A hen is only an egg’s way of making another egg.
Samuel Butler
Today, chickens outnumber humans on the planet by at least three to one at any time. They are the most common birds on earth, and around 60 billion of them are raised and slaughtered each year to feed our hunger for their flesh. Chickens have become the most important agricultural animal on the planet. But it wasn’t always this way. In fact, the chicken’s rise to global domination happened very recently, and very fast. And it all started with an American competition launched in 1945 – to find the chicken of the future.
The idea behind the competition was to refocus chicken breeders on meat, not just eggs, and to find the plumpest chicken in the United States of America. The sponsors of the competition, leading poultry retailers, A&P Foodstores, made a film about it in 1948, ingeniously entitled Chicken-of-Tomorrow.
The film starts with a close-up on a crate of fluffy chicks, while an oboe plays a plaintive air. Then the music fades, and the picture changes so that now we see two women in white shirts, fondling the cute little cheeping chicks and throwing them from one crate into another. ‘Did you know that poultry is the nation’s third largest agricultural crop, a 3-billion-dollar business?’ intones the American infomercial-style voiceover. The informative script is read by no less than the film-maker and broadcaster Lowell Thomas – the voice of 20th Century Fox’s newsreels until 1952.
Then we’re looking at more women, this time transferring eggs into a rack. ‘Breeders have achieved great results in boosting the egg output of the average hen. Today’s hen averages 154 eggs per year. Some birds produce over 300 annually.’ This sounds good, but it’s not good enough. ‘But with this emphasis on egg production, poultry meat has been more or less a by-product of the industry,’ continues the voiceover. Now we see two men in white coats, inspecting very skinny, dead chickens and then hanging them back up by their feet on hooks. The poultry industry got a boost in wartime, we’re told, filling a gap in the market produced by a shortage and rationing of red meat. Poultry leaders were worried about maintaining the demand after the war, so A&P Foodstores – originally the Great Atlantic & Pacific Tea Company – stepped into the breach, sponsoring a national competition. They were quite clear about what they wanted from farmers and breeders: ‘A broad-breasted bird with bigger drumsticks, plumper thighs and layers of white meat.’ They’d even made a wax model of what they wanted the future chicken to look like. Essentially, they wanted a chicken that looked more like a turkey.
The film goes on to describe the state contests, though it’s hard to take this seriously – the accompanying jaunty music, ‘The Liberty Bell’ march, was later hijacked by Monty Python, of course. Then we’re on to chick embryology, with footage of chicken embryos developing inside their eggs, a section of eggshell removed at each stage to provide a window on their development.
Back to racks of untampered-with eggs, as we’re told that all entries in the national final were incubated, hatched and raised under identical conditions. We see five men in suits from the poultry industry inspecting the chicks, approvingly. Then a woman in a pretty white blouse and a string of pearls pops up. Her dark hair is pulled up at the sides, and she’s wearing bright red lipstick. She’s also cupping two chicks in her hands – and then she lifts the chicks to her cheek and smiles. ‘Pretty chicks? Yes, sir!’ the voiceover comments, enthusiastically, as the double entendre misses its mark. After that light relief, it’s back to the men for the ‘enormous task’ of wing-banding the chicks with their flock number.
We follow the chickens through their short twelve-week lives, as they grow into big, handsome birds, some brown, some with grey stripes, some white as snow. They get put into crates for transport, transferred to cages … and suddenly they’re carcasses hanging from hooks, ready to be judged. ‘Twelve birds from each of the samples were packed for display purposes. Others,’ the voiceover explains, ‘went on the eviscerating line.’ Here are women again, pushing along chickens strung up from their feet on what look like coat-hangers. One man is in there, inspecting the birds. Then we see the final display – a few exemplary cockerels in cages, and boxed-up chicken carcasses draped with lametta. But outside, something extraordinary is approaching: a chariot, covered in white fur, and flanked by two American flags, carrying a woman in a white robe, wearing a crown. Nancy McGee, described as a ‘supplementary attraction to the programme’, is the Del Marva Chicken-of-Tomorrow Queen.
Still, Nancy doesn’t detract attention from the real champions for long. They’re the small flock bred by Charles and Kenneth Vantress, who crossed Red Cornish cocks with New Hampshire hens. It proved to be a winning combination, securing the Vantress brothers first place for both weight of birds, and efficiency of feed conversion into live weight (translating into more food for your money). But this is a beginning, not an end. The film isn’t there just to announce results, but to launch another national contest, to take place in 1951. More men in suits are looking pleased about the prospect of future competitions. The voiceover wraps it up, ‘Even today, housewives are enjoying improved meat-type chickens’ – and there are all the housewives, in a line, eating fried chicken thighs and drumsticks with their greasy fingers and grinning.
This film was clearly made in a very different world. A world where only men did serious work, while women either held fluffy chicks to their cheeks and looked decorative, or did the boring, mundane jobs. It’s also a world where chickens were skinny things, while the poultry industry dreamed of making them what they are today: fast-growing, plump, white-fleshed monsters. The thing that hasn’t changed is the approach. Right from its inception, the breeding of broiler chickens was clearly, already, an industry. How telling that chickens are referred to, in the opening sentence of the voiceover, as a ‘crop’. And the genes of the winning chickens from 1948 are scattered amongst our commercial flocks today.
The victorious Red Cornish cross from the contest was bred together with a white-feathered Leghorn which had won in the purebred category. The result, the Arbor Acre breed, became immensely successful. What had been a small farm focusing on fruit and vegetables, with a sideline in chickens, became the major supplier of America’s broiler companies. In 1964, Arbor Acres was bought by Nelson Rockefeller and exploded on to the global stage. Half of the chickens in China are descended from Arbor Acres lineages – descendants of the competition chickens. It sounds astonishing, and it’s hard to imagine how breeding has changed chickens so quickly, and so completely.
The transformation of chicken production into an enormous global industry involved not only selective breeding on an unprecedented scale, but also extremely tight regulation of breeding. Today, chicken breeding and chicken rearing by farmers are completely separated. The very fact that chickens are laid in eggs which can be incubated by machines rather than hens allows for this complete division. Chicken farmers rear chickens – often on a huge scale – but they’re not the ones breeding the chickens. That task is carried out by breeders – and just two, huge multinational companies that dominate the market: Aviagen and Cobb-Vantress.
