Sex began 50 years ago, Larkin said. How has the Earth moved since 1963?

http://www.guardian.co.uk/society/2013/apr/27/profumo-affair-sex-1963
Vanessa Thorpe
In 1963, the Profumo affair and the sexual revolution took Britain by storm in a few short months. Half a century on, we trace the long-term impact of a tumultuous year.


Mandy Rice-Davies and Christine Keeler leave the Old Bailey after the first day of the Stephen Ward trial concerning the Profumo scandal Photograph:Hulton-Deutsch Collection/CORB

One of Philip Larkin's best-known poems, Annus Mirabilis, picks on 1963 as the year when sex was invented in Britain. The poet may not have been entirely serious, but his claim has a lot to support it. In the summer of that year, due to a convergence of cultural and political events that centred on London, an impression of both glamour and seedy intrigue was created that has never quite gone away.

Fifty years ago last Wednesday a feisty blonde call girl, Mandy Rice-Davies, was arrested at Heathrow airport on her way to Spain. She was charged with possessing a fake driving licence and she spent the next nine days in Holloway prison. Her incarceration for this paltry crime turned out to be one of the last factors in the unravelling of the Profumo Affair that in a little over a month would have forced the resignation of the war minister over his affair with Christine Keeler and revealed a world of vice and deceit at the heart of the British elite.

In the early days of that summer, while John Profumo was still battling to salvage his reputation, other events were also helping to change the way the country saw itself. In America the first Bond film, Dr No, premiered, finally selling the idea that the British could be sexy, while in June a British-made contraceptive pill became available for the first time. And, all the while, the hits from the Beatles' first album were being played throughout the country, as the Fab Four were packaged and made ready for their triumphant American tour in the first weeks of 1964.

"It was the beginning of the separating out of babies from sex," comments novelist Fay Weldon. "The pill made an enormous difference to women quite quickly and Keeler, although she was naughty, became a sort of role model, so that you would have been quite pleased if she came to dinner, as long as she stayed away from your husband."

Larkin's poem's opening lines –

"Sexual intercourse began

In nineteen sixty-three

(which was rather late for me) -

Between the end of the "Chatterley" ban

And the Beatles' first LP"

– also refer to the lifting of the ban on Lady Chatterley's Lover. Since the obscenity trial over DH Lawrence's explicit novel in 1960, unexpurgated copies were now readily available – further evidence of how liberated the country was becoming. But it was to be another trial – the pivotal case in the Profumo scandal – that dominated the headlines half a century ago and has now caught the eye of Andrew Lloyd Webber. The composer has begun auditioning for a new musical, Stephen Ward, to be produced next year. Written by playwright Christopher Hampton, it is based on the mysterious life of the society osteopath who was charged in June 1963 with pimping for both Rice-Davies and Keeler.

"Stephen Ward really intrigues me and was a fantastically interesting character," Lloyd Webber has said. "The most popular man in London who ended up with absolutely nobody. I think he was the fall guy."

The Profumo affair began with rumours that Harold Macmillan's war minister had slept with Keeler while she was also seeing a military attaché at the Soviet embassy, Yevgeni Ivanov. The issue became a public matter once it was claimed national security had been compromised. So Profumo stood up in the House of Commons in March to deny the affair.

During April and May the politician kept up a front, suing foreign publications that had relayed the rumours, such as Italy's Tempo Illustrato, which offered unqualified apologies in the high court, and the French magazine Paris Match. A Guardian report from 50 years ago shows Profumo was still gamely sticking up for press freedom too. "I don't grumble at all," he told Berkhamsted Young Conservatives. "I am all in favour of a free press and the moment we start to try to control it in any way, we would be in serious trouble."

Keeler had first met Profumo three years before at Cliveden, the country home of Viscount (William) Astor, where her friend Ward was staying in a cottage on the estate. Viscount Astor also owned this newspaper at the time and his younger brother, David, was editor, so at least part of Fleet Street had access to the information that Profumo had lied about his affair. The net finally closed when a chief inspector visited Rice-Davies in prison to offer her a deal. He made it clear that if she helped the police with an investigation into Ward, she would be released.

On 5 June Profumo confessed to parliament that he had lied, and tendered his resignation. Three days later Ward was arrested and that weekend theSunday Mirror printed a letter from Profumo to Keeler that had been circulating among journalists all spring. Known as "the Darling letter", it made it clear the pair had been lovers.

The social historian David Kynaston was not yet in his teens in 1963 but he remembers the sensation around the trial. "It certainly sold newspapers and in the summer holidays that year I noticed my father reading a paperback calledScandal:63 that had been rushed out. The Profumo affair was one of the things that switched the English default position on politics from deference to scepticism, if not yet to cynicism," he said.

Larkin's tongue-in-cheek lines from Annus Mirabilis express the feeling that he had missed out by being too old and Kynaston suspects this sense of missing out is central to the myth of the birth of the permissive society. "We still tend to see that era through the eyes of the young," he argues. "Youth culture was not widespread yet, and although higher education was slowly expanding, students were just a minority. We should not really privilege the young in history, although it is the new that always attracts attention."

Kynaston agrees there was a surge of social movement, but is wary of assuming that changes in London were mirrored across Britain.

"I was at university in the early 1970s when my great friend from Lancashire said to me, 'I can tell you, David, the 60s never happened in Blackburn'," he recalls. The geographic divide is one the Liverpudlian poet Roger McGough felt keenly too. "I was brought up Catholic in the north and a lot of my work has been about that feeling of being outside, looking in," he said. "I may have been in [60s band] the Scaffold and part of the Mersey Beat, but it all seemed to be happening in Carnaby Street. Then, when I did get down to London, it was always happening somewhere else. I guess there were some people who for a time, due to drugs or drink, were able to see themselves at the centre of things."

In Liverpool though, remembers McGough, it felt like the end of things, as industries shrank and the docks closed. "The 60s were a party being given by the government to hide what was really going on," he said. Britain, Kynaston explains, was still predominantly working class in 1963 and "still very much an industrial economy".

Yet the modern young woman, personified by Julie Christie's adventurous character in the 1963 film Billy Liar, was sold to the public as the face of the future. For Kynaston, though, this notion of sexual liberation was at least partly a construct of the entertainment and advertising industries. (This was also the year that David Ogilvy's influential book Confessions of an Advertising Mancame out, celebrating new sales techniques.)

Feminist writer and psychotherapist Susie Orbach agrees that, while some women embraced modern sexual freedom, many more were held back by convention for at least another 10 years. "This was pre Women's Lib, so women might have seen it in terms of their own agency, but the idea that was really being sold, along with the glamour of sex, was still marriageability," she said.

