CRISPR and Nobel Prizes on The Future, This Week

Disclaimer We'd like to advise that the following program may contain real news, occasional philosophy and ideas that may offend some listeners.

Sandra Given that it's only Megan and I today in the studio, I thought you could get a first stab at what we should talk about today.

Kai Well yes, so I'm staying at home today, because our suburb has COVID cases, and you didn't want me in the studio, which is fair enough. So with a bit of luck, we'll be back in the studio next week, we shall see. I thought we could talk about Instagram, which turned 10 years old. And there have been a few stories about how Instagram has evolved from a fairly low-key way of sharing nice compressed pictures online with friends via your phone, using filters, to a global phenomenon, which has shaped the world. And we've actually talked about this, how, you know, coffee shops all seem to look alike, because they all became Instagrammable.

Sandra Now, we've done quite a few episodes over the last three years on Instagram, and we'll make sure to put all of them in the shownotes. But it's definitely come a long way.

Kai Yeah, so we've looked at what we've done. And we figured, you know, we could put together a special of that and reflect on all of these things. But we felt there isn't really too much new other than the platform discussion that we have around antitrust. So we thought we parked this for the

Sandra GPT-3 is back again in the news. We could talk about that a GPT-3 bot posted comments on Reddit for about a week and no one noticed. It's a bot, although it was interacting with people on Reddit and it's a general chat forum with about 30 million users.

Kai Well, that might say more about Reddit and its users than GPT-3, but I shall not comment.

Sandra Well, GPT-3 was posting roughly once a minute, and it had actually fooled people into believing it was a human, much like it did back in August, and we've covered this on the podcast a couple of times both GPT-2 and GPT-3, it had initially published a blog post and written an op-ed for The Guardian, so to speak.

Kai Or did it, right? Because, you know, it was eight different ones that were pasted together by a human editor. But this Reddit one seems a new level and a new scale at which GPT-3 has interacted.

Sandra Indeed. And it raises many of the points that we've discussed in previous episodes that, again, we'll add in the shownotes around the types of conversations that bots that don't disclose that they're really bots do to people, this particular one was posting about a colony of humans living in an elevator shaft. And that's harmless enough, but it also engaged in conspiracy theories and sensitive topics like suicide and offer the opinions and advice on that. And of course, it raises many of the concerns that we've discussed before. Even though GPT-3 is under fairly strict control as only a few people have access to it, and it's licensed exclusively to Microsoft, but definitely something that will stay in the news, and that we'll come back to.

Kai Yeah, and it's significant, because let's remember, it's just text matching, there's no intelligence behind it. So it might say some things that are plausible, but it will also say a lot of nonsense and when interjected into a human conversation, it is easy for it to contribute to conspiracy theories or spread false information when humans take what the bot says as being true. So a real problem, potentially. But there was another interesting news, which is about Elon Musk, of course, It's a Musk. And to be more precise, Elon Musk's car, the Tesla Roadster that has been shot into space is making an approach to Mars.

Sandra Yes, Starman, the spacesuit mannequin behind Elon Musk's Tesla Roadster has done a flyby very close to Mars. By very close, we mean about 5 million miles away.

Kai Well, you know, my view is that Elon, who wants to colonise, probably immigrate to, Mars has just sent his car there to claim the first parking spot. You know, I'm going to Mars because my car's already there.

Sandra And speaking of parking spots, we should do Nobel prizes. They've been quite a few awarded over the past week. We always do the Nobel Prize in Economics on the future this week. But there's been an even bigger story maybe with the Nobel Prize in Chemistry being awarded for the discovery of CRISPR-Cas9.

Kai But it is your annual chance to tell our listenership why the economics Nobel Prize isn't really a Nobel Prize.

Sandra Well, because It's not one of the original ones. It just started with a donation from one of the large banks in Stockholm in 1968. It was their 300 year anniversary and it was awarded for the first time in only 1969. It's got the same principles as the actual Nobel prizes that have been awarded since 1901.

Kai But it makes for a nice Jeopardy trivia fact. So who won the economics Nobel Prize this year?