These companies keep a very tight rein on their pedigree breeding-bird populations. Three generations down the line from their protected pedigree flocks, they create ‘parent stock’ which is sold to broiler-breeder farms, where chickens from separate genetic lines are bred together to make the final mix. The resulting chicks are sent on to broiler ‘Grow-Out’ farms – even your free-range, organic birds can come from those industrial chicken breeders, though there are some smaller breeding firms that specialise in slow-growing chickens for the traditional and organic market. Most chickens, though, grow fast – and are slaughtered at just six weeks old. When we eat chickens, they’re really just overblown, overgrown, big chicks. The ends of their bones haven’t even begun to turn from cartilage to bone yet. A single great-grandmother hen, back in the pedigree flock, can have an astonishing 3 million broiler-chicken descendants – who never make it to adulthood.
As well as carefully controlling the characteristics of their pedigree chickens from a phenotypic point of view – scrutinising their growth trajectories, their weight, their feed consumption – chicken breeders are now using genomics to hone their selective-breeding techniques. But advances in genetics also hold out the possibility, not just of genotyping chickens, and identifying advantageous genetic variants, but of genetically modifying the birds. No commercial chickens have been genetically modified – yet. But the techniques are being tested out in research institutes. The tools to edit the DNA of chickens and other livestock – to remove deleterious pieces of DNA and to insert advantageous genes – already exist. It’s been an arduous journey just to get to the point where the method works. Now the race is on to find ways of using that method to improve flocks. And just a seven-minute drive from the beautiful fifteenth-century Rosslyn Chapel in Scotland, mythologised in Dan Brown’s The Da Vinci Code, is the Roslin Institute – where they’re busy investigating a different kind of bloodline, a different kind of code. I travelled to Midlothian to meet these new code-breakers.
The Roslin Institute is a suite of state-of-the-art buildings, some designed to contain chickens, to get the best out of them, and others designed to hold scientists – to get the best out of them. The scientists here are focused on optimising their chickens – and not just through selective breeding. That’s worked wonders on chickens over the last millennia, and then in a truly extraordinary way over the last sixty or so years. But now we can interact directly with the genetic code of an organism, selective breeding looks positively archaic in comparison. Domestication is a continuing process – and this is where the forefront of domestication currently lies.
New techniques in genetic modification promise the earth – literally. With their help, we could be farming in a much more efficient, sustainable, egalitarian way in the future. And yet we’re afraid. Selective breeding is one thing, but for many direct genetic manipulation – using enzymes to modify DNA – seems a step too far, a Rubicon we should not dare to cross.
Instinctively, I feel there could be something wrong here. Science fiction has primed me – even me – to be wary of genetically altered organisms. Novelist and journalist Will Self is a master of writing about uncomfortable, unsettling otherness. In his Book of Dave, there are genetically modified pig-like animals called ‘motos’ which are both pets and livestock. They are intelligent; they talk – in toddler-ish broken phrases – but they will be slaughtered and eaten. The motos challenge our perception of the animals that we deliberately breed for consumption. We deem our tastebuds more important than their lives. There was too much dissonance there for me – I was completely vegetarian for eighteen years. Now I eat a little fish, managing my guilt, but other flesh is still a step too far.
We create a division in our minds between us and other animals – a necessary division if we are to eat them. You’d never consider eating another human (I imagine). But most people don’t have a problem with farming animals, slaughtering them, and eating them. So what about changing them? This seems to be acceptable – if achieved through selective breeding. When it comes to plants, it seems we’re comfortable with the idea of creating mutations using radiation or mutagenic chemicals, then selectively breeding these genetic changes into our crops. If that sounds novel and dangerous, it’s actually something we’ve been doing regularly since the 1930s. More than 3,200 types of mutagenic plant have been created and released since then. Some of them are now grown and promoted as organic products. The majority of groundnuts grown in Argentina are bred from irradiated mutants. The majority of rice grown in Australia is bred on from an irradiated mutant type. Mutant rice is grown in China, India and Pakistan. Mutant barley and oats are widely grown in Europe. In the UK, Golden Promise barley, a mutant created by zapping plants with gamma rays, is grown to make beer and whisky. There’s no danger at all from the radiation in the crops that are being grown – it’s already done its work, scrambling DNA in their ancestors, and producing useful variants.
These plants are, quite clearly, all genetically modified. So why is it more acceptable to modify genes using an instrument as blunt as a beam of gamma radiation, whilst using an enzyme to do the same sort of thing – in a much more precise and controlled way – feels like it could be more dangerous? The International Atomic Energy Agency is keen to separate ‘radiation breeding’ from biological, genetic modification. Radiation breeding is described as being simply an accelerated version of the spontaneous mutation that occurs in organisms and which is the stuff of variation, the lifeblood of evolution itself. But if we’re already modifying DNA using radiation, and calling that ‘radiation breeding’, it strikes me that we should be calling the – more exact and directed – biological version ‘enzyme breeding’.
So I was keen to get inside the Roslin Institute and talk to the researchers themselves about their own take on genetic engineering, and the newest tools for doing it. They are pioneers, operating right at the frontier. They understand the science, as well as the swirling vortex of perception and prejudice and valid concerns, better than perhaps anyone else. And they know the genes of the chicken – the first domesticated animal to have its full genomes sequenced, back in 2004 – very well indeed. Adam Balic explained the techniques and their potential uses; Helen Sang talked to me generally about this science and the politics around it; and Mike McGrew told me about the exciting new developments – and his vision for this technology as a force for good in the world.
Adam met me and escorted me up to his light-filled office on the first floor of the steel, glass and copper-clad building that houses the scientists at Roslin. There were posters showing the stages of chick embryological development on the walls. We sat down and he pulled up images on the screens that took up most of the space on his desk. There were islands of bright green glowing against a black background. These were photographs, taken down a microscope, showing a developing chicken embryo. We were looking at its neck, and the patches of green were showing up a specific type of tissue – lymphoid tissue, the same sort of stuff that makes up our own lymph nodes. This tissue doesn’t usually glow green: Adam had engineered the chicken embryo, inserting a ‘reporter gene’ into the chick’s genome that would produce a green, fluorescent colour wherever lymphoid tissue developed.
