In Conversation with Professor John Rasko AO

Professor Carolyn Evans, Vice Chancellor and President of Griffith University 

Good evening, ladies and gentlemen and welcome. My name is Carolyn Evans. I’m the Vice Chancellor and President of Griffith University, the co-host of this event along with HOTA, Home of the Arts here on the beautiful Gold Coast. Can I begin by acknowledging the traditional custodians of the lands on which we meet Kombumerri and the Yugambeh people and pay my respects to elder’s past and present and to all Aboriginal and Torres Strait Islander people here today. Could I also acknowledge Councillors of the City of Gold Coast Mr. Mark Hamell and Mr. William Owen Jones, Chair of the Board of Directors of HOTA Professor Emeritus Ned Pankhurst, CEO of HOTA, Ms. Criena Gehrke, and, of course, our wonderful guest speaker, Professor John Rasko AO, pioneer in gene and stem cell therapies. And thank you all, also for joining us here today at HOTA for another thought-provoking conversation as part of our series, a Better Future for All. We launched last year, not in the easiest of circumstances, but we persevered. And since that time, a better future for all has welcomed some of Australia’s most influential and inspiring individuals, and tonight’s installment, I’m sure, will be no exception. Of course, we remain immensely grateful to have award-winning journalist Kerry O’Brien in the driver’s seat for this series. Kerry is a renowned broke broadcast for almost 40 years, and no stranger to anyone with even a passing knowledge of Australian journalism. He’s arguably best known for his time hosting the 7:30 report and Four Corners. But as a six-time Walkley award winner, he has a phenomenally rich and broad base of experience as a journalist, writer and interviewer. Speaking with Kerry tonight, we’re privileged to welcome Professor John Rasko AO ahead of his appearance at Griffith’s feature event for our Integrity 20 series in Brisbane tomorrow night, presented in partnership with a Better Future for All. Professor Rasko is a respected, decorated and pioneering clinical hematologist pathologist and scientist, with a self-professed passion for excellence in patient care and in research. He currently serves as the head of both the gene and stem cell therapy program at the University of Sydney Centenary Institute, as well as cellular molecular therapies at the Royal Prince Alfred Hospital. Over the course of his esteemed career, Professor Rasko has contributed to more than 150 publications on the topic of stem cells, gene transfer technologies oncogenesis, and more. Not only adding to, but fundamentally changing our understanding of human illness and recovery. In February, Professor Rasko released his new book, Flesh Made New: An Unnatural History of Broken Promises and Stem Cells. I’m going to try that again. Flesh Made New: The Unnatural History and Broken Promise of Stem Cells, penned with his coauthor, the writer and historian Carl Power. And you might have noticed it is available not only from good bookshops everywhere but also from the foyer. Publish to HarperCollins ABC Book Imprints, Flesh Made New is a judicious examination of the history of stem cell research, a field whose significant potential has often been overshadowed by a troubled and scandal ridden past. In the book, Professor Rasko and his coauthor explore both the champions and the charlatans of stem cell research, looking beyond the decades of promise and propaganda to find the genuine prospects for the field’s future. Of course, the release of Flesh Made New is just the latest in a long line of career achievements for Professor Resco. As one of the foremost minds in the field, he serves on a number of hospitals, state and national bodies, including as chair of gene technology Technical Advisory Committee for the Office of the Gene Technology Regulator, Chair of the Advisory Committee on Biologicals for the Therapeutic Goods Administration, co-founder and past president of the Australasian Gene Therapy Society, and many more both in Australia and globally. Given his history as a prominent and pioneering researcher, it should perhaps come as no surprise that Professor Rasko has won multiple awards for his work, including from national bodies such as the Royal College of Pathologists of Australasia, the Royal Australasian College of Physicians, and the Australian society for Biochemistry and Molecular Biology. Last but by no means least, in 2012, he was deservedly appointed as an Officer of the Order of Australia, in recognition of his service to biomedical research in the field of gene and cell therapies, as well as his experience as a clinician, author and administrator, and his long history as an executive in professional organizations, and indeed, as a philanthropist. We’ve got a lot to learn tonight. I’m looking forward to the conversation. So please join me in welcoming Professor Rasko and Kerry O’Brien for a conversation on science, medicine and stem cell research. 

Kerry O’Brien

Thank you, Carolyn and John Rasko, to start, I have to commend you on your choice of socks. You’ve managed to make a statement without having to open your mouth. So, having broken the ice, as a pioneer and the application of stem cells and genetic therapies, you’ve come to the view that and I’m quoting, “we have reached a point in human history where we can now direct the course of our own evolution”. So, for somebody who is the enemy of hyperbole in your scientific field, as you are, that’s a big statement. How literally, should we take that? 

Professor John Rasko

Thanks, Kerry, easy first question to kick off. I think we are at a pivotal point in the grand scheme of things in terms of our technical prowess. I think most people who are attending this session, appreciate that as a society, we are obsessed with science and technology. And for good reason. We bypassed many previous obsessions, philosophy, perhaps, a couple of 1000 years ago, the arts and perhaps the nuclear evolution and genetics and now at a phase of manipulating our very own hardwire, and that is our genetic information which we pass on to our children. We have now achieved technical prowess sufficient to alter the genetic material that we transmit to our offspring. That’s currently illegal in this country and just about every other country in the world, because of the moral, ethical, and some technical hurdles that presents, but the technical ones are the least challenging, to be honest. We now have that technology available to us. And so, it is a question of responsibility, and appetite as to how we might go along the pathway to embracing that potentiality. And I should say, amongst the many other things, the roles that Carolyn mentioned, I have been very much engaged over the last couple of years in the expert, in HMRC, and the government committee in terms of changing the Australian acts and policies regarding mitochondrial donation, which literally does require a change in the law, to allow these very rare families who suffer from a horrible genetic disease that women pass on to their children and cause muscle problems, hearing problems and early death, the potential for having a family of their own, and using the phrase, three parent babies, a third donor, a second mother, if you will, to give the mitochondria, the normal mitochondria, to the mother and father give them the primary genetic material. So, Australia is embarking on a path to cross that ‘Rubicon’, to cross that inheritable genetic modification barrier, and dividing line between altering that which we pass to our descendants. And conceptually, as human beings, you don’t need to be a scientist, you can ponder what that means to be able to control our genetic destiny and participate in what we contribute rather than it being a random thing or who we’re attracted to, or who we partner with, or reproduce with. So, it’s real, it’s here, and it’s now and it is being explored in various areas of the world, both illegally and legally. Because you would know that China also had a horrible case a few years ago, when somebody did it on purpose by accident. And I think he’s in jail in China at the moment. 

