Remaking ourselves human genome editing The Royal Society

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MARIA: Okay, good evening, everybody. Shall we get started? So, welcome to the Royal Society. My name is Professor Maria Fitzgerald, I am a neuro scientist and a fellow of the Royal Society.

It's a great honour to be joined by all, the audience here and also those watching online to listen to this lecture tonight. But, just before we get started and I introduce our lecturer, there is just one or two things I should say. Please could you make sure that your phones are turned off. There is no planned fire alarm test this evening, so if it does go off, we will need to evacuate and we should go out through the door over here, I hope I am pointing in the right way. This

door at the back, on the right is where we should leave. And please note also that this event is being livestreamed on the Society's YouTube channel and it will be available to watch afterwards. afterwards. So now let's get on to the business of the evening, which is to celebrate the 2022, Wilkins-Bernal-Medawar Prize, which is being presented to Dr Philip Ball. This prize is given annually for excellence in presenting the social function of science, the philosophy of science, or the history of science. And Dr Philip Ball

joins a list of exceptional individuals who have won this prize before, historian, philosophers and science communicators, including Professor June Barrow-Green, Professor Jim AlKhalili, and Professor Simon Schaffe. To name just a few. But the winner tonight, Dr Ball is a science writer who has written for numerous publications, including the New Scientist, the New York Times, the Guardian, the Financial Times and he regularly contributed to Prospect Magazine's science blog. He previously worked at Nature for over 20 years and he now regularly writes columns for Chemistry World, Nature Materials and BBC Future.

He has broadcast on radio and TV, including a York Times, the Guardian, the Financial Times and he regularly contributed to Prospect Magazine's science blog. He previously worked at Nature for over 20 years and he now regularly writes columns for Chemistry World, Nature Materials and BBC Future. He has broadcast on radio and TV, including a three-part series, entitled "Small Worlds" for BBC Radio Four. Phillip regularly gives engaging public lectures at the Royal Institution, here in London, but and has delivered lectures to scientific and general audiences across the world. ip regularly gives engaging public lectures at the Royal Institution, here in London, but and has delivered lectures to scientific and general audiences across the world. His work covers a huge range of

topics from quantum physics to the composition of music and he consistently bridges the gap between science and art. Also considering the history of science and its interaction with society. I had the pleasure of meeting and talking to him earlier this evening and the breadth of his knowledge and the areas of science that he has covered is really impressive and I am looking forward very much to his lecture tonight. He has written many popular science books, including his 2004 book, Critical Mass: How One Thing Leads to Another, which won the Royal Society Winton Prize for science books.

His book Serving the Reich: The Struggle for the Soul of Physics under Hitler was also shortlisted in 2014. But tonight he has won this prize and a great honour it is for him and a great honour it is for us that he has won it. And he is going to give a lecture called Remaking Ourselves. So without further ado, it is my great pleasure to welcome him to the stage , Dr Philip Ball. APPLAUSE.

PHILIP: Thank you so much, Maria. I am grateful and humbled actually, not just to receive this award, but because so many of you, friends and family and colleagues who have supported me and what I do have come tonight. And thank you so much for doing that.

I realise that at no time during a talk is the audience more attentive than at the beginning, so I am going to give you the take home message straight away. I have been writing and commentating on science now for more than three decades and I would argue that science communication is more important today than ever it was. We see that, for example, in the coverage of the COVID pandemic as well as discussions about AI, genome editing, stem cell technologies, climate change and many other issues that have becoming increasely central to our lives. To my mind the pandemic has showed more clearly than any other episode I can recall how intimately science is entrained with politics in both the narrow and the broad sense. This means that our job was not just as explainers and translators who could explain R zero values remember them? Or mRNA vaccines. But as critics, interpreters and context

makers. So contributions like these, probably didn't please some scientists, but I felt they were an essential and I hope a useful part of the job. In the US Ed Yong one of the finist science writers of our times seems to have reached the conclusion. His bird's eye view of the politics of the pandemic in the US in the Atlantic completely warranted the Pulitzer Prize that he has been awarded.

