?’.

Host: Benjamin Thompson

Ali had a slightly less traditional first day experience at the Sheffield Institute for Translational Neuroscience, or Sitran for short.

Alison Twelvetrees

So Dan had a space that was allocated to him. I turned up, and I sat in my office for a few weeks and then at a meeting, I sort of raised ‘Er, can I have a bench, maybe?’.

Host: Benjamin Thompson

While she waited for some space, she got going on plans for her group’s future, and started to think about what she would need and how to budget for it. Ali’s aim is to peer inside neurons and see how their motor proteins carry cargo. For this, she will need some very expensive kit.

Alison Twelvetrees

Ah, so my fantasy microscope. Currently the quote that I have is around £250,000. Yep.

Richard Van Noorden

A quarter of a million.

Alison Twelvetrees

Yeah. I always think of it more as like ‘science tokens’, because obviously you can buy a house for £250,000. The reality of spending science budgets and then actually living in the real world as a person, like a normal home budget are very different. And so I just separate it. It’s like ‘science tokens’ I can buy this much science. Yeah £250,000 is a lot of money, but it’s a lot of microscope, so...”

Host: Benjamin Thompson

Dan too was making a list of everything he needed – not just the big ticket items, but the little things that are crucial for a smooth-running lab: fridges, pipettes, various chemicals and so on.

Daniel Bose

Suddenly you start to have the opportunity on the horizon when you can start to diversify your ideas and take all of your terrible ideas, or your crazy ideas, that you’ve had during your postdoc and say ‘let’s try and push them onto my own research now’.

Host: Benjamin Thompson

This is Dan’s excited voice – he’s got lots of ideas. But at this point, ideas are about all he has got. Just like Ali, he’s starting at square one. Neither has a team, and they have almost no money. Dan and some other new lab heads even started playing a game: how many experiments could they do just using only free samples from suppliers.

Not every new lab head shares Dan and Ali’s experience. In the US, for example, it’s pretty common for new PIs to get enough money to run for at least the first couple of years. But in the UK, a university will often offer you a job and then expect you to win grants in order to prove that they should keep you.

Ali and Dan need funding – and if they don’t find it their newborn labs could struggle to survive. Their first priority is to apply for grants.

Daniel Bose

Right from the off it's tough to get to the bench because: a) the resources aren’t there in lab and b) you have instantly other things to think about.

[Music]

Host: Benjamin Thompson

But it’s kind of a Catch-22. The longer it takes him to get money, the more his hypotheses go stale.

Daniel Bose

The worry is that you don’t get the round of funding that you’re going in for now. So then you apply again, and with each grant that doesn’t get funded, instead of being right at the cutting edge of what you want to do, you’re slipping back and you’re not able to generate the data to keep up with where you want to be and where the field is.

Host: Benjamin Thompson

Of course, even well-resourced scientists worry about their ideas getting old or getting scooped. But at the beginning of the journey the frustration is even greater.

Alison Twelvetrees

I have so many ideas and so many things I want to do and no resources to carry any of that out at the moment.

Host: Benjamin Thompson

And that takes us right back to Ali, standing on London’s Euston Road in the pouring rain, waiting to give the five minute presentation which could change everything.

Kerri Smith

How does it feel to be here again?

Alison Twelvetrees

It's good. It's like the end of a process. I think, you know, certainly the end of something whatever happens. Then I have to rapidly figure out how we're going to stay afloat as a research lab.

[Music]

Benjamin Thompson

When we come speak to you in a year, what will have happened?

Daniel Bose

First Nature paper, big funding, and a holiday.

Host: Kerri Smith

This is just the sort of positive thinking Dan and Ali will need to carry them through. And as hard as it might be to keep their heads above water, at least Ali and Dan have found jobs. So, how did they get them? What did it take to get to the starting line? That’s next time on Starting up in science.

This episode of Starting up in science was written by me, Kerri Smith, and narrated by Benjamin Thompson. Benjamin Thompson and I produced the series, with editing help from Noah Baker. Heidi Ledford, Richard Van Noorden, Benjamin Thompson and I reported the story for the podcast – and for the text version of this story on our website. Read that at nature.com/news.

[Music]

Host: Kerri Smith

One evening in the summer of 2004, coach loads of students from Imperial College London rocked up at Alexandra Palace, a cavernous entertainment venue in north London. Dressed for the occasion, they were there for their university summer ball – a celebration of the end of a long year of study, and for some the end of their time at university putting them on the cusp of stepping out into the big wide world. Among the crowd was Alison Twelvetrees.

Alison Twelvetrees

I was wearing the bridesmaid’s dress from my sister’s wedding, and was single, and feeling quite cheerful, and having a nice time, and probably drinking too much, because young, and all that.

Host: Kerri Smith

Sitting down for the dinner part of the evening, Ali saw a familiar face… Dan Bose.

Alison Twelvetrees

Me and my friends that I was there with, we were sat around a big round table, and Dan and his friends were a couple of tables over. And I was trying to convince myself to go and chat to him.

Host: Kerri Smith

You see Ali had been interested in Dan for a while, but hadn’t quite plucked up the courage to ask him out.

Alison Twelvetrees

I finally decided I had nothing to lose. Like, well, I won't see him again, so it doesn't really matter. But I still wasn't brave enough to ask him out in person.

Host: Kerri Smith

So in the time-honoured style, Ali asked one of her friends to ask Dan out on her behalf, a gamble that paid off, eventually.

Alison Twelvetrees

It wasn’t until the ball was over, and they were loading us back on buses, and so we were leaving. He sort of came up to me, and we had this very awkward chat in the lobby where we exchanged phone numbers, and he couldn’t work his phone, so I had to put my number into his phone for him. And then we said goodbye we went on different buses and went home.

Host: Kerri Smith

And that was it – Ali and Dan’s first halting steps into a joint life in science. From Nature this is episode two of Starting up in science, a series about what it takes to launch a lab.

[Music]

Last time we met researchers Ali and Dan, both working at the University of Sheffield, as they took their first steps as Principal Investigators. But before they got to that point, a lot more had had to happen – both in and out of the lab. They’d done PhDs, post docs, moved countries, had a family, and lived apart. Every scientist’s journey is different, and in this episode, we’re going to tell you about Ali and Dan’s.

Reporter Richard Van Noorden takes it from here.

Host: Richard Van Noorden

Ali and Dan’s story begins in 2001 – when they were both studying biochemistry at Imperial College London.

Daniel Bose

I started off with just a fascination for science, right back to high school. We have students coming at the moment in the university for interviews, and you ask them why they want to get into doing biochemistry, “Oh I love biology, I love chemistry, and putting those two together.” And really that’s where I started out as well. I wanted to put these things together and learn more about them.

Alison Twelvetrees

My experience of biology in school was that all the practical stuff that we did never really worked. But all the stuff in chemistry really worked. I was like, ‘So, OK, biochemistry – I’ll do the life stuff but the experiments will work.’ And that was basically where I came from.

Host: Richard Van Noorden

Dan focused in on structural biology, while Ali’s classes ignited a passion for neuroscience.

Alison Twelvetrees

All cells are special but I love neurons the most. Like, they’re these enormous, ridiculous shapes – and just how a cell manages to be this big and everything goes to the right place and the synapses form. And you have them your whole life, and they have to function your whole life. It's crazy.

Host: Richard Van Noorden

But although their scientific passions may have been awakened, it took rather a lot longer for their relationship to reach the same stage.

Daniel Bose

I didn't speak to Ali for three years. I was kind of shy. She was kind of dating someone.

Alison Twelvetrees

Yeah.

Daniel Bose

I sat at the back of the lecture theatre, and Ali sat at the front.

Host: Richard Van Noorden

After they finally got together, Dan stayed on at Imperial to start a PhD looking at how genes are switched on and off in bacteria, and a year later, Ali finished her degree, and having enjoyed the taste of lab work she’d gotten so far, found a neuroscience PhD, also in London, which meant that the two could stay together.