Kerry O’Brien

Not hard sometimes. But the loaded word for me in your quote is the word “evolution”, because what we understand by evolution is, is the changing, evolving nature of life itself. And so, the idea that we can deliberately, consciously, make decisions that are going to change the course of our evolution from here. That’s the big one, isn’t it? 

Professor John Rasko

It is, and if that is daunting or threatening and causes anyone concern, reflect on the fact that we’ve been doing it for very many years, to the extent in directed evolution of crops; humans have been managing crops and directing their evolution, our pets out the little subspecies of dogs, and beagles, and kaboodles and God knows every variation, all of those us to some extent, directed evolution. However, the difference is that now we can intervene on purpose. And I reflect on the fact that people talk about different crops in Australia and the United States and elsewhere. We talk about the cotton crop, for example. The technology has been around, for now more than two decades, to be able to introduce Roundup Ready protected crops so that now weeds can be easily prevented. And the crops can be much more fertile, much more productive in terms of yield, because the weeds aren’t there. It’s a straightforward technology. And it’s widely applied. Most people say, in an America 95% of cotton is genetically modified right now. And the other 5% of farmers are liars, because that’s how widespread it is. We have learned to overcome the technical barriers to do those genetic changes, and in doing so, anticipated the possibility of doing with other organisms, and as we go up the tree back to ourselves, that is a looming on the horizon possibility, 

Kerry O’Brien

And there are so many tributaries, we can go down on this whole thing, because it is such a huge topic and eugenics comes into it. Human nature comes into it, human frailty, our capacity for mistakes, our capacity even for evil, you know, at times. 

Professor John Rasko

100%. And not only that, it changes everything, Kerry, just briefly, because if you make that mistake, it’s not necessarily the person that you advised, informed consent, but this might cause some problems. It’s the children and their children’s children, forever. It’s the descendants of that germline now forever if you change that to the worse, and that’s a grave responsibility and brings up legal questions that have never even been considered before. And what is our responsibility to future generations if we intervene? 

Kerry O’Brien

So, I’m going to try and cover as much of all of these complexities as we can. But what I want to start with is, on the face of it a simple question, what is it about stem cells that makes them so important in all this? 

Professor John Rasko

Well, let’s start with a quick definition. These are the master controllers of regeneration in our bodies. Each of our organs have got stem cells in them – but my favorite, of course, being the blood stem cells being a hematologist – they’re responsible for changing millions of lives in curing diseases like leukemias and lymphomas and multiple myelomas in the context of bone marrow transplantation. These curative technologies were developed in the 50s and 60s by Don and Dottie Thomas and a group of others in Seattle, where I did my postdoctoral research in the late 90s. And that’s changed the world. But even in those early days in the 50s, and 60s, they were not using terminology like stem cells, they were just trying to provide a treatment for leukemias. It was only later that we understood that there are cells in various organs that are capable of regenerating and repopulating those organs when they’re damaged, or at risk. Right now, you and I are making 2.5 million red blood cells every second and if we bleed badly, we might tune that up five or 10 fold. 

Kerry O’Brien

Can I just say, john, I need every one of them. 

Professor John Rasko

You’re welcome. You’re welcome. And some generous donors may even participate in contributing from the blood bank. But that said, all of our tissues have to a greater or lesser degree, that level of regeneration or regenerative capacity. And it is in the stem cells in our bone marrow that make the blood in our hearts that regenerate cardiac tissue, even in our brain that can regenerate to some extent, brain tissue, and all of the other organs to a greater or lesser extent, of course, then you ask the question, “well, John, what’s the cause of those stem cells? How did they come to be”? And immediately it becomes clear, we have to go back to the human embryo, we have to see the lineage from where those cells came. And we can go backwards because every division of a cell is binary, two gives rise to four, eight, 16, 32, 64. So when we look back at these rare cells, the precursor cell of all of the cells in our body is the embryonic stem cell, the fertilized egg, and that is the controversial cell that has been mired in controversy for since they were first conceived in humans by Jamie Thompson, in 1998, following a large amount of work, and then a derivative concept of those won the Nobel Prize with Shinya Yamanaka and Sir John Gurdon in 2012. 

Kerry O’Brien

And then along came politics.   

Professor John Rasko

And religion.  
 
Kerry O’Brien

I’m going to come back to that about religion and politics. They’re supposed not to mix. How far has our capacity to reedit genetic scaffold developed? 

Professor John Rasko

A long way, a long way. So, the Nobel Prize only last year to Doudna and Charpentier was this new technology called CRISPR. And although the idea of editing the genome, in other words, actually changing the sequence of the C’s, A’s, G’s and T’s in our 3 billion bases that make up our chromosomes in all of our nucleated cells, although that idea has been around for a couple of decades and the technology, make no mistake, has been around for a couple of decades, it became a lot easier about 10 years ago when they did their Nobel Prize winning work. And now every student in every biology lab has the ability to genetically modify not just by adding genes, which we’ve been able to do for decades, but now actually literally manipulating small sequences of the genetic information. So, technically, it’s no longer a big deal. 

Kerry O’Brien

So, let me just say here that all these questions are coming from a definite layman. But in that, in that context, with that caveat, I’m imagining, for instance, a straight line of genes. And and let’s say that you take your scissors, and you can now identify the gene that might cause a particular disease. You just snip it? 

Professor John Rasko

It depends if it’s a disease-causing gene that you want to put something back into correct that gene. But that technology is here now in the laboratory, not proven in the clinic yet, if we’re talking about gene therapy, over the last two decades, which, as you know, I’ve been passionate about, and we’ve seen some great successes in diseases like hemophilia, thalassemia, a few others, indeed, are using CAR T cells for immunotherapies. And all of those technologies are gene addition. So, we don’t do any snipping, per se, with molecular scissors, we just plunk that new gene in and that’s called gene addition technology, and usually we use viruses to introduce that genetic material. And bizarrely, we often use the HIV the human immunodeficiency virus, which we’ve now tamed to follow our commands, as scary as that may sound. 