He’d made this change to the embryonic chick’s DNA using a traditional method, or at least, one that’s been used for around twelve years in chickens. He’d used viruses to do the work for him. Many viruses work by inserting DNA into a host’s genome, and so it’s possible to hijack this mechanism, getting the virus to insert the gene that you’re interested in, into the cell of another organism. These ‘viral vectors’ were originally developed for human gene therapy, but they work well for chickens, too. Although it’s not generally possible to direct the virus to a specific position in the new genome, they seem to be pretty good at finding places to insert genes where that gene will have a good chance of being read, or expressed, by the cell.
Adam was using this tried and tested technique to illuminate lymphoid cells in his chick embryos. The way he’d done it was to identify a protein that was normally made in those cells, but not in others, and then to find the ‘on-switch’ – the regulatory sequence of code that sits just upstream of the code for the protein itself. Then he could construct a new length of DNA – combining that particular ‘on-switch’ with a gene for making a green fluorescent protein – originally isolated from a jellyfish. Using a viral vector, Adam could insert that whole new package – the switch plus the jellyfish gene – into the chicken embryo. Then, in any cell where the switch was thrown to make the normal lymphoid-cell protein, the gene for the glowing protein would also be switched on. The genetically modified embryo obligingly ‘stained itself’, revealing its lymphoid tissue with stunning clarity, when illuminated with UV light under the microscope.
‘These aren’t just pretty pictures. They will allow us to quantify things too,’ Adam explained. The images showed precisely where lymphoid tissue – associated with the immune system – was developing in the embryo. Adam was studying the development of the chick immune system and these striking images were crucial to working out how the relevant immune cells and tissues formed. We were looking at how the chick’s defences were being laid out, almost like mapping ancient fortifications and trying to understand how a battle was fought. Birds have a very different immune system from mammals, so unusual in comparison that it prompts us to question how they’ve managed to survive without the tools that mammals have developed?
‘Almost everything we’ve learnt from mammals tells us that birds shouldn’t exist,’ said Adam, ‘but they cope with the same environment, the same pathogens – coming up with different solutions.’ Noticing differences like this, and trying to understand why those differences exist – that’s often how science proceeds. Lymph nodes seem so critical to mammals, including us. Birds possess patches of lymphoid tissue, but nothing as discrete and definite as a lymph node – and they manage perfectly well without them. It’s an interesting conundrum. Lymph nodes seem like quite complex things to invent. Why do mammals need them while birds don’t? By default, we’ll understand a lot more about the human immune system if we find out how birds manage to fight off infections with their quite distinct immune systems.
Genetic modification has enabled embryological development to be mapped more precisely than ever – it was clearly an important tool for fundamental scientific research like this. But what about the applications for genetic modification that could take it, out of the lab, into chickens bred for food? The Roslin researchers were looking at that angle too, using the combination of a quirk of embryological development together with an astonishingly precise new gene-editing technique.
Spreading a particular version of a gene through a flock of chickens relies on getting that gene into the cells which produce gametes – the eggs and sperm. The gamete-producing cells in the gonads of chickens (and humans) are known as primordial germ cells. They are essentially immortal cells – they will divide and divide, with some progeny ‘growing up’ into eggs or sperm, depending on the sex of the animal, and some staying as germ cells, ready to divide again – to make more eggs and sperm, and to replace themselves. The conventional way of getting your gene of choice into those primordial germ cells is indirect and more than a little haphazard – by selective breeding. You identify chickens with a particular trait, and breed those chickens together, hoping that the gene for the trait is there in some eggs and sperm, and will make it into some birds in the next generation. It takes generations to spread a trait through a flock. But imagine if you could short-circuit that process, by ensuring that all the eggs of a hen or the sperm of a cockerel contained the desired gene – then all their offspring will have that gene and exhibit that trait, straight away. This is precisely what the newest gene-editing tool allows the geneticists to do. And, serendipitously, it’s relatively easy to remove primordial germ cells from a chick embryo, in order to modify them.
Chicks have fascinated embryologists ever since Aristotle followed the three-week development of hens’ eggs. It’s possible to raise a section of the eggshell and to observe the developing embryo – and even interact with it – without killing it. The embryo develops on one side of the ovum – and you’ll be familiar with what that ovum looks like. Before it gets covered in albumen, and a shell, it’s the yellow bit that is mostly a massive yolk.
While the ovulated hen’s ovum measures about 2.5cm across, a human egg is just 0.14 millimetres in diameter. But that’s actually a very large cell, compared with the size of other cells in the body. It contains enough cytoplasm – the stuff inside the cell – to get embryonic development under way after fertilisation. The fertilised human egg is able to divide itself up into a ball of cells, without actually growing in size. In comparison, the hen’s unfertilised egg is huge. It’s the size of the yolk in a laid egg – and that’s exactly what most of it is. One huge cell, stuffed full of yolk nutrients to support the developing embryo, with a tiny, tiny bit of cytoplasm at one end – it’s there on your breakfast plate if you bother to look for it. In that cytoplasm are the chromosomes that represent the female genetic contribution to the embryo. The male genetic component is delivered to the egg by the sperm. And that’s when things start to get interesting. Whereas mammal eggs divide slowly, with the first cell division, into just two cells, complete after approximately twenty-four hours, the fertilised chicken egg doesn’t hang around. By the time the hen lays the egg – twenty-four hours after fertilisation – a disc of around 20,000 cells has already formed. If you opened up the egg immediately, you’d see it – a whitish disc on one side of the yellow egg yolk. If the laid, fertilised egg is kept nicely warm, the blastodisc (those 20,000 cells) continues to grow, multiply and develop into a chick embryo.