But it’s a long road from getting a doctorate to becoming a PI. Before you get a lab of your own, you usually have to spend some time working in someone else’s.

Dan spent two years working as a postdoc in London, looking at a group of enzymes involved in the remodelling of DNA, while Ali wrapped up her PhD.

They both wanted to stay on in science – but this time, they looked further afield. Ali found a position split between a lab in London and one in the US, at the University of Pennsylvania in Philadelphia. Dan also managed to get a postdoc there, and so in late 2011 the pair packed up and moved to the US. And they got married! Just three weeks before their flight.

Daniel Bose

It was kind of nice because it was a wedding and leaving party at the same time so we got to see bye and lots of people.

Alison Twelvetrees

And cry lots. I just remember crying a lot. and being very emotional.

Host: Richard Van Noorden

Moving to another country would be a big step in anyone’s lives, but as scientists, both Dan and Ali say their time working as postdocs in the US was invaluable for their scientific careers. It gave them time to develop their skills, and come up with their own research avenues.

Alison Twelvetrees

That’s kind of where I found my confidence and independence of ideas about the directions that I thought were important, and that I felt that my opinion was just as valid.

Daniel Bose

That was a really big jump in techniques and in ways of doing experiments. So instead of where the goal was what you would work towards, ‘I’m going to solve the structure of this and then find out what it tells me,’ I totally switched to thinking in a hypothesis lead way, so ‘I think this is happening and now I’m going to plan out a series of experiments that’s going to let me show whether this is true or whether it’s not true.’ And so, the second postdoc made me a much better scientist in the way that I think about how systems work.

Host: Richard Van Noorden

Three years passed, and their research skills continued to grow. And so did their family. In 2015, the couple had a daughter, Ada. By that point they were nearing the end of their postdoc positions, and things were about to get pretty complicated. Ali’s split postdoc meant that after her maternity leave, she had to return to the UK to finish her research. But Dan couldn’t leave.

Alison Twelvetrees

So we ended up moving back at different times, and ended up in different countries. I moved back and went back to work in London and brought Ada with me, and Dan stayed in Philadelphia to finish his postdoc work. And we didn’t really know how long that was going to be when we moved and I think we hoped it was going to be a few months.

Host: Richard Van Noorden

Dan was working on a research paper he was planning to submit to the prestigious journal Cell, which was vital for his future career prospects, so he had to stay in the US. Despite working around the clock, it took almost a year before everything was completed.

Alison Twelvetrees

It was fairly brutal to be honest. There’s no way of dressing that up, it was horrendous. And on top of that trying to be productive as a postdoc, trying to get independent positions, it was just everything all at once. It was exhausting.

Host: Richard Van Noorden

Living on different continents meant that Dan had to get creative when it came to being a Dad to Ada.

Daniel Bose

So she would do things like carry the iPad around and tuck it up with her toys at bedtime and Daddy would be part of that, but it was clearly difficult and really tough on Ali, and you know that this is having an impact on her career as well because she can’t spend as long in lab as she necessarily needs to because she’s got to do single parenting alongside finishing off her research projects as well. So it was a very conflicted time, I think, for us.

[Music]

Host: Richard Van Noorden

Ali and Dan are still pretty hard on themselves about this time apart.

Alison Twelvetrees

What kind of mother would separate their child from a loving father who wanted to be there for them.

Daniel Bose

Similarly, what kind of father would leave his wife and daughter in another country and get on a plane and fly back to do science for a year.

Alison Twelvetrees

But at the same time it was what we felt was necessary to make sure we were both, had a chance of having jobs. And you know, I couldn’t ask Dan to come with me and Dan couldn’t ask me to stay and this is the sort of situation that you end up in, basically.

Daniel Bose

And it’s not unique to us. It’s a really common problem.

Host: Richard Van Noorden

Around the world researchers are making sacrifices like this for the sake of their careers. And even so, the numbers are stacked against them – one study from 2014 suggested that fewer than 1 in 10 scientists become PIs, meaning that competition is fierce among those who want to take the step up. In fact, Nature’s first postdoc survey run in 2020 revealed that more than half of respondents had a negative view of their career prospects.

Of course, as well as 11 months of living apart, and all the juggling of home- and work-life that entailed, Dan and Ali also had to apply for PI positions – and they focused their search on the UK.

Alison Twelvetrees

We’d never really thought we were going to be lucky enough to find somewhere that would give us two jobs, so our Plan A was basically that one of us had to be employed. We’ve got a daughter, you have to put food on table, you have to pay the mortgage, you have to pay the bills. And then whoever did not have a job would then try and bring in an external fellowship and create a job, that kind of thing.

Host: Richard Van Noorden

However, things actually worked out a bit better than that. In October 2016, Dan was offered a position at the University of Sheffield. Later in the year, Ali was offered a position there too, in the Sheffield Institute for Translational Neuroscience, or SITraN, for short. So the family upped sticks once again.

Alison Twelvetrees

It was such a stressful time anyway just that whole year before we moved here. And it felt like it took a long time to move. It takes a long time for somewhere to feel like home, I think – I think we’re finally getting there. But I think we were just exhausted, to be honest, by the time we got here, I think, that’s the reality.

[Music]

Host: Richard Van Noorden

Exhausted yes, but finally, after a gruelling time, Ali and Dan had some stability and were free to focus on their scientific passions.

Alison Twelvetrees

It was really nice to have the security to kind of sit and think about science for a little bit. Which is mainly what I did – I can’t speak for Dan – but when I started in Sheffield, I really… just sort of coming into work every day, thinking about my science and how it was going to fit into Sheffield and reaching out and making connections across other departments and stuff. It was a much needed pause to collect my thoughts and put something coherent together in terms of a plan for doing my science.

Host: Kerri Smith

Ali and Dan have come a long way from the two undergraduates we met at the start of this episode. But their biggest challenges still lie ahead. In the next episode of Starting up in science Ali and Dan actually start running their labs, hiring, teaching, grant writing and sometimes even a bit of research. There’s a lot to juggle – and they’ve never done it before, what could possibly go wrong? Find out how they get on, next time.

This episode of Starting up in science was written by Benjamin Thompson and narrated by Richard Van Noorden. The series was produced by me, Kerri Smith, and Benjamin Thompson, with editing help from Noah Baker. Heidi Ledford, Richard Van Noorden, Benjamin Thompson and I reported the story for the podcast – and for the text version on our website. You can read that at nature.com/news.

Host: Kerri Smith

Ali Twelvetrees is on her way to the physics department carrying an icebox full of proteins.

Benjamin Thompson

So, is this a journey you have to do multiple times a day then?

Alison Twelvetrees

It can be, yeah. No more than twice. I try to make no more than twice.

Host: Kerri Smith

The proteins in the cooler are motor proteins, taken from neurons – where they shuttle cargo up and down to keep the cells healthy. They have already taken Ali several days to prepare. Now it’s the fun bit. She is going to see if she can make out their shapes under a special microscope.

Alison Twelvetrees

So we're just walking up past the Students’ Union. And the physics building is behind the Students’ Union and that's where the microscope is.

Host: Kerri Smith

Ali wants to image her motor proteins one by one, to get a nice clean picture of what shapes – or conformations – they take under different conditions. One day, she hopes, knowledge like this could help unlock what goes wrong in conditions like motor neuron disease, when motor proteins don’t work properly.

For a while she only had the idea and no way to do it – she can’t buy her own microscope until she wins some funding. But before she even joined Sheffield she had a lucky break. Her husband Dan, a biochemist, ran into another scientist at the university, Tim Craggs, and got chatting about his microscope that could see single molecules. It was a eureka moment for Ali – this was what she needed to answer the questions ticking away in the back of her mind.

Ali and Tim have been collaborating since she officially joined the University, and back in October 2018 they invited Nature into the optics lab, to take a peek.

Tim Craggs

Hello, welcome!