Here is the message, while a big part of the goal of science communication is to convey new discoveries and technologies in a language that is accessible to everyone I believe that we who strife to do this would be failing in our role if we don't, at the same time, explore the social and cultural contexts against which these fast-moving and impactful developments can be evaluated and understood. We have a duty, not just to illuminate, but sometimes to complicate. I believe that those contexts have to be very broad, embracing historical, philosophical, societal, cultural and ethical considerations. The very factors that this medal stands

for. That is my understanding of the contested notion that all science is political. It's not to say that all science is politicised or should be, but to recognise that it doesn't take place in a social vacuum and that the questions that science asks and the framing of the answers as well as the way in which it is received and integrated into our societies, are inevitably saturated with agendas and conditioned by the intellectual heritage from which they emerge. Now all of this might sound rather abstract, so I want to put some flesh on the bones, as it were, by looking at a particular area of current interest and activity and controversy in science. I am going to begin it with this 1956 essay by Peter Medwar which is an example of his ability to write about science that brings out the wider context of the title, the Uniqueness of the Individual suggests a fist solvical theme, but he explores it through the lens of skin grafts which was then still a nascent technique which had been rendered salient by the two world wars.

So Medawar explains that typically what happens is a sheet of skin would be removed from some uninjured part of the patient's body, ideally the thigh and laid over the area from which skin had been lost. Where upon it will eventually merge with the skin at the borders. But what if the patient doesn't have skin to spare for this process? Why not then use skin from a donor? Well we know the answer of course, there will be immune rejection. So that in general the graft won't take. But why

not? The problem is that our immune system learns, during our development, to recognise our own cells and tissues and to distinguish them from other organisms. This self-recognition is clearly connected to the individuality of our genomes, because skin grafts can be exchanged between identical twins and in fact Medawar describes a case where grafting was used to establish a genetic relationship between two children. These were in the days before genetic sequencing was possible. So one possible way to define the uniqueness of the individual then is immunological, the self is that which the immune where grafting was used to establish a genetic relationship between two children. These were in the days before genetic sequencing

was possible. So one possible way to define the uniqueness of the individual then is immunological, the self is that which the immune system recognises and accepts. As Medawar put it "the concept of immunological tolerance has implications which are deeply philosophical in the worst sense of the word. " I love that recognition. For it bears directly upon the recognition and the awareness of the self. This is a contingent idea of the selfhood. What if we suppress the immune system as is

routinely done for organ transplants today. Are we then suppressing a sense of self? What about breakdowns of the immune self-recognition exhibited in auto-immune diseases. Well, immune self-recognition is, as I say, acquired during development. It's not innate. As Medawar points out, it doesn't apply to embryo. An embryo will accept a graft from another embryo quite happily.

What does that mean? For one thing it means that what we think of as the individual in this sense is not uniquely defined at conception. It means that our cells at the embryonic stage don't work from any global view of the individual organism, their goal, and I think we can consider it a real goal, is to collaborate with the other cells around it, in a way that defines a collective and emergent, but also contingent developmental path. It also means we won't get very far in seeking a definition of self-hood in the genome either. But how strongly we are now encouraged to believe otherwise? This is the DNA sampling kit supplied by the company, 23andMe, which will sequence your genome after a fashion, by mail order. Welcome to you.

Well that is just marketing, right? Not really. When the pioneering geneticist, Wally Gilbert used to give lectures he would carry a supplied by the company, 23andMe, which will sequence your genome after a fashion, by mail order. Welcome to you. Well that is just marketing, right? Not really. When the pioneering geneticist, Wally

Gilbert used to give lectures he would carry a CD which he would brandish and say to the audience "this is you. " This sort of thing still happens today and I find it curious to watch this dance that modern genomics performs with the idea of DNA as self. On the one hand geneticists will complain about the crude genetic determinism in a lot of contemporary discourse whereby genes are regarded as the source of all that we are and all that we think. It's not as simple as that, they will say. On the other hand, there is that insistence that this, this genome is you. And the mantra, whether it comes from the Crick Institute, or the US National Human Genome Research Institute that your genome is your blueprint. Your instruction

book, your manual. A book that the Wellcome Institute has been kind enough to print out in 117 volumes of genomic data. When you see a disnoons of this magnitude you know something is happening beneath the surface. The unspoken agenda, this

modern myth was explored by Dorothy Nelkin and Susan Lindee. It's a notion that is aptly called DNA as soul. A mobilisation by scientists of the ancient yes or noing to find a vessel for our selfhood. Now there is another reason why that recreptive embryo that Medawar mentions undermines mines a genomic view of selfhood. He mentioned Mrs McK, who at the age of 25 was found to find two genetically different types of red blood cell belonging to different blood groups. The doctors puzzled about how this was possible, until Mrs McK told them she had a twin brother who had died at three month gestation, so they figured that the blood producing cells of the two feet uses must have been exchanged in the womb. Something that was known to occur in non-identical

cattle. When this case of Mrs McK was described in a 1953 paper by Robert Race and his colleagues he gave her condition a name. She was, he said, a human blood group chimera. Her condition is relatively rare, but we now know that some degree of human chimerism isn't that uncommon.

