Remaking ourselves: human genome editing | 91TV
Transcript
- Maria Fitzgerald:
- Okay, good evening everybody. Shall we get started? So welcome to the Royal Society. My
- name is Maria Fitzgerald, I'm a neuroscientist and a fellow of the Royal Society. It's a great
- honour to be joined by you all the audience here and also for those who are watching online to
- listen to this lecture tonight. Just before we get started and I introduce our lecturer,
- there's just one or two things I should say. Please could you make sure that your
- phones are turned off. There's 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'm
- pointing in the right way. This door at the back on the right is where we should leave.
- Please note also that this event is being live streamed on the Society's YouTube channel and
- it will be available to watch 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.
- Dr Ball joins a list of exceptional individuals who have won this prize before, historians,
- philosophers, and science communicators including Professor June Barrow-Green,
- Professor Jim Al-Khalili and Professor Simon Schaffer to name just a few. 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 contributes
- to Prospect magazine's science blog. Philip previously worked at Nature for over 20 years,
- and he now regularly writes columns for Chemistry World, Nature Materials and BBC Future, and he has
- broadcast on radio and TV, including a three part series entitled Small Worlds for BBC Radio Four.
- Philip 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 cognition of music,
- and he consistently bridges the gap between science and art, always considering the history
- of science and its interaction with society. I had the pleasure of meeting him and talking to
- him earlier this evening, and the breadth of his knowledge and the areas of science that he
- has covered is really, really impressive and I'm 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,
- and his book Serving the Reich: The Struggle for the Soul of Physics under Hitler was also
- shortlisted in 2014. 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.
- Philip Ball: Thank you so much, Maria. I'm 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 realised that at no time
- during a talk is the audience more attentive than at the beginning. So I'm going to give
- you the take home message straightaway. I've been writing and commentating on science now for more
- than three decades, and I'd 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 are
- becoming increasingly 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 broad sense. This means that our job was not just as explainers and translators
- who could explain R0 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 that they were an essential, and I hope, a useful part of the job. In the US, Ed Yong,
- one of the finest science writers of our times, seems to have reached the same conclusion and his
- bird's eye view of the politics of the pandemic in the US for the Atlantic completely warranted
- the Pulitzer Prize that Ed has been awarded. So here's the message, while a big part of
- the goal of science communication is to convey new discoveries and technologies in a language
- that's accessible to everyone, I believe that we who strive to do this will 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, sociological, societal, cultural and ethical considerations,
- the very factors that this medal stands for. That's 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 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'm going to begin it with this
- 1956 essay by Peter Medawar, which I think is a classic example of his wonderful ability to write
- about the science of his day in a way that brings out the wider contexts. The title The Uniqueness
- of the Individual suggests a rather philosophical theme, but Medawar explores it through the lens
- of skin grafts, which was then still a nascent technique that had been rendered particularly
- salient by the two world wars. So Medawar explains that typically what happens is that 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, whereupon 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 those of
- other organisms. This self-recognition is clearly connected to the individuality of our genomes
- because skin grafts can be exchanged between identical twins. 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 testing, 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 admission
- of discomfort, I think, for it bears directly upon the recognition and awareness of the self.
- This is a very contingent idea of selfhood, as Medawar recognises. 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 autoimmune 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 embryos, and 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 selfhood 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's just marketing, right? Not really. When the pioneering geneticist Wally
- Gilbert used to give talks to the public on genome sequencing in the 1990s, he'd carry with him a CD
- loaded one had to assume with genomic data which he would brandish and say to the audience, this
- is you. This sort of thing still happens today. I find it very 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'll say. On the other hand, there's that insistence that this genome is you. 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 even been kind enough to print out in 117 volumes of genomic data.
- When you see a cognitive dissonance of this magnitude, you know that something interesting
- is happening beneath the surface the unspoken agenda this modern myth of selfhood, as genome.
- Was explored in the 1995 book The DNA Mystique by the sociologist Dorothy Nelkin and the historian
- Susan Lindee. It's a notion that the developmental biologist Scott Gilbert has aptly called DNA as
- Soul, a mobilisation by scientists of the ancient yearning to find a vessel for our selfhood.
