Hospital(ity)

What happens when angels of mercy go walkabout, leaving patients bereft? Why, the boss of the Royal College of Nursing weighs straight in. If his angels are too busy, Dr Peter Carter wants patients' families on the ward and on the job as well, looking after lonely grannies in distress. "Somehow we have sleepwalked, in some parts of society, into assuming this is someone else's responsibility." Cue predictable outrage over this NHS betrayal, plus even more predictable warnings about lowered standards. It's a hospital's job to care and tend, we're told. It's what nurses are for. And the last thing we want is upmarket union leaders passing the buck. But pause: let's take a short trip.

Three times in the last 12 years I've seen what happens in Spanish hospitals when my grandchildren are born. What's that at the side near my daughter's bed? It's a bunk. Her husband isn't merely there for the birth; he's on the spot night and day, bringing this, fetching that, always on hand while she recovers. That's normal, totally expected. Active paternity service, not paternity leave. And now my Spanish grandson has broken his arm rather badly in two places. He's in pain. And, in quite another hospital, the bunk is there again. His mother spends two nights with him, comforting, reassuring, nipping out to buy food, a stabilising presence in an unsettling world.

Which means I too remember how, a few years back, I was in trouble myself, bleeding internally and causing manifest alarm. A Spanish ambulance shrieks through the night. Another hospital to the collection. I'm dosed and monitored non-stop behind curtains in A&E. And there's an airline-type seat beside the bed there. My wife can try to sleep close by. The next morning I'm wheeled upstairs to a small ward – and of course there's another recliner seat close by. The guy to my left, just recovering from open heart surgery, has visitors almost 24/7. They're a bit noisy; they come and go constantly – but hey, join the party. What's the point lying around feeling sorry for yourself? The gang's all here.

And the deeper point, revealed time and again, has absolutely nothing to do with cost-saving – or with graduate angels too proud to plump a pillow. The Spanish experience is instinctive and positive. It doesn't make family involvement a passed parcel of sneaky budget savings. It says, simply, that this is what family life is all about. Hospitals aren't carved up between them and us. Hospitals are more joint community centres in a society used to doing the right thing.

Long ago, as a child, I was in a faraway Nottinghamshire hospital for well over a year: visiting hours, on Saturday and Sunday, 2.30pm to 5pm. My mother, a widow without any hope of a car, had to travel 20 miles via three separate bus journeys to see me. Get there for two-thirty. Get out at five. That's your lot. In retrospect it seems cruel and pointless – but still somehow natural. The mystique of medicine says life is a waiting room. Doctor knows best. Nurses have duties: please keep out of their way.

Of course you can produce due justifications as required. But in fact there's a more fundamental chasm opened here. We pay for and bang on about the NHS because it has almost god-like status. Leave your flowers on the altar and go. Family care ends at the hospital door. Busy professionals are taking over now. Thank you, and good night.

That's a generalisation, of course: it can't wrap millions of cases in a single bundle of blame. But how does any society go truly big on compassion or cohesion when families are deemed a nuisance, a fact without a function? And what does it say about families when they not only accept that divide – but bristle at the thought of bridging it?

SanFran is not The Big Apple

Steve Jobs in his Los Angeles office in 1981, five years after he co-founded Apple.
Photograph: Tony Korody/Corbis

Steve Jobs's resignation was the most discussed in corporate history. Because his illness has been public knowledge for so long, and because Wall Street and the commentariat viewed his health as being synonymous with that of his company, for years Apple share prices have fluctuated with its CEO's temperature. If all the "Whither Apple without Jobs?" articles were laid end to end, they would cover quite a distance – but they never reached a conclusion.

Still, you could understand the hysteria. After all, he's the man who rescued Apple from the near-death experience it underwent in the mid-1990s. When he came back in 1996, the company seemed headed for oblivion. Granted, it was a distinctive, quirky outfit, but one that had been run into the ground by mediocre executives who had no vision, no strategy – and no operating system to power its products into the future.

Jobs came back because Apple bought NeXT, the computer workstation company he had started after being ousted by the Apple board in 1985. By acquiring NeXT, Apple got two things: the operating system that became OS X, the software that underpinned everything Apple has made since; and Jobs as "interim CEO" at a salary of $1 a year. But it was still a corporate minnow: a BMW to Microsoft's Ford. Fifteen years later, Apple had become the most valuable company in the world.

It was the greatest comeback since Lazarus. Because only an obsessive, authoritarian, visionary genius could have achieved such a transformation, it's easy to see why Wall Street has had difficulty imagining Apple without Jobs. He was, after all, the only CEO in the world with rock star status. And Apple is a corporate extension of his remarkable personality, much as Microsoft was of Bill Gates's. But Jobs has something Gates never had – a reputation so powerful as to create a reality distortion field around him.

This field has blinded people to some under-appreciated facts. While it is true, for example, that Apple – under Jobs's influence – is probably the world's best industrial design outfit, it is also a phenomenally well-run company. Proof of that comes from various sources. For example, not only does it regularly dream up beautiful, functional and fantastically complex products, but it gets them to market in working order, on time and to budget; and it has continually done so despite exploding demand. Compare that with slow-motion car crashes such as Hewlett Packard's Touchpad, RIM's BlackBerry Playbook or Microsoft's Vista operating system.

Then there's the way that Apple – in the teeth of industry scepticism – made such an astonishing success of bricks-and-mortar retailing with its high-street stores. Or ponder the fact that it became the world's most valuable corporation without incurring a single cent of debt. Instead, it sits atop a $78bn (£48bn) cash mountain: enough to buy Tesco and BT and still have loose change. Compare that with the casino capitalism practised by so many MBA-educated company leaders in the US. And finally there is the stranglehold Apple now has on a number of crucial modern markets – computers, online music, mobile devices and smartphones.

If you ask people what Steve Jobs is best remembered for, most will name a particular product. If they're from my (baby boomer) generation, it will probably be the Apple Macintosh, a computer that changed many of our lives in the 1980s. Younger generations will credit him with the iMac, iTunes and the iPod. Today's teenagers will revere him for the iPhone. But there's a good argument that Jobs's greatest creation is Apple itself in its post-1996 incarnation. If that's true, the great test of his career legacy is whether the organisation he built around his values will endure and remain faithful to them.

What are those values? He usually expressed them as aphorisms and, as news of his resignation spread , people began raking through them for clues. Many focused on what he said to John Sculley, CEO of Pepsi, when he was trying to persuade him to run Apple.