Sandra So the Economics Nobel Prize this year was Paul Milgrom and Robert Wilson for their work in the exciting field of auctions. And it is actually a lot more exciting than it sounds, their work underlies much of today's economy from the way Google sells advertising to how telecom companies acquire radio frequencies from the government, to the way we buy and sell things like diamonds and minerals and oil and so on.

Kai And let's not forget flowers, the famous Dutch flower auctions, the way in which truckloads of flowers are being auctioned away in the matter of seconds, or indeed, eBay. And I remember when I got into the field of Information Systems in the very early 2000s, during the dotcom boom, we did a lot of work around auctions, because it was the beginning of e-commerce, eBay was new, and there was a lot of startups that were experimenting with electronic marketplaces and various auction mechanisms. So really important work, because it's not trivial to find the best auction mechanism that keeps the market parties engaged, but also leads to fair outcomes.

Sandra Or does it? Both Wilson and Milgrom came up with a lot of theories to explain how much bidders will offer for a good or service in different types of auctions finding out for instance, that people will always offer less than they think something is worth because they're afraid of overpaying, or the fact that they will underbid in auctions where the prices start low. And then there are raised English auctions, rather than in Dutch auctions when prices start high, and then they're reduced. But their best known contribution is their work in designing new auction formats for really complex situations. That includes how governments allocate radio frequencies for instance, or how we think about carbon pricing.

Kai Well, you are a lapsed economist, which explains your interest in the minutiae of the Economics Nobel Prize. But let me ask you, what does that have to do with parking spots?

Sandra Oh, parking spots? Yes, ah that gets me to the one I really think we should discuss today, which is the Nobel Prize in Chemistry. It went this year to Emmanuelle Charpentier and Jennifer Doudna, for the development of CRISPR-Cas9, so a method for genome editing.

Kai And one of the biggest innovation stories of the past decade, and definitely something that we should be talking about that we haven't talked about enough on the podcast, and what a perfect occasion to take up this topic. But again, parking spots?

Sandra Well, if you'd let me finish, if you're a faculty member at Berkeley, and you receive a Nobel Prize, you receive an even bigger prize than a million kronor or share thereof. You receive a free parking spot for life on the Berkeley campus.

Kai The most coveted of prizes in science, the parking spot at the University of Berkeley. Most excellent, but I think this is the story we should be focusing on.

Sandra Cool.

Kai Cool.

Sandra So let's do this. This is The Future, This Week from Sydney Business Insights. I'm Sandra Peter.

Kai And I'm Kai Riemer. Every week we sit down to rethink and unlearn trends and technology and business.

Sandra We discuss the news of the week, question the obvious, explore the weird and the wonderful and things that change the world.

Kai So the story this week is the Nobel Prize in Chemistry 2020 for the development of the gene editing methodology CRISPR-Cas9.

AUDIO The Royal Swedish Academy of Sciences has today decided to award the 2020 Nobel Prize in Chemistry jointly to Emmanuelle Charpentier and Jennifer Doudna for the development of a method for genome editing.

Sandra And of course, Emmanuelle Charpentier and Jennifer Doudna were part of a group of 12 other Nobel Prize Laureates in 2020 for achievements that have confirmed the greatest benefit to humankind. So Nobel Prizes in Physics, in Chemistry, ranging from the formation of black holes to genetic scissors to efforts to combat world hunger, to indeed new auction formats.

Kai But among those, CRISPR really stands out for its future potential, its potential for creating new business opportunities, and indeed, its medical potential in curing many of the genetic inherited diseases that plague humankind. So CRISPR has been around for a little while, the initial discoveries were made in the early 2010s. And there was some hype in the media back then, it has gotten a little quiet in the meantime, but real benefits are now flowing from CRISPR, among them tests for COVID, potential cures for diseases. So we thought we'll have a look at what CRISPR actually is, what CRISPR does, why it is such a big deal, but also some of the ethical implications around it.

Sandra And CRISPR really is one of the biggest science stories of the decade, not only for its potential application in health in curing genetic diseases, or developing new antibiotics or new antivirals, but also its potential in things like agriculture, for modifying crops that are climate resistant, for augmenting livestock, for getting rid of pests. So really the applications are endless. But first, let's hear from Jennifer Doudna herself about what CRISPR actually is and how it works.