Life on Earth… but not as we know it

http://www.guardian.co.uk/science/2013/apr/14/shadow-biosphere-alien-life-on-earth
Robin McKie

Never mind aliens in outer space. Some scientists believe we may be sharing the planet with 'weird' lifeforms that are so different from our own they're invisible to us


Animal figures cut into desert varnish by Native Americans in Utah. Photograph: BWAC Images/Alamy

Across the world's great deserts, a mysterious sheen has been found on boulders and rock faces. These layers of manganese, arsenic and silica are known as desert varnish and they are found in the Atacama desert in Chile, the Mojave desert in California, and in many other arid places. They can make the desert glitter with surprising colour and, by scraping off pieces of varnish, native people have created intriguing symbols and images on rock walls and surfaces.

How desert varnish forms has yet to be resolved, despite intense research by geologists. Most theories suggest it is produced by chemical reactions that act over thousands of years or by ecological processes yet to be determined.

Professor Carol Cleland, of Colorado University, has a very different suggestion. She believes desert varnish could be the manifestation of an alternative, invisible biological world. Cleland, a philosopher based at the university's astrobiology centre, calls this ethereal dimension the shadow biosphere. "The idea is straightforward," she says. "On Earth we may be co-inhabiting with microbial lifeforms that have a completely different biochemistry from the one shared by life as we currently know it."

It is a striking idea: We share our planet with another domain of life that exists "like the realm of fairies and elves just beyond the hedgerow", as David Toomey puts it in his newly published Weird Life: The Search for Life that is Very, Very Different from Our Own. But an alternative biosphere to our own would be more than a mere scientific curiosity: it is of crucial importance, for its existence would greatly boost expectations of finding life elsewhere in the cosmos. As Paul Davies, of Arizona State University, has put it: "If life started more than once on Earth, we could be virtually certain that the universe is teeming with it."

However, by the same token, if it turns out we have failed to realise that we have been sharing a planet with these shadowy lifeforms for eons, despite all the scientific advances of the 19th and 20th centuries, then we may need to think again about the way we hunt for life on other worlds. Robot spacecraft – such as the Mars rover Curiosity – are certainly sophisticated. But what chance do they have of detecting alien entities if the massed laboratories of modern science have not yet spotted them on our own planet? This point is stressed by the US biologist Craig Venter. As he has remarked: "We're looking for life on Mars and we don't even know what's on Earth!"

Cleland – working with her Colorado colleague Shelley Copley – outlined her vision of the shadow biosphere in a paper in 2006 in the International Journal of Astrobiology. Other astrobiologists have also proposed ideas along these lines. They include Chris McKay, who is based at Nasa's Ames Research Centre, California, and Paul Davies, who put forward his vision of this alternative living zone in a paper in Astrobiology in 2005.

These researchers believe life may exist in more than one form on Earth: standard life – like ours – and "weird life", as they term the conjectured inhabitants of the shadow biosphere. "All the micro-organisms we have detected on Earth to date have had a biology like our own: proteins made up of a maximum of 20 amino acids and a DNA genetic code made out of only four chemical bases: adenine, cytosine, guanine and thymine," says Cleland. "Yet there are up to 100 amino acids in nature and at least a dozen bases. These could easily have combined in the remote past to create lifeforms with a very different biochemistry to our own. More to the point, some may still exist in corners of the planet."

Science's failure to date to spot this weird life may seem puzzling. The natural history of our planet has been scrupulously studied and analysed by scientists, so how could a whole new type of life, albeit a microbial one, have been missed? Cleland has an answer. The methods we use to detect micro-organisms today are based entirely on our own biochemistry and are therefore incapable of spotting shadow microbes, she argues. A sample of weird microbial life would simply not trigger responses to biochemists' probes and would end up being thrown out with the rubbish.

That is why unexplained phenomena like desert varnish are important, she says, because they might provide us with clues about the shadow biosphere. We may have failed to detect the source of desert varnish for the simple reason that it is the handiwork of weird microbes which generate energy by oxidising minerals, leaving deposits behind them.

The idea of the shadow biosphere is also controversial and is challenged by several other scientists. "I think it is very unlikely that after 300 years ofmicrobiology we would not have detected such organisms despite the fact that they are supposed to have a different biochemistry from the kind we know about today," says Professor Charles Cockell, of the UK Centre for Astrobiology at Edinburgh University. "It is really quite unlikely," adds Cockell, whose centre will be officially opened this week at a ceremony in Edinburgh.

Ways need to be found to determine whether or not the shadow biosphere exists, says Dimitar Sasselov, professor of astronomy at Harvard University and director of the Harvard Origins of Life Initiative. "If you want a clue you can count up the amount of carbon that is emitted by living things – cows, sheep, grass, plants, forests and all the planet's bacteria. When you do, you find there is a discrepancy of around 5% when you compare the amount given off from Earth's standard biosphere and the amount you find in the atmosphere."

In other words, there is slightly too much carbon dioxide in the atmosphere than can be explained by the emissions of standard lifeforms on Earth. There could be an error in these calculations, of course. Alternatively, the shadow biosphere could be responsible for this excess, says Sasselov. "There is plenty of room for a shadow biosphere. That is clear. Certainly, it is not true, as some allege, that we have strong evidence to show that it does not exist. In fact, the opposite is true: we do not have good enough evidence to dismiss it."

A key point to note is that scientists – although describing the inhabitants of the shadow biosphere as weird – still assume they will be carbon-based entities. Complex chemistry based on other elements, such as silicon, is possible, they acknowledge but these alternatives cannot create the vast range of organic materials that carbon can generate. In other words, the shadow biosphere, if it exists, will almost certainly be inhabited by carbon life, albeit of an alien variety.

"Billions of years ago, life based on different types of carbon biochemistry could have arisen in several places on Earth," says Cleland. "These varieties would have been based on different combinations of bases and amino acids. Eventually, one – based on DNA and on proteins made from 20 amino acids – formed multicellular entities and became the dominant form of life on Earth. That is why we find that life as we know it, from insects to humans and from plants to birds, has DNA as its genetic code. However, other lifeforms based on different bases and proteins could still have survived – in the shadow biosphere."