It's not so unusual for a pregnant mother and the fetus to exchange cells. These are generally cleared from the mother's body eventually, but that can be a slow process and in some cases they can persist in the body for years after the child's birth. But more extreme forms of chimerism are possible too.

Very rarely two non-identical embryos, even of different sexes can fuse in the very early stages of gestation to become a single person with a mosaic of genetically distinct cells throughout the body. So if some of those cells have two X chromosomes , chromosomally female, you might say, while some are XY chromosomally male then. This reflects the tremendous tolerance of embryonic cells which can find their way to a normal developmental path even in such extreme circumstances. And chimerism can go still further. Embryos will even accept cells from another species.

That they will incorporate into the organism, producing a cross species, chimera and here is one. A chimeric embryo of a human and a monkey. We don't know how far an entity like this would continue to develop if implanted in a womb because doing that experiment would be unethical. We do know that cross-species chimeras are fully viable.

They have been made from rats and mice for example or from sheep and goats. Attempts are now being made to grow animals from embryos, containing human cells in which those human cells are used specifically for the development of a given organ and the idea here is that to grow human organs for transplantation within livestock such as pigs or cows. We call these individuals with a mixture of genetically distinct cells a chimera. That word was first used in biology in 1907 by the German botanist, Hans Winkler when he grafted a tomato and a nightshade, but what was a chimera originally? An mythological monster. Part goat and lion and snake.

They were considered not just aberrations of nature, they had a meaning are the word monster derives from the Latin monstrare to show, or monere to warn. A modern study of developmental anomalies is called terratology and is named for the Greek word often used to denote the monstrous terras which means portent. Monsters were unnatural, but that doesn't mean they were outside of the natural order, it meant that for that very reason they were to be shunned with moral aprobation. So labels like these, whether

awarded by science or by Society, tend to come freighted with cultural baggage. To call a child born by IVF a test-tube baby, or a child born by mitochondrial replacement therapy as we just heard has just happened, a three-parent-baby, or by so matic cell nuclear transfer, if that ever happens, a clone, is already to invite interpretation and judgment. Words like unnatural and artificial, metaphores of machines and selfishness, of instructions and code and programmes. These aren't neutral, but they have a heritage.

The job of a science commentator is to excavate and interrogate that heritage. The idea that there is a unique genomic self also runs into problems in the other direction too. Because not only can a self be genomically diverse, but our putative genomic self might not be bounded by our skin. Look at this. These are neurons, grown in a petri dish. They are not just any neurons, or at least as far as I am concerned they are not, because these are my neurons. They were grown in the lab of UCL neuro scientist, Selina Ray, who I think is here tonight.

I will be forever amazed at what you did, because she grew them from a piece of my skin, extracted by biopsy from my upper arm. 20 years ago many biologists would have considered this impossible. Skin cells were considered to have reached their final state and couldn't switch to be another cell type or tissue type entirely, but they can. In 2006 the Japanese biologyist, Shinya Yamanaka and Kazutoshi Takahashi announced they had transformed mouse fibroplasts into stem cell like pleuripointent cells. This he did this by treating the cells with a cocktail of four genes inserted into the cells using viruses. Those four

so-called Yamanaka factors are all genes known to be very active in the embryonic state in stem cells. It seems that they alone were enough to reprogramme these mature cells into a stem cell-like state, called an induced pleuripotent, an iPSC. So once reprogrammed as iPSCs, these cells became capable of differentiating along a new pathway to become a tircht tissue. Although that possibility was already inherent in earlier work done in the 1960s, in work on cloning, the relative ease with which Yamanaka's method could be used to transform cells was a revelation and the, and it had enormous potential for cell biology.