Jennifer Doudna A few years ago with my colleague, Emmanuelle Charpentier, I invented a new technology for editing genomes. it's called CRISPR-Cas9. The CRISPR technology allows scientists to make changes to the DNA in cells that could allow us to cure genetic disease. You might be interested to know that the CRISPR technology came about through a basic research project that was aimed at discovering how bacteria fight viral infections. Bacteria have to deal with viruses in their environment. And we can think about a viral infection like a ticking time bomb, a bacterium has only a few minutes to defuse the bomb before it gets destroyed. So many bacteria have in their cells an adaptive immune system called CRISPR that allows them to detect viral DNA and destroy it. Part of the CRISPR system is a protein Cas9, that's able to seek out and cut and eventually degrade viral DNA in a specific way. And it was through our research to understand the activity of this protein Cas9, that we realised that we could harness its function as a genetic engineering technology, a way for scientists to delete or insert specific bits of DNA into cells with incredible precision, that would offer opportunities to do things that really haven't been possible in the past.

Kai So this was Jennifer Doudna, already in 2015, in a TED talk, and we'll put the link in the shownotes. And so CRISPR is one of those technologies that operates at a level that is very hard to grasp for humans. So we tend to use metaphors to explain exactly what is happening. And so CRISPR-Cas9 is often described as 'genetic scissors', as a way for locating certain parts in the DNA, cutting out that part and replacing it with new DNA, with the help of the Cas9 protein that carries that new bit of DNA into the DNA strand of a plant, of an animal, or indeed, a human.

Sandra And there's of course, a whole range of CRISPR tools that control how genes are expressed by for instance, deleting undesirable traits by replacing them with more desirable traits, or by introducing new traits into plants, animals, and potentially even humans.

Kai But this is a really big deal because gene editing did exist for decades before, that was always very expensive, unreliable, a lot of things could go wrong. Whereas CRISPR really allows scientists to scale and experiment with all kinds of new ways of gene editing. And we'll put an article from Medium in the shownotes that outlines how exactly CRISPR is, first of all, much more precise than previous methods, it's comparatively very cheap. It can be done with reasonably little training. There's now citizen science initiatives, there's even middle schools where students are working with CRISPR. it works on any type of cell and importantly, it works on live cells, on living organisms.

Sandra But let's just make a small footnote here to say that was these are tremendous advances, from things costing hundreds of thousands of dollars and taking months to develop to things, to now being a few hundred dollars and taking a few hours to develop, it still means that for any significant work, you need an entire high tech lab to perform these things. It's not like people can edit human DNA successfully in their garage still, so we're not quite there yet. But the field is advancing extremely quickly, whilst about 10 years ago, there were less than 100 papers all together published around CRISPR, by 2018, there were more than 17,000 papers with all sorts of refinements, new techniques, new improvements, new ways to be more precise.

Kai And before we have a look at some of the challenges and ethical implications, we thought, we'll have a look at some of the potential applications and future innovations that CRISPR will bring about.

Sandra So one of the first areas that people think about when they think CRISPR and gene editing is of course, stopping genetic diseases. And scientists are already using CRISPR-Cas9 to try to cure things like heart disease, or mutations that cause Huntington's disease or cystic fibrosis, or even trying to tamper with the mutations linked to breast cancers and ovarian cancers. And under lab conditions, scientists have even shown that CRISPR can help with HIV infections.

Kai And research has already shown that CRISPR-Cas9 can cure sickle cell disease in mice and help reduce conditions such as genetic deafness, for example.

Sandra And of course, the health applications or medical applications don't stop here. It's also a powerful new way to develop new antibiotics and new antivirals.