At just four days after being laid, the blastodisc has already rolled itself up into what will become the body of the chick. The developing eye is clearly visible and the chick embryo’s heart is already beating. (The human embryo only reaches an equivalent stage of development a full four weeks after fertilisation.) A network of blood vessels has also developed around the chick embryo by this point, reaching out around the yolk of the egg. If you shine a light through a four-day-old, fertilised and incubated hen’s egg, you can see these blood vessels quite clearly, radiating out like spidery red tendrils from a central red spot which is the embryo itself. If you were able to make an opening in the egg, and insert a tiny needle into one of those embryonic blood vessels at this stage, you’d be able to draw out a minute sample of blood. Within that sample there will be early blood cells – but also some extremely important stem cells. These are the primordial germ cells – which would eventually settle in the gonad of the developing chick, ready to make eggs or sperm, depending on the sex of the chicken.
Mike McGrew is working on taking blood from slightly younger embryos, only two and a half days old. At this stage, just a tiny sample contains 100 germ cells. The next trick he’s pulled off is to get the cells to grow in culture, away from the embryo, for months and months. That gives him the opportunity to edit their genes – using a new technique to make precise modifications, cutting out some pieces of DNA and splicing new ones in.
Having made those adjustments, the primordial germ cells can then be injected into a chick embryo that has already been genetically manipulated so that it doesn’t produce any of its own germ cells. Amazingly, development then proceeds as normal – the genetically altered primordial germ cells migrate to the ovary or testis of the developing chick. When that chick hatches and grows up into a hen or cockerel, that bird will be producing eggs or sperm which all contain the adjusted DNA.
The instrument which is allowing the geneticists to make precise adjustments to genomes is called CRISPR – the sharpest new tool in the genetic-engineering, neo-Neolithic toolbox. It’s much more refined than the traditional, viral vector method, but it’s also borrowed from nature, and based on years of painstaking research into the ways in which viruses and bacteria wage war on each other.
Some bacteria have a clever method of defending themselves against viral attack – a system which essentially provides them with immunity against viruses. When bacteria are exposed to viruses they copy a section of the viral genetic code into their own genome. It seems foolish – aiding and abetting the virus in this way – but it’s not. It means they can ‘remember’ the pathogen and fight it off effectively the next time. The piece of pathogen DNA is flanked by strange, repeating sections of genetic code: bookmarks for the bacterium. These bookmarks that are known as CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats. When the bacterial cell becomes infected, it looks up the bookmark and reads the short section of pathogen DNA – copying that sequence, using a slightly different molecule, RNA (which stands for ribonucleic acid, whereas DNA is deoxyribonucleic acid). That copy, the RNA ‘guide’, links up with a DNA-cutting enzyme in the bacterial cell which acts like a molecular pair of scissors. The RNA guide homes in and locks on to DNA arriving with an invading pathogen – and the enzyme neatly cuts it up, disabling it. So, if you wanted to make a very precise cut in a piece of DNA, you can specify your own target by creating an RNA guide – then giving it to the scissor-enzyme, to make a snip exactly where you wish. You can make as many cuts as you like, where you like.
The potential applications for this new tool are myriad. With this new gene-editing technology, it’s possible to snip out particular genes much more precisely than ever before, creating a ‘knockout’ embryo. As this embryo develops it will reveal what the function of that gene would have been, by demonstrating what happens in its absence. Understanding embryological development better will help us tackle diseases in the future – not only in chickens, but in vertebrates more generally, including in us humans. CRISPR could also be used therapeutically – to remove damaged DNA in living organisms. It’s already been employed, in the lab, to remove cancer-causing pieces of viral DNA from human cells. In fact, the technique is so refined that it can be used to snip out a single base pair – effectively just one nucleotide ‘letter’ on a chromosome – from a genome. But it’s not all about removing DNA – CRISPR makes it possible to precisely remove a section of DNA, and to splice in another. Cells are never happy about having their DNA snipped up. Molecular machinery will swing into action to repair the damage. The cell will usually look at the other chromosome in the pair to help it reconstitute the damaged DNA. But you can make a suggestion to the cell, by introducing your own piece of template DNA for it to copy instead. This has already been done – in the lab – to modify yeasts to make biofuels, to alter crop strains, to engineer mosquitoes resistant to malaria. The American Association of the Advancement of Science branded this new gene-editing technique the scientific breakthrough of the year in 2015. The field is moving fast – the range of potential applications is dramatic – but ethical questions abound.
Helen Sang has been studying vertebrate development and using genetic-modification techniques for more than forty years. She’s still interested in uncovering the fine detail of embryological development, but she’s also worked on chickens to genetically modify them to produce valuable proteins – things they never normally manufacture. Helen had done this with hens’ eggs and human interferon, a protein made naturally in the human body but also used as a drug to help fight viral infections. The egg white that hens make contains the protein ovalbumin. If you take the regulatory sequence, the ‘on-switch’ for ovalbumin, and join that up with the human interferon gene, you can stick that package into hens and they’ll start to make interferon alongside ovalbumin. So it’s possible to modify chickens to make it easier to study their development, as Adam had done with his green fluorescent protein in the lymphoid cells, and it’s also possible to get chickens to make other useful proteins for you, in their eggs – such as that interferon.
But in recent years, the focus of Helen’s research at Roslin had moved to looking at ways of modifying the chickens we eat. She was interested in something of immediate, real world relevance – promoting disease resistance in chickens. She was excited by the potential of CRISPR to achieve results precisely and quickly. She explained how it could work. You’d start by screening birds for disease resistance – to avian flu, for example – and then looking for genes associated with that resistance. That gene may only differ by a few nucleotides from the sequence in another bird, but those tiny differences can be crucial. Having identified a useful gene, you can use CRISPR to cut out the equivalent in another bird, and then replace it with the one you know will be beneficial. Using the technique in this way, you’d simply be spreading a genetic variant which already existed in chickens through a flock, without having to go through the laborious process of selective breeding. But of course there is another possibility: as well as introducing a variant of a gene from the same species, the same technique can be used to bring in a gene from a separate species. ‘We can move genetic information from anywhere to anywhere,’ Helen said, quietly in awe of the technique. ‘I think that’s a possibility which causes more worry – the idea that you move genetic information across the species boundary,’ I observed. ‘Well, it’s all DNA,’ replied Helen, ‘and anyway we know that DNA gets around – you can find things in us which have come in from other species.’ And that’s true, you can – especially from viruses, which love to go sticking their genetic oar into other genomes.