- Now there's another reason why that receptive embryo that Medawar mentions undermines a genomic
- view of selfhood. He mentions the case of one anonymised Mrs McKay, who at the age of 25 was
- found to contain two genetically different types of red blood cells belonging to different blood
- groups. The doctors were initially puzzled about how this was possible, until Mrs McKay told them
- that she had had a twin brother who had died in utero at three months of gestation. So they
- figured that the blood-producing cells of the two foetuses must have been exchanged in the womb,
- something that was already then known to occur in non-identical cattle. When this case of Mrs McKay
- was described in a 1953 paper by the British physician Robert Race and his colleagues,
- he gave her condition a name. She was, he said, a human blood group chimaera. Now 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 instance, for a pregnant mother and the foetus to exchange cells,
- and 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.
- More extreme forms of chimerism are possible too. Very rarely, two nonidentical 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, they're chromosomally female you might say, while some XY chromosomally male,
- then the reproductive organs are decided by which set of cells in a merged embryo happen to produce
- them. This reflects the tremendous tolerance of embryonic cells which can find their way to a
- normal developmental path, even in such extreme circumstances. Chimerism can go still further.
- Embryos will even accept cells from another species that they will incorporate into the
- organism producing a cross-species chimaera, 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 clearly be unethical. We do know, though, that cross-species
- chimaeras are fully viable. They've 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 to grow human organs for transplantation within livestock, such as pigs or cows.
- As I said, we call these individuals with a mixture of genetically distinct cells a
- chimaera. Now, that word was first used in biology in 1907 by the German botanist Hans
- Winkler when he grafted together a tomato and a nightshade. What was a chimaera originally, it
- was a mythological monster part goat, part lion, part snake. Monsters like this were considered not
- just aberrations of nature. They had a meaning. The word monster itself derives either or perhaps
- jointly from the Latin monstrare to show, or monere to warn. The modern study of developmental
- anomalies is called teratology and is named for the Greek word often used to denote the monstrous,
- teras, which actually means portent. Monsters were unnatural, but that didn't just mean that
- they were something outside of the natural order. It meant that for that very reason
- they were to be shunned with moral approbation. 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 have just heard, has
- just happened, a three-parent baby, or by somatic cell nuclear transfer. If that ever happens,
- a clone, is already to invite interpretation and judgement. Words like unnatural and artificial,
- metaphors of machines, of selfishness, of instructions and codes and programs. These
- aren't neutral, but they have a heritage. The job of a science commentator is then sometimes
- to excavate and to interrogate that heritage. The idea that there's a unique genomic self
- also runs into problems in the other direction too, so to speak. Not only can a self, as I say,
- be genomically diverse, but our putative genomic self might not be bounded by our skin. Look at
- this. These are neurones grown in a petri dish. They're not just any neurones or at least as far
- as I'm concerned, they're not because these are my neurones. They were grown in the lab of UCL
- neuroscientist Selena Ray, who I think is here tonight. Thank you Selena. If you are, I'll 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 just switch to being another cell
- type, another tissue type entirely. But they can. In 2006, the Japanese biologist Shinya Yamanaka
- and his student Kazutoshi Takahashi announced that they had transformed mouse fibroblasts,
- the kind of cells that form connective tissue into stem cell like pluripotent cells. That means
- that the cells are able to develop in principle into any tissue type in the body. They 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, and it seems that they alone were enough to reprogramme these mature cells
- into a stem cell like state called an induced pluripotent stem cell an iPSC. The following year,
- Yamanaka and Takahashi and independently James Thompson at the University of Wisconsin achieved
- the same reprogramming of human cells. So once reprogrammed as iPSCs, these
- cells become capable of differentiating along a new pathway to become a different tissue. Now,
- although that possibility was already inherent in much earlier work done in the 1960s by John Gurdon
- at Cambridge in work on cloning, the relative ease with which Yamanaka's method could be
- used to transform cells was a revelation, and it had enormous potential for cell biology, and he
- shared the 2012 Nobel Prize with Gurdon. 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 for making skin grafts. One great advantage is that the patient's
- own mature cells can be used, and so there shouldn't be the problem that Medawar warned about
- of immunological rejection of foreign tissue. This isn't just about transforming cells. It's
- about determining what they can make. This is what some of my induced neurones became.