Kai And that is important, of course, when the world is living through a pandemic. And one of the more exciting recent developments is actually done by a research team led by Jennifer Doudna. Using a different protein, this time, Cass13, which is also known as the SHERLOCK protein, which is very good at finding certain genetic sequences. And that is used in a new five minute test for COVID-19. Which has certain advantages, not only because it's faster, but also because it can determine the viral load in a sample. And it's really very clever, what it does, it inserts an RNA into the virus, it finds the characteristic DNA. And when it does, so it emits fluorescent particles in a test solution. And then with laser light, you can determine whether or not a sample is infected. And the brighter the light shines, the more viral load is actually in the sample which, as researchers hope, will help doctors determine much better the dosage of antivirals in patients, the more viral load they carry. So really exciting applications here.

Sandra But as we've mentioned, it's not just about medical applications and health care, it can also revolutionise agriculture. So for instance, the ability to edit crops, for instance, to be tastier or to be more nutritious, or to better survive climate change. So creating staple crops that survive better in heat and extreme temperatures, or even taking out the allergens that exist in peanuts, or going back to an episode with it quite a few weeks ago, helping banana populations survive deadly fungal diseases, or helping out the coffee crops.

Kai #SaveMyLatte, and of course we will put the link to this episode in the shownotes. And I think it was our Christmas food special a couple of years ago.

Sandra And if it wasn't, Megan cut that out.

Kai I'm pretty sure it was.

Sandra Well, it's not just crops that you could alter. You could also improve livestock. For instance, scientists have shown that CRISPR can create hornless dairy cows, which would provide huge advantages in animal welfare. Not sure how, but...

Kai Don't have to have their horns clipped as often.

Sandra Or lean pigs, speaking of.

Kai #WheresMyBacon.

Sandra Or they could help us better deal with pests, whether that is pests that threaten our crops or our livestock or even human population. For instance, CRISPR could allow us to wipe out entire populations of malaria-spreading mosquitoes.

Kai And this is of course where things get not only more interesting, but controversial because as we said earlier, gene editing can be done on any cell. So what works on plants, what works on animals, obviously also works in humans. Which leads us to the gene editing of human foetuses. But it also raises fears of so called 'designer babies'.

Sandra And we're not just talking about choosing a baby's gender or choosing their eye colour, but in time, you could, in theory select for children who are taller, or who are more prone towards athletics, have better eyesight, have better hearing, or indeed have higher intelligence. And of course, today, we don't really know enough about how genes work, or how genes interact in people, to be able to induce higher intelligence, for instance, but many other features, we do actually have some ability to manipulate already. And this controversy really came to the forefront two years ago.

Kai And you're talking, of course, about the 2018 case of scientists at Southern University of Science and Technology in Shenzhen in China, who in gross ignorance of any ethical science standards, use CRISPR on live babies to try and make those twins, in fact, immune to HIV. While we do not know what happened to these children, and whether this experiment was successful or not, it shed a stark spotlight on the dark side of uncontrolled use of CRISPR. And this controversy was quickly followed up, and the scientists have since been sentenced to prison sentences actually, by Chinese courts, sending a strong signal that the world will not tolerate the rogue use, or uncontrolled use or unethical use of CRISPR in humans.

Sandra And of course, the concern here is first and foremost, with the fact that there is not enough known about the technique to ensure that no harm comes to the foetuses that this was performed on. And of course, in this case, the researcher did not tell their university about the experiment ahead of time, nor did they fully inform the parents of the risk involved, and so on and so forth.

Kai And so the ethics here are still up for grabs. On the one hand, there is the promise to cure disease or to make us immune to certain kinds of viruses. On the other hand, there is the risk involved, mind you, CRISPR is not 100% precise technology in that it's use can introduce undetected gene defects as well, we don't know its efficacy. And there is, of course, also not just the public unease being shown in polls about gene editing in humans, there are also legitimate concerns about how to actually do controlled studies. In living humans, for example, we would have to genetically engineer humans and then later try and infect them with the disease in order to see if it was effective. So big promises, but also a minefield of ethical concerns that need to be navigated.

Sandra So this brings us to the future of CRISPR. And if we look forward, there are a number of issues that still need to be worked out. And first, as you mentioned, was the fact that there are still actual technical hurdles to be overcome. CRISPR can misfire or lead to cancer or potentially create new diseases down the line. So much research still to be done. But there are also some very interesting business concerns around the future of CRISPR.