In fact, it isn’t just naturally occurring genes that geneticists could move from one species to another; they can now make entirely novel, artificial genes. It sounds extraordinary, but it’s already bearing fruit in chickens, if that’s not too mixed a metaphor. Geneticists are already exploring this avenue, designing artificial genes – specifically designed to throw a spanner in the works of viral replication – from scratch. One promising gene has induced chicken cells to make a small RNA molecule which caused problems for viruses, but Helen’s experiments have shown that it doesn’t confer complete resistance – there’s clearly still much more work to be done in the lab before a geneedited, flu-resistant chicken is a reality. What I was convinced of at Roslin is that it’s certainly on its way, and not too far over the horizon.
Working on aspects of biology which have such obvious benefits as disease resistance may encourage acceptance of the use of genetic modification in livestock and crop development. Helen thought that CRISPR itself may help to allay some fears. The precision of the technique meant that you could insert a gene somewhere where it wouldn’t derail any other operations in the cell – geneticists call such locations ‘safe harbours’ – while at the same time maximising its chances of being read, or expressed, by cells. With traditional modification, using viral vectors, you couldn’t predict where the gene would be inserted – though of course you can check afterwards. But with CRISPR, you can go straight in and make sure that gene is placed exactly where you want it.
Helen was eloquent on public perceptions of GM. She believes that the debate has been hijacked by certain lobbying groups with rigid agendas, and that the public in general isn’t being given the chance to choose: to accept the technology – or not. ‘At the moment, GM isn’t a choice. You can’t go to a supermarket and buy a GM chicken. We don’t sell anything that’s genetically modified. It’s very unusual to have a whole technology which is excluded, rather than giving people a choice.’
Helen told me that when she first started working in this area of science, and told people what she was doing, the reaction was generally positive – ‘They thought it was really neat, a great idea. Then suddenly it became anathema as far as food goes.’ I asked her if she thought that it all went back to the debacle that ensued when the biotech company Monsanto tried, controversially, to introduce its GM soy to Europe in the 1980s – and she does think that this played a significant role. Somehow, the debate over GM became hopelessly entangled with concerns about the domination of big, multinational companies. But this is something that worries Helen, too. ‘There are many things that I would be just as concerned about as somebody from Friends of the Earth, about where our food is coming from,’ she said, somewhat surprisingly, ‘but I think it’s a complete distraction to focus on GM. It’s a technology which has something to contribute. And we should be able to find a way of allowing that to happen, and allowing people to make their own choices. GM’s been used to epitomise bad, big business – whereas it’s actually just another tool.’
Not only is the conflation of GM and big business unhelpful to working out how, as a society, we feel about this technology, Helen also believes that it’s become a positive distraction from the real issues facing us about the future of food production. ‘There’s a smaller and smaller number of very large companies controlling food production. That’s not a scientific problem – it’s a political and economic one,’ she explained. ‘And it’s a tricky one. You have to accept that it’s been very efficient. We do need to feed a lot of people. But we need to have more sophisticated conversations about how we can take advantage of those efficiencies while protecting the environment and feeding the financial reward back to society.’ In some ways, the concern over GM, and the ensuing, incredibly tight regulations placed on this technology, only makes that problem worse. The cost of meeting the regulators’ demands is so high that it is effectively prohibitive. Only big multinationals can really afford to invest in GM – it’s stifling innovation and placing it solely in the hands of a small number of huge companies.
I asked Helen a difficult question: what did she think might happen over the next decade? Was it possible that GM would become more acceptable? She thought so. Younger people seem less likely to reject the idea out of hand. ‘But then, in the States, we’re seeing a backlash,’ she said. There have been moves in some US states to enforce labelling on GM foods – something they’ve never done previously. The idea of labelling something ‘GM’ is strange in many ways, especially if you’re only going to include enzyme-induced modifications, and not the ones created by irradiating organisms. There’s no risk to human health from eating GM food, even if you disagree with the methods used to produce it. And what does a ‘GM’ label tell you anyway? To be even moderately informative, it needs to describe what the modification is, and what its consequences are. ‘But on the other hand, if people want to know, then they have the right to know,’ said Helen. ‘It’s a really tricky argument.’
We discussed Golden Rice – a GM form of rice with enhanced levels of vitamin A, designed to combat dietary deficiency – which has provoked such a variable response from the public. Some accept it as a genuine philanthropic effort, and believe that it could really help to reduce vitamin A deficiency, particularly in some of the poorer countries of the world. Others see it as merely a poster child, something the ‘GM industry’ has bought into, simply as a tool of persuasion – the acceptable face of GM and the thin end of the wedge. It seems entirely reasonable to distrust the motives of some large companies who are trying to sell more of their own herbicide off the back of selling GM crops. But perhaps we should be more trusting of efforts to help the poorest farmers and communities – as Bt Brinjal, a disease-resistant GM aubergine produced as an entirely not-for-profit exercise, has already done. ‘If we want to be producing food efficiently and sustainably, we shouldn’t cut ourselves off from some of the ways we can do that,’ Helen concluded.
Perhaps it’s too easy to be cynical. It seems a shame that this technology wasn’t first developed and implemented by universities or not-for-profit enterprises. I have no doubt that there wouldn’t have been such a backlash and a collapse of trust if that alternative historical scenario had played out. But genetic modification has become so tainted by its connection with big business and questionable motives. It’s hard to shake that off – even where research is now being carried out by publicly funded, university research institutes.
For Mike McGrew at the Roslin Institute, one of the most exciting prospects for gene editing, if it is ever allowed out of the lab into the real world, lies in its potential for promoting disease resistance in farmed animals, particularly in developing countries. ‘We’re working with the Bill Gates Foundation in Africa,’ Mike told me, with undisguised pride. ‘Anything that would make these commercial chickens survive and thrive better over there, and actually lay eggs in a non-ideal climate, would be such a huge benefit.’ But Mike’s not just interested in the potential of these new techniques for breeding better commercial poultry, particularly in Africa, but in possible applications amongst wild birds too.
