against president trump's decision to impose tariffs on steel and aluminium imports. the european union, canada and mexico are all proposing duties on american goods in response. there is a risk of a global trade war, with an escalating round of tit—for—tat tariffs worldwide. the top aide to north korea's leader is to present a letter from kim jong—un to president trump at the white house on friday, as preparations for next month's summit go on, but it is clear the us and pyongyang have very different definitions of denuclearisation. it has been announced that kim jong—un will also visit moscow for a summit this year. for the second time in eight days, italy's president has asked giuseppe conte to be the next prime minister. he will now try to assemble a government of two populist parties, five star and the league. his previous attempt was vetoed because the man nominated to be economy minister was seen as so anti the euro. now on bbc news, hardtalk. welcome to hardtalk, i am sarah montague.

crispr—cas9 has been described as the greatest biological breakthrough in decades. it is a gene editing tool and the hopes that rest on it are immense, that it can be used to cure cancer and other intractable diseases, stop mosquitoes carrying malaria, create drought resistant crops and through that does not rot, even that it can recreate extinct animals. the scientist who led the discovery in 2012 is my guest today. drjennifer doudna, what does she make of the great taking pace of innovation since her discovery, and does she fear where it could lead? drjennifer doudna, welcome to hardtalk.

thanks very much. what is crispr—cas9? well, crispr—cas9 is an incredible tool. it is molecular scissors that can cut dna at targeted sites in a genome of a cell, changing the genetic code in a precise fashion. i think you described it as like being able to edit a book, to change one word or even a letter. that's right. it is essentially like being able to rewrite the code of life. we can change the dna sequence at will. now, i think it was, as well, although there have been obviously huge advances in genetics over decades now, it was a bit of a eureka moment for you when you discovered this tool, wasn't it? this is true, it was a project that started as a collaboration with emmanuelle charpentier and we were working on bacterial immune system known as crispr, which led to the discovery

of the mechanism of this protein cas9 and how it can be programmed to cut dna. i guess you are looking at bacteria. are we — you did not have that much hope that it would have much wider applications. would that be fair? that would be fair. i think that is the beauty of doing curiosity—driven science, is that you do not necessarily know where it will lead. so what was it about the bacteria that intrigued you 7 i think it was the possibility that bacteria use a programmable system to protect their own cells from viruses that intrigued us and made us want to understand how. so rather like humans, they have a memory of previous invasions that they can then protect against? exactly. and this is — you then realised that the components that made this up were what, two elements of rna, ribonucleic acid? correct. two elements of rna that can be changed and matched too much a dna

sequence, and that is what does the programming. that's how this particular protein cas9 can be engineered to recognise any desired dna sequence. because — can you talk as to what it does? it goes along and what, it reads the dna? it reads the dna and looks for a matching set of 20 letters in the dna, matching the letters in the rna guide and when that match occurs, the protein functions like a scissors, cuts the dna and then cells can repair that break in the genetic code by making a small, sometimes a large change, in that genetic sequence. and you can programme the scissors to say look at this bit, look at that bit? exactly. there was a moment when you thought what? what was the moment when you thought this is different? this is going to have far greater applications? i think it was really the research that was going on in our labs and the work that was done by two

individuals, martinjinek and krzysztof chylinski who were studying the latest enzyme cas9 functions. once we understood how it could be programmed with rna and how to engineer the rna into a simpler form than what we find in nature, we have sort of realise that this would be an incredibly powerful tool for manipulating genomes. because at that stage, you knew that it would work in humans too. because it would be possible to cut any type of dna from our experiments, yeah. do you remember how you felt at the time and what you did? well, i remember leaning over the light box in the lab and looking at the results of an experiment with martin, and looking at each other and saying "wow, this is an incredible protein and it seems likely to be useful for genome editing." 0k, well, let's look at a few of the things that even in a few years, that was back in 2012, in the year since that it

has already started to be useful in labs all around the world. there are people looking at all sorts of diseases to try to cure, not least the chinese, the blood disease, there are people who are looking at applications to cancer, to trying to get mosquitoes to not be able to carry malaria, to the treatment of hiv, to make tomatoes that do not rot, you have even got somebody trying to create a woolly mammoth. you heard about all these things, obviously. i have. but which is the one application which you thought "that is amazing, that is what will make a difference"? there is a lot. i think a couple of things have amazed me. i think the ease at which it's been possible to create the cells that cause sickle—cell anaemia in the laboratory, this has not been done yet in a person but when i saw scientists, initially at harvard, that were actually doing these experiments, i was really,

really blown away. and then i think that also it is important to point out that the pace of scientific research has accelerated tremendously with this technology. it has been incredible to see all the different ways that this tool is being used in fields of agriculture, biomedicine, what i would call synthetic biology, it is very, very profound changes. 0k, well, starting with medicine and you have used the example of sickle—cell anaemia and how easily it can work. how would it be used in humans? well, currently, the idea would be to edit the cells that are the, really the precursors to blood cells, these are called stem cells and the strategy is to remove the cells from a patient that has this disease, make the corrections to the dna, and then replace those cells so that they can repopulate the blood supply system. so from the patient‘s point of view, it would be as simple as an injection?

