September 01, 2020

Biotech food industry inspiration

By Conor McKechnie and Dodi Axelson

The brewer, the baker, and the biotech makers

Biotech has taken inspiration from many places, including the food industry. Tune in as Dodi and Conor explore this topic and learn why biochemistry labs used to be near breweries. Cheers!

DODI: Conor, you know that old saying that imitation is the sincerest form of flattery?

CONOR: Yes. And it pains me quite a lot that there aren't lots of people walking around the business with no hair and big beards, but I can live with that. So what does flattering me have to do with biotech discoveries?

DODI: Well, you don't have to take it so personally. It's a question of flattering other industries. And I'm going to tell you that without baking or brewing, there would be no biotech.

CONOR: Okay, so we are standing on the shoulders of culinary giants. Is that right?

DODI: Yeah, maybe those shoulders are a bit bloated on bread or drunk on beer. But yeah, those shoulders.

CONOR: And that's what matters today.

DODI: Let's go.

CONOR: So, tell me does beer have a claim to be the first biotherapeutic, or are we going to say that bread was the first biotechnology that people came to use? What came first, the baker or the brewer?

DODI: Well, there are competing legends.

GUEST 1: Using fermentation and using bacteria in other parts of science, I guess that originates in ways from baking and making food years and years and years ago. Someone left a bowl of porridge sitting out in the sun. And after a day or two, it started bubbling and they tried to bake it. And it got even bigger. They learned how to make more food from less, kind of. And that must have sparked many ideas and questions about how we can use this in different ways.

GUEST 2: If you leave any type of fruit, it's going to ferment.

CONOR: So who have we got here?

DODI: Well, first, that was Anna, the baker. And then it was Michel, the brewer.

ANNA: My name is Anna Roswall from The Bakery. I've been working as a baker and a bit of pastry as well for about 10 to 12 years now.

MICHEL: My name is Michel Ahlin-Wigardt, and I'm the head brewer at Stockholm Brewing Company.

CONOR: So hang on a second. You went to a bakery and a brewery to record this episode?

DODI: My dedication knows no bounds, Conor.

CONOR: I think we need to do that episode on biotech raw materials coming from Chile and all sorts of exotic places, don't you think?

DODI: I think so, as soon as travel starts again. Yeah, indeed. But seriously, I did have good reasons to visit both Anna and Michel. Because together they showed me examples of what biotech has stolen or borrowed with pride from them over the years.

CONOR: Stolen seems a bit harsh.

DODI: Yeah, okay. Not my words. Those are the words of our good friend and colleague Nigel Darby.

NIGEL: Biotech is one of those industries that's lived up to a very good motto, which is steal with pride. Which is not about, as you might think, stealing other people's results. It's about having an open mind to what's going on in the rest of the world, finding technologies and ideas that you can bring into your own industry, and you can exploit to the benefit of your own industry. And I think interestingly, what you've seen is biotech developed essentially through people with very diverse backgrounds. I think that's the other important thing, diverse backgrounds coming into the industry and using technologies from outside the industry.

DODI: Nigel says this 'stealing' is not new.

NIGEL: Historically, if you think about it, biotech probably started maybe really 10 000 years ago, which is kind of the era when people first learned about the benefits of fermentation, whether it's the fermentation of sugars to produce alcohol or the acidification of milk products as a way of preserving them.

DODI: Beyond baking and brewing, biotech has also borrowed from another industry.

GUEST 3: The dye that's in your blue jeans, if you wear blue jeans, is identical or extremely similar to the dye that pathologists use to stain the nucleus of cells. And pink dyes that are used for staining, particularly silk, are very closely related to how pathologists study the spaces between the cells in a pathology sample. A lot of these tools are borrowed from the textile industry.

DODI: That's our colleague, Paul Goodwin, and he talks to us in a future episode about mapping tumors and tissues. So, look forward to that when we hear more from Paul Goodwin. But you know, thanks to the textile industry, we also have fantastic tools and filters for the biotech industry. Am I right?

CONOR: I think you might be. Let's get into specifics here. Can we focus a little bit on alcohol, on wine, for example, and yogurt? So, how old exactly is the invention of yogurt?