Kai And one such concern is a pending patent dispute, which tells us a lot about how science intersects with business. And again, a minefield being introduced.

Sandra The expectation would be, of course, that Jennifer Doudna and Emmanuelle Charpentier who were awarded the Nobel Prize for developing the CRISPR-Cas9 process that they and their respective institutions would hold the patents for this. But there's actually current litigation with conflicting patents, one out of the University of California at Berkeley and the University of Vienna, where the two scientists were working at the time.

Kai And the other one filed by the Broad Institute at MIT, where researcher Feng Zhang was the first one to publish a paper showing the use of CRISPR-Cas9 in humans. And the controversy on the one hand centres around whether this was already implied in and shown by Doudna and Charpentier's research, or whether it is Zhang who actually made the discovery of CRISPR in humans. And the other controversy is that while Berkeley and Vienna filed their patents first, it was MIT who paid the patent office a fast track fee, and were therefore awarded the patent first, leaving Berkeley and Vienna to file an interference claim. The problem is that this patent dispute has been pending now for a number of years, and it threatens to stifle further research and commercialisation in the area as scientists and venture capitalists, for example, are reluctant to engage with CRISPR-Cas9 as long as it is not clear what the situation is.

Sandra And incidentally, this is not just about patents, and who will get the royalties out of new biotech that will be built on top of CRISPR-Cas9, but it's also about how the story of this invention gets told and who stars in it.

Kai And there's an article in Fast Company that we'll put in the shownotes that discusses this story. And it points out that there was a controversial piece in the journal Cell titled, "The heroes of CRISPR", written by Eric Lander, who was at the time the head of the Broad Institute who lays claim to the invention with its patent application, and Fast Company points out that it amounts to a retelling of CRISPR as a male-dominated story, featuring all these men who were instrumental in building these technology and downplaying the role of Doudna and Charpentier.

Sandra And whilst winning the Nobel Prize in Chemistry this year will cement Charpentier and Doudna’s place in the history of gene editing, historically it actually has been quite difficult for women in particular to get the recognition they deserve, even within the Nobel Prize committee.

Kai In fact, besides Doudna and Charpentier only five other women, among them, Marie Curie, as well as her daughter, have won the Nobel Prize in Chemistry, which represents a paltry 3.8% of all the 186 laureates in chemistry. And the picture is even worse in physics and in economics, for example.

Sandra And we'll include a BBC podcast in the shownotes that tells the story of how in physics, the woman who discovered pulsars, made the discovery in her PhD, lost the Nobel Prize, which was awarded to her male supervisor.

Kai And so the awarding of Nobel Prizes is not without controversy, not only because of the glaring gender bias, controversies around who won or who didn't, but also because it tends to cast science as an endeavour of individuals, when in fact any scientist always stands on the shoulders of giants, as the saying goes, always builds on prior work. It is often, these days, the collaboration of large teams of researchers that is at the heart of discoveries and developments in science. And yet, the Nobel Committee always picks one or two people who then become famous and known worldwide, for those discoveries, casting a dark shadow on all those who might have contributed to the discoveries.

Sandra And that situation is likely to hold because the Nobel Prize can go at most to three people in fields where always the contributions are made by hundreds of people.

Kai But let's get back to the patent story, which shows the vast interest that is tangled up with CRISPR because of its potentials for spurring innovation for commercialisation of not only products in health, but also in agriculture, as we've outlined, which raises the question around policy here, and should this technology actually be awarded with a patent?

Sandra And the argument here really is that CRISPR has this huge potential to benefit people, to benefit the public. Shouldn't then this be universally available, especially since the universities where it was developed, like the University of California and Berkeley and the University of Vienna are public universities that use public money.

Kai So it sheds a light on the way in which universities these days urged to an aim to commercialise the inventions and discoveries of their scientists vis-à-vis the public interest in the wide availability of something like CRISPR, which could become really an infrastructure and the basis for a whole range of innovations in science, agriculture and health.

