NEB Podcast #34 -
Interview with Kate Creasey Krainer: Enabling Global Agricultural Growth

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Transcript

Interviewers: Lydia Morrison, Marketing Communications Writer & Podcast Host, New England Biolabs, Inc.
Interviewees: Kate Creasey Krainer, Ph.D., President & Founder, Grow More Foundation


Lydia Morrison:
Welcome to the Lessons From Lab and Life podcast. I'm your host, Lydia Morrison, and I hope that this interview offers you some new perspective. Today, I'm speaking with Kate Creasey Krainer, founder of the Grow More Foundation, whose mission is to help end world hunger by bringing synthetic biology tools to developing countries and enabling communities to grow more fruitful crops.

Lydia Morrison:
Hi, Kate, thanks so much for joining us today.

Kate Creasey Krainer:
Thank you, Lydia. It's a pleasure to be here.

Lydia Morrison:
So, you're here today to tell us about the Grow More Foundation. Could you tell us what the foundation's all about?

Kate Creasey Krainer:
Well, it's about applying plant science. I'm a basic plant scientist by training, and, you know, for the longest time, we always want to actually see the application of our work. And it's, sort of, very rare. This is predominantly due to the fact that plant biotechnology, to take it from lab to field to table, is really expensive. The regulatory costs associated and the time from development to product is just ... In my opinion, it's worse than drug discovery and development.

Kate Creasey Krainer:
But, then again, hunger and food insecurity is pretty much the biggest disease that will affect us, so why not see biotech food as the potential cure for that? And so, Grow More Foundation was founded five years ago, where a group of plant scientists came together and were just like, "Okay, then, let's see if we can use some of the basic science that we dream about applying in the lab to an actual problem, predominantly in developing countries, and see the outcome."

Kate Creasey Krainer:
And this really, really wouldn't be possible if it wasn't for the advent of CRISPR. CRISPR technologies and the evolution of the regulatory process mean that really the time is now for applying plant science and CRISPR to solve agricultural issues around the world.

Lydia Morrison:
Interesting. So, how are you go about applying this science? How are you getting the science into, sort of, the hands of the growers?

Kate Creasey Krainer:
Basically, it's all about the connections of scientists in the developed world and in the developing. And then, scientists in the developing taking on their work to share it with, not only the top-down, the policymakers and those in charge of the regulatory decisions, but also the bottom-up, the consumer and then the growers themselves, the smallholder farmers. And our approach is basically, will we be able to provide capacity-building resources that can have an impact all the way through, not just in the lab for the fun of the science, but really solve problems that are affecting the people in that community and that country.

Kate Creasey Krainer:
And so, it's obviously a very big problem, very big issue that decades other groups have been involved in this kind of work. It's going to take more than one organization. But we're just focusing predominantly on plant science and how that can be applied and have an impact.

Lydia Morrison:
So, as you're thinking about how that can be applied and have an impact, is that what led you to develop the Enable platform?

Kate Creasey Krainer:
Exactly. So, Enable, enabling others, it's the arm, the actual functionality of Grow More Foundation. So, we envision many Enable kits, but for the first one, Enable 1.0, is Enable gene editing. And this has been a wonderful collaboration with Dr. Florian Hahn at the University of Oxford and NEB. If it wasn't for New England Biolabs providing our reagents... These kits are basically made up of a cloning system, where the user will just basically learn how to apply CRISPR to their plants.

Kate Creasey Krainer:
So, we're talking about a simple two-step mechanism for cloning in the components that are necessary to CRISPR to knockout deletion system. And this is what scientists and why my colleagues in Nigeria, Ghana, Ethiopia are really excited about this technology. But the majority of the time, scientists in developing countries, they always feel like they have to leave their country to learn the technique, especially the newest up-and-coming biotech.

Kate Creasey Krainer:
And so, it's an issue that they can't get hold of it, or the education or basically the understanding of applying the new technologies. But majority of time as well, the technologies are predominantly developed for model species to economically important crops. And so, we developed the cloning system for basically, predominantly for orphan staple crops, so these other crops that don't receive as much funding or attention traditionally and a bit more complicated to work with because there's a lot of protocols that need to be worked through. But our hope is basically with Enable gene editing being our first cloning kit that we provide pro bono to developing countries, we'll enable the scientists to take on this new technique and apply it to whatever problem they see fit.

Kate Creasey Krainer:
They're solving their agricultural issues themselves. We're providing a resource, but they're the ones doing the work with their own hands, in their own lab, for their own outcome in their own country. So, it's all about enabling. I personally don't believe that people in the developed world should be solving the problems for those in others and that the scientists in the developing countries are more than capable of doing this work. It's just a case of giving them the resources in a very, sort of, simplified and starter process. They wouldn't normally get hold of the first thing about setting up a CRISPR experiment.