Kerry O’Brien

Well, hopefully, that’s a good thing. You’ve compared what you’ve called the genetic lottery to a regular lottery. So, what is the genetic lottery? 

Professor John Rasko

Well, the genetic lottery is very clear. That is the fact that whether we’re attracted to a person for various reasons, our offspring receive the compliment of half and half from mum and dad. And to that extent, it’s a lottery, you may receive a compliment of genes that make you intelligent, fast, smarter, more beautiful, and so on, or even have red hair, perhaps, when you’re a young man. 

Kerry O’Brien Beauty is a very subjective, John. 
 
Professor John Rasko

Not touching that question. On the other hand, you may succumb to a disease gene. And, for example, in so called monogenic disorders, you know, we’re talking 3 billion of these C’s, A’s, G’s, and T’s all lined up on our chromosomes. And we’re talking about 20-25,000 genes, one of those genes, hopefully everyone in this room has a gene called factor nine, it’s a clotting factor. If you’re born with a single error, in one of those 3 billion happens to find itself, in that factor nine gene, you’re born with a bleeding disorder, that means that you’ll bleed to death, possibly at circumcision, but certainly spontaneously bleed into your knees or your ankles or your elbows, all through your life, unless you replace that with clotting factor all through your life. Unless someone comes along and says I can put the gene back into your liver that you were lacking from birth and see if we can make a benefit. And what we’re seeing right now is I’ve got patients five years down the track who continue not to need any factor concentrates having required three times a week prior to that after a single infusion. So, that’s here now, that’s gene addition. 

Kerry O’Brien

So is this an open field? I mean, in the sense that there are no limits to where we can go with this from on the basis, theoretically, on the basis of what we know. I mean, what are the scientific limits to what we can reasonably hope for? 

Professor John Rasko

In the first instance, we’re really at the proof of principle stage. We want to show that we can do it safely and we require long term studies for safety follow up, and we require larger numbers to see the variations in the way people respond. In the first instance, the proof of principle is required targeting single gene disorders, diseases like hemophilia, thalassemia, cystic fibrosis, perhaps, but the big problems like cancer, Alzheimer’s, diabetes, Parkinson’s, and so on, these are multigenic disorders, they have a multitude of different genetic causations, as well as environmental and that multiplicity of causations, are much more daunting. That said, if you flip the question and ask, well, how can we then treat a cancer that may have multiple genes causing it and multiple different genes in different people, we can use the immune system to say we don’t care what the genetic cause is, just attack it with that particular marker. And that’s where immunotherapies come in and have been shown great success in certain leukemias and lymphomas. 

Kerry O’Brien

So scientific limits, what about the ethical limits now? Because that word, eugenics, will always quite rightly cast a shadow over the whole debate. 

Professor John Rasko

It will and that’s where I started, being a son of a Holocaust survivor, having not had paternal grandparents because they were murdered in concentration camps. I take it very, very seriously and Appreciate the gravitas of the word eugenics, a word that I think most of us he would regard as foreign, but one only need reflect on the history of eugenics to know that there were many eugenics societies at the turn of the last century in Melbourne, various other places in Australia, embraced by politicians and scholarly luminaries, Charles Darwin’s cousin, Sir John Golton was one of the great founders of the word ‘eugenics’ and develop the mathematical basis for it. So, this was founded in science, but then it was corrupted by those who would seek genetic purification and the views of the Nazis in genocide to eradicate that which they saw as impure, not including just the Jews, but beyond that homosexuals, people of a certain political persuasion, as well as people who were regarded as genetically and intellectually defective. And that covered a lot of ground for people who were the enemies of the Nazi Party. 

Kerry O’Brien

And putting, putting that worst of it to one side and just presenting it as a, as a simple notion, the simple notion that we could scientifically improve, “improve” the lot, yes, and again, subjective, of every person on the planet who suffered one or other perceived afflictions. And then you can just, again, just as one complexity about this, people who are born with what is termed a disability, don’t necessarily regard themselves as disabled. And if you’re making a decision with a, I’m going to use the simplistic term of genetic re editing, you are going to remove the possibility of somebody being born. That’s not an omen of somebody being born with that disability. There would be people with disabilities who would say, my life is rich.  

Professor John Rasko

Indeed. And that opens up a whole complex question in terms of the real definition of eugenics, which means by good birth, or by good development. And truly, who would not want the best for their offspring, not only a lack of disease, but also why not have some of the features that many of us would regard as attractive, be they beauty, intelligence, athletic prowess, or so on. The challenge here has been encapsulated by that film Gattaca, which I think many people are aware of, where in the world had become a place where there was an obligation to participate and avoid the genetic lottery and have genetic certainty. And that of course, afforded some with an attractive end. But it clearly ethically raised the biggest questions and indeed, the coder to Gattaca which many people didn’t see, because it was cut out of the final release, said, you know, the kind of people that would no longer have existed in a world of Gattaca include Stephen Hawking, who of course, had muscular dystrophy, and so many others who suffered from genetic diseases, that perhaps meant that the world would have been less a richer place, had we eradicated those genetic abnormalities, you know, by doing a routine eugenics activity. So, I think it raises questions even of hubris, and an absolute arrogance that humanity is often guilty of, and back to the Nazi Party, I mean, the goal originally was built on ideas that were developed in the United States of America. And some of those ideas that then followed on from the UK that they were they were developed actively, in many, many cases where people were put into places where they were not allowed to reproduce. Australia had an active policy of non-reproduction and they absolutely caused some people who were regarded as not being capable of worthy of reproducing, they were made infertile. So, we are not guiltless and we are guilty of that hubris that I think you’re referring to. And nonetheless, the idea that one day, we may improve the genetic lot of humanity is a compelling one. And I think we have to learn to crawl before we walk, before we run fast. And I think that’s the crucial point. If we take a cautious step, and treat diseases rather than enhancement, which is that dichotomy and where you’re pushing me towards, but I won’t cross it. I’ll say, let’s see if the first steps can allow us to treat disease, clear disease-causing genes like mitochondrial diseases, or hemophilia, and maybe one day in the decades to come. Yes, prevent the genetic propagation of the hemophilia gene, yeah I’m perhaps up for that under the right circumstances in the future. But the idea that you want to make everyone a redhead I’ll step back. 

Kerry O’Brien

It’s not bad. You mentioned briefly before the three-parent family, explaine the three-parent family and the moral dilemma that throws. 