well, no, because at the moment, this would have to be done as a bone marrow transplant. so it would involve a bone marrow transplant, but with the patient‘s own edited cells. so in terms of the chances of success, you are talking 100%. well, i think it would be very high, given that routine nature now doing these sorts of bone marrow transplants. i do think in the future there is an exciting alternative that might involve doing the editing in the patients, and without having to do a bone marrow transplant, but the field isn't there yet. so there are various diseases that people are looking at to see how it can help. right. what about for agriculture — in some senses that is almost more advanced, isn't it? i think in agriculture, there are exciting opportunities. it is very exciting to think about technology that can allow plants to be altered in a very precise fashion without introducing other changes to the dna and quite quickly, relative to traditional plant breeding.

so what sort of things could you do to them? things like creating plants that are more drought resistant, that are resistant to pests, that do not require the same input of nutrients or fertilisers for growth. i think the opportunities are really vast and i think also, this tool could be used in plants that are grown in various niches around the world, notjust in crops that are grown commercially. but there is a risk, people are concerned about genetically modified food. do the same concerns not exist if you're modifying the genome in this way? i think it is important to understand what genetic modification involves when we talk about traditional plant breeding versus using a tool like crispr—cas9. in traditional plant breeding, mutations are introduced randomly in the plant dna and then selected for traits. it takes a long time and they cannot control what other mutations are coming along in the dna.

with a tool like crispr—cas9, the changes that are made are precise. they occurjust at the desired place in the dna of a plant cell. there is also dr george church at harvard trying to recreate a woolly mammoth by using the technique. yeah. i mean that, it seems extraordinary that that is possible and, are you concerned when you hear things like that? is there a reason to be concerned? well, whether or not it is possible, i am not sure. but i think the sort of larger point there is that it is possible now to use genome editing to introduce dna sequences into cells in a controlled way, and so whether we are trying to create a woolly mammoth or even make a small change that introduces new genetic traits into an existing organism... so he is doing this with elephants. this is the idea, right. would be possible to

create a woolly mammoth? i think it will be hard, honestly. it is going to require figuring out exactly what pieces of dna to reintroduce into an elephant, and obviously finding an appropriate habitat for that resulting animal. one of the other things that has been done is double—muscled animals, this is the argument... correct, yeah. ..and you can imagine police dogs which are more muscly. yeah. this is also, of course, something that humans could do. in principle, that is true, yes. one of the things that obviously people have been looking out so far has been changes to — it is just seeing what is possible, we are at that stage — but one of the things that is clear is that aside from making changes to an individual, you can make a change

to their descendants? right, yeah. i guess it is important to point out here that when we talk about making heritable changes, that can be inherited by descendants, this means making dna changes in the germ line, so eggs, sperm, or embryos, and that is a fundamentally different type of dna editing than what is called somatic cell editing, where changes are made to dna in a patient but not in a way that they can be inherited by future generations. so there is two different kinds of editing that we can do. indeed, and i know you were originally not that in favour of editing the germ line, but you have come around to the idea, haven't you, in the future? well, i guess my views have changed little bit. i think when we first did this research and understood this technology was going to be deployed globally and could be accessed very easily by people in that it could be used for germ line editing, i was fearful of the possibility that that kind of experiment would be done that too quickly, in a way it, before appropriate discussion and consideration

of all the implications of that kind of work. i think in the intervening six years, i have, i guess i have started to recognise the potential for that kind of editing to remove dangerous mutations from the human germ line in a way that could really alleviate human suffering and i think that kind of purpose, i think it could be an important technology. what sort of cases? well, cases like inherited disease, so i have met with many people that have genetic disease in their family that is inherited by their kids, so things like huntington's disease, which is a degenerative neurological disorder, this is an example of a disease where we have known about the mutation that causes it for several decades but there's currently no way to treat these patients. and the possibility of actually removing it from the germ line

of a family affected by this i think is actually profound. profound, and it has raised a lot of ethical concerns about playing god. yeah. you are changing something forever. yeah. you are relaxed about that? i would not say i am relaxed about it, and i think that the potential has to be weighed versus the sort of potential of... ..the way that this technology could be used to help people has to be weighed against risk, and there always has to be a sort of a risk benefit calculation that is made. so i do think that for certain kinds of diseases, at some point in the future — we are not there today for sure — but this could be useful for the kind of application that removes a genetic disease from the family.