"Do you want to spend the rest of your life selling sugar water," he asked, "or do you want to change the world?" (Sculley accepted the invitation, then presided over Jobs's expulsion.) But for Jobs it was a serious question. What he was asking, as the blogger Umair Haque put it, was: "Do you really want to spend your days slaving over work that fails to inspire, on stuff that fails to count, for reasons that fail to touch the soul of anyone?"

Jobs is famously fanatical about design. In part this is about how things look (though for him it also involves simplicity of use). When the rest of the industry was building computers as grey, rectangular metal boxes, for example, he was prowling department stores and streets looking for design metaphors. For a time he thought the Mac should be like a Porsche. At another stage he wanted it to be like the Cuisinart food-processor. When the machine finally appeared in 1984, Jack Tramiel, the grizzled macho-boss of Commodore, thought it looked like a girly device that would be best sold in boutiques. What Tramiel did not realise – and Jobs did – was that ultimately computers would be consumer products and people would pay a huge premium for classy design.

In that sense he is the polar opposite of the MBA-trained, bean-counting executive. "The cure for Apple is not cost-cutting," he said in 1996, when the company was on the rocks. "The cure for Apple is to innovate its way out of its current predicament." At another point he said: "When you're a carpenter making a beautiful chest of drawers, you're not going to use a piece of plywood on the back, even though it faces the wall and nobody will ever see it."

This delight in elegant work has always been the most striking aspect of Jobs's celebrated speeches introducing new Apple products in San Francisco. As he cooed over the iMac or the iPhone or the iPad, words like "beautiful", "amazing" and "awesome" tumbled out. For once they didn't sound like cynical, manipulative corporation-speak. He spoke from the heart.

It goes without saying that he is impossible to work with; most geniuses are. Yet he has built – and retained the respect of – the most remarkable design team in living memory, a group that has been responsible for more innovation than the rest of the computer industry put together. For that reason, when the time comes to sum up Jobs's achievements, most will portray him as a seminal figure in the computing industry. But Jobs is bigger than that.

To understand why, you have to look at the major communications industries of the 20th century – the telephone, radio and movies. As Tim Wu chronicles it in his remarkable book, The Master Switch, each of these industries started out as an open, irrationally exuberant, chaotic muddle of incompatible standards, crummy technology and chancers. The pivotal moment in the evolution of each industry came when a charismatic entrepreneur arrived to offer consumers better quality, higher production values and greater ease of use.

With the telephone it was Theodore Vail of AT&T, offering a unified nationwide network and a guarantee that when you picked up the phone you always got a dial tone. With radio it was David Sarnoff, who founded RCA. With movies it was Adolph Zukor, who created the Hollywood studio system.

Jobs is from the same mould. He believes that using a computer should be delightful, not painful; that it should be easy to seamlessly transfer music from a CD on to a hard drive and thence to an elegant portable player; that mobile phones should be powerful handheld computers that happen to make voice calls; and that a tablet computer is the device that is ushering us into a post-PC world. He has offered consumers a better proposition than the rest of the industry could – and they jumped at it. That's how he built Apple into the world's most valuable company. And it's why he is really the last of the media moguls.

by John Naughton

Children Glued to Screens

Parents should be aware of the rise of "multiple screen" viewing among children on devices including televisions, smartphones and portable games consoles, when monitoring whether they are being active enough, researchers say.

A sedentary lifestyle – linked to spending lots of time watching TV and playing computer games – is thought to increase the risk of obesity and mental health problems, researchers at Bristol and Loughborough universities said in a study published on Wednesday.

They questioned 63 10- and 11-year-olds and found that children enjoyed looking at more than one screen at a time.

Russ Jago, of Bristol University's centre for exercise, nutrition and health sciences, said: "Health campaigns recommend reducing the amount of time children spend watching TV.

"However, the children in this study often had access to at least five different devices at any one time, and many of these devices were portable."

In the study the children would move the equipment between their bedrooms and family rooms, depending on whether they wanted privacy or company, said Jago. "This suggests that we need to work with families to develop strategies to limit the overall time spent multiscreen viewing wherever it occurs within the home."

The children would use a second device to fill in breaks during their entertainment, often talking or texting their friends during adverts or while waiting for computer games to load. The television was also used to provide background entertainment while they were doing something else – especially if the programme chosen by their family was considered "boring".

One respondent said: "I'm on my DSi [handheld games console] and my laptop. On my DSi I'm on MSN and on my laptop I'm on Facebook and then the TV is on."

There has needs to be more research into multi-screen viewing.

Jago said: "There is a shortage of information about the nature of contemporary screen viewing amongst children, especially given the rapid advances in screen viewing equipment technology and their widespread availability.

"For example, TV programmes are watched on computers, games consoles can be used to surf the internet, smartphones, tablet computers and hand-held games play music, video games provide internet access, and laptop computers can do all of the above."

The research paper, entitled I'm on it 24/7 at the moment: A qualitative examination of multiscreen viewing behaviours among UK 10-11 year olds is published in the International Journal of Behavioural Nutrition and Physical Activity.

No Jobs at Apple

Saving Strangers

Going to Extreme

By PAUL KRUGMAN

I admit it: I had fun watching right-wingers go wild as health reform finally became law. But a few days later, it doesn’t seem quite as entertaining — and not just because of the wave of vandalism and threats aimed at Democratic lawmakers. For if you care about America’s future, you can’t be happy as extremists take full control of one of our two great political parties.

To be sure, it was enjoyable watching Representative Devin Nunes, a Republican of California, warn that by passing health reform, Democrats “will finally lay the cornerstone of their socialist utopia on the backs of the American people.” Gosh, that sounds uncomfortable. And it’s been a hoot watching Mitt Romney squirm as he tries to distance himself from a plan that, as he knows full well, is nearly identical to the reform he himself pushed through as governor of Massachusetts. His best shot was declaring that enacting reform was an “unconscionable abuse of power,” a “historic usurpation of the legislative process” — presumably because the legislative process isn’t supposed to include things like “votes” in which the majority prevails.

A side observation: one Republican talking point has been that Democrats had no right to pass a bill facing overwhelming public disapproval. As it happens, the Constitution says nothing about opinion polls trumping the right and duty of elected officials to make decisions based on what they perceive as the merits. But in any case, the message from the polls is much more ambiguous than opponents of reform claim: While many Americans disapprove of Obamacare, a significant number do so because they feel that it doesn’t go far enough. And a Gallup poll taken after health reform’s enactment showed the public, by a modest but significant margin, seeming pleased that it passed.