Alison Twelvetrees

We’re bringing a team.

Tim Craggs

Wow, everybody’s here, cool.

Host: Kerri Smith

In the room is a stainless steel surface with tiny holes in it – like an air hockey table – tricked out with lasers, lenses and mirrors to direct light onto the samples and make them fluoresce.

Alison Twelvetrees

So it allows us to take measurements that tell us about the conformation, like the shape that the kinesin molecules are in, and how they respond to different environments.

Host: Kerri Smith

Being able to see the kinesin molecules in their different shapes is key – but it’s step one of about 1,000 towards getting the result that Ali hopes for. Doing science from scratch is slow.

[Music]

Host: Kerri Smith

And there’s so much prep and trial-and-error at every stage. It’s the same for early career researchers worldwide, and that’s assuming you can find time to get to the lab, in between all the other tasks that fill a PI’s diary. So how do you juggle it all – and, try and get some science done along the way?

Reporter Heidi Ledford takes it from here.

Host: Heidi Ledford

Two years after he started his lab, Dan Bose heads down to the basement of the biology department at the University of Sheffield. He enters a small, dark room, dominated by a large metal cylinder with an eyepiece at the bottom and an instrument panel that looks like a flight deck. Dan sits down in front of the microscope like a nervous pilot.

Daniel Bose

I am very rusty with this microscope. So I did this for years and years before my second postdoc and then I didn’t touch a scope again for six years. So part of this whole process for me is getting back on the scope. Actually, it’s amazing how much of it is muscle memory, and you know where the right knobs and dials are, and how to get the grid in and out without, I’m going to jinx myself now, doing too much damage.

Host: Heidi Ledford

Dan has been studying this protein, called CBP, for seven years at this point. As a postdoc, he figured out that it binds to snippets of RNA and that, together, the pair affect how genes are turned on.

If the experiment today works, and he can see the samples well, his next step is to zoom in even further, and look at the protein-RNA partnership under a much more powerful microscope – where he can get a clearer picture of how the complex is bound together at an atomic level.

But let’s not get ahead of ourselves. Dan has brought some samples with him: hundreds of thousands of CBP-stuck-to-RNA molecules dried onto tiny copper grids about the size of sequins. He carefully extracts one grid from a box using tweezers.

Daniel Bose

This is where too much coffee doesn’t really pay.

Host: Heidi Ledford

He places the sample into the holder and inserts it into the microscope.

Daniel Bose

So this is a CM 100, which is kind of like a workhorse electron microscope. It has a filament at the top, which generates electrons…

Host: Heidi Ledford

It turns out Dan is being too modest about his rusty skills. His confidence soon kicks in as he starts getting the microscope ready.

Daniel Bose

...so it behaves pretty much like a light microscope, except you’re focusing electrons instead of light.

Benjamin Thompson

It does make me think a little about the old movie Alien, it’s got that delightful screen there, right, like retro-futuristic.

Daniel Bose

So actually on one of the Alien movies – I was watching it on a plane, on a really turbulent plane – I was watching it and was like ‘I recognise that bit of equipment’ and they’d used an old electron microscope as some of their kit.

Host: Heidi Ledford

He consults the laminated user guide and after a while, some grainy, grey images appear on the screen.

Daniel Bose

This is just a big lump of gunk, dirt.

Richard Van Noorden

I was getting excited.

Daniel Bose

Yeah, no. If I saw something this big I'd be worried.

Host: Heidi Ledford

The first sample is a dud – not enough protein, or maybe not stained clearly enough. He tries another, flies around the sample for a few minutes. The hum of the room is comforting. And then…

Daniel Bose

Oh, wow that is actually pretty good. So these are protein complexes. They’re slightly bigger than CBP looks on its own on a grid, so it looks like we’ve got protein and RNA binding together. Which… I’m smiling anyway. You can’t see this on here.

Kerri Smith

What’s it like to see it?

Daniel Bose

It’s pretty amazing. Like I say, I’ve been looking at it for years as a band on a gel and a band-shift and to start to see things interacting like this is… nice.

Host: Heidi Ledford

You can’t really tell, but Dan is thrilled. It’s a nice victory for today – and a crucial step in his plans for his lab. He wants to hire a postdoc to focus on this work.

Daniel Bose

To start to feel like there’s a sample that we can look at and to start to build the structural side of the lab up is pretty exciting.

Host: Heidi Ledford

It’s as if some alarm goes off in Dan’s head when he’s too effusive, because the next thing he says is:

Daniel Bose

There’s sample on a grid and it looks like it might work. So this is not bad.

Benjamin Thompson

“Not bad.”

Richard Van Noorden

Amazing

Daniel Bose

It is amazing. It’s pretty cool.

Benjamin Thompson

Good, We’ll take that. Nice one.

Richard Van Noorden

Just say ‘amazing’ again.

Daniel Bose

Amazing. Astounding.

Host: Heidi Ledford

This is one of those special moments in science where the theory and the hours of prep work come together – that’s what attracts many scientists to research in the first place. But the truth is that these moments are few and far between.

[Music]

Host: Heidi Ledford

And for PIs it can feel like the science itself is a background hum, and the din of other demands overwhelms it. There’s always admin to do; both Ali and Dan have PhD students to recruit – and their current students to look after. And for Dan, an additional job: giving lectures and setting exam questions for undergraduates, something he didn’t have much experience of before starting in Sheffield.

Daniel Bose

To stand in front of a class and to see them, they behave as a single body you can see them tune out when you tell them something that’s maybe not quite connecting. And how do you get that back and that interaction has been really quite fun and quite exciting and terrifying also.

Host: Heidi Ledford

But the biggest demand on their time and stress levels remains getting money. And Ali and Dan, who have a young daughter, have to take turns applying for grants, so that someone can keep the household running.

Alison Twelvetrees

When one of us has a big deadline, kind of the other person has to be responsible for picking up our daughter and, you know, feeding her and putting her to bed and that kind of thing. And, yeah, so kind of, we can't both be in a panic about a deadline at the same time. Because it doesn't work.

Host: Heidi Ledford

In the UK, remember, often PIs are hired but have to go out and find their own funding to keep their labs alive. In 2017, Dan tried and failed to win a big grant. In 2018, Ali had her first go on the funding rollercoaster.

Alison Twelvetrees

And I just knew as soon as I saw the email even though I hadn’t seen the content of it that it was negative. So then I forced myself to read the email, and then I called my husband, and then ran away and had some lunch, and a big piece of chocolate brownie, and a small cry, and then got back to work again.

Host: Heidi Ledford

Ali doesn’t wallow – she knows it’s rare to get the first big grant you go for and she also has a PhD student to supervise. Plus she’s also agreed to work on a paper with a fellow new PI, about the experience of being a new PI in science, for which they have been collecting data.

A few months later and it’s Dan’s turn to stand up in front of a panel and sell himself and his work. He’s applied for the same fellowship Ali missed out on. This is the second time he’s applied to the scheme and the first time he’s made it this far.

Daniel Bose

I think it's a great skill to have to be able to stand up and defend your work like that. You know, in theory, everything about your project, and you're trying to communicate that and, and defend it. Do I like it? No I'm scared, but I can see the value of it.

Host: Heidi Ledford

A few weeks later, Dan was on the train on the way down to London to give a talk, and checked his email. There was a message from the grant scheme.

Daniel Bose

I read as far as "I am pleased to confirm" and then I skipped through to “successful”. And then I put it down and then I had to pick it up again and reread it and make sure that I hadn't misread it. I broke out in a massive grin to start off with and I think everyone thought I was acting very weirdly.

[Music]

Host: Heidi Ledford

Dan forwarded the email on to Ali to share the good news.

Daniel Bose

I phoned her up before she read the email that I sent her. So she was reading it on the phone to me, and she was just delighted as well, I think, we do all of this together, you ride the ups and the downs, and the pain and the rejections and all of this stuff you do at the same time. And so it's just lovely to be able to share that kind of happiness and release with her. And then we went though a tunnel, and that was the end of it.