i think where it gets tricky is figuring out all the sort of associated factors that come along with that kind of application of gene editing, that include things like the ethics of enhancement, who pays for this for people? who gets access to it? who decides who is able to use it? what we have seen, and i mention about, sort of, people doing it themselves, there have been biohackers, they're called, where people in their bedroom, they can buy dna online and inject themselves with it. there's somebody famously... well—known guy who streams what he's doing via a camera. what do you make of that that has sort of sprung up in the wake of...? it's attracted media attention but it's very unlikely to actually work because one of the current technical challenges of gene editing currently for any kind of clinical application is the challenge of delivery. that means how do we deliver the gene editing molecules into cells or tissues.

it's actually not trivial to do that. somebody like josiah zayner, a former nasa scientist, who does a lot of this stuff online and has become a bit of a hero in the group of people who are doing this, i mean, he edits a gene into this muscles. are you saying that couldn't work? i'm saying it's unlikely to work the way he's doing it because i don't think there will be enough editing that happens in muscle cells to have the desired effect. he's very relaxed about enhancements. this argument is, if i want to be muscly, if i want to have endurance, why wouldn't i do it or try to do it. is he right? to me it gets back to the question of who decides and who regulates such a thing. i think for the first time really, we, as a species, we have the power to control our own dna at that level. and it's obviously... the technology is still developing and there are technical challenges to work out, but we can see this is coming. so it does raise the very important question of how we regulate this,

how we decide as a species how to use this tool appropriately. he talks of being in the midst of a genetic revolution, he's right? he's right. but he also goes on to say, i think this is a new era of human beings, it's going to create a whole new species of humans. is he right with that too? beings, it's going to create a whole new species of humans. is he right with that too? probably not any time soon. how soon? decades at least, it's not going to happen soon. but it's going to happen? well, i think this type of use is coming. i really do. i think there's going to be a lot of interest in using it in the human germ line in the future and the question is who does it and how and how it's controlled. and at the moment it's not?

at the moment it's controlled in different ways in different countries i would say. i would say in my country in the us, we're actually prohibited from using any federal government money to do research of any kind on human embryos. so it would not be possible to do it with federal money, although if somebody had access to private funds they could in principle do this kind of work. in the uk and in other countries, the regulations vary. in the uk we have kathy niakan at the crick institute doing effectively using crispr—cas9 for research on embryos under 14 days to remove genes to see what they do in development, their role in development. that is research on embryos. yep, yep. and is acceptable? well, ithink, she's following guidelines that have been in place for a while, since before crispr—cas9 came along. these are regulations that have been in position to govern the way that

scientists do research. but you have said that, "i feel personally uncomfortable about the idea there could eventually be factories pumping out lots of human embryos for the purpose of human experimentation." you have said, "i can't put my finger on why but it cheapens something about human life." i do feel that way. i don't like the idea of embryos being created for the purpose of research somehow. it feels uncomfortable. in this case they were the by—product of ivf. right. in a way that's a bit different because they have been created for a purpose, and if they're not actually used for implantation and the donors are comfortable with it, then, you know, this is... of course the pressure will be on because there's more research required. i think that's true, yeah. you make the point about the rules in the united states. in the wake of the development of crispr—cas9, james clapper in february, 2016, the us director of national intelligence, in a report included gene editing as a threat, a threat posed by weapons of mass destruction and proliferation because of the concerns. that's a threat you see too? i think it was included on that list because of the need to dedicate funds to study it.

i think it was really... there was a purpose to including it on that list. that being said, i think the reality is this technology, like many technologies, has the potential to be used for harm. so it is important to be understanding that and taking appropriate steps to prevent it. you have talked before of a dream that you had where you were being asked by somebody in another room questions, and when you open the door, it was hitler.

yeah. is that because of your fears of who will be using this? that was a dream that i had fairly early on. it was around the time that i was reading a paper that was published from a group that was doing human germ line editing in monkeys... sorry, isaid human, i meant germ line editing in monkeys and it made me realise this had the potential to occur in humans as well for human germ line editing. it started me thinking about the whole eugenics movement and government—sponsored programmes that could use a technology like this in principle for purposes that i think many people would find repugnant.