But back to the main theme. What has been really striking has been the eliminationist rhetoric of the G.O.P., coming not from some radical fringe but from the party’s leaders. John Boehner, the House minority leader, declared that the passage of health reform was “Armageddon.” The Republican National Committee put out a fund-raising appeal that included a picture of Nancy Pelosi, the speaker of the House, surrounded by flames, while the committee’s chairman declared that it was time to put Ms. Pelosi on “the firing line.” And Sarah Palin put out a map literally putting Democratic lawmakers in the cross hairs of a rifle sight.

All of this goes far beyond politics as usual. Democrats had a lot of harsh things to say about former President George W. Bush — but you’ll search in vain for anything comparably menacing, anything that even hinted at an appeal to violence, from members of Congress, let alone senior party officials.

No, to find anything like what we’re seeing now you have to go back to the last time a Democrat was president. Like President Obama, Bill Clinton faced a G.O.P. that denied his legitimacy — Dick Armey, the second-ranking House Republican (and now a Tea Party leader) referred to him as “your president.” Threats were common: President Clinton, declared Senator Jesse Helms of North Carolina, “better watch out if he comes down here. He’d better have a bodyguard.” (Helms later expressed regrets over the remark — but only after a media firestorm.) And once they controlled Congress, Republicans tried to govern as if they held the White House, too, eventually shutting down the federal government in an attempt to bully Mr. Clinton into submission.

Mr. Obama seems to have sincerely believed that he would face a different reception. And he made a real try at bipartisanship, nearly losing his chance at health reform by frittering away months in a vain attempt to get a few Republicans on board. At this point, however, it’s clear that any Democratic president will face total opposition from a Republican Party that is completely dominated by right-wing extremists.

For today’s G.O.P. is, fully and finally, the party of Ronald Reagan — not Reagan the pragmatic politician, who could and did strike deals with Democrats, but Reagan the antigovernment fanatic, who warned that Medicare would destroy American freedom. It’s a party that sees modest efforts to improve Americans’ economic and health security not merely as unwise, but as monstrous. It’s a party in which paranoid fantasies about the other side — Obama is a socialist, Democrats have totalitarian ambitions — are mainstream. And, as a result, it’s a party that fundamentally doesn’t accept anyone else’s right to govern.

In the short run, Republican extremism may be good for Democrats, to the extent that it prompts a voter backlash. But in the long run, it’s a very bad thing for America. We need to have two reasonable, rational parties in this country. And right now we don’t.

Smile! You´Ve Got Cancer

If you had asked me, just before the diagnosis of cancer, whether I was an optimist or a pessimist, I would have been hard-pressed to answer. But on health-related matters, as it turned out, I was optimistic to the point of delusion. Nothing had so far come along that could not be controlled by diet, stretching, painkillers or, at worst, a prescription. So I was not at all alarmed when a routine mammogram aroused some "concern" on the part of my gynaecologist.

How could I have breast cancer? I had no known risk factors, there was no breast cancer in the family, I'd had my babies relatively young and nursed them both. I ate right, drank sparingly and worked out. When the gynaecologist suggested a follow-up mammogram four months later, I agreed only to placate her.

The result of the mammogram, conveyed to me by phone a day later, was that I would need a biopsy, and, for some reason, a messy, surgical one with total anaesthesia. Still, I was not overly perturbed and faced the biopsy like a falsely accused witch confronting a trial by dunking: at least I would clear my name. I called my children to inform them of the upcoming surgery and assured them that the great majority of lumps detected by mammogram – 80%, the radiology technician had told me – are benign.

My official induction into breast cancer came 10 days later with the biopsy, from which I awoke to find the surgeon standing perpendicular to me, at the far end of the bed, down near my feet, stating gravely, "Unfortunately, there is a cancer." It took me the rest of that drug-addled day to decide that the most heinous thing about that sentence was not the presence of cancer but the absence of me – for I, Barbara, did not enter into it even as a cation, a geographical reference point. I had been replaced by it, was the surgeon's implication.

I know women who followed up their diagnoses with weeks or months of self-study, mastering their options, interviewing doctor after doctor, assessing the damage to be expected from the available treatments. But I could tell from a few hours of investigation that the career of a breast cancer patient had been pretty well mapped out in advance: you may get to negotiate the choice between lumpectomy and mastectomy, but lumpectomy is commonly followed by weeks of radiation, and in either case if the lymph nodes turn out, upon dissection, to be invaded – or "involved," as it's less threateningly put – you're doomed to months of chemotherapy, an intervention that is on a par with using a sledge hammer to swat mosquitoes.

The pressure was on, from doctors and loved ones, to do something right away – kill it, get it out now. The endless exams, the bone scan to check for metastases, the hi-tech heart test to see if I was strong enough to withstand chemotherapy – all these blurred the line between selfhood and thing-hood anyway, organic and inorganic, me and it. As my cancer career unfolded, I would, the helpful pamphlets explained, become a composite of the living and the dead – an implant to replace the breast, a wig to replace the hair. And then what will I mean when I use the word "I"? I fell into a state of unreasoning passive aggressivity: they found it, let them fix it.

Fortunately, no one has to go through this alone. Forty years ago, before Betty Ford, Rose Kushner, Betty Rollin and other pioneer patients spoke out, breast cancer was a dread secret, endured in silence and euphemised in obituaries as a "long illness". Today, however, it's the biggest disease on the cultural map, bigger than Aids, cystic fibrosis or spinal injury, bigger even than those more prolific killers of women – heart disease, lung cancer, and stroke. There are hundreds of websites devoted to it, not to mention newsletters, support groups and a whole genre of first-person breast cancer books.

The first thing I discovered as I waded out into the relevant sites is that not everyone views the disease with horror and dread. Instead, the appropriate attitude is upbeat and even eagerly acquisitive. There is, I found, a significant market for all things breast cancer-related. You can dress in pink-beribboned sweatshirts, denim shirts, pyjamas, lingerie, aprons, shoelaces and socks; accessorise with pink rhinestone brooches, scarves, caps, earrings and bracelets; and brighten up your home with breast cancer candles, coffee mugs, wind chimes and night-lights. "Awareness" beats secrecy and stigma, of course, but I couldn't help noticing that the existential space in which a friend had earnestly advised me to "confront [my] mortality" bore a striking resemblance to a shopping centre.

This is not entirely a case of cynical merchants exploiting the sick. Some of the breast cancer accessories are made by breast cancer survivors themselves, and in most cases a portion of the sales goes to breast cancer research. It is also clear that the ultrafeminine theme of the breast cancer marketplace – the prominence, for example, of cosmetics and jewellery – could be understood as a response to the treatments' disastrous effects on one's looks. There is no doubt, though, that all the prettiness and pinkness is meant to inspire a positive outlook.