Professor John Rasko

Yeah, we don’t like that phrase. And I don’t want to provoke any confusion. But here we have an interesting challenge. There are some 40 or so genes carried in what are regarded as the batteries of all of our cells, the mitochondria. And interestingly, the mitochondria only transmitted through the maternal line, mens’ mitochondria cease at their life. The mitochondria only go through from mother to daughter, and so on. And so mitochondrial myopathy or mitochondrial diseases are only transmitted through the maternal lineage. The idea is if a woman finds that her offspring have suffered with mitochondrial disease, and we’re talking about perhaps 5-10 families a year at most in Australia, it’s a very, very rare disease, she clearly would love to be able to reproduce. And if given the alternative, she would like to reproduce biologically, there are many alternatives for which she needs to be counseled, including adoption and non-reproduction and so on. And all of those need to be discussed as part of informed consent. But be that as it may, there is now a technical possibility, which was first explored in the United Kingdom by the Warnock Commission, and it’s now approved and under trial in the in the UK and being explored in the USA and other countries. But the Warnock commission spent 10 years considering the ethics of embarking on this, in I think, a few years ago, now, it approved, the Parliament of the UK approved that this could go ahead. And indeed, a number of babies have been born using this three-parent baby technology. And it is the idea that the mother and the father, the biological mother, who carries the mitochondrial disease and the father have in vitro fertilization, so now they have a fertilized egg, the nucleus of that egg is removed, which is possible to do these days quite routinely and shoved into a third-party egg, which has had its own nucleus removed, believe it or not, it can work. It works in animal models, and it can work in humans. And that egg can then be implanted in the biological mother’s uterus and come to term. And that baby can be born with the nuclear genetic material from mum and dad and the mitochondrial DNA from the third party, which hopefully will correct that disease. But the big key now is that child’s mitochondria, will be from a third party, and that child’s daughter will also carry the third-party mitochondria. Now, some have said, I’ll look, it’s really not to worry about because it’s just a battery, it’s powering the cell. Let’s not worry, you can get your copper tops and God knows and just plug it back in. It’s really not. Because we know that there are some of these mitochondrial disease, sorry, mitochondrial genes that are normally present in all of our cells and all of our mitochondria that for example, can determine sports prowess. Some Olympic athletes have a specific type of mitochondrial gene, so called haplotype, that we recognize as being linked to their site of their sporting prowess. 

Kerry O’Brien

So, at some point, you might be going into the marketplace, you know, as a parent, but you might want to go into the marketplace and-  

Professor John Rasko

give me those Olympic mitochondria. Absolutely. So we are crossing a dividing line by embarking on this, what on the surface is a very straightforward, hey, let’s help these families. It’s not going to be cheap. But this sounds like a good idea. And indeed, the Parliament has had a second reading, Minister Hunt, it’s called Maeves law,was read into the Parliament for the last sitting for the second time. And it will be one of the first conscience votes actually, that Parliament will have considered in some years, very soon. But that said, the idea that we will be doing this does provoke real questions about inheritable genetic material, because once we do it, the offspring will, there’s no what no way around it, the offspring will carry the mitochondria and the DNA of the mitochondria from a third party donor.  

Kerry O’Brien

Yes, and as you’re sitting here, and I’m marveling at what you’re describing, but I’m also thinking, the sort of the ingenuity of the discovery of that process, that technological process, and what it has led to what it has allowed. And I’m sitting here thinking what is the next level of ingenuity down that road and the next one after that, and that to me is the real, extraordinary element of this whole discussion. We don’t know where this can end up, we just don’t know. And, it can lead to amazing things. But we just don’t know. What did we learn from how the Human Genome Project was developed? Going from public ownership to commercial and so on? What have we learned from that whole project? 

Professor John Rasko

Well, I must say, back in the day, and we’re talking about the late 90s, you will recall this, perhaps like yesterday, Kerry, when there was a public private fight to see who would be first, Francis Collins, on the one hand from the National Institutes of Health and the government of the United States of America represented, and his opposition in industry, who was flamboyant and did things by industrial grunt and might. And an extraordinary degree of demonstration of what money can do. Francis Collins had a very measured careful methodologically sound approach. And his opposition came in and very actively said, No, no, no, we’re going to do a brute force and ignorance approach, we’re going to sequence everything, and just kind of sew it all together at the end. Both approaches required one another to some extent. But it raised questions of ownership of genetic material. And that then raised questions of who owns the information of particular genes like the BRCA One gene, predisposing individuals to cancer, and whether we screen for that, and whether that’s a test that we should be paying for it should be publicly available. It also led to questions I think, that really caused one to reflect on how industry can drive discovery and force, what would be a more, not complacent, but more steady and methodologically sound approach to go faster and go harder, because it really was Craig Venter versus Francis Collins, and they were both on the cover of Time Magazine, when the Human Genome Project was announced by Bill Clinton. And he described it in biblical terms.  

Kerry O’Brien

Of course he would. 

 
Professor John Rasko

He would. I think Hillary was laughing in the background. But perhaps that was Monica was probably there too. I don’t recall the details. But something with the blue dress. 
 
Kerry O’Brien

Bit of science involved in that too.  

Professor John Rasko

But there was DNA involved, I understand.  
 
O’Brien: Yes, that’s right. You are surprising me . 
 
Professor John Rasko

To the extent that it changed the world, I was skeptical, because it was a hell of a lot of money at the time. And I was a little resentful at the diversion of funds to something that seemed to me to be an academically interesting pursuit that would give us the human genome in all its glory and the sequencing was announced. And about two or three years later, we actually got the real, the real details, but there it was, we got the bare bones, and did the big announcement with Bill and colleagues. And I think on reflection, I was wrong. Because the benefits of that have, like stem cells gene therapy, and like so many human discoveries, taken decades, decades to realize. But please make no mistake, I was wrong. And the benefits of that Human Genome Project have driven revolutionary changes in medicine, in diagnosis, in prognosis. Genetic medicine is a technology that allows us to categorize disease, to give much more refined prognostications about any different diseases, cancer, in particular, choosing rare drugs that might work out can be it can be, you know, discovered through using genetic information, and not only diagnosis, but also the prognostication – whether you’ve got a good version of the disease, or a bad version of the disease – all those things come into genetics. But it’s not a therapeutic avenue that then leads to gene therapy, where we use the genetic information of a disease and say, why don’t we put back the normal version of a disease gene, put the normal version to create a benefit. And so that’s where I think the Human Genome Project has contributed incredibly to driving discovery, helping us understand disease causation in much finer detail than we previously did, and offering as new targets for the clever pharmaceutical industry to be able to really drive Information Technology, it is a revolution, it is still ongoing, and it’s taken a lot longer, and it will take a lot longer to fund fully so that ultimately we will all have our genetic sequence available to us, I’m sure.  