A different prospect is highlighted by Sasselov, who points out that a complex organic chemical can come in two different shapes even though they have the same chemical formula. Each is a mirror-image of the other and are said to have a different chirality. "Amino acids are an example," says Sasselov. "Each comes in a right-handed version and a left-handed version. Our bodies – in common with all other lifeforms – only use left-handed versions to create proteins. Right-handed amino acids are simply ignored by our bodies. However, there may be some organisms, somewhere on the planet, that use only right-handed amino acids. They could make up the weird life of the shadow biosphere."

But how can scientists pinpoint this weird life? Microbes are usually detected in laboratories by feeding nutrients to suspected samples so they grow and expend. Then the resulting cultures can be analysed. A weird lifeform – such as one made only of proteins formed out of right-handed amino acids – will not respond to left-handed nutrients, however. It will fail to form cultures and register its existence.

One solution to this problem is being pursued by Sasselov and colleagues' Harvard Origins of Life Initiative. They are building an artificial cell – or bionic system – made only of right-handed components including right-handed DNA and right-handed ribosomes. "If there are right-handed lifeforms out there, many of them will be viruses – which will attempt to hijack the DNA of our bionic cells," adds Sasselov. "When they do that they will leave evidence of their existence. Essentially we are building honey traps to catch any right-handed viruses that might live in the shadow biosphere and so reveal their existence."

Other scientists suggest a different approach – by looking at Earth's most inhospitable ecological niches: hot vents on the seafloor, mountaintops, highly saline lakes, Antarctic ice sheets and deserts. Standard lifeforms, mainly bacteria, have been found in these places but only a few. Some niches, researchers speculate, may prove to be just too inhospitable for standard life but may just be tolerable enough to support weird life. Microscopic studies would reveal their existence while standard culture tests would show they had a different biochemistry from standard lifeforms.

Stripes of desert varnish line the canyon walls of Capitol Gorge in Utah. No laboratory has been able to re-create the phenomenon. Photograph: Larry Geddis/Alamy

And a promising example is provided by the desert varnish proposed as a target by Cleland and backed by David Toomey in Weird Life. "No laboratory microbiologist has been able to coax bacteria or algae to make desert varnish," he states. "It is also possible that the stuff is the end result of some very weird chemistry but no one has been able to reproduce that either." So yes, these sites could provide proof of the shadow biosphere's existence, he argues.

Not surprisingly, Cleland agrees. "The only trouble is that no one has yet got round to investigating desert varnish for weird life," adds Cleland. "I confess I find that disappointing."

Seven Days of Creation

http://www.wired.com/wired/archive/12.01/clones_pr.html
The inside story of a human cloning experiment
By Wendy Goldman Rohm


Robert Lanza (left) and Young Chung


DAY ONE 5:10 pm
It's late on a Sunday afternoon and nearly dark inside the tiny, windowless lab; fluorescent light is said to be bad for human embryos. I'm sitting beside Robert Lanza, medical director at Advanced Cell Technology. He's breathing softly, hands folded neatly in his lap, his head bowed as if in meditation. For years he's been preparing for this day - making plans, conducting preliminary tests, losing sleep. Now, on October 12, we're six hours into the experiment and all he can do is watch.

By the glow of a microscope's light, research scientist Young Chung gingerly grasps a recently harvested human egg. He does this with a micromanipulator, a microscope outfitted with several diminutive, strawlike instruments called pipettes. Using a holding pipette, he keeps the fragile egg in place while he maneuvers a second pipette into position.


The eggs were donated by two women who were paid $4,000 each by ACT. A doctor at a clinic just outside of Boston this morning harvested the eggs - 18 in all thanks to fertility drugs - and ACT rushed them to its labs in Worcester.

Chung steps on a foot pedal to activate an ultraviolet light underneath the micromanipulator, briefly illuminating the DNA inside the egg. It's the only way he can see the genetic material without hurting the egg. If the UV is on for more than a few seconds, the egg could be damaged. Chung steps on a second pedal to control the second pipette, called a piezo, which acts like a tiny drill. The micromanipulator click-click-clicks like a minuscule jackhammer as Chung begins enucleation, the delicate task of puncturing the egg's protective membrane and sucking out its nucleus. He must be certain to retrieve all of the chromosomes inside the egg - 2 meters' worth, if they were unraveled and stretched end to end - without collapsing the membrane.

For several minutes, the only sound is the click of the machine and the tap of Chung's feet on the pedals. Finally, he looks up. "One down," he murmurs.

In recent months, Chung and Lanza have done other experiments leading up to this one, and during their last trial, an egg collapsed and died when Lanza left the room. He will not leave this time. Instead, he worries about the lab environment. There must be no unnecessary vibrations on the table where Chung works, no exposure of the eggs to fluorescent light, and no deviation from a room temperature of 85 degrees Fahrenheit. Lanza is especially concerned with CO2 levels inside the incubator; he keeps an eye on the digital display, believing that an experiment conducted in September, in this same lab, may have failed because of improper CO2 levels. Glancing at the wall-mounted thermometer, Lanza notices that the temperature has slipped to 83 degrees. He turns on a small space heater, asking Chung: "Is that OK?"

"Fine," the Korean-born scientist answers, beads of sweat forming at his brow. Chung wears black-framed glasses and blue-gray scrubs. At 42 years old, he's not as well known as Lanza, but he is highly regarded among his peers for his dexterity when manipulating cells. Nine additional freshly harvested eggs await enucleation.

Once he's emptied them, Chung performs the most critical step of the cloning procedure. In a process known as nuclear transfer, he will inject the 10 hollow eggs with donor DNA in the form of cumulus cells, which nourish the ovaries and, like other body cells, contain a full set of genetic information. These, too, were collected from the egg donors. The injected eggs will then be chemically stimulated to begin dividing as if they'd been fertilized. Taken together, it's very close to the way UK scientist Ian Wilmut created Dolly the sheep. The big difference: Wilmut implanted the sheep embryo to grow a cloned animal; Lanza will keep the resulting embryos in a petri dish to grow stem cells.

If it works, Lanza will have accomplished two amazing things: He will have cloned human embryos, and he will have harvested stem cells from them.

Embryonic stem cells are prized for their magical potential to become any type of cell in the body. Researchers see them as healthy replacements for cells damaged by diseases - including diabetes, osteoporosis, Alzheimer's, and Parkinson's - that affect more than 130 million people in the US, according to the National Academy of Sciences. Clone embryos would produce stem cells that are exact genetic matches of the donors and consequently run little chance of rejection.