I needed whatever help I could get, and found myself searching obsessively for practical tips on hair loss, how to select a chemotherapy regimen, what to wear after surgery and eat when the scent of food sucks. There was, I soon discovered, far more than I could usefully absorb, for thousands of the afflicted have posted their stories, beginning with the lump or bad mammogram, proceeding through the agony of the treatments, pausing to mention the sustaining forces of family, humour and religion, and ending, in almost all cases, with an upbeat message for the terrified neophyte.

I couldn't seem to get enough of these tales, reading on with panicky fascination about everything that can go wrong – septicemia, ruptured implants, startling recurrences a few years after the completion of treatments, "mets" (metastases) to vital organs, and – what scared me most in the short term – "chemobrain" or the cognitive deterioration that sometimes accompanies chemotherapy. I compared myself with everyone, selfishly impatient with those whose conditions were less menacing, shivering over those who had reached Stage IV (there is no Stage V), constantly assessing my chances.

But, despite all the helpful information, the more fellow victims I discovered and read, the greater my sense of isolation grew. No one among the bloggers and book writers seemed to share my sense of outrage over the disease and the available treatments. What causes it and why is it so common, especially in industrialised societies? Why don't we have treatments that distinguish between different forms of breast cancer or between cancer cells and normal dividing cells? In the mainstream of breast cancer culture, there is very little anger, no mention of possible environmental causes, and few comments about the fact that, in all but the more advanced, metastasised cases, it is the "treatments", not the disease, that cause the immediate illness and pain. In fact, the overall tone is almost universally upbeat. The Breast Friends website, for example, features a series of inspirational quotes: "Don't cry over anything that can't cry over you"; "When life hands out lemons, squeeze out a smile"; "Don't wait for your ship to come in… swim out to meet it," and much more of that ilk.

As in the Aids movement, upon which breast cancer activism is partly modelled, the words "patient" and "victim," with their aura of self-pity and passivity, have been ruled un-PC. Instead, we get verbs: those who are in the midst of their treatments are described as "battling" or "fighting", sometimes intensified with "bravely" or "fiercely" – language suggestive of Katharine Hepburn with her face to the wind. Once the treatments are over, one achieves the status of "survivor", which is how the women in my local support group identified themselves, AA-style. For those who cease to be survivors, again, no noun applies. They are said to have "lost their battle" – our lost brave sisters, our fallen soldiers.

The cheerfulness of breast cancer culture goes beyond mere absence of anger to what looks, all too often, like a positive embrace of the disease. Writing in 2007, New York Times health columnist Jane Brody quoted bike racer and testicular cancer survivor Lance Armstrong, who said, "Cancer was the best thing that ever happened to me", and cited a woman asserting that "breast cancer has given me a new life. Breast cancer was something I needed to experience to open my eyes to the joy of living." Betty Rollin, one of the first American women to go public with her disease, was enlisted to testify that she has "realised that the source of my happiness was, of all things, cancer – that cancer had everything to do with how good the good parts of my life were".

In the most extreme characterisation, breast cancer is not a problem at all, not even an annoyance – it is a "gift", deserving of the most heartfelt gratitude. One survivor writes in her book The Gift Of Cancer: A Call To Awakening that "cancer is your ticket to your real life. Cancer is your passport to the life you were truly meant to live." And if that is not enough to make you want to go out and get an injection of live cancer cells, she insists, "Cancer will lead you to God. Let me say that again. Cancer is your connection to the Divine."

The effect of all this positive thinking is to transform breast cancer into a rite of passage – not an injustice or a tragedy to rail against but a normal marker in the life cycle, like menopause or grandmotherhood. Everything in mainstream breast cancer culture serves, no doubt inadvertently, to tame and normalise the disease. Indeed, you can defy the inevitable disfigurements and come out, on the survivor side, actually prettier, sexier, more feminine. In the lore of the disease – shared with me by oncology nurses as well as by survivors – chemotherapy smoothes and tightens the skin and helps you lose weight, and when your hair comes back it will be fuller, softer, easier to control, and perhaps a surprising new colour. These may be myths, but for those willing to get with the prevailing programme, opportunities for self-improvement abound. Breast cancer is a chance for creative self-transformation – a makeover opportunity, in fact.

In this seamless world, dissent is a kind of treason. As an experiment, I posted a statement on a message board, under the subject line "Angry", briefly listing my complaints about the debilitating effects of chemotherapy, recalcitrant insurance companies, environmental carcinogens and, most daringly, "sappy pink ribbons". I received a few words of encouragement in my fight with the insurance company, which had taken the position that my biopsy was a kind of optional indulgence, but mostly a chorus of rebukes. "Suzy" wrote to tell me, "I really dislike saying you have a bad attitude towards all of this, but you do, and it's not going to help you in the least." "Mary" was a bit more tolerant, writing, "Barb, at this time in your life, it's so important to put all your energies toward a peaceful, if not happy, existence. Cancer is a rotten thing to have happen and there are no answers for any of us as to why. But to live your life, whether you have one more year or 51, in anger and bitterness is such a waste..."

Exhortations to think positively – to see the glass half full, even when it lies shattered on the floor – are not restricted to the pink ribbon culture. A few years after my treatment, I ventured out into another realm of personal calamity – the world of laid-off white-collar workers. At the networking groups, boot camps and motivational sessions available to the unemployed, I found unanimous advice to abjure anger and "negativity" in favour of an upbeat, even grateful approach to one's immediate crisis. People who had been laid off from their jobs and were spiralling down toward poverty were told to see their condition as an "opportunity" to be embraced. Here, too, the promised outcome was a kind of "cure": by being positive, a person might not only feel better during his or her job search, but actually bring it to a faster, happier conclusion.

In fact, there is no kind of problem or obstacle for which positive thinking or a positive attitude has not been proposed as a cure. Having trouble finding a mate? Nothing is more attractive to potential suitors than a positive attitude, or more repellent than a negative one. Need money? Wealth is one of the principal goals of positive thinking. There are hundreds of self-help books expounding on how positive thinking can "attract" money – a method supposedly so reliable that you are encouraged to begin spending it now. Practical problems such as low wages and unemployment are mentioned only as potential "excuses". The real obstacle lies in your mind.

Like a perpetually flashing neon sign in the background, like an inescapable jingle, the injunction to be positive is so ubiquitous that it's impossible to identify a single source. Oprah routinely trumpets the triumph of attitude over circumstance. A Google search for "positive thinking" turns up 1.92m entries. A whole coaching industry has grown up since the mid-90s, heavily marketed on the internet, to help people improve their attitudes and hence, supposedly, their lives.