Kerry O’Brien

Of course, one of the aspects of all of this, it’s always you know, it’s always a part of just about any equation and that is the issue of we’re talking cost and equity. I mean, the cost can be huge- 

Professor John Rasko

Yeah.  
 
Kerry O’Brien

For therapies. We’ve seen the shocking inequity in how COVID-19 vaccines are being distributed around the world or not. I mean, it is offensive, in a sense to watch the way it has unfolded that we the with the privilege of wealth, are able to access it in a way that countries with little or no wealth are essentially being ignored. And the medicine, as I say that we’re talking about, now and the future, can be usually expensive, is it a real possibility, that we’ll see those with the money and the privilege, genetically reediting their offspring, to the extent that they might be taller, they might be more athletic, they might be more attractive looking, looking by traditional standards, he should carefully, less prone to suffer genetic disease, that might be confined, not confined completely, but substantially to those with the money? 

Professor John Rasko

I think the answer is inevitably, yes, there is a strong risk of that happening. It won’t be government sanctioned to the best of my understanding, and it won’t be done explicitly. But it will be offered in centers that are free from government supervision. So, it’s not out of the question for people to fly to places that are not widely recognized, and unnecessarily under the direct supervision of our regulatory authorities that would insist that those things not be undertaken. But one when one reflects on what money can buy, and what money can do and the temptation to intervene and avoid the genetic lottery, it seems to me that that is going to be too attractive for some to avoid. 

Kerry O’Brien

So we go all the way back to the Hippocratic oath and this is almost the opposite in a sense, isn’t it? I mean, how do you head the off at the pass?  How do you how do you legislate for equity in this field? How? What part does the medical profession play in trying to forestall a circumstance, and I’m you know, let’s not go down the path of talking about a super race, that would be a gross extreme, but if we are talking about the enhancement of life, and that the path to the enhancement of life is much more available for those with the money than the rest, that surely you have to move heaven and earth to prevent that if you can, don’t you? 

Professor John Rasko

You would think so that inequity is something we must all reflect on fundamentally because we are in a privileged part of the world. That said, stem cells and gene therapy partners, together in future health and future medicine, offer a possibility, for what I think most would agree is a better world if it reduces disease and suffering and harm. That said, it has a flip side. And that’s no more better revealed than in the case of the unproven stem cell clinics that spread all over the world, and that we’ve spent some considerable time a few years ago documenting these clinics that we thought perhaps were, you know, in the Ukraine or in the Philippines, or some parts of Southeast Asia. And when we actually went online, and we documented the methodologically sound way, looking at direct to consumer marketing of stem cells, we found that they were all over the world. There were more clinics in the United States of America than any other country in the world. But the country with the highest per capita, direct to consumer marketing of stem cells was Down Under. And indeed, perhaps that’s because we have a low, low population and high medical services. But it took the Therapeutic Goods Administration, many years of people like me and others lobbying them to say there is a loophole that is allowing these clinics to continue. And people don’t need to flock to the Ukraine or the Philippines or somewhere else. They can flock to the local supermarket and be offered stem cells from the belly for whatever it is that ails you. And these are unproven and untested and may cost you $10,000, for the fun of it. And the key was when the FDA Commissioner, at the time, was asked exactly the question you just put, namely, how do we stop this big problem? And his answer informed me so much, he said, “you can’t boil the ocean”. You can’t boil the ocean, by which he meant this is such a bloody big problem that no one country can control it.  

Kerry O’Brien

So, that doesn’t mean you sit on your hands.  

Professor John Rasko

So, that’s why people like myself have gone to the World Health Organization through the International Society for cell and gene therapy, which I was President of for the last couple of years, and lobbied them, as well as places like Google to say, hey, Google, you shouldn’t be advertising these stem cell clinics online and they took that up in a ridiculously fun way, which tells you a lot of a story about the hype and hope of stem cells. Google basically said, you know what, after about a year of lobbying them, they said, you know what, you’re right. We’re going to ban these stem cell clinics, we’re going to hit them at their, you know, they can’t advertise on Google anymore. It’s this is a win for everyone saying everyone who embraces rational medicine, no more unproven cell stem cell therapies, because what they did was also inadvertently ban all of the bone marrow transplant centers of excellence in all of the hospitals all over the world that were had their medical centers online, because they hadn’t appreciated that there are unproven stem cells and proven stem cells that have won Nobel prizes. And so, excuse me, Mr. Google a little bit of a mistake there. Could you please back off a little bit? But the answer to your question at the key is, how do we do it? We do it by meetings like this. We do it by raising awareness. We do it by educating an already interested population in science and technology, partly because of COVID, it’s never been a better time to talk about science and medicine. But to simply say, not everything is as good as it seems and there’s no such thing as a free lunch. You know, you need to be mindful that every discovery that you hear is not necessarily a cure for cancer or whatever it is that ails you. And there are some sources of reputable information and there are others that you need to verify independently and always take care and always seek independent advice. 

Kerry O’Brien

So, I mean, there are two strands to what you’re touching on here. One, one is probably misrepresentation, false claims, or unsubstantiated claims, and a lot of money turning over on the basis of that, and then there’s outright fraud. As being a part of the history. So, and I associate fraud with criminality. Looking back now at the depth of actual fraud, and misrepresentation on genetic therapy and stem cells that you’ve chronicled, in your book, gas it shocked you to contemplate the extent to which reputable people in science and medicine were prepared to throw their ethics out the window? 

