Saved by the cell

Two recent cases show the progress being made by stem-cell researchers – but their work is still und

In early October, someone - we don't know who - in or around Atlanta, Georgia, became paralysed. This is not exceptional - spinal injuries paralyse 12,000 Americans each year. The victim, however, is exceptional: for this is the first person to receive a treatment that might restore his or her damaged cells. Imagine, then, how that patient feels to know that a nearby judge is considering forcing the American government to stop funding further research into this treatment because it uses embryonic stem cells (ESCs).

There has been so much fuss about ESCs that it is startling to realise that this patient in Atlanta was the first person to get them. But he was not alone for long. On 16 November, doctors in Glasgow announced that they had injected a slightly different kind of stem cell into the brain of a man disabled by a stroke.

The trials will continue. The next few years are their make-or-break time. The bottom line is that stem cells are not yet a panacea. Many scientists are convinced that they could be used to treat injured spines and brains - as well as diabetes, Parkinson's, Alzheimer's, MS and other conditions. Yet research is under renewed threat after Republican victories in the US midterm elections reinforced opposition to it.

We all start as a clump of identical cells. Their descendants then differentiate into our 200-odd specialised components - nerve cells, blood cells and the rest. But if you lose nerve cells, nearby blood cells do not revert to their embryonic state and re-differentiate into the nerve cells that you need. Very early embryonic cells, however, can become anything. ESCs come from surplus embryos created during in vitro fertilisations - abortions, as far as the US religious right is concerned. They are coaxed to become differentiated cells that can, in theory, be given to those in need: insulin-producing cells for diabetes patients, for example.

Geron Corporation of San Francisco has turned ESCs into a kind of cell that insulates nerves. In most paralysing spinal injuries, says Anna Krassowska of Geron, it is those cells that are damaged. If Geron's cells are injected into rats soon after such an injury, they restore some normal movement. But the trial in Atlanta must first ensure that they are safe in humans: ESCs can become confused and proliferate into an unhelpful mass. So the team is waiting, Krassowska says, to see if the cells behave, before starting on a second patient.

Federal funds

Geron's cells were taken from an embryo created before 2001. On 9 August that year, President George W Bush decreed that federal funding could be used only for work with the 21 lines of ESCs already established. Hundreds of new lines, with useful genetic differences, have since been established - but US scientists could not use federal money to study them.

Funding does exist elsewhere: Glasgow is a case in point, while the London Project to Cure Blindness hopes to treat age-related degeneration of the retina with ESCs by 2012. But the political uncertainties have stifled private investment in stem cells, analysts say, while the sheer scale of US science funding meant that the ruling was a blow. "Federal funding just for work with those 21 permitted cell lines between 2001 and 2009 was still more than the rest [of the funding] put together," Chris Mason of University College London tells me.

In 2009, President Obama lifted the restrictions. But in August this year, a US district court halted ESC research under a budget law banning the use of federal funds to destroy human embryos. If the decision is upheld, government-funded ESC work, even on previously permitted lines, must stop. Plaintiffs in the case charge that ESCs take funding away from research on non-embryonic stem cells, an argument that anti-abortion groups have seized on.

Non-embryonic cells are already used therapeutically. Doctors can culture a patient's own skin or cartilage cells to create grafts or rebuild windpipes. But these are differentiated and are not stem cells. Bone-marrow cells that normally generate blood cells are stem cells, however, and have been transplanted routinely for years. Similar, relatively undifferentiated "adult stem cells" are thought to lurk in most organs, capable of becoming that particular tissue. Such cells in the eye are used to regenerate corneas after chemical burns. In humans, these cells do only so much and there are lots of tissues we can't regenerate. The long-term hope is to induce them to do more - maybe even regenerate lost limbs. This is fine with those who oppose ESCs, but it's also far in the future.

More immediately, cells in the developing human foetus, at a later stage than embryos, are already committed to a certain range of types - skin and nerves, say - but are still flexible. These sorts of cells, from a line derived by ReNeuron, based in Guildford, were injected into the stroke victim's brain in Glasgow. However, their foetal source means they attract the same opposition as ESCs.

Mouse key

Induced pluripotent stem cells (IPSCs) are another story. These are differentiated cells that have been turned back into something like embryonic cells by reversing four kinds of chemical change in their DNA. It is IPSC research that plaintiffs in the US legal battle claim is unfairly deprived of funding by work on ESCs. Many hope that IPSCs will make ideological opposition to other stem cells moot. "It is understandable that individuals should feel uneasy about the use of foetal cells," says Darren Griffin, professor of genetics at the University of Kent. But IPSCs "have the potential to get around many of these ethical concerns".

The key word is potential: IPSCs are far from ready. Differentiation flips thousands of chemical switches in a cell's DNA. Flipping just one the wrong way can make a normal cell into a cancerous one - and we don't know where all the switches are in any given IPSC, Mason says. "In ESCs, we know where they are." There's also something not quite right about current IPSCs. You can breed a normal-looking mouse from them - but it doesn't live long. Does this make them unsafe for repairing a broken spine? We don't know yet. But for ESCs, we soon will.