In my case, however, there was, I learned, an urgent medical reason to embrace cancer with a smile: a "positive attitude" is supposedly essential to recovery. During the months when I was undergoing chemotherapy, I encountered this assertion over and over – on websites, in books, from oncology nurses and fellow sufferers. Eight years later, it remains almost axiomatic, within the breast cancer culture, that survival hinges on "attitude". One study found 60% of women who had been treated for the disease attributing their continued survival to a "positive attitude". In articles and on websites, individuals routinely take pride in this supposedly lifesaving mental state.

"Experts" of various sorts offer a plausible-sounding explanation for the salubrious properties of cheerfulness. A recent e-zine article entitled Breast Cancer Prevention Tips – and the notion of breast cancer "prevention" should itself set off alarms, since there is no known means of prevention – for example, advises that: "A simple positive and optimistic attitude has been shown to reduce the risk of cancer. This will sound amazing to many people; however, it will suffice to explain that several medical studies have demonstrated the link between a positive attitude and an improved immune system."

You've probably read that assertion so often, in one form or another, that it glides by without a moment's thought about what the immune system is, how it might be affected by emotions and what, if anything, it could do to fight cancer. The link between the immune system, cancer, and the emotions was cobbled together somewhat imaginatively in the 70s. It had been known for some time that extreme stress could debilitate certain aspects of the immune system. Torture a lab animal long enough, as the famous stress investigator Hans Selye did in the 30s, and it becomes less healthy and resistant to disease. It was apparently a short leap, for many, to the conclusion that positive feelings might be the opposite of stress – capable of boosting the immune system and providing the key to health, whether the threat is a microbe or a tumour.

You can see the theory's appeal. First, the idea of a link between subjective feelings and the disease gave the breast cancer patient something to do. Instead of waiting passively for the treatments to kick in, she had her own work to do – on herself. At the same time, it created expanded opportunities in the cancer research and treatment industry: not only surgeons and oncologists were needed, but behavioral scientists, therapists, motivational counsellors and people willing to write exhortatory self-help books.

The dogma, however, did not survive further research. In the May 2007 issue of Psychological Bulletin, James Coyne and two co-authors published the results of a systematic review of all the literature on the supposed effects of psychotherapy on cancer. The idea was that psychotherapy, like a support group, should help the patient improve her mood and decrease her level of stress. But Coyne and his coauthors found the existing literature full of "endemic problems". "If cancer patients want psychotherapy or to be in a support group, they should be given the opportunity to do so," Coyne said in a summary of his research. "There can be lots of emotional and social benefits. But they should not seek such experiences solely on the expectation that they are extending their lives."

It could be argued that positive thinking can't hurt, that it might even be a blessing to the sorely afflicted. Who would begrudge the optimism of a dying person who clings to the hope of a last-minute remission? Or of a bald and nauseated chemotherapy patient who imagines that the cancer experience will end up giving her a more fulfilling life? Unable to actually help cure the disease, psychologists looked for ways to increase such positive feelings about cancer. If you can't count on recovering, you should at least come to see your cancer as a positive experience.

But rather than providing emotional sustenance, the sugar-coating of cancer can exact a dreadful cost. First, it requires the denial of understandable feelings of anger and fear, all of which must be buried under a cosmetic layer of cheer. This is a great convenience for health workers and even friends of the afflicted, who might prefer fake cheer to complaining, but it is not so easy on the afflicted. One 2004 study even found, in complete contradiction to the tenets of positive thinking, that women who perceive more benefits from their cancer "tend to face a poorer quality of life – including worse mental functioning – compared with women who do not perceive benefits from their diagnoses."

Besides, it takes effort to maintain the upbeat demeanor expected by others – effort that can no longer be justified as a contribution to long-term survival. Consider the woman who wrote to Deepak Chopra that her breast cancer had spread to the bones and lungs: "Even though I follow the treatments, have come a long way in unburdening myself of toxic feelings, have forgiven everyone, changed my lifestyle to include meditation, prayer, proper diet, exercise, and supplements, the cancer keeps coming back. Am I missing a lesson here that it keeps reoccurring? I am positive I am going to beat it, yet it does get harder with each diagnosis to keep a positive attitude."

Chopra's response: "As far as I can tell, you are doing all the right things to recover. You just have to continue doing them until the cancer is gone for good. I know it is discouraging to make great progress only to have it come back again, but sometimes cancer is simply very pernicious and requires the utmost diligence and persistence to eventually overcome it."

But others in the cancer care business have begun to speak out against what one has called "the tyranny of positive thinking". When a 2004 study found no survival benefits for optimism among lung cancer patients, its lead author, Penelope Schofield, wrote: "We should question whether it is valuable to encourage optimism if it results in the patient concealing his or her distress in the misguided belief that this will afford survival benefits... If a patient feels generally pessimistic... it is important to acknowledge these feelings as valid and acceptable."

Whether repressed feelings are themselves harmful, as many psychologists claim, I'm not so sure, but without question there is a problem when positive thinking "fails" and the cancer spreads or eludes treatment. Then the patient can only blame herself: she is not being positive enough; possibly it was her negative attitude that brought on the disease in the first place.

I, at least, was saved from this additional burden by my persistent anger – which would have been even stronger if I had suspected, as I do now, that my cancer was iatrogenic, that is, caused by the medical profession. When I was diagnosed, I had been taking hormone replacement therapy for almost eight years, prescribed by doctors who avowed it would prevent heart disease, dementia, and bone loss. Further studies revealed in 2002 that HRT increases the risk of breast cancer, and, as the number of women taking it dropped sharply in the wake of this news, so did the incidence of breast cancer. So bad science may have produced the cancer in the first place, just as the bad science of positive thinking plagued me throughout my illness.

Breast cancer, I can now report, did not make me prettier or stronger, more feminine or spiritual. What it gave me, if you want to call this a "gift", was a very personal, agonising encounter with an ideological force in American culture that I had not been aware of before – one that encourages us to deny reality, submit cheerfully to misfortune and blame only ourselves for our fate.

by Barbara Ehrenreich

(You Lucky) FourEyes!!

It was a chance conversation on March 23 1985 ("in the afternoon, as I recall") that first started Josh Silver on his quest to make the world's poor see. A professor of physics at Oxford University, Silver was idly discussing optical lenses with a colleague, wondering whether they might be adjusted without the need for expensive specialist equipment, when the lightbulb of inspiration first flickered above his head.