- You can see that it's not just a featureless tangle of neurones. There's structure here
- as well as different cell types that are shown here by the different coloured stains. This is
- called a brain organoid, and it exhibits some of the structure found in a developing brain.
- Here's a better example. Not one of mine of that, but you can see what's going on
- here. It shows that neurones 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, for example, they might organise themselves into organoids that are hollow tubes
- lined with the little hair like structures called villi that absorb nutrients. If they're
- reprogrammed to become kidney or liver cells, they develop into structures resembling little livers
- or kidneys. The resemblance of these organoids to the real thing is far from perfect, but it might
- be close enough to enable the real process of organ growth to be studied in the petri dish and
- perhaps to allow the testing of new drugs without the need or the ambiguities of animal experiments.
- What's more, some researchers are getting better and 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 bloodstream, if you like, allows them to get bigger without
- the innermost cells dying of starvation. That's all very well. In fact, that'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 raises some ethical quandaries. Brain organoids have been used to study neurological defects
- and diseases such as Alzheimer's and Zika. That's what Selena generally does with them,
- and the more truly brain like they become, the more reliable they are as lab models for the real
- thing. With a brain-like entity, we're forced to ask at what point do we have to consider the
- possibility that these structures might harbour a degree of consciousness or sentience? What
- can that even mean for a disembodied brain-like structure? How can we even know what's going on
- inside a brain organoid when we have still 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 and ontological 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 long been a
- popular thought experiment in philosophy. Here's a famous philosopher contemplating that. It's
- been used there for exploring 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 that it raises are now very real. Organoids would have delighted this chap,
- Alexis Carrel, the French surgeon who pioneered tissue culturing in the early 20th century. Carrel
- won the 1912 Nobel Prize for his work on the suturing of blood vessels, but his subsequent
- work took a different turn. He was inspired by the discovery in 1907 that tissues can be sustained
- outside the body in a culture medium of nutrients. So Carrel, working at the Rockefeller Institute in
- New York, developed that technique to culture a wide range of tissue types from mammals and
- from birds. In particular, he found that pieces 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 heart chicken heart tissue alive for 20 years,
- and on its anniversary, The New York Times suggested that human immortality might be just
- around the corner. If that's so, the newspaper said, 'The immortal chicken heart may become
- as sacred as a venerated religious relic.' This theological language shows that public conceptions
- of Carrel's work had entered mythic territory. The research was tapping into another ancient
- dream, going back to alchemical elixirs and resurrection stories the dream of cheating death.
- One thing I've insisted on repeatedly in my work is that science doesn't banish these old
- fantasies, but on the contrary, sustains them in new technological guises. We shouldn't suppose
- that scientists try to suppress these fantasies. Carrel himself was a theatrical showman who
- positively encouraged them, but he wasn't alone. Tissue culture was also developed in the 1920s
- at the Cambridge Research Hospital led by Thomas Strangeways, after whom the lab was subsequently
- named. In 1926, Strangeways gave a public lecture called Death and Immortality, in which he asked
- his audience if they would to imagine a dead body ground up and made into sausages, provided they
- were kept in cold storage like my own, induced pluripotent stem cells I think. Those sausages
- might weeks later, be used as a source 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 Johns Hopkins Hospital in Baltimore in 1951.
- Lacks' cancer cells proved to be abnormally and astonishingly capable of renewal and
- so-called as so-called HeLa cells. They're now the standard strain for many experiments,
- many lab studies in cell biology, but her story raises complicated issues of race and racism.
- It's not, as sometimes implied, simply a case of the exploitation of a disadvantaged black
- person. The notion of patient consent for things like this simply didn't exist in those days,
- and culturing samples of patient tissue that had been surgically removed was a fairly
- common practice in the Baltimore Hospital and elsewhere. No, we have to look deeper than that.