But Lanza can't get stem cells until he grows an embryo that has divided into at least 16 cells, which usually takes about five days. At that stage, embryos become morulae, from which stem cells have already been obtained in animal studies. Even better would be blastocysts, embryos that have 64 to 200 cells and are distinguished by the development of an inner cell mass from which stem cells can more readily be derived. Just one problem: There have been no published reports of a human clone embryo surviving beyond a few cell divisions, let alone to 16 or 64 cells. Which raises the question of whether Lanza's project is even possible.

If Lanza can get to morula stage, well, that's when the controversy is sure to begin. It's at this point that the embryo's genome - the donor's complete DNA - will have kicked in. No larger than the head of a pin, the morula has enormous potential. An embryo at this stage could be implanted in a uterus, a process typically done after 48 hours in the 100,000 in vitro fertilization procedures done in the US each year. Thus, a human clone - should a scientist choose that path.

But that's not what ACT wants. This experiment is central to its pursuit of therapeutic, not reproductive, cloning. Simply put, ACT wants to create stem cells, not human beings. "We have patients dying for lack of transplantable tissue on one side of the scale, and on the other someone who wants to clone a human being," explains ACT chief executive Michael West. "Do you save the lives of hundreds of thousands of people, or stop everything for fear someone would abuse this? I'd prefer to help sick people."

Back in the summer of 2001, stem cells and cloning dominated the headlines. In July, the House of Representatives passed a bill that would prohibit the cloning of human embryos for any purpose; similar legislation stalled in the Senate. The following month, President Bush announced that he would limit federal funding to the 60 or so stem cell lines already in existence. (Scientists later complained that less than 20 are viable for research purposes.) "I strongly oppose human cloning, as do most Americans," Bush said from his ranch in Crawford, Texas. "We recoil at the idea of growing human beings for spare body parts, or creating life for our convenience."


Advanced Cell Technology�s Lanza takes a break near his island home outside Boston. An avid conservationist, the 47-year-old has cloned such endangered animals as a gaur, which died two days after birth, and an Asian banteng, now at a San Diego animal park.


But there was no ban on privately funded research, so at ACT, Lanza and his colleagues pressed on. That summer, his team achieved a controversial first, the creation of several early-stage human clone embryos - one of which grew to six cells. ACT announced its breakthrough in November 2001 and immediately came under fire. "The pro-life and evangelical groups were particularly well organized with members of Congress," recalls West. "They launched an attack on these technologies as being 'brave new world.'" As criticism mounted, a crucial round of venture capital funding evaporated. Cash-starved ACT had little choice but to shut down its human research program.

Outside ACT, there was progress. The National Academy of Sciences issued a report acknowledging the medical value of therapeutic cloning. California in 2002 authorized the use of public funds for embryonic stem cell research, and several other states are considering similar bills. Last June, the American Medical Association, which sets the tone for accepted medical practices nationally, endorsed therapeutic cloning but acknowledged the right of doctors to decline any role in it.

Meanwhile, ACT centered its stem cell research on animals. The company cured spinal injuries in sheep and successfully cloned kidney cells that were a genetic match to their DNA donor, a cow. They even rejuvenated the immune system of a cow with a teaspoon of stem cells.

On the strength of these and other studies, ACT received a cash infusion and approval from its external ethics advisory board to again clone human embryos. In spring 2003, Lanza recruited two scientists: Chung, from Temple University, and Irina Klimanskaya, a Harvard researcher who played a key role in deriving 17 new stem cell lines (with private funds, of course) from frozen human embryos for the Howard Hughes Medical Institute.

By October, Lanza was ready. In an attempt to derive stem cells, he would take human cloning further than it had ever gone.

DAY ONE 5:40 pm
It takes 30 minutes for Chung to successfully enucleate six eggs, all from the first donor. He invites me to peer into the microscope. The empty eggs, gleaming in white light, resemble beautiful little sequins. Chung takes out the second batch of donor cells and turns off the lab lights. The mood is cheery. "It's not as stressful when things are going well," says Lanza. "There's no drama."

A moment later, Chung's body tenses. Lanza seems worried. Chung mutters that the eggs "look vacuolated"; their wrinkled appearance suggests an inability to withstand piercing and nucleus removal. Several long minutes pass. He clenches his jaw as he works the micromanipulator. Then, again: "One down."

"Wow," Lanza whispers with relief.
Chung removes the nuclei from the three remaining eggs without incident and by 6:10 they have 10 enucleated eggs. The scientists are jubilant. A 100 percent success rate is practically unheard of. "I'm pretty sure they'll all survive," Chung says.

"I just did some arithmetic," Lanza says, trying to nail down the best time to perform the injection of cumulus cells into the enucleated eggs. He knows the optimal window for nuclear transfer hinges on exactly when the donors received the medicine that induced ovulation. The scientists quickly agree on a cutoff of 8 pm.

Chung removes vials of cultured cumulus cells from the locked incubator. They've been sitting for several weeks in a nutrient-rich solution. It's a special sauce, one of many variables critical to this experiment.

"Cooking with Young," Lanza laughs.

"It's a cable show, How to Make Your Own Stem Cells," Chung jokes back. He places the cultured cells next to a red ice bucket, which holds another batch of vials, freshly harvested cumulus cells from the egg donors. Both groups of cells will become the genetic payload for the enucleated eggs. Neither Chung nor Lanza is sure whether cultured or fresh cells work best, so they will try some of each.

At 6:40, Chung starts on the empty eggs from the first donor. This time he uses an even smaller piezo to drill into the egg. The micromanipulator produces a clicking that's more insistent, and seems to last longer than during the enucleation process.

"OK, great," Chung finally says. He has penetrated the membrane of the first egg, and seconds later he injects the cumulus cells through the piezo, moving a copy of donor DNA into the enucleated egg. It's the essence of cloning.

Chung wipes his palms on his pants. The clicking resumes, then suddenly he eases off the pedals. Lanza grimaces. Chung swears under his breath. The second egg's protective membrane is surprisingly tough; he cannot pierce it with the piezo. He quickly switches pipettes. Every second counts; it's 7:10 and the 8 pm deadline looms. It's taken nearly 30 minutes to inject the first two enucleated eggs. The next two go more smoothly. By 7:15, four of ten eggs are done. Chung smiles at me, relieved.

Thirty minutes later, the nuclear transfer is finished. Ten eggs - six from one donor and four from the other - have been injected with DNA and now have the potential to become human clone embryos. But first the eggs need to be activated, which is basically a jump-start to prod them to begin dividing. In the early days of cloning, researchers did this with electric shocks. Chung's approach: dribbling a prepared chemical reagent into their petri dishes. It's the easiest part of the process. So far, not a single egg has been lost, and he has beaten the deadline.