What if it were possible, he thought, to make a pair of glasses which, instead of requiring an optician, could be "tuned" by the wearer to correct his or her own vision? Might it be possible to bring affordable spectacles to millions who would never otherwise have them?

More than two decades after posing that question, Silver now feels he has the answer. The British inventor has embarked on a quest that is breathtakingly ambitious, but which he insists is achievable - to offer glasses to a billion of the world's poorest people by 2020.

Some 30,000 pairs of his spectacles have already been distributed in 15 countries, but to Silver that is very small beer. Within the next year the now-retired professor and his team plan to launch a trial in India which will, they hope, distribute 1 million pairs of glasses.

The target, within a few years, is 100 million pairs annually. With the global need for basic sight-correction, by his own detailed research, estimated at more than half the world's population, Silver sees no reason to stop at a billion.

If the scale of his ambition is dazzling, at the heart of his plan is an invention which is engagingly simple.

Silver has devised a pair of glasses which rely on the principle that the fatter a lens the more powerful it becomes. Inside the device's tough plastic lenses are two clear circular sacs filled with fluid, each of which is connected to a small syringe attached to either arm of the spectacles.

The wearer adjusts a dial on the syringe to add or reduce amount of fluid in the membrane, thus changing the power of the lens. When the wearer is happy with the strength of each lens the membrane is sealed by twisting a small screw, and the syringes removed. The principle is so simple, the team has discovered, that with very little guidance people are perfectly capable of creating glasses to their own prescription.

Silver calls his flash of insight a "tremendous glimpse of the obvious" - namely that opticians weren't necessary to provide glasses. This is a crucial factor in the developing world where trained specialists are desperately in demand: in Britain there is one optometrist for every 4,500 people, in sub-Saharan Africa the ratio is 1:1,000,000.

The implications of bringing glasses within the reach of poor communities are enormous, says the scientist. Literacy rates improve hugely, fishermen are able to mend their nets, women to weave clothing. During an early field trial, funded by the British government, in Ghana, Silver met a man called Henry Adjei-Mensah, whose sight had deteriorated with age, as all human sight does, and who had been forced to retire as a tailor because he could no longer see to thread the needle of his sewing machine. "So he retires. He was about 35. He could have worked for at least another 20 years. We put these specs on him, and he smiled, and threaded his needle, and sped up with this sewing machine. He can work now. He can see."

"The reaction is universal," says Major Kevin White, formerly of the US military's humanitarian programme, who organised the distribution of thousands of pairs around the world after discovering Silver's glasses on Google. "People put them on, and smile. They all say, 'Look, I can read those tiny little letters.'"

Making and distributing a billion pairs of spectacles is no small task, of course - even at a dollar each (the target cost), and without Silver taking any profit, the cost is eye-watering.

This is what Silver calls "the challenge of scaling up".

For the Indian project he has joined forces with Mehmood Khan, a businessman whose family trust runs a humanitarian programme based in 500 villages in the northern state of Haryana, from where he originates.

There will be no shortage of takers in the region, Khan says. "One million in one year is straightaway peanuts for me. In the districts where we are working, one district alone will have half a million people [who need the technology]." Khan's day job is as Global Leader of Innovation for Unilever, and though his employer will have no direct connection with the scheme, having contact with 150m consumers a day, as he points out, means he is used to dealing with large numbers.

But surely finding funding on this scale will be impossible? "I share a vision with Josh," says Khan. "A thing like this, once it works, you create awareness, you enrol governments and the UN, and the model becomes scaleable. People begin to believe." And from a business point of view, he notes wryly, when poor people become more economically developed they also become potential customers.

In addition to the enormous manufacturing and distribution challenges, Silver has one other pressing problem, namely addressing the sole complaint about the glasses - their rather clunky size and design.

"Work is going on on several new designs, and further work will be required to get the costs down. The truth is that there is, at the moment, no device that can be made for a dollar in volumes of 100 million.

"But I am entirely confident that we can do that."

Such is his determination, you wouldn't bet against it. Oxford University, at his instigation, has agreed to host a Centre for Vision in the Developing World, which is about to begin working on a World Bank-funded project with scientists from the US, China, Hong Kong and South Africa. "Things are never simple. But I will solve this problem if I can. And I won't really let people stand in my way."

Big ideas

Life-changing inventions

Wind-up radio

Invented by Trevor Baylis, the crank-powered device brought radio to remote villages and was inspired by the need to disseminate information about Aids.

Solar cooker

Uses sunlight instead of solid fuel. Used in refugee camps in Darfur and while Gaza was under siege. Improvised solar cookers replaced regular ones as gas supplies diminished.

LifeStraw portable water filter

Half of the world's poor suffer from waterborne diseases and this tool contains a halogen-based resin which is claimed to kill 99.9999% of bacteria and 98.7% of viruses that can cause deadly diseases.

The XO laptop

A textbook-sized computer with built-in wireless and a screen that is readable under direct sunlight. It was designed with extreme environmental conditions such as high heat and humidity in mind. It is an educational tool created expressly for children in developing countries. For each laptop bought at around $400 (£267), one is given to a child in a developing country.

Br(a)in Scan

Enlightenment man

A FORMER vice-president, Al Gore, and one of the co-founders of Google, Larry Page, were already seated on the stage of Google’s “Zeitgeist” conference, an exclusive gathering for the intelligentsia, but the third chair was still empty. After a few minutes, Sergey Brin, the other founder of the world’s biggest internet company, joined them. Messrs Gore and Page gave him the floor, because Mr Brin had something important to say.

The global “thought leaders” in the audience at Zeitgeist had just spent two days talking about solving the world’s biggest problems by applying the Enlightenment values of reason and science that Google espouses. But Mr Brin, usually a very private man, opened with an uncharacteristically personal story. He talked about his mother, Eugenia, a Jewish-Russian immigrant and a former computer engineer at NASA, and her suffering from Parkinson’s disease.

The reason was that Mr Brin had recently discovered that he has inherited from his mother a mutation of a gene called LRRK2 that appears to predispose carriers to familial Parkinson’s. Thus Mr Brin, at the age of 35, had found out that he had a high statistical chance—between 20% and 80%, depending on the study—of developing Parkinson’s himself. To the surprise of many in the audience, this did not seem to bother him.

One member of the audience asked whether ignorance was not bliss in such matters, since knowledge would only lead to a life spent worrying. Mr Brin looked genuinely puzzled. First of all, he began, who’s talking about worrying? His discovery was merely a statistical insight, and Mr Brin, a wizard at mathematics, uses statistics without fretting about them. More importantly, he went on, his knowledge means that he can now take measures to ward off the disease. Exercise helps, as does smoking, apparently—although Mr Brin, to laughter, denied taking up cigarettes (a vice of his father’s).