Kate Creasey Krainer:
I'm always invited to give lectures, seminars, workshops, and I always find it's very difficult. Obviously, the Zoom issue with COVID, everyone's aware of. You really need that hands-on. So, as many times I've given talks about how to go about searching for a gene candidate, or identifying a guide RNA, or just even how to do the stitching together of the vectors through the Golden Gate System with type II restriction enzymes. Unless you're really doing it yourself with your own hands, the molecular work, it, sort of, doesn't have the same kind of resonance of what I think could really make a huge impact, especially if the regulatory decisions go the way that they're predicted to, based on what I've heard from my colleagues in Kenya and Nigeria.

Kate Creasey Krainer:
So, it's really just about getting that resource to the people and then them deciding how they apply and what they target.

Lydia Morrison:
Yeah, it sounds like you're doing a great job empowering those local individuals to really take the reins of their own crop development. How do you provide the training so that those people can realize the functionality of the kits?

Kate Creasey Krainer:
Right. So, the idea is that the kit is that simplified that any scientist with Ph.D. students, they basically get it in the hand and follow a protocol, understanding it comes from the complexity of there's control guides that can be cloned, but to understand basically the simple, molecular cloning pathway. And then, we hope that these kits not only will be used for scientists to apply to their problem but also in their teaching programs, so they can train the next generation to just be exposed to this technology.

Kate Creasey Krainer:
We know that videos are going to have to supplement whenever we can't physically have people there to demonstrate the use of the kit, but the kit is really designed to be that straightforward that anyone with a basic rudimentary molecular background and can hold a pipette can follow the microliters and the timing. There are a few other pieces of equipment that are necessary. For example, for restriction ligation, they need the PCR machine, a thermal cycler, but it's pretty much if they're able to do any kind of cloning, which molecularly, it's what we tend to use in biotechnology, they'll be able to perform CRISPR.

Lydia Morrison:
That's really great. And so, what's the adoption been like?

Kate Creasey Krainer:
Well, because of, obviously, the setbacks of 2020, we are still yet to send out our beta testing kits. And this is really frustrating because we want to see how all the different issues that we might face when we're trying to get these reagents in one piece and usable when they get there, but also the feedback of what we might need to change and literally edit in this editing system.

Kate Creasey Krainer:
But the desire for these kits is very strong. Again, the colleagues that I've come to know in the last couple of years of listening basically to the scientists in these countries that are wanting ... They've heard about it, but they think it's something that's a lot more difficult and challenging than what it really is. I try to explain to them, actually, the difficult part, when it's not the genomics, which is basically upstream, is a completely separate part to CRISPR. It's actually the transformation and regeneration. That's the trickiest part for getting any technology into the plant.

Kate Creasey Krainer:
So, the middle part, the actual molecular part with CRISPR, it's very straightforward. It can be made as complex as you need it. So, you're swapping out restriction markers, swapping out promoters, the bits that make it expressed in the plant, but in our simplified kit, it's just giving them an introduction to how it works. And then they can actually, after two weeks of doing the cloning, get it into their plant and see the outcome. So, it's just a really amazing technology, and scientists in developing countries should have access. They should be enabled to have it and shouldn't rely upon trying to forge new collaborations elsewhere in order to utilize this skill, this technique.

Kate Creasey Krainer:
That's the same for any biotechnology that's developed. The next new wave of technology, that would be Enable 2.0, Enable 3.0. The idea is to grow as the science develops but make it specifically applicable to orphan staple crops. Whether that's codon optimization or looking for new promoters or just doing feasibility and, sort of, testing, but to see if it actually can go to plan as easily as we envision or aim it to be to simplify it down as much as possible.

Lydia Morrison:
Yeah, that's amazing, and a really surprisingly quick workflow, I think, too to be able to actually get those genetic edits into the crops themselves.

Kate Creasey Krainer:
Right. I mean, it's taking advantage of the cellular repair mechanisms for double-stranded DNA breaks. That work's been out for decades. We're trying to understand how to actually lead to different repair mechanism to then lead to more edits. It's still, sort of, anything can happen, but in terms of the biotech, to go through each stage, it is less expensive and quicker than other techniques.

Kate Creasey Krainer:
I mean, for gene editing, which, obviously, the advent of TALENs and zinc fingers years ago, CRISPR, sort of, just exploded, and everyone should be able to apply it to their plant if they want to. It's always been, sort of, associated with developing countries. The science has always been a little bit behind, not benefiting ... Their orphan staples never benefited from the Green Revolution as much and from the genomics era. The orphan crops were lagging behind with their genomes.