Host: Heidi Ledford

Back in Sheffield the next day, Dan, Ali and his colleagues met up to celebrate. He marked his big achievement – by firing a champagne cork as far down a corridor as possible.

[Audio crowd and of cork firing]

Host: Heidi Ledford

This fellowship, worth well over a million pounds over five years, transforms Dan’s ability to do research. Instead of trying to stretch his dwindling funds, suddenly he can afford to buy new equipment, to try new experimental approaches, and to hire a postdoc to ramp up the group’s research. But for Dan and Ali, this fellowship also buys something else: time. Five years of funding means the family can start putting down some proper roots.

Daniel Bose

That stability just means a lot. It means you can start planning to look for schools and know that Ada will be in school in five years time and in terms of building a life that's normal, I guess, it makes a big difference.

[Music]

Host: Kerri Smith

At Christmas dinner organised by Dan, Ali and a fellow PI at the end of 2019, the pair look around. There are now over 20 people in attendance, where three years ago there were only five, including the three PIs. There is a real sense of momentum.

But in the back of Ali’s mind she knows that this isn’t permanent – she is reapplying for the same grant Dan won. And if she doesn’t win it this time around everything could change. And unbeknownst to her a personal crisis and a global pandemic are about to throw everything into chaos. That’s next time, on Starting up in science

This episode of Starting up in science was written by me, Kerri Smith, and Benjamin Thompson. It was narrated by Heidi Ledford. Benjamin Thompson and I produced the series, with editing help from Noah Baker. Heidi Ledford, Richard Van Noorden, Benjamin Thompson and I reported the story for the podcast – and for the text version that you can find on our website. Read that at nature.com/news.

Host: Kerri Smith

We met Ali Twelvetrees for the first time in Episode 1, she was outside the Wellcome Trust building on a very rainy day in March 2020, ready and waiting to give her presentation. She’s trying, for the second time, to win a grant to keep her lab alive.

Alison Twelvetrees

It’s like the end of a process. Certainly the end of something, whatever happens.

Host: Kerri Smith

She called us when she got out, and Benjamin ran down the road to meet her in the cafe next door. She was pretty upbeat.

Alison Twelvetrees

I didn’t say anything that I regret,

Host: Kerri Smith

We know that laugh by now. The Ali laugh. The laugh that says, ‘I’m nervous, but I’m trying to keep it light’. The self-deprecating laugh. Still, the last time Ali did this interview, she wasn’t laughing at all afterwards.

Alison Twelvetrees

I met Richard and Kerri and I think they were hoping for me to be really happy that it was over, and I was a bit like, ‘I don’t think that went very well’, like, I could tell I’d been rattled. I just wasn’t confident, I didn’t have the conviction of my ideas. It’s a lot of emotional investment, you want it to be really analytical and like, whatever, and it’s just not.

Host: Kerri Smith

She’s no less invested this time around. Probably more, when she thinks of the students she’s left beavering away in the lab, reliant on her to attract resources. This time, she’s come to the same building, given a similar five minute presentation to a similar 30-person panel, in a room just across the hall from the one she’s in today. But this time felt different.

[Music]

Alison Twelvetrees

So the last time, I remember that room. I was in on the left hand side. I remember it just being very dark, it was wood-paneled still, I think. It was incredibly dark. I had made my slides with a dark background, so there was no illumination from my slides, and I couldn’t really see. But this time it was very light and bright.

[Music]

Host: Kerri Smith

So that was the 5th of March. Ali went back up to Sheffield that night and tried not to think about when she would hear back from the panel.

For a couple of weeks she helped her PhD students to get their experiments working, gathering data on the shape of the kinesin motor protein. But then something much more seismic took over.

Cases of the new coronavirus had been drifting upwards in the UK, and the first deaths are reported in early March. Italy, the first European country to be hit with an outbreak, put its whole population into lockdown on March the 9th. Around that time, the UK government advised people with symptoms of a cold to stay at home. Nature’s offices were still open, like most others in London. But Dan and Ali started to make plans.

Alison Twelvetrees

So it’s kind of weird, because last week, last two weeks even, I’d already started talking to my team, and like, well if we need to go to working from home, because you could kind of see what was happening in Europe, right? Like you watch the news, you see it happening. So we sort of talked about what would happen if they couldn’t come into lab. And it’s hard, because I don’t want to pretend they’re going to be productive in this time, because they’re not. But at the same time, we don’t really know how long we’re going to be in this state, so it was more like, these are useful things that you could concentrate on, if you want to.

Host: Kerri Smith

A week drifted by, then two. By the 18th of March, the university had stopped face-to-face teaching – Dan had to broadcast his lecture from an empty theatre – but they hadn’t issued any official instructions on lab closures. Not prepared to wait, Ali and Dan made some difficult choices.

Alison Twelvetrees

Yesterday we made the decision that we were just shutting everything down, because it wasn’t – it's difficult to move on unless you make a decision, right?

Daniel Bose

Obviously, it's sad from a personal perspective, but obviously it’s the the right thing to do for people’s safety, and so there's no debate about it. But I think having the last few weeks before the virus, you were starting to see that there’s a community in the lab, which was nice and people interacting, and science happening. There were days when even I managed to get into the lab over the last few weeks. So there were four or five people all working in lab. And having battled quite hard to get to that point. It was really satisfying. So it's quite sad from that perspective to see it all close down.

Host: Kerri Smith

There are things they can do while the labs are closed. Some of Dan’s students have results to play with, some can design new experiments ready for the return. But neither lab has a repository of data just sitting waiting.

Alison Twelvetrees

It’s really, really hard for us. It’s so hard. We’ve only just started, right? So we’re not sat on stacks and stacks of data waiting to analyse, it’s not how that works when you’re starting out, right? And I think it’s a little bit frustrating seeing the big established labs kind of, mouthing off on Twitter, ‘Oh yeah just going to write papers, and do all this analysis.’

Host: Kerri Smith

More than the science, though, it’s the social implications of the shutdown that Ali and Dan are most concerned about.

Daniel Bose

The social side is really difficult. And I think that's what I miss most. Yes, science is happening, but that will happen again. But again, having worked really hard to build a coherent lab that get on with each other and enjoy working together. To see that dissipate is quite difficult.

Host: Kerri Smith

It’s a period that’s likely to affect those on the lower rungs of the scientific ladder most profoundly, Ali says. New PIs in barely-stable situations, some who might have young children at home. Students, with limited time and funding.

[Music]

Alison Twelvetrees

I don’t think anybody has really begun to grasp how massive an effect this is going to have.

Host: Kerri Smith

On the 23rd of March, UK Prime Minister Boris Johnson addressed the nation.

Boris Johnson

From this evening I must give the British people a very simple instruction. You must stay at home.

[News bulletin]

Lockdown for three weeks enforced by the police. Johnson declares a national emergency in an historic address to the nation.

Host: Kerri Smith

Ali and Dan, already working from home, were now looking after Ada too – her school closed at the end of the week.

Daniel Bose

I told him the other day when we were talking about homeschooling the other day, and how she felt about it. And she said, "I think that’s a great idea, Daddy, I'm going to be the teacher." I think that's pretty much the basis for how homeschooling is going to happen.

Host: Kerri Smith

They decide to focus on fun, rather than hardcore learning, since Ada is only five. They draw flowers in the garden and do an online exercise class as a family.

Daniel Bose

So our neighbours must think we’re crazy, jumping around. Which is quite hard work! So that's our nine o'clock routine for getting out of bed to do some PE. And then we dissected a daffodil before lunch today, which is quite nice and drew a picture of it.

Host: Kerri Smith

The following Wednesday, two days into lockdown, reality sets in a bit more. Ali still hasn’t heard from Wellcome, and both she and Dan are trying to keep their teams motivated and occupied. But this pause is the last thing they need.