But Mr Brin was making a much bigger point. Isn’t knowledge always good, and certainly always better than ignorance? Armed with it, Mr Brin is now in a position to fund and encourage research into this gene in particular, and Parkinson’s in general. He is likely to contact other bearers of the gene. In effect, Mr Brin regards his mutation of LRRK2 as a bug in his personal code, and thus as no different from the bugs in computer code that Google’s engineers fix every day. By helping himself, he can therefore help others as well. He considers himself lucky.

The moment in some ways sums up Mr Brin’s approach to life. Like Mr Page, he has a vision, as Google’s motto puts it, of making all the world’s information “universally accessible and useful”. Very soon after the two cooked up their new engine for web searches, in the late 1990s at Stanford University, they began thinking about information that is today beyond the web. Their vast project to digitise books has been the most controversial so far, prompting a lawsuit from a group of publishers in 2005 that was resolved in October. But Messrs Brin and Page have always taken a special interest in the sort of information that most people hold dearest: that about their health.

From Russia with maths

Mr Brin’s faith in the transformative power of knowledge also has personal roots. He was born in the Soviet Union, an opaque society and one often hostile to his Jewish parents. His father, Michael, wanted to be an astronomer, but Russia’s Communists barred Jews from the physics and astronomy departments at universities. So Michael Brin became a mathematician, as his father had been. This too was difficult for Jews, who had to take special, more difficult entrance exams. Both Michael and Eugenia passed nonetheless.

But it was clear that they had to get out to lead fulfilling lives. They applied for an exit visa in 1978. Michael Brin was fired for it, and his wife resigned. Fortunately, they received their visas, and in 1979 emigrated to America. Sergey was six at the time. He went to a Montessori school and learnt English, though he retains a hint of a Russian accent to this day. Language did not come naturally to him. Maths did. So Sergey followed his father and grandfather into mathematics, adding computer science at the University of Maryland, and then went to Stanford to get his PhD. Silicon Valley, with its casual dress, sunshine, optimism and curiosity was an instant fit.

At an orientation for new students he met Larry Page, the son of computer scientists and also of Jewish background. They instantly annoyed each other. “We’re both kind of obnoxious,” Mr Brin once said—as ever, half in jest, half serious. They decided to disagree on every subject that came up in conversation, and in the process discovered that being together felt just like home for both of them. They became intellectual soul-mates and close friends.

Mr Brin was interested in data mining, and Mr Page in extending the concept of inferring the importance of a research paper from its citations in other papers. Cramming their dormitory room full of cheap computers, they applied this method to web pages and found that they had hit upon a superior way to build a search engine. Their project grew quickly enough to cause problems for Stanford’s computing infrastructure. With a legendary nudge—from Andy Bechtolsheim, a prominent Silicon Valley entrepreneur and investor who wrote a $100,000 cheque to something called Google Inc—Messrs Page and Brin established a firm by that name.

Suspending their PhD programmes with Stanford’s blessing, the two became entrepreneurs of a typical Silicon Valley start-up. They even worked out of a garage for a time, as Valley lore seems to require. One advantage of this particular garage was that its owner, an early Google employee, had a sister, Anne Wojcicki, who got along well with Mr Brin and has since become his wife. Ms Wojcicki, moreover, had an interest in health information, and began talking to Mr Brin about ways to improve access to it.

Google began its astonishing rise. On the advice of their investors, the founders hired Eric Schmidt, a technology veteran, as chief executive, to provide “adult supervision”. Mr Schmidt’s role was to reassure Wall Street types that Google was responsibly run, in preparation for a stockmarket listing. As Google filed its papers, the world discovered that Google had added to its breakthrough in search technology a fantastically lucrative revenue model: text ads, related to the keywords of web searchers, that charge an advertiser only when a consumer actually clicks and thereby expresses an interest.

“Solving big problems is easier than solving little problems,” Mr Page likes to say.

As Google’s share price went up, Messrs Brin and Page became multi-billionaires. Wealth has its effects, and stories began leaking out. There was, for instance, the Boeing 767 that Messrs Page, Brin and Schmidt began sharing and that Mr Brin was eager to turn into a “party plane” with beds sufficiently large for comfortable “mile-high club” membership.

Yet their indulgences tend to share three less decadent features. First, they enjoy being just plain goofy. During their rare meetings with the press, Mr Schmidt will typically talk the most but say least, rattling off official company positions until the journalists succumb to exhaustion. Messrs Page and Brin, meanwhile, will sit next to him and exchange the odd knowing look, then add the occasional short, inappropriate and mildly embarrassing—but often hyper-perceptive—aside that livens things up and forces Mr Schmidt to backpedal for a few minutes.

Second, they are drawn to pranks and diversions that are educational—and ideally outrageous. They used to be regulars at Burning Man, a festival in the Nevada desert where oddballs display innovative art and mechanical creations. And Mr Brin has invested $5m—in effect, the price of his ticket—in a company based in Virginia that arranges trips for private individuals to the International Space Station on Russian Soyuz spacecraft.

Try not to be evil

Third, Messrs Brin and Page appear to be trying to do good. They have been mocked endlessly, and understandably, for their corporate motto (“Don’t be evil”), but probably mean it. When they start to look evil, it is usually out of naivety. Google went into China agreeing to censor its search results to appease the Communists, but did so in the belief that a lot more information, with omissions clearly labelled, makes the Chinese better off. Mr Brin certainly had the Russia of his youth in mind, but agonised over the decision.

Despite the best intentions of Google’s founders, privacy advocates worry that it knows a dangerous amount about its users, which might be released inadvertently if something goes wrong. And there is growing concern about Google’s dominance of the internet-advertising market.

But Messrs Page and Brin have other things on their minds. “Solving big problems is easier than solving little problems,” Mr Page likes to say, and both preach a “healthy disregard for the impossible”. They hope, for instance, to help solve the world’s energy and climate problems via google.org, Google’s philanthropic arm. Health is another big problem. Mr Page, Mr Brin and his wife, Ms Wojcicki, have brainstormed with people such as Craig Venter, a biologist who helped map the human genome. Mr Brin instinctively regards genetics as a database and computing problem. So does his wife: she co-founded, with Linda Avey, a firm called 23andMe that lets people analyse and compare their genomes (made up of 23 pairs of chromosomes).