- Perhaps to this, which appears in A Tribute to George Gey, written in 1971, in which the
- author commented that HeLa cells, if allowed to grow uninhibited under 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 resonances are incidental. In the late 1960s,
- the geneticist Stanley Gartler claimed that HeLa cells carry a biological 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 the biologist Julian Huxley,
- a rare venture into fiction for him because he had really none of the literary prowess of his
- brother Aldous, who the author, of course, of the 1932 dystopian satire on biotechnological control
- of society, Brave New World. Julian Huxley was a major figure in science at that time and in
- the popularisation of science in the mid-20th century, and he became the first director of
- UNESCO. His story The Tissue-Culture King borrows a scenario from his friend HG Wells, specifically
- from The Island of Dr Moreau. So it tells of a rogue scientist conducting weird experiments in
- a remote location. This scientist is an expert in tissue culture, explicitly inspired by Carrel's
- work. He's 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 venerated
- relics and are thought to have supernatural power. Over this tale looms the spectre of European
- condescension and superiority, with the biotechnological mastery of the
- West conferring power over more primitive cultures, and these social currents flowing
- beneath the science are even more perceptible with Carrel himself. His quest to extend the
- human lifespan with tissue culture and organ preservation outside the body was intimately
- bound up with his ideas of white supremacism and eugenics, and his paranoid fear that Western
- society was under threat from inferior cultures. These views were shared by his unlikely assistant,
- the American aviator and Nazi sympathiser Charles Lindbergh,
- who, after his famous solo transatlantic 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 the 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's how many people, including scientists, used to think. Today, thank goodness, we are
- objective and free from ideological agendas. It's a line that becomes harder to sustain as
- it creeps ever closer to the present day. So yes, we are happy to remove the name of
- Francis Galton, the architect of pseudo Darwinian eugenics in the late 19th century from our lecture
- theatres. How then, do we feel about Francis Crick, for whom the hub of biological research
- in London is now named? Who was still advocating for eugenics in the 1970s. That was an enthusiasm
- he shared with Julian Huxley, who was president of the British Eugenics Eugenic Society from
- 1959 to 1962. No, it didn't go out of fashion with the Nazis. This isn't or it shouldn't be
- simply 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's 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. 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 pluripotent cells in the right growth medium, they will organise
- themselves into an embryo-like structure and begin to develop. Here for comparison, is a real
- mouse embryo at the same stage of development. So these artificial structures are kind of like
- full body organoids, sometimes called embryoids or sembryos for synthetic embryo, or embryo models.
- They can be made from human cells too. Here is one assembled from a… We've lost that one? Okay,
- not quite sure what's happened there. That's 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. Again,
- which 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 now been attempted by researchers in China very recently using
- embryoids made from monkey stem cells, which might be expected quite closely to resemble human ones
- and in that case, implantation of seven-day-old embryoids happened in three out of the eight
- female monkeys who received them. All the pregnancies were terminated spontaneously within
- 20 days before actual foetuses were formed. Still, there's no obvious reason why eventually it may
- not become possible to gestate these embryo-like structures for longer. In fact, some are already
- 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 after fertilisation. Synthetic embryos are not currently covered by these laws because they
- don't meet the formal definition of an embryo. That 14-day rule was recommended by the Warnock
- Committee in 1984. Formed after the advent of IVF in the mid-1970s and it became UK law in
- 1990. The scientific justification for it was that this is around the point at which a developmental
- feature called the primitive streak appears, which marks the beginning of the emergence of
- a body plan and the point at which the embryo can no longer divide into twins. So it was taken as a
- kind of threshold of personhood of selfhood. In truth, it was a rather arbitrary choice,
- because there aren't really any such clear thresholds in embryogenesis at all. 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. 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 advise 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 thresholds when the science
- itself seems to offer us none? Must we always be prepared to revise regulations to keep pace with
- scientific advance so that society has to follow where science leads. Well, these are complicated
- enough matters for human embryos, but for synthetic embryos, we don't even have the moral
- and ethical frameworks to really think about them. What we're really seeing here is a collision
- between the human, as we've long imagined it to be, and the human that biology reveals the self
- that Medawar talked about, the unique individual, bounded 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 circumstances,
- 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 Goethe's telling of the Faust myth, Faust's assistant Wagner, shown here, creates an
- artificial humanoid homunculus that longs to be reborn as a real human being with a soul.