Sandra And the question of who will get to use it and benefit, but also who will get to regulate how CRISPR is being used, is still a very lively one. Even though we've had the technology for quite a few years now, shaping the guidelines and the regulations that scientists would have to abide by when they use CRISPR are still very much a work in progress. And scientists have been coming together at meetings such as the international summit on human gene editing to address the implications of crispers, much like the Asilomar conference that addressed molecular cloning back in the 70s. Aiming to figure out what are the guidelines by which people should engage with this technology. But to this date, there are no commonly abided by standards in the use of this technology.

Kai Some points that were highlighted were that there needs to be public awareness and wide societal buy in into the use of CRISPR. For example, when the population is against the use in babies for certain aspects, then the technology should not be used for that. There should also be no use in what is called 'inheritable editing', where editing might lead to altering of genes that can be passed on to children and therefore inherited by future generations.

Sandra And this is why public understanding of the technology is so important because it will play a large part in how CRISPR is regulated. And in spurring on early efforts to regulate this, we've seen how difficult it is once the technologies have taken hold, such as in the case of social media to get broad international consensus on how these things can be regulated.

Kai And raising public awareness in the right way is really important, because two things can happen. Technologies can be left unchecked and fly under the radar, as you said, creating all these problems. On the other hand, it could also lead to an alarmist reaction where widespread fear could curb the legitimate and beneficial uses of the technology, in health for example.

Sandra And this is of course, not to say that some of these fears are not legitimate, because of course, with the development of this technology, bioterrorism is an increasingly likely possibility with bacteria or viruses that are resistant to treatments, but also with modified organisms that can then multiply, or indeed through what is still a science fiction scenario, but the development of designer humans.

Kai Where people could inherit certain characteristics that make them you know, stronger, taller, more handsome, more intelligent, that gives them traits that would be seen as super human.

Sandra And, of course, the challenges that that would have to how we think about equality or the foundations for whether it's democratic systems or communist systems in which we are all equal. If some people are demonstrably better than others, it could lead, if not to nightmarish scenarios, to at least significant inequalities that would not be easily overcome.

Kai So this Nobel Prize has shed a timely light on one of those basic technologies with the potential to revolutionise entire industries and unlock for the human race potentials to get rid of pernicious diseases for good, but which comes with a whole range of ethical and policy issues and legitimate concerns around the abuse of the technology in areas that we might not even have envisioned right now.

Sandra But for now, congratulations again to Emmanuelle Charpentier and Jennifer Doudna for their Nobel Prize in Chemistry in 2020.

Kai And before we go, we want to say it is World Food Day, and the Nobel Peace Prize this year has gone to the United Nations World Food Program. Congratulations to that as well.

Sandra But that's all we have time for this week. Let us know your questions, suggestions for stories, and also your favourite episodes

Kai And leave a comment on your favourite podcast platform. Until next week.

Sandra Thanks for listening.

Kai Thanks for listening.

Megan Sandra Peter is the Director of Sydney Business Insights. Kai Riemer is Professor of Information Technology and Organisation here at the University of Sydney Business School.

Sandra With us every week is our sound editor Megan Wedge.

Kai And our theme music was played live on a set of garden hoses by Linsey Pollak.

Sandra You can subscribe to The Future, This Week wherever you get your podcasts.

Kai If you have any weird and wonderful topics for us, send them to sbi@sydney.edu.au.

Kai So this economic stuff, that's riveting shit. By the way, I learned recently in a podcast from the BBC documentary where the word riveting is coming from.

Sandra Go on.

Kai Do you, do you want to know where the word riveting is coming from, that's riveting?

Sandra Mmm hmm.

Kai During the Second World War, when the, when they built the Spitfire to win the Second World War, the plane in Britain, they had to move around the factories because they were being bombed. So they move them into innocuous places. And one of the things that had to happen was that when they moved, they moved all the materials. And they had all these rivets that had to be sorted. So they set up a facility in a, in a, like a country house where a lot of the local women would then work sorting rivets. So literally, they were riveting. And it was riveting work to sorting the rivets, so that they could basically build the Spitfire and there was lots of different rivets that had to be sorted because they were at different functions and so this big pile of rivets that were all tangled up. Anyway, riveting.