Alison Twelvetrees

I'm really worried because we don't really have any money at the moment. And it becomes very difficult in these circumstances to write another grant or create more preliminary data, or... I dunno, we might just sink.

[Music]

Host: Kerri Smith

Later that afternoon, Ali was making Ada a snack when she saw an email from Wellcome on her phone. The subject line was the same as it was when she last heard from them about a grant.

Alison Twelvetrees

And I opened it up, and read the first couple sentences. Well I don't even think I read them? I just kind of scanned them. And then ran upstairs and cried on Dan.

Host: Kerri Smith

Ali read us the email later that day.

Alison Twelvetrees

Dear Dr Twelvetrees, I am pleased to confirm that your application was successful.

[Music]

Alison Twelvetrees

It sounds melodramatic, but it kind of just means everything, like this is everything that I've worked for, and knowing that we can do all of the things that we're excited about for five years. That's the most certainty you ever get in a scientific career. Like that we're going to do all the things that we're most excited about. And get really cool data and see things that people haven't seen yet. It's really cool. Yeah, it's a bit like winning the science lottery.

Host: Kerri Smith

Ali has won 1.26 million pounds. She assembled her team on zoom and gave them the news.

Alison Twelvetrees

So I have something important that’s just happened. We’ve got a million pounds.

[Excited chatter]

Host: Kerri Smith

Lockdown continues beyond the three weeks the government initially planned, into April, and then into May. By the second month, there is a rhythm to Dan and Ali’s days. They split the day half and half. They keep office hours so that their team members know when they can find them online. Ali has designed projects for the masters students who were due to start in the lab the week it closed.

She and Dan are both worried about how they are going to extend the funding that their students will need after the gap. These positions are often funded by a patchwork of separate studentships. Many have had to pause or re-focus their projects; one of Dan’s students has taken a leave of absence to volunteer in a Covid testing lab.

But they’re also making tentative plans for reopening – its own logistical headache with social distancing guidelines and personal thresholds for feeling safe. Dan’s lab is its own space with four walls, but Ali’s is open plan, making timetabling a nightmare.

Alison Twelvetrees

It’s not just about what we want to do, it’s about what every other lab in the building wants to be able to do as well. Because if there’s density of people and stuff, we have to work together as a department to make sure that it’s fair, basically, and that people have the access that they need.

Host: Kerri Smith

In the summer of 2020, Dan’s lab opens again and his group can come and go as they please, as long as they are socially distanced. Ali’s lab at SITraN is a tighter space, there’s no room for them all at once. The whole building works on a shift pattern.

Alison Twelvetrees

One of the biggest hurdles we've got at the moment is access to microscopes, because it involves moving between buildings to try and do experiments, which is really hard on everybody.

Host: Kerri Smith

Several lab members have fallen foul of the arrangement, preparing samples all morning at SITraN and taking them to another building for microscopy, only to discover they don’t have all the reagents they need, at which point they can’t go back to SITraN. Mostly the team has found ways around it.

Alison Twelvetrees

Yeah, it's totally different way of doing science because people in there, they're all doing bits of experiments for each other now. And they’ve been brilliant at it. They've taken care of each other.

Host: Kerri Smith

At the end of 2020 we touch base again. Ali has just sent out an email to start the process of getting her grant money. It won’t all flood in immediately – in fact, it might be months until the more expensive items can be procured – but it’s a start. And the team has already decided what they want their first purchase to be – it’s practical, rather than flashy.

Alison Twelvetrees

We also collectively quite like being very organised, and they wanted to take it a step further, and I think we’ve decided on a label maker.

Host: Kerri Smith

In Dan’s lab, the students are more and more self-sufficient, making decisions without him. And, his first ever PhD student is about to fly the nest. That’s making him feel like a real lab head.

[Music]

Daniel Bose

It’s kind of handing off from being an early career group, to one that’s up and running. And I haven’t quite noticed it happen, but suddenly the first student is thinking about writing up, and we’re three years in, and we’ve got money, and we’ve got a group that’s growing.

Host: Kerri Smith

By the end of 2020, Dan and Ali had hit their stride. Ali decided to release her grant money in January, Dan was recruiting for a postdoc, and together they’ve weathered what the COVID pandemic has thrown at them so far. At Nature, we had started to write up their story and make this series – when we got some news that came as a shock. When we called them next, they looked sombre and tired.

Daniel Bose

Yeah, I mean it’s obviously a big curveball that none of us were really expecting. And... I was just biking home from work and I woke up in hospital.

Host: Kerri Smith

In December, Dan was on his usual route home from work, past the children’s hospital.

Alison Twelvetrees

I think when I first got the call. The guys who found you weren’t... couldn't rule out... No one saw Dan fall off his bike. And there was no CCTV footage, so it sort of looked a bit like a hit and run. And I found that… I mean, in terms of it being a road accident and Dan being on his bike that’s something that I have a fear of in general.

Host: Kerri Smith

In fact, Dan had had a brain haemorrhage. He was found by a team of doctors coming out of the children’s hospital.

Daniel Bose

They diagnosed me before they put me in the ambulance so they knew what to look for in A&E when I got there. And there is a brain injury, stroke unit in the Sheffield hospital. So they were able to do everything really quickly. But otherwise, I would have been in real trouble.

Host: Kerri Smith

The doctors treating Dan put him into an induced coma.

Alison Twelvetrees

And it wasn't really clear when Dan when went in, that Dan was ever gonna wake up. I think the doctors were not particularly beating around the bush in terms of the condition in which he entered hospital about what his chances were. So I think that he is here at all, is one thing, let alone that he’s basically working as normal.

Daniel Bose

Almost fully functioning.

Host: Kerri Smith

Dan spent three weeks in hospital before being able to come home to continue his recovery. Ali and fellow lab head Emma Thomson took over the day-to-day running of his lab, and colleagues picked up his teaching.

Daniel Bose

I woke up in hospital and I had lectures starting in January. I’m like ‘Right, I'm well, I need to go back and do my lectures.’

Alison Twelvetrees

He was not well, he was on a lot of drugs.

Daniel Bose

I think that was drugs talking, indeed.

Host: Kerri Smith

In the months since, Dan has made a remarkable recovery. He can walk and speak basically as before. He’s still not back to normal – whatever normal looks like now – he still gets very tired, and if he forgets to do his physio one of his feet goes numb.

But both labs are running well. Dan has appointed a postdoc to continue the microscope work he began last year, and Ali has started the paperwork required to buy her £250,000 dream microscope. She’s also getting some interesting results from her collaboration with the optics lab which could change her theory of how motor proteins work.

[Music]

Host: Kerri Smith

Of course, like all PIs they have half an eye on the horizon and their next big cheque. After all, it’s now two years since Dan’s five-year grant started, and there’ll be more grants needed after that.

But for now, they have some time.

Daniel Bose

I think we’re just going to enjoy not feeling like the clock’s ticking for a little bit.

Alison Twelvetrees

Yeah, I think you get used to being on a perpetual cliff edge of…

Daniel Bose

Unemployment.

Alison Twelvetrees

Unemployment, yeah! So I think we’ll just try and enjoy, hopefully, a period of stability to build some really strong foundations.

Host: Kerri Smith

There are thousands of scientists like Ali and Dan, and thousands of versions of this story every year, as they take their first steps into independent science.

Every successful lab head has been a new PI, but not every new PI has allowed four reporters to follow them for three years. We’d like to say thank you to Ali and Dan for sharing their journey so far with us – and now with you.

And of course, Ali and Dan’s journey has only just begun. They have built strong foundations, now we leave them to build their house.

This episode of Starting up in science was written by me, Kerri Smith. Benjamin Thompson and I produced the series, with editing help from Noah Baker. Heidi Ledford, Richard Van Noorden, Benjamin Thompson and I reported the story for the podcast – and for the text version that you can find on our website. Read that at nature.com/news.