He shared the 2012 Nobel Prize. This cell reprogramming raises the prospect of regenerating lost or damaged tissues, for example to treat and perhaps heal injuries of the spinal column, or of the retina, or indeed from making skin grafts. One great advantage is that the patient's own mature cells can be used. So there shouldn't be the problem that Medawar warned about, of immunological rejection of foreign tissue. But this isn't just about transforming cells, it's about determining what they can make.

This is what some of my induced neurons became. You can see that it's not just a featureless tangle of neuron, there is structure here as well as different cell types that are shown by the different coloured stains. This is called a brain organoid. It exhibits some of the structure found in a developing brain. Here is a better example, not one of mine, of that, that you can see what is going on here. It shows that neurons have some

intrinsic knowledge of how to act together to create the proper structures and forms of their respective tissues, even when they grow outside the body. The same is true for any other cell type made from iPSCs. So if reprogrammed to become the epithelial cells of the gut they might organise themselves into organoids that hollow tubes lined with the little hair-like structures called villi that absorb new tree events. If they are reprogrammed into liver cells they are develop little livers or kidneys.

The resemblance of these organoids is far from perfect, but it might be close enough to enable organ growth to be studied in the petri dish and perhaps to allow the testing of new drugs without the need for animal experiments. What's more some researchers getting better at guiding organoid growth towards more realistic mimics of real organs and perhaps to allow them to grow vascular systems, so that the supply of nutrients, a blood stream, allows them to get bigger without the inner most cells dying of starvation. That is all very well, in fact it's all very exciting for growing replacement organs and tissues this way.

For example, growing functional pancreatic organoids for people with Type 1 diabetes. For brain organoids it raised some ethical quandries. They have been used to study neurological diseases such as Alzheimer's. And the more truly brain-like they become, the

more reliable they are as lab models for the real thing. But with a brain-like entity, we are forced to ask at what point do we have to consider the possibility that these structures might harbour a degree of consciousness, of sentience. What can that mean for a disembodied brain-like structure. How can we know what

is going on inside a brain organoid when we still have no agreed theory of consciousness itself. Now, I don't believe there was any reason to worry about these things for my own brain organoid, it was far too primitive for that. Even so the philosophical implications are dizzying.

What is the moral status of this object that was made from a piece of me and in some ways recapitulates the growth of my own brain, with presumably all the same genetic influences. Where does the self start and end? This notion of a brain in a vat has been a popular thought experiment. Here is a famous philosopher contemplating that.

It's been used to explore how we create and experience our own reality. In a sense the movie The Matrix was one long riff on that idea. But the experiment is no longer purely hypothetical and some of the issues it raises are now very real. Organoids would have delighted this chap, Alexis Carrel, the French surgeons who pioneered tissue culturing in the early 20th century. He won the 1912 Noble prize for his work on the suturing of blood vessels. He was inspired by the discovery in 1907 that tissues can be sustained outside the body in a culture medium of nutrients.

So working in New York developed that technique to culture a wide range of tissue types from mammals and from birds. In particular he found that piece of tissue taken from the embryonic hearts of chickens could be sustained for weeks and weeks and this heart tissue, in a dish, even pulsed as waves of electrical activity passed through it from cell to cell. Carrel began calling his chicken heart tissue immortal. from mammals and from birds. In particular he found that piece of tissue taken from the embryonic hearts of chickens could be sustained for weeks and weeks and this heart tissue, in a dish, even pulsed as waves of electrical activity passed through it from cell to cell. Carrel began calling his chicken heart tissue immortal. The New York Times claimed that "Carrel's new miracle points the way to avert old age. " By the 1930s, Carrel claimed to have kept his

chicken heart turny alive for 20 years. On its anniversary the New York Times suggested that human immortality might be just around the corner. If that is so, the newspaper said, the immortal chicken heart may become as sacred as a vennerated religious relic. This theological language shows that public concrepeses of Carrel's work had entered mythic territory. It was tapping into another ancient dream, going back to our chemical elixires and resurrection, the dream of cheating death. One thing I have insisted on is that science doesn't banish these old fantasy, but sustains them in new technological guises. And we shouldn't suppose that scientists

try to suppress these fantasies, Carrel was a showman who encouraged them, but he wasn't alone. Tissue culture was also developed in the 20s at the Cambridge Research Hospital led by Thomas Strangeway's after whom the lab was named. In 1926 Strangeway's gave a public lecture Called Death and Immortality in which he asked the audience to imagine a dead body ground up and made into sausages. Provided they were kept in cold storage, those sausages might weeks later be used as a sauce for making a colony of the dead person's living cells.