Chung directs his attention to the eight remaining eggs. Instead of cloning, now he's going to try a different process to get at the all-important stem cells. It's called parthenogenesis, a form of reproduction that occurs naturally among aphids, snakes, even turkeys - but not mammals. Chung's goal is to create parthenotes, embryo-like balls of cells that, like clone embryos, can lead to stem cells. But we're not cloning here; Chung uses a different reagent to fool the embryos into dividing as if they were fertilized.

Parthenotes lack the necessary male chromosomes to form a placenta, making it unlikely they could ever become a human. Because of this, some scientists see parthenotes as a way to avoid the ethical issues surrounding therapeutic cloning. ACT hopes to use parthenogenesis to derive hundreds of broadly transplantable stem cell lines, enough to match the tissue types of nearly everyone in, say, the US.

At 8:30, the waiting game begins. If all goes according to plan, the eggs will grow into early-stage clone embryos and parthenotes over the next 72 hours. It is possible, however, that nothing will happen and they all will die.

Lanza announces that he's taking the incubator key to guarantee peace, quiet, and darkness for the nascent cells. The incubator is not to be opened for three days. He is convinced that prematurely opening it can kill embryos. It has happened to his experiments before.

While Lanza and Chung work in the lab, CEO West goes looking for money. The controversy surrounding cloning - and the simple fact that there's little revenue in it - has made it difficult to keep Advanced Cell Technology afloat. West attributes the financial woes to two years of plummeting biotech stocks and private investor disdain for the sector. "Little biotech companies can't do it on their own," he laments. Several times during recent months, the 16-person ACT barely made payroll.

For months, West has been speaking with potential investors, and today he's talking to someone about taking a large stake in ACT, perhaps even buying the company outright. A source close to the possible deal says West's target is Exeter Life Sciences, a biotech holding company owned by American billionaire John Sperling. Sperling also owns pet cloning firm Genetic Savings & Clone, which pays royalties to ACT for use of its cloning technology.

Money problems have plagued ACT for years. Founded in 1994 as Avian Farms, an agbio concern engaged in poultry genetics and animal cloning, the company appealed to West, who had a growing interest in stem cell therapies. In 1998, West left Geron, a biotech firm he founded, and joined ACT as CEO; two years later, he led a group of investors to buy the company. Under West, ACT expanded into human research and hired several top biomedical scientists, including Lanza. By 2001, the company was preparing for what would be its breakthrough experiment: the successful cloning of several human embryos.

That summer, West and Lanza traveled to Washington to meet with regulators at the Food and Drug Administration. Their point: that ACT's research did not violate a 1998 agency directive prohibiting cloning experiments where "human subjects are or would be exposed to unreasonable and significant risk of illness or injury." The FDA, recalls Lanza, said "this would be easier for us if you put it in writing." So he and West composed a letter stating that ACT was interested only in stem cells and had no intention of engaging in the risky business of cloning a human.

Since that time, the FDA has left ACT alone, allowing its therapeutic research to continue provided it draws the line at stem cell treatments. "If we actually wanted to do a human clinical trial where we made cells and put them into a patient who was sick, we'd go back to the FDA for approval," West says.

In fact, ACT's future depends on developing additional technologies - for creating embryos and parthenotes and for deriving stem cells - that it can patent and license. But first the medical value of stem cells must be proven and therapeutic cloning embraced by the marketplace. "We'll need tens of millions to carry the research through to clinical trials and to the successful launch of the product," admits West.

DAY FOUR 3 pm
"It would be foolish for us to expect a home run," Lanza cautions. After three days of suspense, he and Chung are about to unlock the incubator.

Of the 10 clone embryos, five have reached the four-to-eight cell stage - quite an accomplishment. (In natural reproduction, the embryo would be at 8 to 16 cells after 72 hours, but clone embryos often develop at a slower pace.) Two have divided past ACT's previous record of six cells. "That's not trivial," Lanza remarks, with classic scientific understatement.

The parthenotes look equally promising. All eight have divided, with several of them cleaving into early-stage embryos. Lanza expects that within two days he'll have two or three blastocysts. But he's wary: "With parthenotes or clones, the embryos can look really good at one point and then nose-dive." Chung shuts the incubator, and the wait continues.

DAY FIVE 10 am
I wait in a hotel next door to ACT's offices. Though today is the big day, Lanza is calm as we sit in the lobby, talking about his personal biocentric theory of the universe. We joke about his wild ideas and don't mention a word of what is growing back in the lab or his plan to open the incubator at 2 pm. He bids good-bye simply by saying, "I'll let you know what happens."

I have witnessed nearly every minute of the experiment Lanza and Chung set in motion. Only today, because of Lanza's increasing obsession with not disturbing the embryos, I have been banished, sentenced to sit in my room and stare at my cell phone. At 2:14 it rings.

"Are you sitting down?" Lanza asks.

My voice rises, almost to a shout. "What have you done?"
"We're so surprised. We did it!" Lanza laughs. "We have one clone at 16 cells, it's a beautiful compacting morula! We could get stem cells now if we want!" Though it's not yet a blastocyst, which is the ideal stage for harvesting stem cells, the clone embryo is at the critical point of development where the injected genes become functional. It's evidence that both the donor DNA and the embryo are thriving, that normal cell division is happening. "Only when you get to a morula are you sure it's occurring," says Lanza.


The results of the experiment pose a challenge to a widely embraced report published by Gerald Schatten, reproductive science professor at the University of Pittsburgh. Last April, he wrote that using current techniques, human cloning would be almost impossible due to errors in early cell division, which are caused by removing the nucleus of the egg.

Lanza's experiments seem to show otherwise. One of his embryos divided successfully to at least 16 cells. That means he has found not simply a path to stem cells, but made a significant if unintended step toward human cloning. After all, if thriving clone embryos can grow to 16 cells and beyond in a lab, those cells could theoretically be tested for genetic abnormalities (as they routinely are in IVF procedures) and then be implanted in a uterus - reproductive cloning. Lanza insists he's not going there, but others surely will.

Meanwhile, Lanza is also excited about his parthenotes. That part of the experiment has led to two blastocysts with inner cell masses, which means they contain stem cells. Lanza is positively ecstatic. "The parthenotes are unbelievable."

DAY SIX 10:15 am
Lanza and Chung reopen the incubator and move the parthenotes to the microscope for observation. Another morula has become a blastocyst overnight; now there are three. Inside their circular membranes is what looks to be a crescent moon with a clump of cells facing inward from its middle. It is the inner cell mass.