Kate Creasey Krainer:
But as that gets more affordable, more accessible, it really is the right time to start actually applying some biotech, which before now, the classical GMO transgenics, because of that 100 million-plus and decade to get it to a product, it's not surprising that very few, if any, scientists were thinking of strategies to develop a product from it. It would have been impossible, practically.

Kate Creasey Krainer:
I mean, even you can tell with vitamin A, the Golden Rice scenario, Rich Roberts' great effort to lead the Nobel Laureates to get Green Peace to agree that this supplemented biofortified crop can actually do some good and should be allowed and accessible. But because it's made with the transgenic technology to overexpress the beta carotene, it's been a massive undertaking. So, lives could have been saved, and lives could have been changed and impacted from the 90s when this was first developed, and it's only, sort of, now, in the last couple of years, that some countries have even deregulated it.

Kate Creasey Krainer:
So, when it's an economically important crop, and it's a trait that impacts the farmer, that's where the classical transgenics was focusing on because of the costs, basically. If it was an academic process, it needed industry collaboration to take it all the way. And now, with CRISPR and the evolution of the regulatory landscape, certain countries are still deciding. And the ones that have made a decision ... For example, in America, if it's no foreign DNA, not a transgenic. It's considered molecular breeding, and therefore, doesn't go through that costly, timely, regulatory pathway. So, I think there's a chance some real good could come out of applying that technology.

Lydia Morrison:
So important because you're communicating the science behind it really well, and that increased understanding of what's actually being done when you're editing a plant genome for a crop can only help increase acceptance of the technology.

Kate Creasey Krainer:
You know, it's a chance for scientists with different kinds of budgets to actually apply to their own crops without needing, kind of, the usual industry collaboration, which means it doesn't always have to be a trait that will impact farmers, but it could be a trait that will be a benefit to the consumer in a crop that wouldn't normally ever receive the kind of attention that an economically important crop would.

Kate Creasey Krainer:
So, I think it's really leveling the field, basically. It's giving any scientist a chance to do some great work, and the outcome can have an impact where there isn't this huge association with costs. But then again, there's always licensing issues as everything goes with patents. But there's some great groups that basically make sure that any benefit for smallholder farmers in developing countries, there's a regulatory pathway that will enable them to take it to product development.

Kate Creasey Krainer:
But we're at the very early stages there. I mean, it would be wonderful to see the actual impact of our products within our lifetimes, basically. And I think CRISPR is allowing that to happen sooner. Fingers crossed, and as Grow More is just developing, we're listening, basically. None of us are, as plant scientists... We obviously enjoy the work. We're excited by it. We want to think about those problems and address whatever issues it is in the process of the crop. And these orphan staples, there's lots of issues that need to be addressed to get systems, from which variety to use or which particular tweaking of the technique for getting regeneration.

Kate Creasey Krainer:
That's what I really enjoy doing. But if it's not getting the chance to be out there and utilized and understood, that's an issue. And then you hit exactly on the problem of society's acceptance, which, again, it's all about the scientists in their own country having this opportunity to share and communicate what they're doing and how they're doing it. And they have to do that both approaches. Unfortunately, some scientists I've been speaking with, that's exactly what they're doing.

Kate Creasey Krainer:
Leena Tripathi has done some great CRISPR work in plantain, and Eric Danquah in Ghana, who's basically founded organizations to not only train the next generation of scientists but really make sure that Ghana's in an impactful place for the crops that they like to grow and consume themselves to get those techniques to apply to them. So, there are some great scientists that are already undertaking this work in developing countries, and it's just a case of, well, how can Grow More come in and provide a resource or facilitate in any capacity because it's just enabling. They can do it themselves. We're not providing the solution. We're not helping anyone. It's just colleagues communicating.

Lydia Morrison:
Yeah. I think that's great, and it definitely sounds like Grow More is working really hard to enable and empower those individuals in developing worlds to do just that. Do you have any stories of things that have happened during quarantine that have been good for you?

Kate Creasey Krainer:
Other than being terrified of loved ones, friends, family catching COVID, or even ourselves. Although, as soon as the first initial, kind of, it came out, as scientists, my husband and I just, sort of, buckled down. We didn't go anywhere, and we didn't do anything. Well, we worked at home. Zoom became very much a daily situation. We would normally travel at least once a month, if not more than that. My husband would travel pretty much every week, nationally and internationally, pretty much three continents in a space of two or three months usually.

Kate Creasey Krainer:
So, it was a very... For everything just to stop was very different. Even the students at university, it was kind of like, "Okay, getting used to teaching online but no one going in the lab, nothing getting done." So, getting over the initial shock, changing some working habits, but I was actually okay. I feel like it was a break needed for me. Normally, I wouldn't give myself that break, so the whole of 2020 turned to be this one long break, month-to-month thinking it was going to change even though nothing did.