‘This is the thing I really care about: conservation biology. Think about the honeycreeper that lives on the Hawaiian Islands. We effectively brought in avian malaria to Hawaii, and the native honeycreeper has no resistance, because it’s never seen avian malaria before.’ All the birds living at lower altitudes have been killed off. The only ones left are those high up in the mountains, where it’s cooler and the mosquitoes don’t survive. But now, with global warming and rising temperatures, the mosquitoes are starting to reach higher altitudes, placing honeycreepers under increased threat of extinction. ‘So imagine if we were smart and we knew the genes responsible for resistance to avian malaria,’ Mike mused. ‘Could we could go into these wild populations, edit their genes, then release them? So there would now be disease resistance and the honeycreepers would thrive. Just imagine doing that.’
Mike understands the antipathy to GM when it’s focused on food in developed countries. ‘But if you’re able to do something useful for the human race, for the planet – there are a lot of different things we can use this technology for – I think people will start to recognise and welcome the potential.’ He spoke with real passion, but without any hype. ‘We need more education,’ he said. ‘Not fake news on the internet or in tabloids. People think DNA is the essence or the soul of an animal – and we’re changing its soul. But when they understand what DNA actually is, and what this technology is, they stop being scared.’ And yet it seems unlikely that the first GM chickens will hatch out of the broiler industry. The commercial firms are too sensitive to lobbyists. And with the Food and Drug Administration in the United States now keen to label any genetic modification – even to a single base pair – as requiring the same level of regulation as a new drug, the technology is unlikely to take off in America. So where did Mike think the first genetically modified chickens would finally enter the human food chain? ‘It’ll be China,’ he said. ‘China without a doubt. They have the genetics. And they have bird flu.’ If I was the betting type, I’d also be putting money on that immediately. I’m sure Mike will be proven right. If not in 2018, then very, very soon.
We can speculate about where the first commercial, directly genetically modified chickens will emerge. But we’ve been indirectly editing the chicken genome for centuries – where and when did that all start? The answer provides us with the solution to an enduring question that has left our best philosophers completely and utterly stumped. A riddle that addles the mind and draws one into a downward spiral with insanity seemingly the only end point.
Which came first? The chicken or the egg.
And here’s the thing. Evolutionary biologists have an answer for this question. Because, before the chicken, there was the junglefowl – and that laid eggs too. And so did its ancestors, all the way back to the dinosaurs, and still further back in time. Eggs, clearly, came first.
With that epic question answered, we still need to pin down the actual origin of chickens. In the 1990s, researchers seemed pretty sure that all chickens came from a single origin, that the ancestral species was the red junglefowl (as Darwin had, once again, rightly predicted), and that domestication had occurred in a discrete area of south or south-east Asia. The genetic diversity of modern chickens is highest across that region, and much lower in China, Europe and Africa. Some researchers have suggested that the chicken homeland was, very specifically, the Indus Valley, 4,000 to 4,500 years ago (2000 to 2500 BCE), during the Bronze Age. References to ‘the bird of Meluhha’ in cuneiform tablets from Mesopotamia, dating to 2000 BCE, could relate to chickens – Meluhha itself is thought to be an ancient name for the Indus Valley. Others, though, have favoured an origin further east. Today, several distinct subspecies of red junglefowl scratch around in forests stretching throughout south and south-east Asia, from India, Sri Lanka and Bangladesh, to Thailand, Myanmar, Vietnam, Indonesia and southern China.
Doesn’t this sound like a familiar story? We know what comes next. As more information came in from wider genetic studies, the theory of chicken origins was rewritten – as one which involved diverse geographic centres of origin, across south and south-east Asia. But that impression of multiple origins is also compatible with a single origin – perhaps across a relatively wide area – followed by dispersal and extensive interbreeding with wild species along the way. Modern chicken genomes contain strands of ancestry woven in through interbreeding with closely related birds including other subspecies of red junglefowl, as well as different species such as the grey junglefowl and Ceylon junglefowl.
In 2014, a piece of research published by Chinese geneticists really put the cat among the pigeons, or the fox among the chickens, for want of a better metaphor. They articulated an astonishing claim – that chickens had been domesticated by 8,000 years ago on the North China Plain. It was so out of kilter with the rest of chicken science – and feathers flew. Most researchers remained sceptical, however, for several reasons. Firstly, the climate of the North China Plain 10,000 years ago was decidedly unsuitable for tropical junglefowl – the accepted wild progenitors of chickens. Secondly, the identification of bones from archaeological sites on this plain seemed rather suspect. Some bones thought to be those of chickens were probably pheasants. And other bones appeared to have been entirely misidentified – not belonging to any bird, even, but to dogs. It seems that this was an extraordinary claim – which turned out to lack the requisite robust, extraordinary evidence. South and south-east Asia remained the most likely homelands of chicken-kind. And from that starting point, chickens set off to conquer the world.
Thousands of miles away from the homeland of chickens, these birds have been drawn into an ongoing debate about the human colonisation of the Americas. The premise is this: if chicken history is so tightly bound up with human history, then elucidating events in the deep past of chickens will shed light on what humans were up to as well. Reconstructing the population movements that led to the colonisation of the Pacific has been a tricky challenge. The peopling of Pacific Islands happened relatively recently, within just the last 3,500 years – but waves upon waves of colonisers have left confused trails behind them. The challenge is like looking for footprints in the sand, to recover the evidence of these ancient journeys. Imagine standing on a popular beach in Britain at the end of a summer’s day, just as the last families are packing up their windbreaks, their towels, and their buckets and spades, and heading off. If you mapped all the footprints on the beach, could you reconstruct all the events of the day? Could you work out how many people had been there, from which direction they’d walked on to the beach, and roughly what time they’d arrived? It would be a huge challenge.
Reconstructing ancient migrations is an even more daunting task. And yet, with archaeological and genetic evidence combined, it is just about possible. Humans didn’t arrive on the remote islands of Oceania alone; they took various other species with them – some deliberately, others less so, but all of them have a story to tell. Geneticists have attempted to track the human expansion into the Pacific by studying the molecular secrets hidden away in species as diverse as bottle gourds, sweet potatoes, pigs, dogs, rats – and chickens.