Chung retrieves the dish cradling the most advanced clone embryo and places it under the microscope. He and Lanza observe at least 16 cells inside a circular outer membrane. The embryo is at rest in the morula stage, just as it was the day before. Lanza refuses to tell me more. Stunned by the progress of his experiment, he insists that he would be condemned by his peers if he allowed Wired to report the fate of the clone embryo. Lanza says he'll publish the outcome in a scientific journal. When I protest, he allows me to follow the less-controversial parthenotes a bit further.

The stem cell specialist Irina Klimanskaya arrives at noon to harvest the inner cell masses of the parthenote-derived blastocysts. She'll "plate out" the ICMs into petri dishes, a process that involves encouraging stem cells to grow on a layer of feeder cells.

Klimanskaya plates out the three blastocysts. She notes that two other parthenotes continue to thrive. By the time she leaves, it's nearly midnight.

DAY SEVEN 11 am
Back at the lab, Klimanskaya opens the incubator to check on the petri dishes. Lanza is forced to watch and wait as his experiment unfolds. Two more parthenotes have grown into blastocysts. The ACT team has obtained five blastocysts from eight eggs. Better still, the ICMs Klimanskaya plated out yesterday have already attached to the feeder cells. Lanza and company cross their fingers that they'll get stem cells.

Meanwhile, I've learned nothing more about the human clone embryo and, as I return to my hotel, I am left pondering a host of questions. Did the embryo progress beyond 16 cells to a blastocyst? Will it yield stem cells? Or has it already died?

For answers, I'll have to wait, like everyone else, until Lanza publishes his results.
But this much is clear: ACT is pioneering new methods to grow stem cells - and along the way, bringing us closer to a fascinating, if ethically complex, future.

Countdown to a Human Clone
The 1978 birth of Louise Brown, the world's first test-tube baby, spurred a series of medical advances - and government restrictions. The past decade's milestones:

May 1990: The Human Genome Project, an international effort led by the US, is launched.
September 1990: USC medical school professor W. French Anderson conducts the first somatic gene transfer experiments.
January 1992: First baby conceived through intracytoplasmic sperm injection - a fertility treatment in which a single sperm is injected into a single egg - is born in Belgium.
July 1996: Dolly, the cloned sheep, is born in Scotland.
March 1997: President Clinton issues an executive order banning federal funds for cloning experiments.
October 1998: The FDA asserts jurisdiction over human cloning.
January 2001: ACT announces birth of a cloned gaur, an endangered relative of the cow.
August 2001: President Bush restricts federal research funds to existing stem cell lines.
November 2001: ACT announces that it grew a six-cell human clone embryo.
December 2002: Clonaid, a company formed by the Raelian sect, claims to have created "Eve," the first human clone.
February 2003: For the second time in two years, the US House passes a bill to outlaw human cloning; no action from the Senate.
February 2003: Dolly dies from a lung infection.
April 2003: The mapping of the human genome is completed.
October 2003: ACT grows a 16-cell human clone embryo in order to derive stem cells.
November 2003: The United Nations defers voting on two proposed bans on human cloning.

6 Steps to a New You

The science isn't a mystery. The question: Are you cloning to get stem cells, or to give birth?

1. Harvest Collect eggs and cumulus cells from female donors. The normal function of cumulus cells is to nourish eggs in the ovaries, but, like other body cells, they also contain a person's complete genetic information.

2. Enucleate Puncture the egg's outer membrane with a pipette and remove the nucleus and, thereby, its DNA.

3. Transfer Inject a cumulus cell - which contains a full copy of the donor's DNA - into the enucleated egg. The result: a renucleated egg.

4. Activate Place the renucleated egg in a chemical solution. This tricks the egg into dividing as if it had been fertilized normally.

5. Incubate The clone embryo begins mitosis. After three days, the embryo typically has four to eight cells, and after five, 16 cells. At this point, the embryo is called a morula, and stem cells can be derived, according to animal studies. If the embryo progresses to a blastocyst, stem cells can be more readily obtained. Now you've done it: therapeutic cloning.

6. Implant The early-stage embryo is inserted in the uterus, where it attaches to the lining. It's a long shot, but if all goes well, the embryo will develop a placenta and eventually become a viable fetus. Now you've done it: reproductive cloning.


On the Front Lines
By Wendy Goldman Rohm

Matt Gunther

Robert Lanza spent 20 years researching heart transplantation and diabetes treatments before joining ACT in 1998. As medical director, Lanza is on a mission to clone human embryos and perfect other techniques in pursuit of stem cells. ACT's ultimate goal: hundreds of stem cell lines to treat everything from Alzheimer's to diabetes to Parkinson's.

WIRED: What have you accomplished here?

LANZA: There was a growing consensus in the scientific community that human cloning both for reproductive and medical purposes was impossible. These studies clearly show that it is indeed possible to generate early embryos via cloning.

What's your position on reproductive cloning?
Aside from the moral and ethical issues, it would be dangerous and scientifically irresponsible. I don't know of a reputable scientist who'd consider using this technology to clone for reproductive purposes.

What's the benefit of your experiment?
This is extremely important if we are to harness genetically matched cells and tissues for human transplantation. For example, if someone has a heart attack, that person would need a ready supply of stem cells and you wouldn't have time to derive those from scratch.

How did you succeed?
This has been a process, a continuation of our ongoing efforts. We've had extensive experience cloning other species and have been troubleshooting problems for years. Also, we have an incredible scientific team. Young Chung is extremely skilled at cloning techniques.

Do you worry about the ethical implications of your research?
Cloning is currently regulated by the FDA. Our intent is to use this technology to generate stem cells to treat serious and life-threatening diseases, not to create a child. The American Medical Association agrees that this research is consistent with the ethical goals of medicine, namely, healing, prevention of disease, and helping to alleviate pain and suffering.

What's next for ACT?
The goal of this research is to generate embryonic stem cells. This is an ongoing research project and there are many steps ahead, including developing the cells into viable therapies. It will require many years of research.

Are you concerned that others might use your results for reproductive cloning?
We can't stop this valuable research from going forward for fear of the few bad apples out there. That's why there are laws.

---

Wendy Goldman Rohm (wwendyrohm@cs.com) wrote about the 25th anniversary of in vitro fertilization in Wired 11.10. She is the author of the soon-to-be-published Miracle Cells: Adventures on the Front Lines of a New Science.
Copyright © 1993-2004 The Condé Nast Publications Inc. All rights reserved.
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The Thatcher effect: what changed and what stayed the same

http://www.guardian.co.uk/politics/2013/apr/12/thatcher-britain
James Ball
From the right-to-buy scheme to social attitudes, James Ballexamines how life changed in Britain under Margaret Thatcher

Perhaps the only undisputed facts of Margaret Thatcher's premiership are that she first entered 10 Downing Street as prime minister on 4 May 1979 and departed with a tear in her eye on 28 November 1990.