- Condemnation of the alchemists claims in the Middle Ages to be able to make homunculi like
- this, didn't come from today's modish accusation of playing God. But from a theological unease
- that these artificial beings might be both without a soul and because they weren't
- descended 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 serves not as a theological notion, but I think as a defence against the horror of materialism. It
- protects us from the thought that we can be manufactured. I don't think we'll be able to
- navigate the ethical quandaries posed by the new biotechnologies until or unless we recognise these
- old fears and fantasies that still inform our judgements. They operate now in a very different
- context to that of, say, Frankenstein. Capek's RUR is I think the Frankenstein story imagined
- for the age of mass production. It portrays humanoid robots and in fact not metal ones,
- but fleshy ones rolling off the production lines of the company RUR. 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 by 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.
- How easy will it be for customers to resist? Don't you want the best for your baby? Doesn't it make
- sense then, to have your IVF embryos genetically screened so that you can select the best of them?
- Genetic screening for inherited disease in IVF is now routine where such dangers are known. There
- is also now talk of screening for positive traits like intelligence or athleticism using a technique
- called polygenic pre-implantation genetic testing. In a recent survey, 43 per cent 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,
- and in any case, the predictions that they offer are inevitably no more than statistical.
- They might say, indicate that there's a 40 per cent chance of the child made from this embryo
- being in the top 20 per cent for educational 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 that it does become
- feasible in principle to grow a human body from an embryo model constructed from stem cells, perhaps
- entirely outside the body in an artificial womb like Aldous Huxley's hatcheries. Imagine then,
- that we could engineer this embryo in some manner that altered the course of the development 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 legitimately and ethically 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,
- will instinctively recoil from that image. John Desmond Bernal foresaw this kind of
- thing in his 1929 essay The World, The flesh, and The Devil. If we're not to
- solely rely on the very 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 plasm that means the genome, or the living structure of the body,
- or both together and in the increasingly cerebral or nevertheless manual world in which we now live,
- Bernal said energy demanding limbs are just mere parasites that we can do without. Let's get rid
- of them. He imagined the endpoint 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 sensory and motor apparatus
- it needed for the task at hand, as if picking up limbs for the job before laying them aside again.
- I can't help but be reminded here of some recent work on actual brain organoids. One
- report describes brain organoids that have developed light-sensitive patches like those
- in the eyes because after all, the visual system is really essentially an outgrowth of the brain. A
- second reports a brain organoid that was hooked up to muscle tissue and that it could control
- that tissue to some extent, making it twitch. In 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. Indeed, there is no human form anymore, 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 Bernal
- said, and with it will 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.' Transhumanism is now a major movement which takes many forms,
- but all of which loosely 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 quote, 'At last consciously fulfilling its
- destiny.' That's a fascinating statement, implying as it does, that we possess the
- theological notion of a destiny at all and moreover, that it's one that demands that
- we escape the world and the flesh that we've 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 of course 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
- inspired by Galileo's Discoveries. Wilkins drew the colonialist analogy with Columbus,
- and here is how it survives in the modern space age. In this document from 1986 of, I think,
- rather staggering entitlement that was signed by Neil Armstrong, amongst others, it's very clear,
- I think, who is and who is not being spoken for in this evocation of a 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
- re-imagining the human, projecting ourselves into 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. I'm also excited by the sheer cultural, philosophical
- and historical richness of the issues that these scientists raise, and 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're 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 broader
- 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.