MICHEL: There is an intense political debate about where yogurt was actually first made and discovered. And we probably shouldn't get into that. But yogurt and fermented milk products have been around probably many thousands of years. I think historically, if you go back the furthest in time people talk about fermentation to produce alcohols, is perhaps 8000 or 9000 years ago. Yogurt came somewhat after that, but perhaps still, maybe 4000 or 5000 years old. And then as you got into the Egyptian period, you saw the use of yeasts for making leavened bread, which is perhaps maybe again 4000 years ago.

There's a bunch of very, very old technologies, which in a way is quite incredible, because you see many of the same technologies being used today for making some of the most modern drugs. So, you have this interesting kind of linkage between, I think when people first discovered yeasts, and we've got to remember that some of those yeasts are still in use today for manufacturing products such as insulin. You've seen this massive history, and that history has really contributed to the refinements of the technology.

CONOR: So, how have we taken the bacterial fermentation of milk and turned that into a biotechnology process?

MICHEL: That's been a long, long, long, long road. In a sense, if you look at it, we've known for very long about fermentation. Yeasts were probably first identified and used thousands of years ago. The practical understanding of yeast and what yeast does in a process or what types of microorganisms do in a process actually dates to relatively recent times when Louis Pasteur first showed that microorganisms were responsible for what we today call fermentation. Beyond Pasteur, again, the end of the 19th century, Eduard Buchner showed that it was actually, although they didn't use the term, enzymes in yeast that are responsible for the fermentation process. So, in a sense, the modern understanding of fermentation actually parallels the modern evolution of what we've always in the past called biochemistry. And that's probably about 150 to 200 years old.

CONOR: That's amazing. So we're using millions of years of biological evolution in our biotechnology. Just mind blowing. I mean, science has been progressing long before we were around. So, if we stick with history for a bit longer, what's the story exactly about how biotech learned from other industries then, either in terms of using materials or manufacturing?

NIGEL: It's really about being able to understand what goes on within a microorganism and how microorganisms catalyze certain types of transformations. Buchner's work basically showed that you didn't need the entire microorganism. You could break the microorganism and you could use a dried extract to catalyze the fermentation process. Now, interestingly, if you are my age, and I went to university first 42 years ago, I went to study biochemistry and many biochemistry departments sat next door to or were a part of brewing departments.

And this is a reflection that probably for 100 years, a lot of the developments of biochemistry were really around the detailed understanding of cellular metabolism, how cellular transformations took place. And a lot of this work used as the the sort of fundamental model, either bacteria or yeasts. And so, I say that from the period of the late 19th century through to the 1930s and 1940s there was a lot of systematic study of the metabolic pathways within microorganisms, which allowed us to understand how the fermentation process really took place.

DODI: That is the past. But if we think of biotechnology today, one of the current trends there is looking at additive manufacturing or 3D printing,

CONOR: This isn't just something that biotech came up with, right? It came from somewhere else.

DODI: And that is what I was wondering. Because to me, it seems like this is something that must have been borrowed or stolen with pride.

CONOR: So, it comes from somewhere else – aviation or the motor industry or...

NIGEL: First there's a concept that you could manufacture something essentially through a controlled build-up process around the scaffold. You can argue about where that idea originally came from. But essentially, when you started to talk about the idea that you can 3D print, for example, organs, again, that borrowed very much from the basic principles of assembly around the scaffold. And indeed, I think some of the technologies such as adaptations of ink jet printing are very similar technologies to those being pioneered in the use of 3D printing to assemble organs.

DODI: So, with all this talk of brewers, I started to get thirsty for knowledge, of course, as well as for beer, so I headed out to the Stockholm headquarters of the Stockholm Brewing Company. Alright, we are now in a room with many huge stainless steel vats, bags of wheat, and supplies. Anything could be happening in this room, we might be making medicine. As it happens, we're making beer.

MICHEL: When we are producing, we are brewing beer with all the steps that includes, and then we're fermenting the wort that we brewed.

DODI: Michel told me about the importance of yeast. And he thinks that we as humans owe yeast a whole lot.