Professor John Rasko

Of course, it has. Yes, it has. It’s a profoundly disappointing experience to reflect on, especially people who you believe are leading the field publishing in the best journals to find that they have cooked the books and actively deceived the medical establishment and everybody reading the work, the amount of wasted time and effort, not just funding of public monies that are thrown down the toilet, because it’s garbage. They just cooked the books, they’ve just manipulated an image or lied about a result. And sometimes it takes months or years to identify these deceits. And in the most egregious example, people’s people die as a consequence of this misrepresentation, 

Kerry O’Brien

Then in your broader body of research, you have to backtrack, 

Professor John Rasko

Indeed, and untie the misrepresentation. Is there any truth in any of this, for example, but just to correct you a little bit Kerry, the book is about stem cells and not really about genetics. So, I don’t think there’s that much fraud. There’s been some pretty sad examples of financial impropriety in the gene therapy field and the death of Jesse Gelsinger, which sends shockwaves in the genetic therapy area some 20 years ago, was certainly an example of that. But you know, almost as a lover on the rebound when gene therapy seemed to fail about 20 years ago, because of a death in the field, we found stem cells is the redemption and it’s been the case ever since. Now, we set out, first of all, to talk about the promise and hope of stem cells. That was our goal 10 years ago, when we wrote a grant to the Brocher Foundation and said, we’d like to write a book, could you please fund us to have a lovely holiday, I mean, research trip in on the shores of Lake Geneva, which Carl I enjoyed immensely. But that led us then to get deeper and deeper into the history. And you know, I’ve been involved in this for decades. And we began unpicking the promise, the triumphs, the successes and the champions and reflected on the fact that there was an equal amount of hype and overhype, as well as downright fraud. And then the analyses that have been done in terms of academic publications show that stem cell research is overrepresented in an objective measure of scientific fraud, which is the retraction of scientific papers so we can measure that. And the fact of the matter is compared to other like scientific and medical disciplines, stem cells are pretty bad and on the nose when it comes to retractions. And so we know that there is something about this that is promoting people who would otherwise compromise their ethics and who are driven down to either fraudulently misrepresent their data or indeed, downright lie. And that is the real challenge. That’s the shock and we’ve seen it in every country. We documented it all the way along from Hwang Woo-suk in Korea. 

Kerry O’Brien

This is the question, who have been the significant villains? 

Professor John Rasko

These are our sinners. We have a patron saint, which is Alexis Carrel, that we described from 100 years ago and Nobel Prize winner,  

Kerry O’Brien

He was both good and bad. 

Professor John Rasko

Indeed, he is our patron saint and patron sinner. And we call him, in the prehistory of stem cells, because he taught the world how to grow cells outside of the body, an extraordinary discovery, that would have been equal in stature to the one that you know, won the Nobel Prize for which was joining blood vessels together, he was a surgeon. But he also inflicted a horrible hoax on humanity and on science for decades, he was the one who had the scientific equivalent of the blob. Namely, he took a chicken heart, an embryonic chicken heart, beating cells, put them into a dish, and he grew them in that dish that he claimed that was able to be nurtured and grown in his special lab at the Rockefeller Institute for decades. And we now know that of course, that’s impossible. But we only learned that after probably dozens, if not hundreds of scientists tried to replicate his data and failed. And so, we do have checks and measures and balances in science, and it is replication, replication and replication. If one lab is saying I can do it, and no one else is saying we can do it too. That’s going to trigger alarm bells. But Alexis Carrel being the grand priest and high priest of developing tissue culture, every year, the press would come and sing happy birthday to these cells, even though we know that they must have been either repopulated from another chicken heart or there was a virus or they transformed into cancer. But nonetheless, it took 30 years and another quite dogmatic scientist to say you know what, this is bull, and it’s not working. And it’s not true. And I can’t reproduce this because he invented the concept. His name was Leonard Hayflick. He invented the concept of cellular senescence, which we now know to be true for all cell types in our in our body, we can’t grow them after a certain number of cell divisions unless they become cancerous or infected by viruses. So, he is our patron saint. He made incredible contributions, and whether inadvertently or by poor technique, whether his research assistants were cooking the books, we’ll never know, because he passed away before this actually came to the fore. But he then started a tradition of stem cell fraudsters, if you will. Hwang Woo-suk in the, in the modern times, claimed to be able to, in South Korea, create clones, using a somatic nuclear transfer in, 2004 was his work. You remember south, South Korea was famous for the Raelians, who claimed that they were cloning people all over the world, which was a marvelous religious bunk. But nonetheless, Hwang Woo-suk was a vet and he was he was a truly the first person on the planet to clone a dog. Interestingly, there is a tradition in naming these cloned animals after famous people and you know, Dolly was named famously after certain cells that were taken from a sheep’s breast. And you may know someone called Dolly who has equivalent fame Snuppy was Hwang Woo-suk’s dog and that was particularly clever name for dog because Snuppy was S-n-u-p-p-y. And that was Seoul National University-puppy, Snuppy and the first cloned dog. Long story short, Hwang Woo-suk, he cooked his books without a doubt and he was he was entitled The Supreme Scientist of South Korea face on the stamps. Given every accolade in South Korea and then an investigative journalist and series of exposes pull him down over a long period of time, it was a dogged fight. But in the end, he then retreated and became famous for starting a company which still exists today that Barbra Streisand has cloned her dogs. You can send your dead dog cell samples to South Korea and have your dog cloned and she’s got two lovely dogs that she adores. Hwang Woo-suk was a fraudster but he was only one and then the next one was probably Pierre and Versa from the United States of America who claimed he discovered stem cells in the heart. Then Haruko Obokata from Japan who claimed that you could just dip cells in the equivalent of a slightly acid solution acid like a Coca Cola and reprogram them to become stem cells. She was called out very early on after her back-to-back Nature papers. But she collaborated with people in Boston who still haven’t been held to account and were allowed to retire early. But the worst I’ve left to last, of course, and that is the infamous windpipe surgeon and very handsome, celebrity surgeon. by the name of Peirro Macchiarini, sorry, Paolo Macchiarini 
and Paolo Macchiarini was famously trained in Europe. He was headhunted by the home of the Nobel Prizes the Karolinska Institute to join them, because he claimed he was able to take decellularized windpipe, that which allows us to breathe, and replace it in individuals by populating that windpipe with bone marrow stem cells. And indeed, virtually all, but not all of his papers, have subsequently been retracted. They were investigations prompted by many whistleblowers at the time who said this can’t be right. But they were pushed down they lost their jobs and they lost their grants as a consequence. Forgive me Vice Chancellor but even the Vice Chancellor of the Karolinska Institute was caught up in this and lost her job, the shockwaves that destroyed many careers at the Karolinska Institute were firmly on a Macchiarini’ shoulders but worst of all, most of his patients died a horrible death, strangulation in, you know, basically unable to breathe because of his fraudulent data. 