- Maria Fitzgerald:
- Well, what a fantastic lecture. Thank you so much. It was really, really thought provoking
- and I'm sure there'll be lots of questions. Unfortunately, we only have five minutes,
- but and I don't know whether we want to sit down, but maybe we'll just stay where we are if that's
- okay. So are there any questions from audience members? Yes. There's one at the back there.
- M1: Well, thank you very much. Thank you very much for the lecture. I was quite interested by
- what you were saying about screening for positive traits in IVF embryos, and I wanted to know that
- if you, for example, took a random sample of IVF embryos and a random sample of embryos,
- eggs that were naturally fertilised, would the ones that are naturally fertilised have a higher,
- I suppose a higher likelihood of having those positive characteristics? Then that would
- have quite significant implications for the ethics of positive screening on IVF embryos.
- Philip Ball: I'm not aware that anyone… It's a very good question. I'm not aware that anyone has
- been able even to do that comparison because you can essentially, because you can only genetically
- screen for IVF embryos. You can't do it in utero. It's interesting and inevitable that we use that,
- that that term that those that have been naturally fertilised, whereas of course fertilisation just
- means sperm entering the egg, wherever that happens. So that's kind of interesting,
- but I'm 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 reproduction. It's certainly a valid question.
- M1: Thank you.
- PF: Yes.
- M2: Thanks, Philip 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. I think the
- interesting thing is it is almost teaching us that our intelligence is actually very limited compared
- to what computers would be able to do. So do we have to think in the future, is the human
- going to be more fleshy? Is the flesh the where we should look for selfhood? I think you were …
- Philip Ball: Yes. Brilliant question, Buzz. I've just written an article
- about this funnily enough. It absolutely raises those questions. I think 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 has the same cognition as us as embodied beings. There
- is a big discussion about what role embodiment has in our cognition. I think it's very clear
- now that it absolutely 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 semantic component,
- has a bodily component for sure. I'm not sure that I think AI is showing that it can go beyond,
- what our minds are like. It's different. I think that's the discussion that's starting to happen
- now that we've for some reason had this idea that there's a kind of a magnetic force that is going
- to draw AI as it gets more and more complicated towards our own mind until it finally gets there
- and does everything we do, there's no reason to think that. Actually, every reason to think that
- it's going on a different trajectory entirely, that there may be a different mode of cognition,
- whether it's sentient or not, and it's certainly not at the moment. A different mode of cognition
- that AI makes possible, certainly with things like large language models that we don't understand yet
- a different kind of mind. That's actually one of the possibilities that really excites me,
- that AI is forcing us to really think more broadly about what mind and cognition can be.
- Maria Fitzgerald: Okay, I think we should leave it there. It just remains for me to thank you
- very much for this. I'm sure the questions can go on later, but thank you very much for a really
- amazing lecture. 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, and you also get
- a beautiful scroll. Thank you very much. Okay, so I think the lecture is over. Thank you very much.
Dr Philip Ball, winner of the 2022 Wilkins-Bernal-Medawar Medal, joins us to discuss human genome editing, and the importance of keeping historical and cultural perspectives visible in these debates.
Our biotechnologies have entered uncharted territory. With the ability to precisely edit the human genome, we have the potential for systematic control over inheritance that goes beyond Darwinian evolution. Stem cells can be used to create embryo-like structures that may or may not develop as normal embryos do, and artificial brain-like organs grown in dishes raise questions about the fundamental definition of consciousness.
We should be prepared to be unsettled by these developments in what zoologist Jacques Loeb in 1890 called “a technology of living substance”. But although it is easy to spin dystopian tales out of them, any consideration of how to regulate these technologies and of their ethical and societal implications will be deepened and enriched by close attention to their historical and cultural dimensions.
Dr Philip Ball, winner of the 2022 Wilkins-Bernal-Medawar Medal, joins us to discuss the importance of these debates, and of keeping historical and cultural perspectives visible and explicit.
The Wilkins-Bernal-Medawar Medal and Lecture 2022 is awarded to Dr Philip Ball, for his outstanding commitments to sharing the social, cultural, and historical context of science through award-winning science communication in books, articles, and as a speaker and commentator.
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