North Sea ship crash, and super spuds

Five years ago this week, the World Health Organisation declared COVID-19 to be a pandemic. The virus that had spread from Wuhan in China went on to shut down the world; we estimate that 20 million perished; economies spent trillions, and the longer term effects - on young people’s education and job prospects and therefore ultimately their life expectancy - will rumble on for a generation. It showed us just how vulnerable the world is to emerging pathogens. Now we still don’t know where COVID came from, or what factors led to its spread in the first place. As such, it may well be down to human error and was, in effect, an “engineered pandemic”. What we do know for sure is that accidents happen, and dread diseases have escaped from labs on many occasions. Safeguarding against this happening again is the priority of an initiative being set up at Cambridge University called The Engineered Pandemics Risk Management Programme. It’s the brainchild of vet and immunologist Clare Bryant…

Clare - It's kind of a flexible beast. We had a meeting where we considered this quite carefully as to what actually is the definition of an engineered pandemic. And it can be anything from the deliberate release of a pathogen, or an accidental release of a pathogen, all the way through to somebody actually manipulating a pathogen to make it more deadly. But in all honesty, pathogens are pretty efficient at being deadly anyway. So we think the most likely thing that's going to happen is the potential for somebody to deliberately release a pathogen, or an accidental release will kind of make most sense.

Chris - Who's actually got the potential to do something like that? Do you need to be a government level actor? Or could someone just do this in their garden shed?

Clare - You do need the right facilities to handle these things. And we've also thought quite carefully about this. Overall, we think it's not highly likely, we think it's possible. And it's that possibility that we're really considering. And I think if you have the right kind of facilities, you can actually do this, but you'd need to be able to have access to a pathogen, you need to be able to grow it, you need to be able to have a means of distributing it. There's a whole host of complex factors, which make it less likely that somebody can do it from their garden shed.

Chris - So it's more the idea that accidents happen. And we need to be prepared for the fact that if you're working on these things, you could accidentally see one escape.

Clare - Potentially, yes. One of the key features then within that is if somebody gets sick, what's causing it? The difference between an accidental or an engineered pandemic versus a normal pandemic, so to speak, is that you usually have a bit of warning that something's coming, but with an accidental release, then you don't know.

Key to this is a rapid understanding of what something is in order to be able to institute an action plan. Those are the kinds of issues that we're thinking about. Beyond that, planning is pretty similar, whether it's an accidental pandemic or an evolving pandemic, because the action plan becomes pretty similar, but actually knowing what you're dealing with is the real difference for an engineered pandemic.

Chris - So, given you've identified that risk, what do you propose to actually do about it? What is this initiative really all about?

Clare - First of all, an important element of this plan is to work with policymakers to understand the potential risks, the potential strategies and what one might want to do about it. From the science perspective, we'll be thinking about model pathogens. What would a disease look like? How would we diagnose it? How might it spread? And how would we work out what's going on and how to intervene? What are the earliest steps to intervene? Rather than thinking about things in a pathogen-centric way, ‘this is all about COVID-19 or avian flu,’ we're actually thinking very much about more general rules that we can apply and learn from using existing data sets to actually learn what might happen and learn how to intervene.

Chris - You mentioned COVID-19, I was talking to the WHO's Director of Emerging Infection just the other day, and she said, we don't know where COVID-19 came from, arguing that they must be entertaining, seriously, the possibility that that was an engineered pathogen. So how does what you're proposing differ from the current framework that we've got to try to pursue outcomes like that?

Clare - In some ways, it does and in some ways, it doesn't. For us, our focus is very much on identification. And that is now a bit more of a challenge than it was because a lot of the surveillance programmes have been shut down. So, it's actually quite hard to work out what's going on globally and to distinguish exactly what's causing an infection. So, I think there's elements of similarity across both programmes, but it is very much thinking about likely candidates as well.

Prior to that, we were very focused on flu and perhaps we should have thought a bit more sensibly because there was MERS and there was the original SARS-CoV pathogen that came through. And we kind of all happily let that sit in a parallel universe. So I think the idea with this programme is to think very much about all possibilities and work accordingly rather than just focusing on one or two pathogens.

Chris - Is this unique or have you got competition or other people doing something similar and you're joining that party? Or are you really striking out on your own saying, well, look, no one's doing it this way. And this is what we're going to try and do.

Clare - I think there's a combination of factors.There are a number of pandemic centres around the globe. And that's good because we all need to work together. I think from our perspective, we're relatively unique in thinking about accidental and deliberately release and thinking about those first steps to begin with. And also, the other really important thing is that we're working with policymakers to make sure that we're thinking about this in the national scale and in the global scale, such that we can really think about ways in which we can inform government and help government and devise suitable strategies. I think those are the two elements that are a bit different about what we're doing.

