Latest / Polymath World Channel / Polymath World Episode 54 - BIS Lecture: Reinventing Space 2025
Transcript
- Sam McKee (Polymath World Channel) (00:06.734) Okay, I'd to introduce our next speaker, Sam McKee, who is a DNA repair researcher for University of Reading, genomic medicine, University of Cambridge. So over to you, Sam. Thank you very much. So I take it that the green button is the next slide. Excellent. Thank you very much. My own research is in the area of DNA repair, and it typically is connected to cancer. And it's on a structural level, so very much the molecular biology of it all. But obviously, health of our astronauts, especially beyond low Earth orbit, is of immense concern given the levels of protection we're afforded on Earth that we're not afforded out there. Now, I'm sure many of you will be familiar with some of the things I'm going to talk about in terms of the revolutions in computational biology, how it's transforming healthcare, but the application of it to space science is immense. Absolutely incredible. It could be the most disruptive thing coming. How will landmark changes in computational biology impact human spaceflight? It can make a tremendous difference going forwards. Biology is so hot right now. I say to my students quite a lot that this is the most revolutionary time in biology since the 1950s. It's an incredibly exciting time in terms of a lot of really disruptive tools have come along in a very short space of time and they cross over and inform one another. cancer is going to be a completely different world 10 years from now than what it is. Up until now with cancer, it's very much been a case of cut it out, burn it or blast it. Whereas now we have immunotherapy, which I'll mention in a moment, and DNA repair therapy, both of which have been awarded Nobel prizes in the last decade and are still very much in their infancy as technologies. So how's the space sector going to benefit from this? Space medicine, bioastronautics, the applications are tremendous and I just want to highlight some as we go through. We are in a crisper world now. I think I said that a year ago when we think of gene editing. Sam McKee (Polymath World Channel) (02:21.857) And we're also in a computational biology world with this. But a quick primer for those of you who may have missed out. I have to put him up because he's my hero. This is Fred Sanger. The case could be made that he's one of the greatest scientists of all time, one of five people to win two Nobel prizes. In 1958, Sanger invented the first form of Sanger sequencing for sequencing the amino acid sequence of the protein insulin. the first time anyone had ever done a sequence before. then sequencing DNA won the Nobel Prize in 1984. And this set the table for the Human Genome Project, which took 13 years from 1993 till 2003. It took over 50 countries, over 4 billion and 13 years. Now you can do DNA sequencing in the field. You don't even have to be in a lab with a handheld device in a few hours for less than $500. That's how much the world has changed. Then next generation sequencing came along because the endeavor of the Human Genome Project gave way to a lot of technological inventions and disruptions to try and make sequencing faster, quicker, more efficient, more accurate. And then you had the race in the early 2000s for the $1,000 genome where can we sequence a whole genome for $1,000 instead of it taking 13 years and $4 billion? Illumina sequencing, have to highlight, is incredibly disruptive there. Before we get to the Minion, and I'm going to show you the Minion in a second, or the Minion Ion, I'm not sure how you pronounce it. Someone from Oxford Nanopore Technologies can correct me. This is recently retired NASA astronaut Kate Rubins. When we're talking about space applications here, in 2016, she performed the first genome sequencing in space on the ISS. And it was a breakthrough for those of us in genetics. We thought this is a real landmark crossed. We can do this. I know the ISS is such a world-class laboratory, but the fact that you can do this on the ISS is very, very promising in terms of what could come next. Well, Rubens went one better on her second mission in 2018, where not only did she do the first CRISPR gene editing in space, but she sequenced the genomes of all of the microbes on the ISS. Sam McKee (Polymath World Channel) (04:41.61) which was so phenomenal, mean, in terms of the data that we got from that, but in terms of the endeavor that was, and she did it with this, the Minion. The Minion reminds me of one of those old school mobile phones that you can flip open, like on the Matrix film and things like that. Basically, any scientist can be out in the field, you could be on safari, could be on desert marine polar, you could be in any environment. Have the Minion, smaller than my mobile phone here. and you simply open it up, you can take a hair sample, cellar, any tissue sample, put it in, close it down, and it will read out accurately the entire genome in two hours or so for the cost of the equivalent of about $500. And so Kate had this in space and she sequenced the genome. She spent ages going around swabbing surfaces, scraping them and sequencing genomes. Not only was it an incredible insight to the microbial activity on the ISS, But I think it was a landmark for what can be done in space by astronauts in terms of genetics. It was an incredible achievement. Right. When we think about astronaut health, bioastronautics, surgery in space is obviously a problem. You don't want to cut people open and have goo floating everywhere in your environment. So how we keep our astronauts healthy when they suffer? ailments is something of immense consideration. Obviously in microgravity it's different from on the moon and the earth where you have varying levels of gravity comparable to earth that will present different challenges or maybe opportunities you wouldn't have otherwise. But it is a problem. It is a problem we're to have to think about a lot. We need it to be non-invasive. And as far as it be possible, we need molecular medicine. Wherever it can replace surgery, we need molecular medicine. Now, here's the good news. Number one, protein growth in space is better than it is on Earth. We've known that for