The islands of Near Oceania, in the south-western Pacific, were colonised way back in the Pleistocene, over 30,000 years ago. But Remote Oceania – including the groups of islands also known as Micronesia and Polynesia – wasn’t peopled until much later, in the Neolithic. It was the last major migration of humans to entirely unpopulated lands. Archaeologists and linguists have suggested that this colonisation had happened in two waves, with an earlier migration of farmers, bearing characteristic Lapita pottery, starting around 3,500 years ago, and a later one, around 2,000 years ago. But chickens don’t seem to bear witness to this two-wave model. Studying mitochondrial DNA from both modern and ancient chickens, geneticists found a distinct signature stemming from a single prehistoric introduction of chickens into Polynesia. The picture was extraordinarily clear – there was a founding lineage, from which all later Pacific Island lineages had evolved. The mitochondrial lineages of chickens, from the Solomon and Santa Cruz Islands in the west to Vanuatu and the Marquesas Islands further east, hark back to the original prehistoric arrival of farmers – and their fowl – in the Pacific Islands. For a while, genetic studies of humans also suggested that the colonisation had happened in one wave, but recent analysis of ancient human genomes has lent new support to that two-wave model suggested by the spread of material culture and languages amongst the islands of Polynesia. The chickens, it seems, were leading us up the garden path – and not for the first time.
For a while, it seemed as though that eastwards spread of farmers – and their chickens – might even have kept going right across the Pacific. The identification of a particular mitochondrial DNA type in chickens both from Rapa Nui (Easter Island) and from South America suggested just such a link. This was exciting, and controversial, as it indicated pre-Columbian contact between Pacific Islanders and the Americas. But the latest research on chickens, with exquisitely careful checks to rule out contamination, have revealed no such link. The DNA of Rapa Nui chickens and South American chickens is, in fact, quite distinct. South American chickens are essentially an offshoot of European chickens, which fits with the – much less controversial – idea of a post-Columbian introduction from Europe. This isn’t to say that there was no early contact between Pacific Islanders and South America, though – sweet potatoes made their way from South America to Polynesian islands long before the arrival of Europeans in the New World. And the genomes of modern-day Easter Islanders show traces of admixture with Native Americans, dating to between 1280 and 1495 – whereas Europeans only reached the island in 1722. But this is still only circumstantial evidence: what’s really needed to clinch this one is DNA evidence of admixture from pre-Columbian bones, either from the Americas, or from Polynesia. And that, for now, is proving elusive.
Genetics adds an important line of evidence, enriching and complementing the story that we can obtain from archaeological, linguistic and historical data – but not displacing those sources. Each provides us with a separate perspective on ancient reality. But when we contemplate prehistory in this way – staring at the past through such a wide lens – it’s easy to forget that these were people, and animals and plants, just as we encounter them today. Not species, but individuals. Science is powerful – it can answer our questions – but sometimes I feel the chill of the abstract quite acutely. We build knowledge in this way, certainly – but perhaps, at times, we lose sight of the personal, the intimate, the moment.
Considering the people, then – we can imagine early farmers making voyages into the Pacific and settling on islands alongside hunter-gatherers. And there would undoubtedly have been a two-way flow of information. The hunter-gatherers shared their local knowledge of plants and animals – where to find them, and what was good to eat. The farmers shared their knowledge too – and their domesticates. It may not always have been this friendly, but by and by, the hunter-gatherers adopted more of the farmers’ ways, and started to grow crops and breed animals. Gradually, and probably without any definite decision to do so, they became part of the Neolithic Revolution.
Chickens were not part of the original spread of people and ideas and livestock that marked the beginning of the Neolithic in Europe – they were domesticated too late for that. By the time chickens made their way into Europe, the Bronze Age had dawned. By 2000 BCE, chickens had spread from the Indus Valley into Iran. From the Middle East, chickens could have spread via a coastal route, to Greece and across the Aegean into Italy. Maritime trade had really taken off by the Bronze Age – this was the era of the Mycenaeans, the Minoans and the Phoenicians. The Mediterranean was crammed with merchant ships plying their trade. An alternative route may have seen chickens spreading north from the Middle East, through Scythia, and then west into central Europe. But it’s also possible that some chickens could have spread from much further east – from China, and then via a northern route, through southern Russia, into Europe.
Several researchers have suggested that differences between the chickens of northern and southern Europe reflect these two distinct routes of introduction. But once again, the history of this domestic species is horrendously complicated – and knottily tangled up with human history. It’s hard to trace those first migrations of chickens into Europe. Since those first feathery pioneers arrived, chickens have been subject to natural and artifical selection; flocks have been lost to diseases and replaced; birds have been brought in from further afield. The chicken breeders of the late nineteenth century picked and chose, breeding for particular traits, creating hybrids and generally mixing up the genetic history of European chickens, until they got what they wanted. And yet it is possible to disentangle the threads – the history is still there, embedded in the DNA of living birds.
A huge survey of chickens from the Netherlands – including sixteen ‘fancy breeds’ as well as commercial varieties – produced fascinating results. Most of these chickens had mitochondrial DNA which formed a neat cluster with that of chickens from the Middle East and India. The Indian subcontinent is the likely geographic origin for this cluster of maternal lineages. But a handful of breeds had mitochondrial DNA which was characteristic of chickens from the Far East – from China and Japan. These included three Dutch fancy breeds – the Lakenvelder, Booted Bantam and Breda Fowl – as well as some commercial egg-laying breeds from the US. It’s tempting to imagine that these breeds, with their Far Eastern mitochondrial genes, provide some support for the idea of a pioneering northern route into Europe. But in fact this handful of eastern lineages, which are not even that closely related, is much more likely to reflect more recent genealogy. It’s likely that these erratic traces of East Asian ancestry have a very short history, deriving not from that first wave of chickens arriving into Europe during the Bronze Age – but from exotic birds imported much later, by nineteenth-century breeders. So far, then, genetic studies of chickens fail to provide any support for that northerly route from the Far East. Instead, the main flow of these familiar fowls into Europe was via the Mediterranean.