Chris - What does your vision look like then? If we sort of wind forward in time, the mature initiative, what will that actually look like?

Clare - Well, what we hope we'll have is some really good plans that we can develop with government to say, OK, something's happened. What do we do? So instead of sitting there and making it up as we went along, which was a little bit like what we had to do in the COVID-19 pandemic., what we're really trying to think about is having formulated plans that we can work out what we would do, almost like a roadmap. What's the ideal roadmap you need to deal with a pandemic when it arrives? Also importantly for me, most people that get an infection, a pandemic-like infection, the people who die tend to die from a very severe inflammatory response.
And so we're reopening therapeutics to actually look at this area, which had been relatively neglected. And it was really clear during the COVID-19 pandemic that this is what was killing people. So, it's elements in and around that, that we'll be looking at detection, intervention, treatment and prevention.

Chris - But isn't this what the COVID inquiry is for? And that's taking years and costing millions, tens of millions.

Clare - The COVID inquiry is looking to find what went on. We're not looking to find what went on. We're looking for ways of intervening now using the data that we learnt from. I can't say many things were good from COVID-19, but a couple of things were. And the amount of data that's come out that allows us to mine that data and work out what was going on and work out what might go on under other circumstances is key. Understanding the mistakes that happened in the past will help inform what we do moving forwards, but we don't need to wait. We can move on and make sure we've got a roadmap that's lining up in place while we're informed about what happens from the COVID-19 pandemic.

As the world searches for more efficient and hardier crops to feed our growing population, one company has been looking into turning the humble potato into a super spud. The work was carried out with the support of UK Research and Innovation. Will Tingle has the story…

Will - Hi, could I get one large chips, please? Thank you.

Potatoes. Boil them, mash them, stick them in a stew.

We love potatoes here in the UK. In 2023, the average person here ate 66 kilograms of spuds. But the potato is in a spot of bother right now.

Extreme weather conditions like flood and drought are lowering the number of potatoes we can harvest here in the UK. Brexit has caused a labour shortage, meaning new potato farms are struggling to stay afloat. Further afield, Russia's invasion of Ukraine has greatly reduced the number that we can import from Europe's breadbasket.

And because of all these factors, the impact of any wasted potato is now felt exponentially more. So to see what's being done to combat these problems, I headed up to B-Hive Innovations in Lincoln to see what their game plan is now that the chips are down.

Vidyanath - Hello, my name is Vidyanath Gururajan. I am CEO of B-Hive Innovations Limited and we are a commercial R&D business in agriculture.

Will - In the pantheon of food, why did you go for the potato? I've spent nearly two decades of my life in the world of potatoes.

Vidyanath - Potatoes are one of the largest growing staple crops. It's exposed to a lot of climate change implications that we are facing. Now, I watched a documentary not too long ago called The Martian, in which a man called Mark Watney was stuck on a red planet. He seemed to subsist quite well on just potatoes.

Will - Is that another thing, another reason why you might have picked them because they are pretty omni-nutritious?

Vidyanath - I'm biased, but I would say yes. Potatoes and milk, I think the satiety that it brings can last longer.

Will - And was there a particular species of potato that you've focused on?

Vidyanath - In this particular aspect of the project that we are looking at, we got Solanum tuberosum, which is a variety that we picked called Maris Piper, which is the most known and used variety in the UK.

The second one that we picked for our experimentation is Solanum phureja, but you then make it a hybrid potato, bringing phureja and tuberosum together to create these varieties.

Will - What are the, I won't say design flaws, but what are the aspects of the potato that you're hoping to improve?
Vidyanath - I like the challenge, but this is a very interesting challenge that we are facing as someone who grows crops, because you've got extremities of climate change happening that you're seeing, whether it's too wet, no water at all, too much of sun, no sun at all, that has an implication on the crop.

The second thing that I would like to say is we are in an age where everybody's racing towards net zero. At the same time, the chemicals that we used to increase the productivity and therefore yield in the crop during the industrial revolution and agricultural revolution are being steadily withdrawn, rightly so in certain aspects, because of the pesticides used and everything else. And then finally, we also want the food to be as cheap as possible.

Simply put, these are conflictory challenges. A continuous improvement or status quo won't solve these problems. If we have to solve these together, I strongly believe we need to break the glass ceiling and that's where innovation comes in. And in this particular subject, I see gene editing as a very useful tool which could help us fast track our innovation to solve those challenges that I mentioned. So the key to unlocking a potato's potential lies in its genes. We all have a recipe book in our DNA that dictates how we look and act and the potato is no different.