MICHEL: Is this what made it approachable to eat grains? it's a lot easier to digest fermented grains than it is digesting nonfermented grains. And also, if you leave any type of fruit, it's going to ferment and you will have an intoxicating beverage, which most likely had an impact on people staying rather than going on and hunting and doing whatever they were doing.

CONOR: So, what's new? We've always liked to party.

MICHEL: Yeah, exactly. I think it's partially a human drive to find ways to escape reality from time to time.

DODI: And a big reason why brewing and biotech are similar, is that it comes to controlling the process of keeping things warm to keep them alive. But we also know when to cool them, too. When Michel talks like this, he almost sounds like a scientist.

MICHEL: We start off by crushing our grains or milling our grains. And that has to be to certain specifications in order to get as much out of the grains as possible and still having a filterability of the grain beds to get the liquid separated from the grains. Then we mash in, which is the process of making a porridge basically.

CONOR: So homebrewing feels like the 1970s again, when everyone had a homebrew kit in their house. But it's very du jour, isn't it? It's hot.

DODI: Why? What do you mean?

CONOR: Well, you know, during lockdowns all around the world people have started making things - making sourdough bread, brewing beer, kind of the home crafting thing that's been going on as we've been rediscovering old skills that have been lost and outsourced to industry somewhere.

DODI: And what a beautiful segue that becomes, Conor, because my next visit in real life, socially distanced, of course, is an example of another profession that in the words of Nigel, we in biotech stole with pride from. And that is baking. Well, apropos those lockdowns, the COVID-19 pandemic has shown up in strange places on grocery store shelves. It's not just toilet paper that people have been buying en masse. Yeast has also been sold out across the world.

ANNA: Well, you're creating life and taking care of something. And I think that is healing for people. I think maybe that's the healing process, taking care of something and seeing good results makes you feel good. You did a good job.

DODI: So, once again, Anna, like Michel, started to sound like any other scientist we've spoken to in the past.

ANNA: A mistake doesn't have to be all through a mistake. It can also be a discovery. That's the same, kind of everyday here as well that you think you screwed something up. On Sundays we make pizza here. So, I made a bit too much dough one day for the pizza, and we had tons leftover. But I decided to just take that dough and dip it in poppy seeds and make a little hole in it. So it became like a crown. Now it's become a really popular thing we have on Sundays, and I need to make that a special one. Not only because I have extra dough for the pizza, but actually just specifically for this poppyseed crown.

DODI: But Anna says this stealing goes both ways.

ANNA: We've learned so much also afterwards, when the scientists have come in and developed new theories and telling us how it actually works scientifically. That's helped us to make even better products as well, nutritious products that last longer.

CONOR: Okay, let's get you out of bakers and brewers and back here into our comfortable home space of biotechnology and science.

DODI: Yeah, right after I thank Michel for the samples that I got to bring home with me. And my thirst was quenched, I'll tell you that. It was delicious beers from the Stockholm Brewing Company. So, thank you for that.

CONOR: I want some! I want some!

DODI: I'm sorry, you're in lockdown, Conor. You can't have any.

CONOR: So, if we get back to Nigel and look at the future, is there a new area or a new field of biotech we're looking at now, thinking about how can we inveigle our way in there and get some new ideas and make manufacturing more efficient or faster? Or maybe a source of new therapeutics? Where's the next inspiration? Yeah, where is biotech going to plunder next?

NIGEL: If you'd asked me this question 5 or 10 years ago, I might have laughed at the answer. But I'm going to give you I think one of the really interesting things we've seen over the last few years. That's this idea about the microbiome. And the idea that the microbial content of your gut can have very significant implications for your overall health. And surprising as it may seem, you can find increasing evidence out there in the literature that, for example, some quite severe diseases like multiple sclerosis can in some way be related to changes that have occurred in your gut microbiome. The theory is that this is actually a result of the fact that the gut microbiome influences your immune system. And diseases like multiple sclerosis are thought to be essentially autoimmune diseases.

So, I think the fascinating thing for me is the idea that in the future for some of these diseases some possible therapeutic approaches are going to be around adjusting your gut microbiome. Then you start to think about identifying the types of bacteria and other organisms that populate your gut microbiome, and how you might enhance them. You know, you're not a million miles away from thinking about, again, fermentation technology, isolating potential candidate microorganisms from different types of cultured foods. And finding ways to deliver those back into the patients.