The supposed choice between funding foetal or embryonic stem cells and adult ones seems more ideological than scientific. "We need to work on all avenues," Mason says. Future IPSCs or adult stem cells - or even remodelled differentiated cells - may one day work better for certain things than ESCs or foetal cells, especially if they are a patient's own. "But research on ESCs is ten years farther along," Mason says. "We'll lose what we've already learned if we stop working with them."

For now, ECSs and foetal cells present the best hope of success soon. And a few successes, researchers hope, could change everything. If the kind of cells now settling into a spine in Atlanta and a brain in Glasgow can make the lame walk and the blind see, ideological objections might melt away as they did for in vitro fertilisation. How soon that happens depends partly on what happens in a US courtroom.

Debora MacKenzie writes for the New Scientist

The American right to life

When the scientist James Thomson and his team first succeeded in isolating human embryonic stem cells at the University of Wisconsin-Madison in 1998, they inadvertently triggered a debate that has dominated political discourse in the US. In the index of George W Bush's memoir, the stem-cell controversy receives more mentions than Osama Bin Laden.

Arguments over stem-cell research have emerged as a virulent offshoot of the abortion debate, with pro-life campaigners seizing on stem-cell research as another assault on the sanctity of life. Bush's decision in 2001 to limit such research was challenged repeatedly by Congress, which tried to pass bills opening up research in 2005 and 2007, when the house was under Republican and Democrat control respectively. Despite Barack Obama's reversal of the restrictions, the issue has not been put to bed.

The recent success of the Republican Party in the midterm elections has been powered in part by the pro-life Tea Party movement. It is unlikely that the current Republican-controlled Congress will support the liberalisation of research.

Advocates of stem-cell research have high-profile backers such as the actor Michael J Fox, who has Parkinson's. But they will need to speak loudly to be heard over the resurgent right.

Duncan Robinson

This article first appeared in the 29 November 2010 issue of the New Statesman, Congo

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The secret anti-capitalist history of McDonald’s

As a new film focuses on the real founder of McDonald’s, his grandson reveals the unlikely story behind his family’s long-lost restaurant.

One afternoon in about the year 1988, an 11-year-old boy was eating at McDonald’s with his family in the city of Manchester, New Hampshire. During the meal, he noticed a plaque on the wall bearing a man’s face and declaring him the founder of McDonald’s. These plaques were prevalent in McDonald’s restaurants across the US at the time. The face – gleaming with pride – belonged to Ray Kroc, a businessman and former travelling salesman long hailed as the creator of the fast food franchise.

Flickr/Phillip Pessar

But this wasn’t the man the young boy munching on fries expected to see. That man was in the restaurant alongside him. “I looked at my grandfather and said, ‘But I thought you were the founder?’” he recalls. “And that’s when, in the late Eighties, early Nineties, my grandfather went back on the [McDonald’s] Corporation to set the history straight.”

Jason McDonald French, now a 40-year-old registered nurse with four children, is the grandson of Dick McDonald – the real founder of McDonald’s. When he turned to his grandfather as a confused child all those years ago, he spurred him on to correct decades of misinformation about the mysterious McDonald’s history. A story now being brought to mainstream attention by a new film, The Founder.


Jason McDonald French

“They [McDonald’s Corporation] seemed to forget where the name actually did come from,” says McDonald French, speaking on the phone from his home just outside Springfield, Massachusetts.

His grandfather Dick was one half of the McDonald brothers, an entrepreneurial duo of restaurateurs who started out with a standard drive-in hotdog stand in California, 1937.

Dick's father, an Irish immigrant, worked in a shoe factory in New Hampshire. He and his brother made their success from scratch. They founded a unique burger restaurant in San Bernardino, around 50 miles east of where they had been flogging hotdogs. It would become the first McDonald’s restaurant.

Most takeout restaurants back then were drive-ins, where you would park, order food from your car, and wait for a “carhop” server to bring you your meal on a plate, with cutlery. The McDonald brothers noticed that this was a slow, disorganised process with pointless costly overheads.

So they invented fast food.

***

In 1948, they built what came to be known as the “speedy system” for a fast food kitchen from scratch. Dick was the inventor out of the two brothers - as well as the bespoke kitchen design, he came up with both the iconic giant yellow “M” and its nickname, the “Golden Arches”.

“My grandfather was an innovator, a man ahead of his time,” McDonald French tells me. “For someone who was [only] high school-educated to come up with the ideas and have the foresight to see where the food service business was going, is pretty remarkable.”


The McDonald brothers with a milkshake machine.

McDonald French is still amazed at his grandfather’s contraptions. “He was inventing machines to do this automated system, just off-the-cuff,” he recalls. “They were using heat lamps to keep food warm beforehand, before anyone had ever thought of such a thing. They customised their grills to whip the grease away to cook the burgers more efficiently. It was six-feet-long, which was just unheard of.”

Dick even custom-made ketchup and mustard dispensers – like metal fireplace bellows – to speed up the process of garnishing each burger. The brothers’ system, which also cut out waiting staff and the cost of buying and washing crockery and cutlery, brought customers hamburgers from grill to counter in 30 seconds.