Everything in between: how she changed Britain, what actually changed, and especially what it means for us today, has been the subject of an intermittent war of words throughout the two decades since her resignation – and it is a war that has intensified in the days since her death.

It's only by trawling through the historical reference – from census data to coal board records, from the World Bank to the Institute for Fiscal Studies, and from more than 30 years of social research – that even the basic facts about the nation reshaped during the Thatcher era take form.

What they show of Britain's new landscape is telling – but, of course, what will always be a matter for argument is how much would have happened with any prime minister, and how much was down to the Lady.

For millions of Britain's better-off working class – the famed C2s targeted by political strategists and tabloid owners alike – the most direct impact of Thatcherism was on levels of home ownership: Thatcher's dream of a nation of owner-occupiers was perhaps one of her most fully realised.

Figures from the 1981 and 1991 UK censuses show the scale of this change. In 1981, two years into Thatcher's premiership, England and Wales had 10.2 million owner-occupiers. A mere decade later, their ranks had swelled to 13.4 million.

Credit: Guardian graphics

Thatcher certainly didn't invent the ideal of home ownership, but she did an astonishing amount to boost it – and far more than any government since. Twenty years later, the 2011 census, reporting on a Britain with a population six million higher than in Thatcher's time, recorded that the number of owner-occupiers had only ticked up to 14.9m households.

Many of the new Thatcher-era first-time buyers gained their ownership through the right to buy scheme, giving council tenants the right, for the first time, to buy their homes at a hefty discount – about which Thatcher had initial reservations, due to her instinctive thrift.

In England alone, more than 970,000 local authority-owned houses were sold through the scheme during Thatcher's premiership, more than have been sold in the two decades since.

Such changes clearly came with a cost, and one of the most direct costs was the gradual decrease in the amount of social housing – and the resultant long waits on housing lists today – from a country with a growing population and atomising households (the number of people per household in the UK is slowly but steadily falling, as more of us live alone).

In 1981, England and Wales had 5.4m households in social housing. By 1991, this had dropped by 900,000 to 4.5m. In the post-Thatcher years, this gradual drop-off has endured, with 4.1m households living in social housing at the last census.

That was only the most direct effect. In addition, many of the first people to buy their council homes through right to buy almost immediately started to struggle with their mortgages.

As a result of the Thatcher government's decision to target and control inflation – seen by many people then and now as a necessary move – interest rates (and therefore mortgage repayments) never fell below about 7.4% during Thatcher's premiership, and peaked at 17%.

This is a figure unimaginable to many of today's younger adults: interest rates have not been above 6% since the turn of the millennium.

For some families these pressures were very real: James and Maureen Patterson were among the first families to buy their council home, and were visited by Thatcher as they did so. In the following years, their marriage disintegrated, apparently in part due to financial pressure on making the mortgage repayments.

Thatcher's housing policies had one other long-term legacy, hailed by some and cursed by others: house prices rocketed during and after her tenure. According to figures from the Department for Communities and Local Government, the average selling price of a house in 1979 was £19,925. By 1990, this had tripled, to £59,785. Over the next two decades, it multiplied again, reaching £251,634 by 2010.

The economy has been subject to the whims of the housing market ever since Thatcher: the housing crash and negative equity of the early 1990s were hardly unrelated to the accompanying recession, while the consumer boom of the early 2000s was fuelled by housing debt – as was the subsequent, interminable, bust.

In this, the coalition government came in to power tacking, tacitly, away from Thatcher, with a vow to rebalance the economy away from such housing-fuelled booms, of which the housewife-frugality-espousing Thatcher may not have approved but nonetheless helped fuel.

But unlike the Lady, George Osborne proved for turning, and plans to revitalise the economy with his help-to-buy policy. The echoes of Thatcher are surely not accidental.

The argument over the wider impact of Thatcherism on Britain's economy makes disagreements over housing policy look trivial.

Looking only at the core measure of economic performance – GDP growth – Thatcher's performance was slightly better than that of her predecessor, James Callaghan, but slightly worse than under Tony Blair, with average growth over her tenure standing at around 2.3% a year.

This kind of generalisation hides every argument that matters, though. Thatcher made changes to the UK's tax system, some changes to welfare, and many to the nature of British jobs, both through privatisation and economic liberalisation – not least in her battle with the unions.

Perhaps the best look at what Thatcherism meant for British families comes from a series of measures calculated by the Institute for Fiscal Studies, which calculated household incomes after tax (and any income from benefits), and put them into monetary amounts relative to 2010-11 prices, stripping out the effects of inflation.

Credit: Guardian graphics

These figures show families got richer. The median household – the household right in the middle, where half are richer, half are poorer – earned the equivalent of £270.74 a week in 1979. By 1990, this had increased by 26% to £341.58.

But, as you would expect, these gains were nowhere near evenly distributed, and the poorest got the least. A family in the bottom 10% had a weekly income of £151.58 as Thatcher came into power. Eleven years later as she left Downing Street, the family had just £158.57 – a mere 4.6% more. Such stagnation for the poorest families was not inevitable: though inequality remained high in the post-Thatcher era, by 2011 that income had risen to £215.86.

The richest families – the top 10% – did far better, with their incomes increasing from the equivalent of £472.98 in 1979 to £694.83 in 1990. The good times for high-rollers continued post-Thatcher, with 2011 incomes of £845.54 a week.

The IFS figures are stark on the dispersion of British society in income terms through the Thatcher era, and this had a knock-on effect onpoverty as it is typically measured.

The common international standard for poverty is a relative one: a family earning less than 60% of the median income, meaning its members are excluded from many aspects of a nation's life. By this measure, though, a family in poverty in 1990 may be richer than one not in poverty in 1979.

It is perhaps illustrative to note that in 1981 3.7m households lacked (or had to share) either an inside toilet or bath. By 1991, only 259,000 did.

Still, the poverty figures don't look good: the number of children in poverty almost doubled under Thatcher, from 1.7 million in 1979 to 3.3 million in 1990. Pensioner poverty in the same period increased too, from 3.1 million to 4.1 million. Those numbers rise still further if housing costs are factored in.