Benjamin Thompson:

Hi, Benjamin Thompson from the Nature Podcast here. Welcome to a special bonus episode of ‘Starting up in science’. Now this one is a bit different from the main four podcasts in the series. Here we're going to go behind the scenes and do a deep dive into how four Nature reporters followed the wins and losses and the trials and tribulations of two researchers. One of those reporters was me, but I'm joined by the other three: Kerri Smith.

Kerri Smith:

Hello.

Benjamin Thompson:

Heidi Ledford.

Heidi Ledford:

Hello.

Benjamin Thompson:

And Richard Van Noorden.

Richard Van Noorden:

Hello.

Benjamin Thompson:

Now I guess we're about to start discussing it. But just a quick PSA for the listeners. Before you go any further, I really suggest you go back and listen to the ‘Starting up in science’ podcast series, or have a read of the written feature over on nature.com/news, or the rest of this discussion won't make a huge amount of sense to you. But with that being said, I guess where do we start, everyone? I mean, at the beginning, I suppose. How did ‘Starting up in science’ start? Now Kerri, I know this was something that you were very much at the front of.

Kerri Smith:

Yeah. So this was an initiative that came out of the features team. And I think it's something that's been discussed before, the idea that we might want to follow scientists over a longer period of time than we usually do. Lots of our stories rely on, you know, momentary findings. And we thought, well, science doesn't really work like that, why don't we see if we can find some people who'd be up for telling us the story of what it's like to start up in science and do science. And we'll have a look at how long that takes. And we'll try and examine the process rather than the results.

Benjamin Thompson:

Yeah, I've gone back through my inbox. And the first mention of what became this project, the subject line in the email was ‘Month in the life of a lab’, and that was from November 2017. Listeners will know at this point that this project went on for a lot longer than that.

Richard Van Noorden:

I think to add to what Kerry said, so often even when we tell the history of something, it's very much looking back and saying how we got to this moment. We've just done a history of mRNA vaccines and all the many scientists that contributed to that. And at the time, clearly, you know, none of them perhaps knew when the big breakthroughs would come and it was built on slowly over decades. But even then we're looking back and saying, here's what led up to this big moment. And here, we are just going upstream and saying whatever comes will come. And we'll see what turns out.

Benjamin Thompson:

Yeah, and I think there's maybe a very different way of doing reporting, just seeing what turns up, right, without maybe a defined goal we were looking for. But maybe before we get into that, let's talk a little bit about Ali and Dan. Why did we decide to follow them in particular? So again, if we go back to the sort of November 2017, when we were thinking about this project. Obviously, we found them since then.

Kerri Smith:

Yeah. So the way that we chose them is that we started polling a whole bunch of Nature staffers, and we put out calls and we said, ‘Do you know any scientists who are in you know, interesting times, are they starting their lab? Are they retiring have they just failed to get funding have, they just won a big chunk of funding?’ And we assembled a really giant list, and we started calling a few people. We quickly realised that it wasn't going to be very practical to do this kind of in depth project, if we weren't physically close to these people. So we had to rule out, sadly, because of where the team that was going to be taking on this project was based, we had to rule out people in far-flung areas of the world and concentrate our search more locally. And you know, after having a first few calls with a few candidates, and crucially, finding people who said yes to this,

Heidi Ledford:

Which is remarkable, I think.

Kerri Smith:

At a time we didn't say it was gonna be three years, I think we probably said a year, tops. But even that length of time is, when you're a new lab head, you don't know what's coming for you. It's a lot to want to share that with someone. And you know, Ali and Dan, basically came out of that search.

Benjamin Thompson:

Do you remember a sense of really what we were trying to convey? What was the feeling that we were trying to get across, do you think?

Richard Van Noorden:

The slow grind of what it's like to do science and the many barriers that are in the way of success and how a scientist starting up their own lab has to be many kinds of people in one, you know, like: a teacher; a fund administrator; a startup person making an elevator pitch; a mentor; and, of course, a researcher. And, you know, people with their own families and all of these sort of personas are just rolled into one. It's just such a difficult job to have, and all without any necessarily secure contract, not knowing that in, you know, where in a few years you're going to be.

Heidi Ledford:

Yeah, I would agree with that. But I think also, in addition to how difficult that road can be, also the motivation and the sort of excitement of doing science, and the reason it's hard to get these jobs is because so many people want them, which I hope is also in the story.

Benjamin Thompson:

Yeah, I mean, obviously, it is a uniquely personal story. But maybe let's talk about our first visit, and 31st May 2018. It was when we went up, we got the train up to Sheffield, all four of us and, and some of the art team came up as well to take some photographs. I mean, what were we expecting, do you think from from this first moment? Because obviously, we spoke to the email, we spoke to on the phone a little bit, but they didn't know us, we didn't know them.

Heidi Ledford:

Yeah, I was amazed from the start, how candid they were and how actually relatively relaxed, I think, given that, you know, you've got all these people following you around and asking you questions. I mean, it was, you know, maybe a little bit of trepidation at the beginning. But, I just all the way throughout the project, but especially at the beginning, I was surprised by how open they were.

Kerri Smith:

Yeah. And I would say it really came across when Richard and I went to talk to Ali, and we had her try to explain, you know, what her scientific aims were, and we tried to understand them. And she was just really into it. I mean, it was so nice to see she was really clearly very motivated by her science and really excited by it,

Benjamin Thompson:

In terms of the process of going about this, in your experience is this, how you would go about a project, just go up and see someone and then keep going to see them and see where it stops.

Kerri Smith:

I think we thought we might follow them for a year and then see what happened. And then we thought two years and by that point, it was getting a little bit of a strain on resources, because it had been a long time. But you know, they hadn't published a paper yet there wasn't anything concrete to sort of say, Well, here's where the story should end. But that was the beauty of this, as well as the slight fear behind this project is that they were going on a journey, but we didn't know what kind of journey and we didn't know what kind of shape it was going to be.

Heidi Ledford:

Do you guys remember some of the rides back to London from Sheffield, where we would sit, and we would talk about how is this story going to end? And what is it going to say? And you know, and we just couldn't see it at the time. And then I think over time we got quite involved in the funding applications. And we saw that as maybe a logical stopping point. But we were also you know, sort of on the edge of our seats, waiting to see how things were going to turn out and everything. So it was an interesting experience, because we really didn't know where this thing was going.

Benjamin Thompson:

I do think you're right that that funding is such a central part of this story, and it's really hard to avoid it.

Heidi Ledford:

Yeah, I think also the fact that, you know, we ended up sort of waiting so long for a resolution to some of those funding applications, it kind of shows also, you know, one reason why it takes a long time to get a paper out, because the researchers have to wait for these funding cycles. And it's a long time by the time you've written the grant and then submitted it and it's reviewed. And there's so many steps along the way.

Kerri Smith:

Yeah, I guess we thought at the beginning, we didn't know whether it was going to be funding that was the driving kind of force behind the narrative or publishing papers or them becoming managers of teams, we didn't really know which aspect of that was going to give us the most interest and the most jeopardy. But certainly it became quite clear that money was, you know, the biggest preoccupation.

Benjamin Thompson:

Heidi, you and I have worked in labs before. And I guess maybe I wasn't necessarily too surprised by the scientific enterprise, right? I know that it's slow. And I know that you need to get the money and all the rest of it. Kerri and Richard was that something that stood out to you at all? I mean, I guess we've worked in around science for a long time, right? But was there anything about how science happens in a very real sense that was interesting or unexpected?

Kerri Smith:

Yeah, I think the pace was a little unexpected. Even for us having worked at Nature for as long as we have, we should know than we perhaps do about it, and Richard, has been, I think, continually surprised during this project of how long it's taken them to get some science done, I keep remembering you saying, ‘When are they going to publish a paper? When are they going to do it?’’