The genes dictate how well a spud grows, how quickly it cooks, how resilient it is to hard knocks that would render it otherwise pretty inedible. So if we can tweak the genes responsibly, perhaps we can turn a puny potato into a super spud.

Barbara - Hello, my name is Barbara Cujalle and I'm Principal Research Scientist here at Beehive Innovations.

Will - How do you know what you're looking for? As in, how can you look at a strand of G's, C's, A's and T's and then go, that is what we want to alter or omit, this is what we want to do in order to make it hardier or quicker cooking, as opposed to something else where you look at it and go, oh that's just skin colour, I don't want to touch that bit.

Barbara - We have what are called reference genomes. So when you sequence and you have the information of the entire genome, you get this entire information. This is part one.

Part two then is actually a combination of what you have now acquired as your sequence genome and what you already know from other works that other scientists have done in the lab regarding these traits. So each trait, each capacity, ability of an organism will be defined with a gene in its genome. So we know which genes will allow a potato to cook quicker or to not bruise as easily.

So once we know what to look for, we go to our big puzzle and we find in our maris piper, what it is, and that's the one we will target in our studies.

Will - How do you then alter that gene in order to make it into what you want?

Barbara - We use a technique called CRISPR-Cas9. So this technique is actually not new, it's a method that was adapted from a naturally occurring process in bacteria. Bacteria use this to defend themselves from viruses, meaning bacteria are able to cut pieces from infecting viruses and insert them into their own DNA.

So this entire technology is based around this and the way we do this, we use something called guide RNA. So this will tell the CRISPR-Cas9, which is this enzyme that will cut, where it should cut. We use this guide RNA that's now, for example, targeting our bruising resistance gene.

We take it there with our guide RNA and then CRISPR-Cas9 will cut it. This cut makes it deactivate this protein, this enzyme, so it's a protein with a function. In this case, the function is to make the tuberosum go black.

So we cut it and it no longer works, meaning the potato now will be more resistant to bruising. The beauty of this is because you are targeting just a very small fraction of your organism, the remaining genome is exactly as it is, so we don't expect any unintended consequences in this organism after doing this process.

Will - That's reduced bruising. Are there any other aspects of the potato that you've been looking to snip out?

Barbara - Within this project, we're also looking at cooking quicker, and the reason for this is there are a few studies that have looked at the pheruja, which is this wild relative of our common potato, that cooks much quicker, in half the time. So we are also targeting this gene within maris piper, so this will have implications like using half of the energy when you need to cook it without, again, hopefully any other effects coming from it.

Will - I cannot wait for the day where I don't have to spend 30 minutes stood by my potatoes waiting for them to boil. Once you've taken out the genes that you don't want, how does that translate into scaling that up? Is it a case of you've then got your potato and you plant it and those genes are passed on to its offspring?

Barbara - Yes, kind of like that. We don't breed two potatoes together, meaning once you have this potato that has this trait, it will multiply it and all potatoes coming from here will have this trait. The only thing against us is there's only so many potatoes you can grow from each potato you have, so it takes time to have a large enough quantity to be able to plant large areas that will be commercially relevant, but it is a matter of time really.

Will - So the science behind a better potato is sound, but it is important to stress that this has to also be viewed under the lens of a business proposition. Whilst being a supreme technical achievement, having a better standard of spud is not much use unless it can be rolled out into supply and onto our plates. So how does this scientific wizardry translate out into the wider world?

Vidyanath - I would like to say it's very simple, but it's as complicated as gene editing, because it's not simple in the aspect of there's a new variety, let's just go and put it in the market. None of this has been nailed in terms of: this is how we're going to do it, because it's very much in its infancy.

Will - Let's talk about the policy terms. What classifies a variety?

Vidyanath - A variety has to be distinct. So if you are gene editing a variety, does it become a new variety or part of an existing variety?

The second thing is the consumer acceptance. As much as this is fun doing the science, would a supermarket stock a gene edited potato? And what are the implications of labelling? What are the implications of the consumer understanding the difference between gene modification, which is not what we're doing, to gene editing?

So there's a number of things that between us we all need to navigate and come to an arrangement where we could see this becoming a gene edited variety that you can buy. I do have my hope that within five years time, we should be in a position where these things have been boxed, released and accepted. You've got your potato.

Will - It looks great so far. But as you said, there's a wide range of foods out there that you're not so much competing with, but you are alongside. Do you ever believe that you might be crossing into a different type of food to create a more durable, better version of them too?

I firmly believe gene editing will become a very important tool if it's not already in the minds of people who are breeding crops. Our team now is working on onion crops, strawberries, a lot of brassica crops and much more. So these things tend to start with the humble spud and spread along any other crop that we can find that we can make value out of.