a long time. We've known that going back to the days of Mir, the shuttle, Space Lab, and of course the ISS. We've been growing proteins in space, and they're better than they are on Earth. I actually, just a little anecdote, when I was at Birkbeck, there was sort of this debate that happened. I threw the grenade in the room and asked, what do you think about growing proteins? Sam McKee (Polymath World Channel) (07:03.951) crystals in space as opposed to on Earth. Everyone agreed it was better. They just didn't want to spend their money on sending the stuff up there in the first place. I'll take a less quality protein on Earth if it saves me a lot more funds. was generally, everyone agreed it was better, but they just didn't want to do it. But we know that we can grow better proteins in space. We've known that for a while. Secondly, cancer immunotherapy is a game changer. I was speaking at the Mars Society at USC in California two weeks ago, and I raised this point. When it comes to DNA damage, it's extremely likely our astronauts are going to get cancer. It's just there's a sense to which it's inevitable. The level of DNA damage, particularly double strand breaks. If you're going to be living on the moon or living on Mars for long periods of time, cancer is the real, real risk. The good news is we can treat cancer noninvasively now. much more effectively thanks to immunotherapy, which can be administered orally or through injections. And it can recover people who've even been sent home to die on Earth. And your body, your immune system is then primed against that cancer in a way that it won't come back. It's everything we've been hoping for and waiting for. We just don't know if we can treat all cancers with it yet. It's still very much in its infancy. When I started as a genetic student, one of my professors even told me that immunotherapy was a fairy tale and a myth. And if you want your career to go nowhere fast, get into immunotherapy. And then five years later, the Nobel Prize was awarded for it. But it is a game changer. Not only that, we have DNA repair therapies such as PARP inhibitors, which are transforming the landscape of breast cancer treatment. So 10 years from now, a lot is going to change. This field is going to look very different. So we know that even illnesses and ailments that are caused by immense levels of space radiation, we know we can treat them on Earth noninvasively. much more effectively. That's also good news. Then we have BioInk. Hands up if you've heard of BioInk. Sam McKee (Polymath World Channel) (09:09.23) A couple of you, the younger ones, interestingly. That's good. And Bioink, this is a photo of Christina Koch experimenting with Bioink. You might have heard Tim Peake speaking about it. He's a big fan of Bioink. Bioink is the three, in a nutshell, the 3D printing of tissues, organs, proteins, and cells in space. It's incredible, absolutely incredible. And much like with protein growth, it's a better quality than what we can do on Earth. Fantastic news. Koch also on her mission here in 2021, She also used CRISPR in space and she used it in a gene editing context for DNA repair, studying DNA damage repair from the double strand breaks that caused by space radiation, galactic cosmic rays, solar radiation, that sort of thing. Again, another landmark thing you can look at. BioWink shows us how we can 3D print human tissue in space and it's viable, it's useful. We've been doing this. partly with a view of can you solve the organ donor crisis on Earth by doing this in space. But what does this mean for traveling to deep space and living off world? Well, it means that we might be able to print tissues that we need. Now, I caused a bit of a stir when I wrote this article for the conversation last year, ended up in a couple of debates I didn't want to be in about the need to perhaps use human genome editing if we want to live on Mars. Hands up if you were here at the British Interplanetary Society for the debate a couple of years ago between Martin Rees and Robert Zubrin. Anyone? I know you were there. Of course you were. Two people I have deep affection for and it was quite sad watching two of my favorites kind of do battle. But Martin Rees is a big advocate in his books that if we're going to live deep into the solar system, we might need to use CRISPR-Cas9, prime editing, base editing to genome edit ourselves. But at that extent, are you really human anymore? You're something else altogether. That's difficult to think about. But I think gene editing in some form is going to be essential, if not for ourselves, for our crops, for the things we need to eat and drink, the medicine we need to make. Gene editing is going to be an essential tool, but it's a tool we didn't have recently. The Nobel Prize was only awarded for it in 2020. It's very new. But genome editing is going to be part of the answer. Sam McKee (Polymath World Channel) (11:31.918) Hands up if you're familiar with AlphaFold, if you've heard of AlphaFold. The Nobel Prize was awarded for it last December to those at Google DeepMind. We live in an AlphaFold world now. AlphaFold is applying artificial intelligence to the protein folding problem. For those of unfamiliar with it, a protein's function is very much determined by its structure. Structure determines function. Proteins are like keys. You need them to be the right shape to do the job. They're also like snowflakes. They're all different shapes. I think they're biology snowflakes, which is why biology is particularly beautiful at this level. We don't know how proteins fold, immediately from the amino acid sequence that you have just to take the shape without much intermediate. Some don't even have an intermediate at all. It's just... It's still something of a mystery, but we have so much data now that we can use statistics to predict. Now, every two years, there's one of the hottest contests in biology called CASP. CASP 16 was last December. And CASP is a competition involving labs and research groups and universities all over the world to compete. And you're all given one amino acid sequence. And you have to predict. the structure of the protein, is then experimentally verified to as close to 100 % accuracy as you can and just using the computational models that