The headline poverty figures have both since fallen back from those levels – particularly pensioner poverty. In today's Britain, 2 million pensioners live below the poverty line – half the 1990 figure – while child poverty has dropped more modesty to 2.3 million.

Incomes, of course, only tell a small part of the story when it comes to Thatcher and the workforce – not to mention the shape of the economy.

Thatcher is perhaps most associated with the death of Britain's mining industry. There is no doubt that the figures show the number of miners collapsed under Thatcher and afterwards: in 1980, the UK had 230,000 coal miners. By 1990, only 57,000 remained. By 2004, the figure was below 6,000.

But what may be missed is that even more mining jobs were lost before Thatcher ever came into power. Over the course of the 1960s and 70s, more than 300,000 coal mining jobs disappeared, while around a million vanished between 1920 and 1980.

Thatcher was the coal industry's most visible foe, but not the one who lost it the most jobs. The root of residual anger at Thatcher lies, perhaps, in that Thatcher was the first post-war prime minister to cut such jobs without finding or creating replacement roles

That isn't to say that manufacturing and mining communities didn't feel devastating change – from which some have not recovered to this day. By the World Bank's measures, industry (including manufacturing) fell from contributing 40% of the UK's GDP in 1979 to just 34% in 1990 – and has since fallen more dramatically still to just under 22%.

Such trends weren't confined to the UK, however: industry in the United States fell from 33% to 27% during the Thatcher era, and to about 20% today. Even Germany went in a similar direction – though to a lesser extent – from 42% in 1979 to 28% now.

The consequences of deindustrialisation hit huge swaths of the UK, particularly Wales and northern England, hard. Unemployment soared from 5.3% in 1979 – a level high enough for the Conservatives' "Labour isn't Working" poster to go down in the annals of great election adverts – to peak at 11.9% in 1984. In 1990, the year of Thatcher's departure, it stood slightly higher than when her era began, at 6.9%.

Credit: Guardian graphics

This, though, hides the plight of millions of Britons who would never work again – those who were listed as ill, rather than unemployed.

In 1981, 772,000 people classed themselves as being out of the labour force because they were "permanently sick". A decade later, this figure had risen to 1.6 million. In numerous towns across the country, the increases were markedly higher – with those signed off sick tripling or even quadrupling in a decade. Twenty years later, in the 2011 census, the figure remained largely unchanged, despite the UK's growing population: 1.7 million people were classed as long-term sick or disabled.

The issue around the welfare bill for supporting people with disabilities, chosen as a priority by the current coalition, owes its genesis far more to Thatcher than to either John Major or New Labour.

Elsewhere in the workforce, Thatcherism did what might be expected. It was certainly bad for union membership, which fell from 13.2 million in 1979 to 9.8 million in 1990 – and has since fallen further, to less than 7.4 million.

Overall, strikes were busted too, through the use of laws that unions still condemn today: in 1979, 6m working days were lost to strikes. This peaked at a massive 29.5m in 1983, but fell to less than 2m in the year Thatcher was ousted. By 2010, whether thanks to diminished union power or improved industrial relations, fewer than 400,000 working days were lost to industrial action.

The Thatcher period was modestly good for women in the workforce, with full-time female hourly wages rising from 72% of those of men to 76% (they have continued their slow rise and are presently at 82% of men's wages).

Thatcher also leaves an unclear legacy when it comes to public spending. When she entered office, public spending made up 44.6% of GDP. After initially rising, this was sharply cut to 39.1% of GDP by the time of her departure. Since then, that trend has been more than reversed: in 2012, public spending accounted for 46.2% of GDP.

Whether you like or loathe the results, it's hard to disagree that Thatcher won her economic battles. But economic liberalism was only part of Thatcher's brand of politics. At the core of her ideology was a social conservatism, accompanied by promotion of "traditional moral values".

Care should be taken before forcing Thatcher into the mould of the US Republican party's fringes on social issues: she voted in favour of decriminalising homosexuality and abortion. However, she was no friend to the gay rights movement, complaining to the 1987 Tory conference that "children who need to be taught to respect traditional moral values are being taught that they have an inalienable right to be gay".

Such attitudes, enshrined in law through section 28, seemed to chime with the public at the time. The British Social Attitudes survey showed the proportion of the UK population who believed same-sex relations were "always wrong" was 50% in 1983, rising – fuelled perhaps by the emergence of Aids – to 58% in 1990.

But since then, the culture wars have moved in exactly the opposite direction. Today, only 20% of the British public answer the question in such a way.

Attitudes to marriage and divorce hardly stayed conservative during Thatcher's tenure, either. The number of weddings fell from 369,000 in 1979 to 331,000 in 1990, while divorces rose from 119,000 a year to 153,000 over the same time. The proportion of the public objecting to premarital sex dropped too, from 28% in 1983, to 22% in 1990, to just 12% today.

It seems that Thatcher also never really had the public believing in the ideological shifts she was making in Britain. When pollsters asked Britons in 1989 whether they would prefer a "mostly socialist" or "mainly capitalist" society, they favoured the former by a margin of 47% to 39%.

A society "which emphasises the social and collective provision of welfare" was favoured over one "where the individual is encouraged to look after himself" by a wider margin still: 54% to 40%.

Thatcher may not have changed the majority of minds during her tenure: but in the long run, the changed Britain she helped build may have continued that work. When Ipsos MORI asked that same question on welfare in 2009, the welfare option lost out narrowly to individualism, by 47% to 49% (with the margin of error, too close to call).

The evidence suggests Thatcher's children, and those who came after, have grown up more individualistic and less supportive of state institutions than their forebears. On those issues, she may well have had the last laugh.

The legacy of Thatcher's social conservatism is modest: Britain is, by and large, a nation marrying less, more accepting of homosexuality, and more accepting of people of other races (if not of immigration). Her cultural legacy is greater. In 2013, almost no one argues about what John Major did or didn't do for the country – while the mere mention of Thatcher's name can induce either exhortations of adoration or paroxysms of utter disgust.

But it's the economic changes during Thatcher's premiership, continued in large part by her successors, that have really shaped Britain ever since.

The rise of the property market and liberalisation of the financial sector shaped the economic booms of the late 1990s and most of the 2000s, and lay at the heart of the bust which followed. The unions remain weaker, and the utilities remain privatised.

Today's levels of economic inequality are roughly the same as those when Thatcher departed. The number of people classed as long-term sick, and relying consequently on the state's support, remains the same.

Whether defined against her or not, the challenges faced by the coalition government – and the circumstances that brought them to be – almost all had their roots in the government of Thatcher. And that legacy affects millions of people every day.