Kerry O’Brien

Was this all part of the boiling ocean, that you can’t boil an ocean in terms of regulation? That these things just escaped for a time? 

Professor John Rasko

I think this was an appetite for fame in the in the place which, you know, really promulgates that greatest- 

Kerry O’Brien

So how do you guard against that? Isn’t that what, what peer review at the most fundamental level is supposed to be about? 

Professor John Rasko

Yes, it is. But ultimately, you can’t. You can’t, unless you can prove it, prove a lie. If I’m determined to tell you that- 

Kerry O’Brien

Well, you can with Donald Trump and a few others. 

Professor John Rasko

Well, let’s not go there. I was going to use other examples. But you know, I can tell you that the color of my wallet is black now. And you can’t prove it unless you somehow obtain it. So I can walk out of here and you can believe what you like, but I can claim it. In the same way. If I give you a straight-faced lie, and I know that you can’t prove it otherwise, then there’s no way of disproving it until somebody- 

Kerry O’Brien

Don’t you know, as the scientists that at some point someone’s going to get you? Someone’s going to someone’s gonna prove it? 

Professor John Rasko

You know, that is a question that I have pondered with Carl and we wrote it in our Guardian article. And the article was basically entitled, what prompts a scientist to lie? Because it cuts to the core, Kerry, of what I would hope that most people respect biomedical scientists respect medicos, and give them the authority and respect that they deserve. But these are examples that call into question that assumption. And what causes a scientist to lie is what my friend and colleague Glenn Bigley has called perverse incentives, those incentives to publish or perish, those incentives to get grants and prove yourself smarter and better than your competitors. Even though five years down the track, you may get caught, but you don’t see it. It’s the same reason why kids steal something in the candy store, and you know, might get caught and punished as a consequence. 

Kerry O’Brien

The kids aren’t reputable scientists who’ve gone through a lifetime developing the discipline and all of the things that go with that discipline.  

Professor John Rasko

And how old Did you say Donald Trump was? Is?  

Kerry O’Brien

He’s a special one, Donald. Speaking of Donald, in the age of fake news, there has been a huge assault on the science of climate change. And the flames have been very effectively fanned by Donald Trump, not just in America. What is that done to public trust in science, generally, including in your field? The sort of fake news aspect of all of this, we’re in climate change, you can have 99% of the world’s climate scientists stating positions or a position, an agreed position, but somehow, the 1% is parlayed into a significant erosion of trust and the other 99%. 

Professor John Rasko

I think you probably know more about this than I, having set on one side of that divide. But it is about twisting the year of those people who would listen. And, certainly, from the Australian perspective, I think it’s fair to say that we’ve observed an American divided 

Kerry O’Brien

But yeah, but what I’m what I’m asking you is, as a scientist yourself, it must raise concerns to you that if established science, from the most reputable person in the field, can have the ground significantly cut from under it by specious argument, if it can happen with climate science, it can happen with any science.  

Professor John Rasko

That’s correct.  
 
O’Brien: Do you think there has been an impact on the credibility of science generally? Including in your own field, that there is this kind of spreading stain effect of this that is not just confined to one field of science? 

Professor John Rasko

Well, I think raising questions is, is reasonable, and I think put two scientists in a room together, and you certainly get three opinions. But 

Kerry O’Brien

Not as many as you get with two economists. 

Professor John Rasko

You’ve forced me to, you know, address a question about public perception. And with COVID, I think our trust in what science is capable of doing in a miraculous timeframe has been reinforced. That is a source that we should be all rejoicing and celebrating in terms of our safety and wellbeing, we’re not wearing masks. And that’s because of public health. And I reflect on the fact that five years ago, most people in Australia had no idea what a public health physician did, let alone the details of all of the different things that we’ve learned over the last 18 months. 

Kerry O’Brien

But imagine, when you look at and California was your kind of sort of number one example of all of these unproven therapies that are out there being flogged on the internet and where wherever they can be flogged. But the internet is there isn’t it as a device like we have never had before in terms of global communication, and global miscommunication. So just think about that in the context of the path and paths that you are headed down with your science in the extraordinary areas we are heading towards including the ethical, the really important ethical issues that relate to that, put that against fake news. Put that against what the internet is capable of doing as a twisting force.That surely is a matter of enormous concern. 

Professor John Rasko

It is, so now to answer the cloud with clarity. The amplification of extreme views is something that the internet has been an unexpected mediator of. It has democratized individual voices in a way that we wouldn’t have anticipated, but also it has perverted many voices by corralling them in more extreme views and forcing them into communities that are sometimes, would otherwise have been socially unacceptable or completely outlawed. So, to the extent that I’m convinced that any new discovery that can be monetized by people who will falsely claim to already have a hearing now, that is the sound and the caution that Flesh Made New seeks most to raise. If you go away after reading that book, a little bit disillusioned, perhaps a little bit worried we’ve done our job.  

 
Kerry O’Brien

I’d say more than a little bit.  
 
Professor John Rasko

Well, we don’t wish to say there is no promise, there’s been great success and there continues to be. But the idea of regenerating tissues, which is what stem cells claimed they would bring to us very soon, after 1998m have not been realized yet and they may it may still be decades away. That said, there have been people claiming to be able to regenerate organs and tissues for not decades, but between 50 and 100 years. Fresh cell therapy was available in the 1930s. And we had, you know, politicians, Mahatma Ghandi, Pablo Picasso, great artists and everybody else flocking to the shores of Lake Geneva to get their fetal cells from cows and sheep to regenerate their tissue. So, the idea that you could, you know, pick on the well of immortality and regenerate tissues has been there. It’s been a fundamental desire. And so, people have preyed on that desire. If somebody tells you with a serious disease or a family member with a serious disease, that they have the treatment, and the reason why no one else is offering it is because they don’t understand or because I’ve developed something extra special. Just give me $20,000, and I’ll give it to you at a special price. That is extremely attractive. 

Kerry O’Brien

And it’s just a variation, isn’t it of, remember Steve McQueen, famous actor diagnosed with a form of cancer that was almost certainly going to kill him. He’s tried everything and hasn’t worked. So, he Nick’s across the border into Mexico to go for the I think it was the apricot kernel treatment. 