The McDonald brothers as depicted in The Founder. Photo: The Founder

McDonald French recounts a story of the McDonald brothers working late into the night, drafting and redrafting a blueprint for the perfect speedy kitchen in chalk on their tennis court for hours. By 3am, when they finally had it all mapped out, they went to bed – deciding to put it all to paper the next day. The dry, desert climate of San Bernardino meant it hadn’t rained in months.

 “And, of course, it rained that night in San Bernardino – washed it all away. And they had to redo it all over again,” chuckles McDonald French.

In another hiccup when starting out, a swarm of flies attracted by the light descended on an evening event they put on to drum up interest in their restaurant, driving customers away.


An original McDonald's restaurant, as depicted in The Founder. Photo: The Founder

***

These turned out to be the least of their setbacks. As depicted in painful detail in John Lee Hancock’s film, Ray Kroc – then a milkshake machine salesman – took interest in their restaurant after they purchased six of his “multi-mixers”. It was then that the three men drew up a fateful contract. This signed Kroc as the franchising agent for McDonald’s, who was tasked with rolling out other McDonald’s restaurants (the McDonalds already had a handful of restaurants in their franchise). 

Kroc soon became frustrated at having little influence. He was bound by the McDonalds’ inflexibility and stubborn standards (they wouldn’t allow him to cut costs by purchasing powdered milkshake, for example). The film also suggests he was fed up with the lack of money he was making from the deal. In the end, he wriggled his way around the contract by setting up the property company “McDonald’s Corporation” and buying up the land on which the franchises were built.


Ray Kroc, as depicted in The Founder. Photo: The Founder

Kroc ended up buying McDonald’s in 1961, for $2.7m. He gave the brothers $1m each and agreeing to an annual royalty of half a per cent, which the McDonald family says they never received.

“My father told us about the handshake deal [for a stake in the company] and how Kroc had gone back on his word. That was very upsetting to my grandfather, and he never publicly spoke about it,” McDonald French says. “It’s probably billions of dollars. But if my grandfather was never upset about it enough to go after the Corporation, why would we?”

They lost the rights to their own name, and had to rebrand their original restaurant “The Big M”. It was soon put out of business by a McDonald’s that sprang up close by.


An original McDonald restaurant in Arizona. Photo: Flickr/George

Soon after that meal when the 11-year-old Jason saw Kroc smiling down from the plaque for the first time, he learned the true story of what had happened to his grandfather. “It’s upsetting to hear that your family member was kind of duped,” he says. “But my grandfather always had a great respect for the McDonald’s Corporation as a whole. He never badmouthed the Corporation publicly, because he just wasn’t that type of man.”

Today, McDonalds' corporate website acknowledges the McDonalds brothers as the founders of the original restaurant, and credits Kroc with expanding the franchise. The McDonald’s Corporation was not involved with the making of The Founder, which outlines this story. I have contacted it for a response to this story, but it does not wish to comment.

***

Dick McDonald’s principles jar with the modern connotations of McDonald’s – now a garish symbol of global capitalism. The film shows Dick’s attention to the quality of the food, and commitment to ethics. In one scene, he refuses a lucrative deal to advertise Coca Cola in stores. “It’s a concept that goes beyond our core beliefs,” he rants. “It’s distasteful . . . crass commercialism.”

Kroc, enraged, curses going into business with “a beatnik”.


Photo: The Founder

Dick’s grandson agrees that McDonald’s has strayed from his family’s values. He talks of his grandfather’s generosity and desire to share his wealth – the McDonald brothers gave their restaurant to its employees, and when Dick returned to New Hampshire after the sale, he used some of the money to buy new Cadillacs with air conditioning for his old friends back home.

“[McDonald’s] is definitely a symbol of capitalism, and it definitely sometimes has a negative connotation in society,” McDonald French says. “If it was still under what my grandfather had started, I imagine it would be more like In'N'Out Burger [a fast food chain in the US known for its ethical standards] is now, where they pay their employees very well, where they stick to the simple menu and the quality.”

He adds: “I don’t think it would’ve ever blossomed into this, doing salads and everything else. It would’ve stayed simple, had quality products that were great all the time.

“I believe that he [my grandfather] wasn’t too unhappy that he wasn’t involved with it anymore.”


The McDonald’s Museum, Ray Kroc’s first franchised restaurant in the chain. Photo: Wikimedia Commons

Despite his history, Dick still took his children and grandchildren to eat at McDonald’s together – “all the time” – as does Jason McDonald French with his own children now. He’s a cheeseburger enthusiast, while his seven-year-old youngest child loves the chicken nuggets. But there was always a supersize elephant in the room.

“My grandfather never really spoke of Ray Kroc,” he says. “That was always kind of a touchy subject. It wasn’t until years later that my father told us about how Kroc was not a very nice man. And it was the only one time I ever remember my grandfather talking about Kroc, when he said: ‘Boy, that guy really got me.’”

The Founder is in UK cinemas from today.

Anoosh Chakelian is senior writer at the New Statesman.