Richard Van Noorden:

Yeah, I mean, spot, the person – me – who didn't actually do a PhD. But, you know, I was amazed that we've come to this project now in 2021. And Dan and Ali’s groups haven't yet published a paper of the science that's been done during their labs, it's coming, I'm sure. But that's partly because a lot of their work has just been about setting up the tools in order to examine the thing they want to be doing, and to show that that is possible. And that's par for the course.

Kerri Smith:

I didn't do a PhD either. So some of this was new to me. I actually felt sometimes bad asking them like ‘So any new results? Any new papers?’ Because I could sort of feel like they were like, ‘Ooh, well, nothing really to report some incremental stuff.’ Yeah, and that made me feel a bit kind of cringe asking those questions.

Richard Van Noorden:

Yeah, I mean, when you report you're just always reporting on some exciting thing that has happened. I mean, otherwise, why are you reporting it? In this case, you know, things didn't happen and in some cases, things went backwards. Ali’s microscopy experiments are going well and then they just didn't work at all and all of the progress she thought she'd made that like it could be undone. And that's just the way things are. So just seeing that happen, you know, and, hey, maybe in five or 10 years, some of this is going to result in a story and all of what we've looked at here will be passed over as ‘In the early years they struggled.’

Kerri Smith:

Yeah, don't you read methods sections quite differently now when they say ‘We decided to engineer a line of mice that lalala’ and you're like, ‘Oh my god that probably took you seven years.’

Heidi Ledford:

And I think maybe just to add a counterpoint to Richard and Kerri’s experience, you know, for me, if they had gotten a really solid paper out within three years of starting a lab from scratch, I would have been kind of surprised, actually. And I think, you know, Ben and I maybe have personal experience with being hung up on some of these basic molecular biology steps in a lab where you've planned this beautiful experiment, and then all of a sudden, just the most basic step that you didn't even give a second thought isn't working, and you're stuck there for months.

Benjamin Thompson:

And Ali and Dan opened the doors, and let us be there and stick a microphone underneath their nose in these moments when they were trying to, you know, get something to work. I mean, that's kind of interesting as well for a couple of reasons for me: one is when we talk to our editors, they’re like: ‘So what happened?’ ‘Well nothing.’ ‘Like, when’s it coming out?’ ‘Well we don’t know yet.’ Like it's difficult to kind of plan it in. But also there's more personal maybe than there is science both in the written one and in the podcast as well. So, I mean, did that require a bit of different thinking for you all, do you find it quite rewarding in sort of flipping it around and in that way, given that we often don't get a chance to.

Heidi Ledford:

I mean, I think the personal is really fun to write about when it comes to just sitting down and writing. And it sort of takes very little writing, because you just, it's the reporting, right? And it's the details are just so I guess emotionally interesting. But I think as far as the reporting goes, I think we asked them a lot of questions about science for a long time. I think it took us a while to sort of realise, ‘Oh, we're actually going to strip out a lot of that and focus more on the personal details.’ And, yeah, so they were very patient with us, you know, I was there for a lot of the interviews with Dan. And, you know, we just had him go through it over and over and over again. And then in the end, you know, just a few sentences in the story.

Kerri Smith:

But it does help you to understand if there is an incremental advance, or it looks incremental to us, but they're very excited about it, it does at least allow us to put that across to readers in the way that it should be put across. So maybe some of the work was worth it.

Benjamin Thompson:

I guess maybe the microscope scene with Dan is a good example of that. He's obviously, you know, quite a softly-spoken guy. He doesn't necessarily go, you know, full punching the air. But seeing that microscope sample being like the first person ever, Richard, I think it was either you or me who said ‘Are you the first person on Earth has ever seen this?’ He's like, ‘Yeah, pretty much’.

Heidi Ledford:

Yeah, that's the nice part of science, I think, when it finally works.

Benjamin Thompson:

But also they were very generous with their time for some very personal moments, as well, of course. And it would be easy to say, like, ‘I can't talk to you now. I've been turned down for this million pound grant. Ben, I just don't wanna talk to you right now.’ But they were so gracious with ‘Yeah, let's talk about it.’

Kerri Smith:

Definitely. I mean for them to say, yes, I'll talk to you before and after every single interview for you know, this million pound grant that could sink or float my lab. I mean imagine yourself in the same situation, so much adrenaline. And you know, they were so generous with their time in those moments.

Benjamin Thompson:

Well, one thing that I've been reading up a little bit about before we have this chat, I've been delving into the world of quantum mechanics, because of course I have, right? Why wouldn’t I have done ahead of a chat about following two scientists for three years. And the ‘observer effect’, right. So if you look at something, you change it,

All:

Ahhh

Kerri Smith:

That’s what’s happening.

Benjamin Thompson:

You can see where I'm going with this one, right? And so often, when we're reporting we're not part of the story, we're telling the story. We’re to one side as best we can be, right? But this one is very, very different. Have you seen a change in Ali and Dan, as we followed them through these years, by observing them by being there with them, do you think they've changed?

Richard Van Noorden:

Well, I think Ali, and she has said this herself, has become more confident about presenting her science, and explaining sort of concisely, what it is that she's doing and how it's different from other people. Now, I don't know to what extent that has been due to us repeatedly asking her to explain it again. She's also, obviously, as you've heard, had lots of interviews and won a grant, and so on. So all of that will have led into it as well. But I do think there was one point at which she did say that having us around, had really helped her hone her explanations, which did lead us to thing ‘Hang on a minute, have we inserted ourselves in this story?’ But you know, in the end if it helped, if it helped, and we didn't provide any coaching along the way. At least I don't think we did. But I mean, in the end, we tried as far as we could to simply observe what was happening in the David Attenborough sense. And, you know, let them get on with it.

Heidi Ledford:

I think Dan said something similar. I think for Dan, it was a matter of explaining things in a way that a non-specialist could understand. And when you've been a postdoc for a long time, and you're really immersed in the details, and you care a lot about the details, and then, you know, becoming better at explaining your research to a wider audience is, I think, part of being a PI as you have to pitch for grants. And, you know, just explain things to your undergraduate students or to other colleagues in other fields. I think it's, it is part of becoming a PI. You know, he says that by talking about it with us that he feels that he's gotten better at it, but I think he would have gotten better at it, you know, without us. So, it's hard to say,

Kerri Smith:

I wonder, and this is speculation, whether knowing that we might ask them about any aspect of their experience in their work has led them to self-examine more. I mean, Ali seems quite big for that anyway, I would say. And I think they both deeply process what's happening in their lives and they would always have an intelligent response to give you about it. But I think if I was being asked every month, what I'd just done in my working life and how everything was, I might start to sort of make more mental notes, I guess. So I couldn't speak for them and I haven't asked him this question. But I do wonder if you know, the experience of being followed. It sounds sinister, doesn't it? By four of us. And at any moment, you know, wondering if someone's going to ask you a question about something whether you, you start to sort of look at your life a bit differently,

Benjamin Thompson:

And flipping it on its head, do you think it has changed any of yourselves at all, maybe? Because I know aspects of their life very, very clearly. Right? But I don't really know them at all, right. Like, we're not friends. But there is that kind of strange, sort of, aspect to this whole thing as well.

Richard Van Noorden:

I think that's some of the joy of being a journalist, you get to ask those questions. But you've always got to be quite careful about the distance between you and the people you're talking to. And as you say, you're not really their friends. So I would say that on this project, we just got to ask more of those questions over a longer and more sustained period of time, which was almost better, because sometimes you have to try and create an instant rapport with someone that, you know, you may not speak too much again. And they were very open to answering those questions. So we got all of this emotional insight that we maybe wouldn't normally get.

Benjamin Thompson:

And I think one episode where there was a lot of sort of emotional insight, and we have to discuss it really, was Dan's accident when he was very, very sick. And I mean, I speak for all of us, we're really pleased that he's doing okay, right. But I think that's a fine example, where I can say, when we were on the video chat talking to them, and they were obviously very, very sombre, and laying it out, my bottom lip was going, like I was I was really cut up during that. It was a difficult conversation to have. And obviously, you know, things, as I say, working out all right, but it really got to me that conversation.