Professor John Rasko

It’s a funny twist on on an extraordinary story because I made a brief mentioned earlier on of the film called The Blob. Did you know that Steve McQueen was the star of The Blob. 

Kerry O’Brien

That’s entirely coincidental. 
 
Professor John Rasko

Indeed, but what a beautiful segue. So, Steve McQueen, what a famous actor he was. The temptation to succumb to false hope is that which I would rail against. And I hate the concept that I might be appear paternalistic, or condescending in the way of saying, well don’t do it, because I’m telling you not to do it. But all I’m saying is reflect on the evidence and seek alternative advice. If you think something is too good to be true, it probably is, namely, too good to be true. And that’s the lesson that we wish to highlight. And whether it be through outright fraud, or misrepresentation, or just outright lies. And we know that there are many, many people who would prey on the unsuspecting public, there are many expensive homeopathies, if you will, none of which work, including homeopathy. Sorry, 

Kerry O’Brien

I’m not gonna go there now, with four minutes to go. There’s just a couple of things quickly that I want to pass by. Before we finish, and one is with Joe Biden, we are now back in America back in the field of of embryonic stem cell use in research, where are you on that? And do you respect those who have a genuine moral or religious objection to the use of human embryos? 

Professor John Rasko

I do. And I believe that our proudest moment in the book is discussing without fear or favor, the true scientific basis for where that profound extreme divide exists. And it exists in a question that science can’t resolve. And that’s why it is such an important question, which is when does life begin? And more importantly, when does personhood begin? and science has allowed us to impact on that question very, very clearly. You know, the Vatican, which has driven a lot of the ethical questions and religious dogma in this issue changed its view on when life begins. It was originally taught by the Vatican, that, that it was when an egg became fertilized when a sperm meets an ovum. But they learnt and the pope announced in the Gift of life, I think, that, in fact, science had learned that it wasn’t when the sperm actually penetrated the egg itself. It was when their genetic material intertwined the sperm and the eggs. And that took 22 hours. So the Vatican to their good credit and respected, it’s not when the sperm meets the egg, it’s actually 22 hours later, and that’s when life begins. That is conception, that is a new life. And we will afford that new life, the respect that you and I and everybody else in this room has – equivalence, equivalence of a single cell to, let’s say, an adult, human or a person. And that has been debated forever. by humans. When does personhood occur? Different religions define it differently. There was a time-  

Kerry O’Brien

But in the science, in the science, when do you believe it is okay, ethical to use a human embryo? 

Professor John Rasko

Well, currently, there is a law in Australia, and we are allowed to do it for a certain number of days, we are allowed to study human embryos for a certain number of days before they must be destroyed. We certainly have legislation that allows us to have in vitro fertilization occurring. There are different laws in different countries. And those boundaries are slowly being pushed by and by people who would study things further. And I think legitimately so, because they will impact on human health, and allow us to understand not just basic biology for academic reasons, but indeed fertility and study how we can help families and understand how some of those technologies can be better applied. But that said, the definition of personhood is a cultural one, a religious one, a moral one, an ethical one. And really, science has less to do with that. I mean, it’s almost arbitrary that the 14 days when the notochord, when we get a primitive neurological system, that’s what the arbitrary definition currently is. Well, when that when the primitive streak occurs. That’s when we say well, beyond that, it’s a no go. But that sounds almost more arbitrary than the Vatican position, which seems to be reasonably low, so far be it for me to be defending certain positions. But I do think that these are questions that are reasonable, and the different positions can be reasonably held. You asked me whether I respect- I do respect the proposition that an alternative view can be held, but in the end, we need to make decisions as a society. And thankfully, that’s what politicians do. 

Kerry O’Brien

So, in this discussion we’re about to come full circle. So, in a clear-headed way – and not that everything you’ve said hadn’t been clear headed – what do you actually feel positive about in terms of where the science is headed? 

Professor John Rasko

Absolutely. So proven stem cells, bone marrow transplant transplantation, over 2 million bone marrow transplants on the planet since Don Thomas first started, cured many leukemias, lymphomas, myeloma is another cancers, done, dusted. Fantastic getting better all the time. Proven. Stem cells work. Thank you very much. Right now, instead of promising, in the distant future, regenerative medicine, which we all hoped for, to be able to grow organs outside of the body regenerate tissues, so that we have off the shelf ability to transplant organs and repair organs. Right here and now, we have technologies based on the Nobel Prize winning work of Shinya Yamanaka in Japan, that allow us essentially, to create fertilized egg cells with embryonic stem cell like cells from every cell in our body. So now we can take a blood sample from anyone, we can create essentially pluripotent cells that if ultimately implanted into a womb and carried to term would create your clone. That’s illegal, please don’t do it. Those cells would also, because they are capable of giving rise to every cell in your body, can be coaxed down those pathways to create, in a dish, liver cells, brain cells, bone marrow cells, heart cells, and those dishes then contain the same genetic material from the donor. And that can be a rare disease, maybe only 100 on the planet, there are four or five or 6000 genetic diseases, only 5% of them have possible treatments at the moment, we can study those diseases in a dish and use the might of industrial screening. We can take a rare genetic disease now and test 100,000 drugs on them in a period of a week. Why is that a big deal? It’s not regenerative medicine, but it’s here and now. And the pharmaceutical industry is using it every day, they were using mini organoids. These mini organs – not mini me, illegal – but mini organs to recapitulate organ development and testing drugs that might cause side effects on heart tissue, testing benefits on screening on cancer cells, or indeed, normal cells, to see whether or not there’s some benefits. That’s here and now, it’s being used. And of course, it’s being used in all aspects of technology, including producing COVID, vaccines and so on. Lung tissue in a dish. Imagine what that technology can afford us. And it’s here now and being used and has been for quite a few years now, based on that Nobel Prize winning work, that inspires me that is here and now and it’s real. And so that’s what stem cells have offered us here and now, proven 50 years ago before we even knew what stem cells were in bone marrow transplants, and induced pluripotent stem cells or reprogrammed stem cells from the Nobel Prize winning work of Yamanaka that is here and now, and maybe in decades to come cells that can give rise to organs for transplantation and cure diseases that currently have unmet medical needs. 

Kerry O’Brien

John Rasko, a great conversation. Thank you very much.