The first evidence of chickens in Britain dates to the late first millennium BCE, in the Iron Age, but it was the Romans who really made chickens popular in this corner of north-west Europe. Chickens are by far the most well represented of any bird species in Romano-British archaeological sites. And yet the evidence is still rather thin on the ground, especially compared with mammal bones – like those of pigs, sheep and cattle. Bird bones are relatively fragile, and easily crunched to bits by scavengers, so it’s somewhat surprising to find any surviving at all. In rural settlements, away from centres of power and Roman influence, there’s not much evidence of chickens. But we glimpse them in more Romanised sites – in towns, villas and forts. Given the slim chances of chicken bones surviving, this evidence suggests that chickens – and their eggs, of course – may have been an important food, at least for the elite, in Roman Britain. It seems that chickens became equally popular further north, beyond the reach of the Romans. In South Uist, in the Outer Hebrides, there’s a little evidence of chicken bones dating back to the Iron Age, though it’s not until the subsequent Norse period that there’s more widespread evidence of domesticated chickens, braving the chill of the Hebridean Islands.
Although it’s tempting to assume that evidence of domestic chickens is evidence of people eating them, and their eggs, we shouldn’t rush to conclusions. It’s been suggested instead that the initial spread of domestic chickens across the Middle East, and then into Europe, was in fact less about meat and eggs – and more about blood sport. Images of cockerels fighting appear on seals and pottery from Egypt, Palestine and Israel, dating to the seventh century BCE. The sport was popular in Ancient Greece, and also seems to have been exported across the Roman Empire. Archaeological collections of chicken bones from Velsen in the Netherlands, and from York, Dorchester and Silchester in Britain, contain surprisingly high proportions of cockerels. Artificial cock-spurs have been found at Silchester and Baldock, but it seems that Ancient Britons may have been indulging in cockfighting even before the Romans arrived. Julius Caesar, in his Gallic Wars, wrote that the Britons ‘regard it as unlawful to eat the … cock … but they breed them for amusement and pleasure’.
The idea that the spread of chickens across Europe may have been about something other than meat is supported by a couple of lines of evidence. Firstly, during the Middle Ages, chickens were relatively small – suggesting that meat may not have been the foremost concern of breeders. Perhaps keeping hens for eggs and cocks for fighting was more important. And there’s written evidence too: geese and pheasants were much more frequently to be found on medieval menus than their now more popular cousins.
Domesticated chickens were transformed during the twentieth century, through the systematic approach to selective breeding largely unleashed by the Chicken-of-Tomorrow competition. But even before this, chickens had started to plump up, diverging away from their red-junglefowl ancestors. In just the last few years, geneticists have been able to identify particular regions of the genome that appear to have changed over time, and which seem to be linked to a size increase. They’re also able to estimate when these changes to the genome took place. A study of modern chickens from around the world revealed that they all carried two copies of a particular variant of a gene associated with metabolism. The gene in question made a protein which was a receptor for thyroid stimulating hormone (TSH). The particular version of the gene which had become ubiquitous in modern chickens made them nice and plump. It seemed like a gene variant that surely must have been associated with the initial domestication of chickens – as essential as large seeds in domesticated wheat or corn. And yet the DNA of chickens from before a thousand years ago was almost completely devoid of this variant. It was only during the Middle Ages that the gene suddenly became much more common, sweeping through chicken populations.
This sudden spread of a gene for plumpness coincides with an equally sudden and significant increase of chicken bones at European archaeological sites in the tenth century, from 5 per cent to almost 15 per cent of animal bones. This seems to tie in with a religious and cultural change – the Benedictine Reform – which prohibited the consumption of four-legged animals during fasts (which could take up a third of the year) but permitted two-legged creatures, as well as eggs and fish, to be eaten. Suddenly fatter chickens became incredibly desirable, and human-mediated natural selection then worked its wonders, promoting the spread of that metabolic gene variant through chicken populations. Urbanisation probably played a role as well: although city-dwellers would have relied heavily on rural-agriculture produce, they could also keep some animals – such as goats, pigs and chickens – in their own backyards.
Hormones can also affect the way animals behave, as well as their metabolism, and are implicated in an extremely important element of domesticated-chicken behaviour: a complete failure of maternal instinct. This sounds as though it should be bad for survival – and in the wild, it certainly would be. A hen who walked off from her eggs after laying them wouldn’t stand much of a chance of passing her genes on to the next generation, but in domesticated hens, that’s exactly what we want them to do. A hen that goes broody, that sits on her eggs and stops laying, is never going to win any prizes for egg production. The original red junglefowl lays fewer than ten eggs a year, whereas the most productive of our modern, domesticated egg-layers manages 300. That’s only feasible because the instinct to incubate the eggs has somehow been bred out of our chickens. That possibility only arose when chicken farmers discovered the trick of artificial incubation. The earliest egg incubators are very ancient – going right back to Ancient Egypt. But the genetic changes associated with the most profound loss of maternal behaviour in chickens appear to have happened much more recently. The loss of broodiness in chickens is the equivalent of the non-shattering rachis in wheat and maize – incompatible with successful reproduction in the wild, but advantageous under domestication.
Geneticists set out to identify the genetic basis of this change in behaviour. They compared the genomes of two breeds of chicken with widely differing levels of maternal instinct: White Leghorns, well known for being prodigious egg-layers and lacking incubation behaviour, and Silkies, who like to sit on their eggs. They found two particular regions in the genome which were substantially different between the two breeds, one on chromosome 5 and another on chromosome 8. Both of these areas were involved – once again – with the thyroid hormone system; and the one on chromosome 5 contains the TSH receptor gene itself. Some changes to this gene were spreading through chicken flocks a thousand years ago – and are now found both in chickens bred for egg-laying, and in broilers, bred for the pot (or more commonly now, the oven). But other changes to the TSH receptor gene may have arisen more recently, explaining differences in egg production and maternal behaviour in modern breeds like the White Leghorn and the Silkie. It seems that tinkering with the thyroid hormone system in chickens may have killed two birds with one stone; or rather, caused two phenotypic changes with one genetic stroke. Once again, we’re seeing how selection for one particular trait may influence another – this single gene seems to affect both plumpness and egg-laying in chickens.
These relatively recent changes to genes, bodies and behaviour remind us that domestication is not in fact a single, discrete event, but an ongoing process. And the arrival of gene editing means that useful changes can now be brought about even more swiftly than could be achieved in the tenth century, by papal decree.