So, what you're starting to see now, and we've had a functional food industry for quite a while producing all sorts of different drinks, yogurts, foods that are enriched in certain types of microorganisms, you're actually starting this move more towards mainstream farmer, business, and biotech companies seriously researching how to adjust the microbiome. And researching how to execute on that type of strategy, which will undoubtedly require fermentation technology and ways of delivering enhanced microorganisms back into patients to improve their microbiome.

DODI: That was a long way around for Nigel to say that fecal transplants might be something that will be further developed as a potential therapeutic.

CONOR: So, remember, we did that episode on the microbiome. This has come back.

DODI: I remember.

CONOR: That's fantastic. So, if we keep the idea of being able to adapt somebody's microbiome in mind and thinking about what we've learned today about the world of biotech, stealing and borrowing, however you want to put that, is there anything we're learning from the IT industry? Can we cut and paste genomes and so on?

NIGEL: I think it's difficult to say exactly what contributions technology like gene editing would have on something like multiple sclerosis. But in principle, any technology that gives you a tool to adapt cells or organisms has tremendous therapeutic potential. I think just parenthetically when we talk about gene editing, we do again make the connection back to food.

CONOR: And which food, exactly?

NIGEL: I'm afraid again, it's yogurt.

DODI: And it's yogurt again, because yogurt understands how not to get destroyed by bacteria.

NIGEL: Exactly. This is it. So, you have to be very careful describing the attributions around things like gene editing, because it's kind of a hot topic. But I think undoubtedly one of the things that was important in understanding how gene editing works and how the tools were, was the discovery by a large biotech business that was really in the area of creating microorganisms for food applications. They face the problems that often their cultures of microorganisms would die or be destroyed, usually because they've been infected with phage. And phage are viruses that essentially feed on or are in fact microorganisms.

What they found was that certain palindromic repeat sequences, the CRISPR sequences, were responsible in microorganisms for conferring a type of immunity on those microorganisms. So, microorganisms that contain certain CRISPR sequences would be resistant to infection by bacteriophage. That was one of the key steps in understanding what the CRISPR sequences did. And also the relationship between the CRISPR sequences, an enzyme called Cas, which is the main tool that you use in gene editing. So, again, there's this really neat kind of relationship between the food industry and our ever-increasing sophistication in the food industry to try and understand the molecular basis of how to create better microorganisms and some of these really cutting-edge types of technologies that we think about when we talk about gene editing.

DODI: And we've learned it before on previous episodes, but we're arriving at the same conclusion. The answer to life and everything is yogurt.

NIGEL: Some people might think the answer to life is something that is more fermented, alcohol or wine. Myself, I think it's bread, because I’ve got to say one of the things that when I was a small child turned me on to thinking about science was when I'd make bread with my mother, and I could never understand why my mother would put sugar into bread, because bread isn't sweet or at least not where I grew up as a child in England. She explained to me as I later learned, it's the sugar that feeds the yeast, which produces the gas that makes bread rise. And so I think fermentation has been an inspiration to many people, whether it's making bread, making wine, making cheese, making yogurt. Medicine making just goes to show that, you know, it's an example of an ancient type of technology that's potentially still being explored and still has much to offer us.

CONOR: I'm now thinking that we can sort of harvest some silver linings that are found during lockdown. What do you think?

DODI: Sourdough bread and home brewing?

CONOR: Yeah, and it makes me wonder how many new bakers and brewers are out there and who are going to stick with it when everything goes back to quote unquote normal.

DODI: And maybe down the line more biotech makers.

CONOR: Yeah, and I'll tell you what, you give me a really good idea for another episode.

DODI: Really?

CONOR: Yeah, because I think there is a pretty good contender to take down the crown that we've just granted to yogurt. We should really do an episode on fungi, mushroom baking and brewing. They both depend on this amazing little yeast fungus and we are so going to do an episode on mushrooms. I mean about mushrooms, not on mushrooms.

DODI: Not on mushrooms. Okay, so I look forward to that. Until then, thank you for listening. We'll see you soon. Take care. Bye.

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