Such mythology infuses the story of Henrietta Lacks. The woman whose cancer cells were removed and cultured by a doctor named George Gey at John Hopkins Hospital in 1951. Lacks cancer cells were capable of renewal and a so-called HeLa cells they are now the standard strain for many experiments, many lab cells in cell biology. But her story raises complicated issues of race and racism. It's not sometimes implied, simply a

case of the exploitation of a disadvantaged black person. The notion of patient consent didn't exist in those days and culturing samples of patients was a common practice in the Baltimore hospital and elsewhere. We have to look deeper than that. Perhaps to this, which was written in a tribute to George Gey, in which the author commented that HeLa cells if allowed to grow uninhinted in optimal conditions would have taken over the world by now. Cells from a black woman taking over the world. We shouldn't assume that these uncomfortable references are incidental.

In the late 1960s a geneticist claimed that HeLa cells carry a biology marker specific to African Americans, they are, you could say, black cells. He said that they are highly, indeed aggressively invasive of other colonies. Some researchers said that it took just a single HeLa cell to doom another culture. Today, the echoes in this discourse sound louder than ever, again the metaphorical language of biology is not value-free. There are complicated racial currents too in a short story about tissue culture written in 1926 by Julian Huxley.

A rare venture into fiction for him because he had none of the literary prowess of his brother, Aldous, the author of Brave New World. Julian Huxley was a major figure in science at the top and in the popularisation of science in the mid20th century. He became the first director of UNESCO. His story the Tissue Culture King borrows a scenario from HG Wells, from Island of Dr Moreau. It tells the story of a rogue scientist conducting experiments in a remote location. This scientist is an

expert in tissue culture inspired by Carrel's work. He is captured by an African tribe but makes himself a figure of power by taking tissue samples from the tribal king and culturing them into pieces of tissue that are treated as vennerated relics and are thought to have supernatural power. Over this tale looms the spectre of European condesense and superiority with the biotechnological mastery of the west conferring power over more primitive cultures.

These social currents flowing beneath the science are even more perceptible with Carrel himself. His quest to expand the human life span with tissue culture was intimately bound up with his ideas of white sprems aism and eugenics. And his paranoid fear that western culture was under threat from other cultures.

His views were shared by the American aviator and Nazi sympathiser, Charles Lindbergh who after his solo flight in 1927 became Carrel's assistant and helped him to build devices for keeping human organs alive and perfused with blood. Carrel himself working in France when the Nazis invaded was happy to collaborate with the Vichy Government and he died after liberation in 1944 while awaiting trial on charges of collusion. Now I notice a tendency in science to regard tales like this as historical curiosities. Well, yes, sadly, that is how many people, including scientists used to think, but today thank goodness, we are objective and free from ideological agendas. It's a line that becomes harder to sustain as it screens ever closer to the present day.

So yes, we are happy to remove the name of Francis Golton, the architect of pseudoDarwinian eugenics from our lecture theatres but how do we feel about Francis Crick? He was still advocating for eugenics in the 1970s. That was an enthusiasm he shared with Julian Huxley, who was President of the British Eugenics Society from 1959-1962. Now it didn't go out of fashion with the Nazis. This isn't or it shouldn't be about taking down monuments to great scientists with feet of clay, but should be about truly excavating the intellectual lineage of themes such as the genetic blueprint of selfhood, themes that still infuse science today. Here is another thing we can do with tissue culture. This mouse embryo was grown in a glass vessel for eight days and has begun to develop to the point where you can see organs starting to appear, including a beating heart and the precursor of a brain. But in fact this

isn't a real mouse embryo at all. It wasn't made by fertilising a mouse egg with mouse sperm. Instead it was made from mouse stem cells. If we simply bring together these cells in the right growth medium they will organise themselves into an embryo-like structure and begin to develop.