so i think that dream really culminated for me the need to be discussing this potential publicly. there are so many amazing things that could follow from this, but there is also, as you say, concerns, and of course einstein famously said if he had known how his research would have been used he would have been a locksmith. do you ever fear you will be thinking something like that? i don't, and the reason is i guess i'm inherently an optimist and i think technologies has been the key to advancement over aeons really. i think the potential for this to be a powerful tool for humans to live better lives in the future, for me, and risks come along with that, but i think it's just important to recognise that and take the appropriate steps that we can to build a global consensus about appropriate use. but without regulation, and relatively soon, is there a risk that people

will create this is perhaps perfect idea of a human, perhaps that's not a risk, perhaps that's a dream, a new species. i sometimes wonder whether in the future there will be a check list of desired traits that parents could select from when they go to an in vitro fertilisation clinic. but right now that's really science—fiction. it's not a reality today. however, given the pace at which the research is advancing and the interest in this kind of editing, i do think it's incredibly important for scientists and everybody else who's interested to be involved in a discussion right now about potential and how to protect the sanctity of human life. but when you talk about the enhancements of being able to choose enhancements, you see that as inevitable? it's hard to imagine that's not coming at sometime in the future, yeah. and where does it stop?

or does it mean we'll be in a world where there's nobody who is deaf, nobody who has asperger‘s, nobody who has qualities that perhaps add to the diversity of the human race? again, that world would be many, many decades off, partlyjust for reasons of how long it takes for a human to gestate. but i think that, you know, the potential for this tool to be used to make those kinds of changes is very compelling to many people, you know? and i think understanding how we can deploy it safely and effectively, in my opinion, to prevent disease, really, is very important. let me add one more thing, and that is just that we don't understand yet another about the human genome to make a lot of the changes that people are imagining, so that would require a lot more research. doctorjennifer doudna, thank you for coming on hardtalk. thank you, sarah. hello there.

the thunderstorms from yesterday took a while to get going but once they did, they did bring a lot of rain and lightning. storms initiated around sussex before spreading across central and southern england, the south midlands and on towards wales and the south—west. bursts of lightning, torrential downpours that brought flooding and reports of a few problems around bristol. some of the worst of it was in west sussex. it was just not cricket. lakes where the boundary should be. the met office amber warning in effect until six this morning.

we could still have one oi’ two more issues. liveliest of the showers working across wales. heavy downpours over the next few hours. a lot of murky weather and low cloud, mist and fog patches, notjust around the coastline but across some of our hills. mild and muggy night, grey and gloomy, really, to start friday morning. friday looks something like this. low cloud, mist and fog taking a long time to burn away and thin out. and then as we head into the afternoon, we will see heavy showers breaking out. this time they will be further north. in the firing line, scotland, northern ireland, north—west england and parts of wales. we could see around 30 millimetres of rain or so falling in the space of an hour. over a two or three hour period, if you are unlucky there will be a few communities who could see some flooding problems again where we could get 50 or 60 millimetres of rain, enough to cause the flooding problems we saw on thursday. muggy day temperature wise. highs into the low to mid 20s. onto the weekend's forecast,

so the thunderstorms will be around. they will head north on the weather will tend to become a little more settled and drier in the south. here is the weather picture. saturday beginning on a gloomy note for many of us, particularly across the north—east. gloomier start to the day generally in scotland but during the afternoon we see thunderstorms breaking out. scotland and northern ireland, parts of northern england has seen the worst of those. localised flooding a possibility. further south, more in the way of sunshine, starting to feel a little bit warmer given that the sunshine will be stronger with less cloud around. that trend continues into sunday, the second half of the weekend is probably the better half weatherwise. showers not far away from south—west england, still a couple showers across scotland but for most of us, sunday will be a dry day with sunshine slowly breaking through in the afternoon. warm as well in the south with highs reaching 25 celsius in london. this is the briefing,

i'm david eades. our top story: the trade tariffs hit now. the us measures are coming into effect, with europe, canada, and mexico saying they will hit back. a double take for italy. after weeks of political stalemate, the preferred candidate of the big two populist parties for prime minister looks set, finally, to be allowed to govern. a personal message from one leader to the other is on its way. a north korean diplomat prepares to hand—deliver a letter from kimjong—un to donald trump. and, in our business briefing, we will look at the options on the table for the eu to counter those huge steel tariffs from the us. i will be speaking to a leading trade lawyer in brussels.