Heidi Ledford:

Yeah, I mean, it really did. But it happens to me, sometimes. I don't have to know someone for a long time, you know, for those sorts of stories to be hard. And sometimes we do biomedical reporting, and you want to have the perspective of someone who's been directly impacted by a particular medical condition, you know, and you'll talk to, a parent or someone who's directly been affected, and you're trying not to show, I guess, the whole time, because you don't want it to be about yourself, right? I mean, there have been times where I'm sort of trying to cry quietly, while I talked to them, and I think, yeah, that was one of those.

Kerri Smith:

Yeah, I mean, in the conversation where he told us, they made a decision to tell us, right? They didn't need to, because there was a little gap between catch ups. And this accident had happened. But he was pretty well recovered by the time we caught up and actually heard the full story. And he was very keen that we did include it in our story and put it across as something that does, unfortunately, happen to a small amount of people.

Heidi Ledford:

Now, he said it's important to talk about these things. And that's, I talked to them again this morning. He said the same thing again, you know, I said, ‘I really hate asking you about this event, because I know and I feel like I'm making you relive it.’ He said it's important to talk about these things.

Benjamin Thompson:

Well, I mean, that was clearly something that we had to include, right. And so you know, it kind of had to go in at the end. That was where the chronology was. But of course, the pandemic happened as we were starting to wrap things up as well. I mean, how do you know, when a story is finished, like these are two momentous events that seemed really important to include. But is there a scenario where we said ‘No, you know what, we just can't’?

Richard Van Noorden:

Well, I mean, I felt a bit like what I imagine Peter Jackson must have felt like when he was doing Lord of the Rings, because there just seemed to be multiple endings. And it could go on and on. I mean, of course, he was telling a fictional story. So, you know, I think it was harder for us. But you know, there were events happened. And then the more events happened, and they were all important and critical, really, to charting Ali and Dan’s life. And at one point, it did seem like we would never stop, but we had to stop. So I think in the end that, you know, once Ali had got her grants, once the labs have gone back, and once Dan seems to be on the way to recovering, you know, that does seem to be a natural place to end. But we could have carried on for longer.

Kerri Smith:

Yeah, I think we were probably ready to publish some form of this story when the pandemic really sort of took over everybody's world. And it would have been a strange story to publish in the beginning phases of a global pandemic, and it possibly would have just sunk and not been read properly. And also, of course, we know that the pandemic had big impacts on how they and other scientists did their work. So it seemed essential to mention that but of course, then the whole thing is still going on. So here we are.

Benjamin Thompson:

Well, in this three year project, any moments that stood out to you that maybe didn't make the story, but you really, really enjoyed hearing about.

Richard Van Noorden:

I think one thing that I really enjoyed was going on a walk with Dan and Ali in the Peak District, which was incredibly windy, so windy, that listeners will not hear this because it's really just white noise. But yeah, it was nice to see the kind of way they take time off from their working day. Sheffield also has some beautiful botanical gardens that we walked through with them on Ali’s route to work. And that was probably a big highlight for me, actually. When we spent a weekend with them to really get to know them very well. Ask them how they met each other, go to dinner, go for a walk. But yeah, it was a lot more difficult to record that side of it.

Heidi Ledford:

I thought that was a beautiful moment of absurdity, that whole walk actually, because we're all wired up with microphones, and we're going to go on this little walk. And I remember, I had gloves and maybe a hat with me, but I sort of looked around, I thought, ‘Hmm, no, not gonna need that.’ And so I just left them in the car. And then we start walking. And I think Richard was dressed for an event later that day, and when we go back to London, you had some sort of a, like a family event. So you had like, nice trousers, and nice, you know, dress shoes on, and the walk is fine at first, but then we start sort of scrabbling a little bit over rocks, and then the wind picks up and I'm freezing, and all five feet of me, I'm just trying not to get knocked over by the wind and we have these microphones on, there's no way we're gonna get any sound. And it was just this hilarious, sort of, you know, two Londoners set off into the Peak District, woefully unprepared.

Benjamin Thompson:

I will say that I did spend a good couple of hours, like, I can rescue this audio. Yeah, there was, there was no way. It is lost, it is lost to time, I think. But Kerri, anything for you that stood out do we maybe didn't talk about in the podcast, or in the written feature.

Kerri Smith:

I guess one thing that we maybe mentioned on the fly, because we did spend, as we've said, a long time talking to Ali about her science, and I already have a soft spot for neuroscience. But at one point, she was talking about the particularly long axons that run you know, down the spinal cord. And some of the proteins that she studies, if she was to study them in the axon that's living, they take, like, weeks to get from one end to the other. And it just gave me this great kind of image of how easily something like that could go wrong in a disease and how important it is that people like her want to study the basic sort of molecules that make up these sorts of processes. So it's very different from a rainy, windy walk in dress shoes. But, you know, listening to her talk about that, and finding some really accessible examples was certainly a highlight for me.

Heidi Ledford:

I actually, I remember learning that for the first time from this experience, and thinking that kind of changes how I think of the body working in a way, I mean, because it's just so slow. I mean, if something takes weeks to go down that far, you can't respond to changing environmental conditions, etc, etc. And it's just yeah, that kind of blew my mind.

Benjamin Thompson:

What do we think that this project has achieved? Now that it's written and the podcasts and made, like, what is it done?

Richard Van Noorden:

I think it's given an upstream view of science as it's done. This is just what life is like. I think it's something that journalists really struggle with, not to tell the triumphant struggle, the story that fits neatly into one of the archetypes of how all stories are told, because we all know that that isn't how science is done. But it's hard to find ways of bringing that across.

Kerri Smith:

It was a real pleasure to get people to say yes to this as well. I mean, we've just been so lucky to work on this, at times, it's felt reasonably overwhelming, but to have people say yes to this project, crucially, to have Ali and Dan allow us to follow them for three years is a really unusual opportunity. And I think something that I'll look back on with a lot of pleasure.

Benjamin Thompson:

And last one then, I mean, can you envision or, I mean, would you like to do something like this again? How's that for a question?

Heidi Ledford:

I keep threatening them with a sequel. Yeah, we'll just check in again, because we've done about five last interviews with them, right? So, you know, in a few years, we'll do the sequel, we'll be back. I would love to do something like this again, actually.

Richard Van Noorden:

Yeah. I mean, so some things that inspired us, as we were doing this kind of project was stories that we and other people have done, where you're in a particular situation, like I've been for 24 hours in a synchrotron, which was very tiring. And when you get locked inside a synchrotron at 3 am, because your passes aren't working, quite frightening as well. And, you know, we have read and listened to great stories where journalists go to a place: the border between the US and Mexico; or the Arctic; or just a diner at midnight, and just report what goes on there. And these stories are situated in particular places in time. And here, it was just such a really open-ended and amazing thing to be part of, and I'd love to do it again, I don't know what I've learned that I would do differently, because I think the hardest thing is that you've got to suck up every detail. And you've got to keep sucking up every detail every time for years and you don't know what's gonna come out at the end, and so much must be discarded. So, yeah, I'm excited to find out what listeners and readers think. But having chatted about this with all of you, I think that maybe our next project should be that some journalists should follow us while we follow some scientists, because I think listening to our reflections is a really interesting discussion about what journalism is, as well as what science is.

Benjamin Thompson:

Is this where we get the Mandelbrot, someone follows them, following them, following us and it goes on forever, right?

Kerri Smith:

I'm not greenlighting that!

Benjamin Thompson:

Well, I think that's about all we've got timefor, for this very special bonus episode of ‘Starting up in science’. Of course, listeners, you can find the podcast and you can read the feature over at nature.com/news. But for now, all that's left to do is say thank you to Kerri, Richard and Heidi.

Heidi Ledford:

Thank you.

Kerri Smith:

Thanks.

Richard Van Noorden:

Thanks.