Here, forecomparison is a real mouse embryo at the same stage of developmentment so these artificial structures are like full body organoids, sometimes called embryos, or embryo models. They can be made from human cells too. Here is one, assembled from, we have lost that one. Okay. Not quite sure what has happened there. That is what happens in translation. There is an image here of a human, what looks like an embryo at the blastocyst stage which is a simpler stage, but again it is assembled from human stem cells at a much earlier stage of development.

It's not known how far, again the development of structures like this, could continue. Probably not at this stage, to full term, which would again require the embryo model, the embryoid to be implanted in a womb. That experiment has been attempted by researchers in China, using embryoids made from monkey stem cells, which might be expected quite closely to resemble human ones. In that case implantation of seven-day old embryoids happened in three out of the eight female monkeys who received them. But all the pregnancies were terminated spontaneously within 20 days before fetuses were formed. Still there is no reason why it may not become possible to gestate these embryo-like structures for longer. In fact

some are talking about the possibility of stem cell babies. Experimentation on ordinary human embryos is subject to strict regulations in the UK, where no experiments on human embryos are permitted beyond 14 days of fertilisation. Synthetic embryos are not covered by these laws because they don't meet the definition of an embryo. That rule was formed by the Warnock Committee following the advent of IVF in the 70s. It became law in 1990. The scientist justification was this is about the point where a development feature called the primitive streak appears and the point at which the embryo can no longer divide into twins, so it was taken as a personhood.

But in truth it was arbitrary, there aren't such clear thresholds. They are a legal, a social and a philosophical requirement, but not a biological one. The 14-day rule was in the end moot anyway while no one knew how to sustain a human embryo for that long outside the body. But recently that has become possible and with it comes the possibility of then investigating human development at these later crucial stages, which have, until now, relied mostly on imperfect analogies with the embryogenesis of other mammals. So such research could be medically valuable. In 2021 the international Society For Stem Cell Research revised its guidelines to advice relaxing this 14-day rule in some circumstances.

That reopened the debate that the Warnock Committee seemed to have settled. By what criteria can we establish regulatory thresholded when the science itself seems to offer us none? Must we always be prepared to revise regulations to keep pace with scientific advance to that society has to follow where science leads. These are complicated enough matters for human embryos, but nor synthetic embryos we don't even have the moral and ethical frameworks to really think them. What we are really seeing here is a collision between the human, as we have long imagined it to be and the human that biology reveals. The self that Medawar talked about, the unique individual bound as it were and sealed with a soul, just can't be made to fit the biological reality that we are a colony of cells each possessing a degree of autonomy and capacity for growth and development. It now seems possible that in principle any part of us could, in the right circumstance, become any other part of us, including another entire organism.

In that vision of proliferating undifferentiated flesh there seems to be a disconcerting dissolution of the self. Now, science has no place for the soul today, but as a concept it performs cultural work. When it appears in old stories about making people and there are many such stories, as I explored in this book, it's not so much as a religious notion, but as a kind of watermark of genuine humanity. In Gerter's telling of the Faust myth, Faust's assistant Wagner, creates an artificial humanoid that longs to be reborn as a real human being with a soul. Condemnation of the alchemists claims to be able to make one of these, didn't come from today's modish accusation of playing God, but from a theological unease that these might be without a soul and because they weren't ascended from Adam, without original sin. When the soul features in Mary Shelley 's Frankenstein and in the Czech writer Karel Capek's 1920 play, RUR which introduced the term robot, it serveds into a theological notion, but against the horror of materialism. It protects us from the thought that we can be

manufactured. I don't think we will be able to navigate the ethical quantries posed by the new biotechnologies until or unless we recognise these old fears and fantasies that still inform our judgments. But they operate now in a very different context to that of say Frankenstein. Karel Capek's RUR is I think the Frankenstein story imagined for the age of mass production. It portrays human oid roe bots rolling off the production line of Rossum’s Universal Robots in the same way that motor cars were then rolling off Henry Ford's production lines. The technology is now, not driven by a lone scientist's curiosity or desire for fame, but by capitalisation and market forces.

Debates about the ethical bounds of these new technologies can't afford to ignore this commercial context in which they operate and to stay simply within the bounds of the technical aspects of safety or of medical value, each step forward with reproductive technology, for instance, potentially becomes an optional add-on that IVF clinics, especially in an unregulated market like that in the US, can offer to clients at an extra cost of course. And how easy will it be for customers to resist. Don't you want the best for your baby? Doesn't it make sense to have your IVF embryos genetically screened so you can select the best of them? Genetic screening for inherited dition seize in IVF is now routine where such dangers are known. But will is also now talk of screening for positive traits like intelligence or at athleticsism.