Kate Creasey Krainer:
We had both said we're not going to, obviously, go anywhere until we get the vaccine and just taking a break from everything. It was really lovely. I hadn't felt that good for some time. So, it's great. I mean, I basically call 2020 my year of peace because of how much I couldn't do because of extenuating circumstances. And it really gave me a chance to, sort of, reflect on well, "where is Grow More going, how can we develop, how can we grow?"
Kate Creasey Krainer:
When I provided the foundation's endowment, it was, sort of, in the mindset of "right, this is to basically start preliminary projects to test what could work and how things could develop" to then the usual seek the collaborators and more funding for having impact. So, it gave me a moment just to kind of ... Everything had stopped, so I could stop, and then, "right, what have we achieved, where is it actually going, what would make a difference?" Because that's pretty much what I ask myself every day, which is unusual because for most of my training and my academic career, Ph.D., post-doc, prof, the problem was so focused.

Kate Creasey Krainer:
So, I could always feel like I made some kind of incremental progress because I always saw how it was going because of that focused problem. But starting Grow More, it's like, the focus just exploded. It's not a particular crop. It's all different crops. It's not just a particular country. It's all different countries. It's not just a particular technique or a particular technology. It's any of the new and up-and-coming. So, it's, sort of, yeah, even for me, it's a bit much.

Kate Creasey Krainer:
So, I was able to make such an amazing network of collaborators, advisors in all aspects of plant fields, from agronomy and plant breeding to the biotechnology in CRISPR. So, it's been wonderful just how many of my colleagues have been very happy to come together and discuss where they think it's going, and what should be done, and how it could be developed versus just listening, basically, to my other colleagues about well, what would they want. What is it they're needing?

Kate Creasey Krainer:
So, at the end of the day, that's what it's all about, I think, in science. We all dream of what we develop to be actually used and applied and have some kind of meaningful impact. It's not just a line on the ground about trying to solve food insecurity or SDGs, and it's not just something we say for the fun of it of this technology could have an impact in agriculture. It really, really could.

Kate Creasey Krainer:
We believe that. We wholeheartedly do, and I just hope Grow More is one of the parts of the puzzle that can just not only enable others to do the work but make sense in the fact that the sharing and the communication of everyone is key. So, we'll see. Hopefully, I'll have some updates to share in the future with you. Fingers crossed.

Lydia Morrison:
Yeah, we'd love to hear about them. And I hope the same thing for Grow More, and I'm glad that you were able to find a silver lining in a moment of pause in your year of peace to step back because scientists, certainly, are up close to the problem. I think it's really important to have been able to have that chance to step back and look at the bigger picture and the bigger impact. And I think Grow More is going to have an amazing impact on the world. So, thank you so much for founding it and working on this problem.

Kate Creasey Krainer:
Oh, just, fingers are crossed, and we'll see. But thank you very much for saying that, and it's just been a pleasure speaking with you today. Thank you to everyone at NEB because not only, obviously, having the connection of Rich Roberts on our board, but Carole Keating even just supporting Enable, the concept in the very first meeting.

Kate Creasey Krainer:
I shared with her the story about how I actually got an NEB starter kit in my first couple of weeks of my Ph.D. years and years and years ago at University of Edinburgh, and I felt enabled to carry out experiments that I wouldn't have normally done because the cost of the reagent or the idea was probably crazy. But it was my kit. It was my reagents. It was my little floaty. I could do whatever I wanted with it, and that was just something that was, sort of, also there with why Enable became Enable.

Kate Creasey Krainer:
I was listening to my colleagues of they wanted to learn these techniques, and then I remembered, "Okay, then, well, now I'm going to basically try and do the same thing for them by providing the reagents that I got once upon a time." So, yeah, Enable really is in part because of NEB.

Lydia Morrison:
Oh, thank you so much for saying that.

Kate Creasey Krainer:
Oh, please thank Penny Devoe as well. She's actually been orchestrating all of the communications and everything. So, big thank you to her and, again, to everyone at NEB.

Lydia Morrison:
Oh, thank you so much. That's so nice of you to say. I'm sure that the team would be delighted to know that they helped inspire the idea of bringing kits of knowledge to people. So, that's really special. And thank you so much for joining me today, Kate. It's been really a pleasurable conversation.

Kate Creasey Krainer:
Thank you.

Lydia Morrison:
Join us for the next episode when I interview Professor Jim Haseloff of the University of Cambridge about his work using synthetic biology to engineer plant growth and his efforts to further low-cost instrumentation and diagnostics.

 

 

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