you've built, the programs that you've built. So at the University of Reading, I'm part of the MacGuffin Lab, and we enter CASP every two years. This is just an image from multi-fold two. We now have multi-fold three out and able to be used. And we compete with alpha-fold. And this is where my supervisor we'll make sure in my ear that I have to mention we do actually beat Alpha Fold at a couple of different things, even though they got the Nobel, but anyway, that's fine. Liam, I said I'd said it. So there we go. And it's quite fierce, but if you go back a couple of casps before Alpha Fold came along, most groups were batting about 50%. And that's actually pretty good. If you're nailing half of it or half the time, you're Sam McKee (Polymath World Channel) (13:52.738) you're getting close, then that's not bad. It's better than it sounds. The thing is, at Cas14, AlphaFold came along and immediately hit 80 % and was doubling what almost everyone else was doing. And it was such an extraordinary game changer to think without crystallography, without cryo-electron microscopy, we can just get so close to what the structure is without ever having to go into a lab. And then at Cas15, alpha-fold 2 hit 88%. And that's when the question started to come, what is going to happen when it hits 100 %? It's going to hit 100%. What are we going to do? What does that world look like if you can absolutely predict to 100 % accuracy the structure of the molecule you want or need without ever having to go into a lab or spending that expense? What does that world look like? What does that world look like in terms of drug discovery? What does that world look like in terms of that pipeline process? What if instead of it taking five years, it took one year? Because in a matter of seconds, you could type in the protein you need, and there it is. You know what you need. That's an exciting world to think about. But now there's lots with multi-fold, alpha-fold, loads of different organizations. that are each beating each other at various aspects. But the world at 100 % is going to look very interesting. Now, what does this mean for space? I think it adds up to a patchwork quilt that is extremely promising a layout for what space medicine can look like in a computational age. Firstly, we know we can sequence genomes in space cheaply, efficiently, and accurately, easily, with a handheld device. It doesn't weigh very much. We need to know your genome sequence. If you have a tumor and we need the genetic sequence of your tumor, we can do that quickly, easily, and accurately now. Secondly, we know we can develop much purer medicine in space because we can grow better quality crystals. We know we can do that in space better than we can on Earth. We know that if our astronauts get cancer, we have immunotherapy and DNA repair therapy that are now non-invasive. Sam McKee (Polymath World Channel) (16:15.118) Like I said, immunotherapy you can take orally or with injections. We know we can treat that if it becomes a hazard for our astronauts. As long as we can get the mechanisms with us on our space flight, we know we can do that. Next, we know that BioInk can 3D print tissues that we might need. Now this is very theoretical still, but we know we can do that now. Add all these things together, it's a good picture. We identify the health need. We print the drugs or the proteins or the tissues as needed. All you need for alpha fold or multi-fold or anything like that is an internet connection. Starlink or its competitors can provide that. So we can answer a huge number of the challenges now quickly and inexpensively in ways that we couldn't before. Now finally, I just want to say this. Genomic medicine is the future. It is the future. The dream is personalized, precision medicine for all. That's the promise. That's been the dream since the beginning of medicine. But we're moving into an era now where everyone should and could, sorry, I said should, maybe I shouldn't have said should, have their genome sequenced. And then patients are treated according to their own unique physiology. Now, I said precision and personalized, but I want to add predictive there as well because we can get we can enter the landscape now where you can see the health problems coming and maybe begin to alleviate them before they arrive or prevent them completely. Let's say you get cancer today. We sequence your genome. We take a biopsy of your tumor. We sequence that too. So we've got the genetic signature of the tumor. We take your immunotherapy drugs and we use CRISPR Cas9 or base editing or prime editing to edit those drugs. so that they're like heat-seeking missiles or sniffer dogs and you inject them or take them orally. They go through your body like heat-seeking missiles, finding and destroying every single one of those tumor cells and then priming your body against it so the cancer doesn't come back. Well, we could do that in space. We can do that. It's not impossible anymore and it's better. But my concern here is that on Earth we may be ahead of space because there's very little published about this. Sam McKee (Polymath World Channel) (18:36.792) There's very little written, there's very little research done on it. I said last year, most of the experiments on the ISS about genetics, they tend to be young people's or students' competitions or things like that, or they're specifically in the cancer realm. If you read about DNA damage in particular, each of the papers of the last two or three years always ends with more data is needed, more research is needed. The NHS here in Britain has 1.3... million staff. It's the fifth largest employer in Europe. And the NHS under the last government and this government has set out its goal, its dream to be a world leader in genomic medicine. Well, out of 1.3 million staff, we only have 200 genetic counselors in the NHS and only 300 clinical geneticists. The cohort that I'm in at Cambridge, there's only 60 of us being trained for this next goal. So it's moving slowly, but it's still moving faster on Earth than it is in space. And it would be great to see that flipped. If you have any questions, you're welcome to catch me afterwards. Otherwise, thank you very much. Sam McKee (Polymath World Channel) (19:53.198) Thank you, sir.