In a recent survey 43% of Americans said they would consider such a service if they were undertaking IVF and it was offered. Yet, it's by no means clear that these methods to select traits would even make much difference at all. In any case, the predictions this they offer are inevitably no more than statistical. They might case there is a 40% chance of the child made from this embryo being in the top 20 percent for education or attainment. How can the public be expected to navigate questions and choices like these? Especially when we still encourage a belief in genetic determinism with talk of genomic blueprints. We need better stories to tell. I want to take finally a step

further into this brave new world. Let's suppose it does become feasible, in principle, to grow a human body from an embryo model constructed from stem cells , perhaps entirely outside the womb like Aldous Huxley's 's book. So that the body doesn't grow a functioning brain, perhaps using the knowledge gained in this new discipline of synthetic morphology.

Does this entity then have any real personhood at all? Or might it better be regarded as a full-size full body organoid, from which organs can be harvested for transplantation when our own wear out? A sort of personalised spare parts store kept on ice. It's hard to say what exactly the moral or philosophical objections might be to that idea. Yet, I suspect that you like me would instinctively recoil from image. This was foresaw by Bernal. If we are not to rely on the slow evolutionary process to change ourselves, Bernal wrote then man must actively interfere in his own making and interfere in a highly unnatural manner.

We must alter either the germ Palace. That means the genome, or the living structure of the body or both together. In the increasingly cerebral world that we now live, energy demanding limbs are mere parasites that we can do without.

He imagined the end point of this process being a kind of human brain. Perhaps who knows, a full-grown human brain organoid that would be hooked up to whatever century and motor apparatus it needed for the task at hand. As if picking up limbs before laying them aside again. I can't help but be reminded on some recent work on brain organoids. One report described brain organoids that have developed light sensitive patches like those in the eyes.

Because, after all, the visual system is really eventually an outgrowth of the brain. The second reports a brain organoid that was hooked up to muscle tissue and it could control that to some extent, making it twitch. Then a third report, a real brain organoid was hooked up and trained to play the computer game Pong. In Bernal's vision the human form becomes totally plastic, there is no human form, but just human tissues arranged and grown to order. He admits that the new man must appear to those who have not contemplated him before as a strange monstrous and inhuman creature. But he is only the logical outcome of the type of humanity that exists at present.

That kind of human would eventually disappear and with it would go our human limitations. We could redesign ourselves to inhabit the seas, the moon, the different gravities and atmospheres of other planets. This was a vision shared by Julian Huxley, who coined a new word for it, the human species, he wrote in 1957, can, if it wishes transcend itself not just sporadically but in its entirety as humanity. We need a new name for this belief, perhaps transhumanism will serve? It's now a major movement which takes many forms but all adhere to a definition like this offered by one of its leading advocates today. In one of the most popular forms transhumanism imagines abandoning the flesh entirely. Uploading our minds to a much more robust and reliable computer circuitry. Well, in fact, not only do we have no

idea whether this could ever be technologically feasible, but we don't even know whether such a vision is meaningful or coherent. It's an act of faith as much as is the religious belief in the immortal soul. I hope you can now see that in fact it is the same thing.

Clothed in the validating language of science and technology. For Huxley transhumanism will see humankind at last consciously fulfilling its destiny. That is a fascinating statement, implying as it does, that we process the theological notion of a destiny at all and more over it's one that demands that we escape the world and the flesh that we have inhabited since the dawn of our species. We are apparently meant for something more.

Bernal's talk of transhuman people colonising other worlds reminds us that space travel itself is really another form of transhumanism. An attempt to transcend our human limitations on this world. The colonisation of space was first mooted by John Wilkins, the first of this trio for whom the award is named and one of the founders of the Royal Society. This was an age when colonialism was becoming the inevitable corollary of the discovery and exploration of new worlds. Here, in Wilkins book the discovery of A World in the Moon, Wilkins drew the colonialist acknowledge geowith Columbus. Here is how it survives in this documentary of 1986 of the staggering entitlement that was signed by Neil Armstrong amongst others.

It's very clear who is and who is not being spoken for this in manifest destiny in the stars. So here too is another technological endeavour, with its often unspoken mythological and theological imperatives ready to be dressed up as science. Here too we ignore at our peril the realities of such visions when played out in the marketplace of commercial imperatives and agendas. Well I told you it would be complicated. All of these endeavours are in one way or another about reimagining the human.

Projecting ourselves on to new places both metaphorically and literally. I want to stimulate a wider discussion of what that enterprise entails. In part because I want us to use science and technology well, which is to say wisely, humanely and for the greatest benefit of all, humanity. But I am also excited by the sheer cultural, philosophical and historicalness of the issue that this raises. I think we do a disservice to our own ingenuity and creativity if we fail to acknowledge that. When we talk about making life, we are at the same time talking about biotechnology and about old myths of creation, of immortality, of hubris and corruption. Much the same applies when we are talking

about space travel, invisibility, artificial intelligence, cosmology, you name it. The history, philosophy and social roles of science are not afterthoughts or decorative embellishments of what goes on in the laboratory or in the symposium, they are its foundation. And recognising this can only enrich the research itself.

They are what embed science within the broadest state of being human. Individually, socially, intellectually and perhaps most of all, within the arena of what seems to be our own cognitive superpower, the imagination. Thank you very much. APPLAUSE. MARIA: Well, what a fantastic

lecture. Thank you so much, it was really, really thought-provoking and I am sure there will be a lot of questions. Unfortunately we only have five minutes and I don't know whether we want to sit down. We will just stay where we are. So are there any questions from audience members? Yes, one at the back there. FLOOR: Thank you very much for the lecture. I was quite interested by what you were saying about screening for positive traits in IVF embryos. I wanted to know that if you,

for example, took a random sample of IVF embryos and a random sample of embryos that were naturally, eggs that were naturally fertilised, would the ones that were naturally fertilised have a higher likelihood of having the positive characteristics? Then that would have quite significant implications for the ethics of positive screening on embryos. PHILIP: It's a good question. I am not aware that anyone has been able to do that comparison. Because you can, eventually because you can only genetically screen for IVF embryos, you can't do it in utero.

It's interesting that we use that term that those who have been naturally fertilised, of course fertilisation just means a sperm entering the egg, wherever that happens. So that is kind of interesting. But I am not aware either of any reason to imagine that the genetic disposition, if you like, of embryos, created by IVF should be any different from those that are produced by the normal method of re production. But it's certainly a valid question. FLOOR: Thank you for a

beautiful talk. Really inspiring. I just want to ask one thing that you sort of touched on but didn't go into detail is about AI. The interesting thing is it's almost teaching us that our intelligence is very limited compared to what computers can do. Do we have to think in the future is the human going to be more fleshy, is the fleshy where we should look for selfhood? PHILIP: Brilliant question, Buzz. I have just written an article about this funnily enough! It absolutely raises though questions. One of the big questions about AI is whether it is ever going to be possible to create a machine-like system, if you like, that it has the same cognition as us as embodied beings.

There is a big discussion in what role embodiment has in our cognition. It's clear that it does have a role. That we conceptualise the world in terms of knowing that we are capable of doing some things and not capable of doing other things because of the nature of the bodies we have. So mind has a somatic component, for sure. I am not sure that I think AI is showing that it can go beyond what our minds are like, it's different. I think

that is the discussion that is starting to happen now. That we have, for some reason had this idea that there is a kind of a magnetic force that is going to draw AI, as it gets more and more complicated towards our own mind, before it gets there. There is no reason to think that and every reason to think it's going on a different trajectory entirely. There might be a

different mode of cognition, whether it's sent event or not, a different mode of cognition that AI makes things possible, certainly with large language model that we don't understand yet. A different kind of mind. That is one of the possibilities that really excites me. That AI is forcing us to think more broadly about what mind and cognition can be. MARIA: Okay, I think we should

leave it there. It just remains for me to thank you very much for this. I am sure the questions can go on later, but thank you very much for an amazing lecture. And also of course to award you the 2022 Wilkins-Bernal-Medawar Prize. And for that you get a lovely medal, which is here for you.

I haven't opened the box, so. APPLAUSE APPLAUSE And you also get a beautiful scroll. scroll. APPLAUSE. MARIA: Okay, so I think the

lecture is over, thank you very much!

2023-05-14

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