The relationship between Google and tiny 23andMe has on occasion raised eyebrows. Google is an investor, although Mr Brin has recused himself from decisions about it. But Mr Brin and Ms Wojcicki are quite the marketing pair. When the global political and economic elite gathered at Davos, a big draw was 23andMe’s “spit party” where the rich and famous salivated into tubes to provide DNA samples. A cynical view of Mr Brin’s Zeitgeist announcement is that it was just a marketing stunt. Ms Wojcicki and Ms Avey were in the room as he spoke.

More likely, Mr Brin and his wife have genuine faith in the value of genetic knowledge for its own sake. They get their kicks by comparing whether they share the gene that makes urine stink after eating asparagus, or the one that determines whether earwax is mealy or oily. But they do ultimately regard it as code. And code, as Messrs Brin and Page often say, benefits from many eyeballs, which is why Google typically uses and releases open-source software, such as its web browser and mobile-phone operating system. (It does, however, keep its search and advertising algorithms private.)

Mr Brin was therefore setting a public example with his announcement at Zeitgeist. Let everybody discover their genomes, through 23andMe or another firm, and then feel comfortable sharing the code so that others—patients, doctors, researchers—can get to work crunching the data and looking for the bugs. Throughout history, the prospect of greater access to knowledge has frightened some people. But those are not the people that Sergey Brin mixes with in Silicon Valley.

Hope

(Dedicated To a Friend of a Friend)

Cancer may be caused by stem cells gone bad. If that proves to be correct, it should revolutionise treatment

MUCH of medical research is a hard slog for small reward. But, just occasionally, a finding revolutionises the field and cracks open a whole range of diseases. The discovery in the 19th century that many illnesses are caused by bacteria was one such. The unravelling of Mendelian genetics was another. It now seems likely that medical science is on the brink of a finding of equal significance. The underlying biology of that scourge of modern humanity, cancer, looks as though it is about to yield its main secret. If it does, it is possible that the headline-writer’s cliché, “a cure for cancer”, will come true over the years, just as the antibiotics that followed from the discovery of bacteria swept away previously lethal infectious diseases.

The discovery—or, rather, the hypothesis that is now being tested—is that cancers grow from stem cells in the way that healthy organs do. A stem cell is one that, when it divides, produces two unequal daughters. One remains a stem cell while the other multiplies into the sorts of cells required by its organ. This matters for cancer because, at the moment, all the cells of a tumour are seen as more or less equivalent. Therapies designed to kill them do not distinguish between them. Success is defined as eliminating as many of them as possible, so those therapies have been refined to do just that. However, if all that the therapies are doing is killing the descendants of the non-stem-cell daughters, the problem has not been eliminated. Instead of attacking the many, you have to attack the few. That means aiming at the stem cells themselves.

Not all investigators support the cancer-stem-cell hypothesis, but the share who do so is growing rapidly. A mere five years ago, few research papers on the subject were presented at big academic meetings. This year there were hundreds at one such meeting alone. Moreover, data from clinical trials based on the hypothesis suggest that it has real value for patients. As a result, drug companies have taken notice and are trying to develop substances that will kill cancer stem cells.

The virtues of self-restraint

The root cause of both cancer and stem cells is multicellularity. In the distant past, when all living things had only one cell, that cell’s reproduction was at a premium. In the body of an animal, however, most cells have taken a vow of self-denial. Reproduction is delegated to the sex cells. The rest, called somatic cells, are merely supporting actors, specialised for the tasks needed to give the sex cells a chance to get into the next generation. For this to happen required the evolution of genes that were able to curb several billion years’ worth of instinct to proliferate without killing that instinct entirely. Only then could somatic cells do their job, and be present in appropriate numbers.

The standard model of tumour formation was based on the fact that somatic cells slowly accumulate mutations. Sometimes these disable the anti-proliferation genes. If enough of the brakes come off in a somatic cell, so the theory went, it will recover its ancestral vigour and start growing into a tumour. Cancer, then, is an inevitable cost of being multicellular.

The discovery of stem cells changed this picture subtly, but importantly. Blood stem cells were found a long time ago, but only recently has it become apparent that all tissues have stem cells. The instincts of stem cells lie halfway between those of sex cells and ordinary body cells. They never stop reproducing, but they cannot look forward to making the generational leap. When the body dies, so do they. However, they are few in number, and because at cell division only one daughter continues to be a stem cell, that number does not grow.

This division of labour may even be another type of anti-cancer mechanism. It allows stringent locks to be put on somatic cells (which, for example, strictly limit the number of times they can divide), yet it permits tissue to be renewed. Without stem cells, such tissue-renewal would be the province of any and every somatic cell—a recipe, as the traditional model observes, for tumorous disaster. The obverse of this, however, is that if a stem cell does mutate into something bad, it is likely to be very bad indeed. That, in essence, is the stem-cell hypothesis of cancer.

Illustration by Noma Bar

One obvious prediction of this hypothesis is that tumours will have at least two sorts of cell in them: a dominant population of daughter cells and a minority one of stem cells. The first person to show that to be true was John Dick, a molecular biologist at the University of Toronto. In 1997 he isolated what looked like stem cells from a blood cancer called acute myeloid leukaemia (AML). Blood cancers are easier to deal with in this context than solid tumours because their cells do not have to be separated from one another before they are examined. One characteristic of AML cells is that they have two sorts of a protein, called CD34 and CD38, on their surfaces. Dr Dick thus used two sets of special antibodies for his experiment. One sort stuck only to the CD34 molecule, the other only to CD38. Each sort was also attached to a fluorescent tag.

By mixing the AML cells from his patients with the two antibodies and running them through a machine that sorted them according to how they fluoresced, he showed that most were positive for both proteins. However, a small fraction (as low as 0.2%) were positive only for CD34. These, he suspected, were the stem cells.

He was able to confirm this by injecting the minority cells into mice. The resulting tumours had the same mix of cells as those from human patients. However, when he injected mice with samples from the majority cells, with both sorts of the protein, no tumours resulted. The CD34-only cells thus acted as cancer stem cells.

Moreover, this phenomenon was not confined to leukaemia. In 2003 a group of researchers at the University of Michigan in Ann Arbor, led by Max Wicha and Michael Clarke, used a similar trick on breast-cancer cells. In this case the surface proteins were known as CD24 and CD44, and the minority were those positive only for CD44. As with AML, these minority cells produced cancers in mice, whereas the majority cells did not.

Since these two pieces of work, the list of cancer stem cells has multiplied. It now includes tumours of the breast, brain, prostate, colon, pancreas, ovary, lung, bladder, head and neck, as well as melanoma, sarcoma, AML, chronic myelogenous leukaemia, Hodgkin’s lymphoma and myeloma.

That is quite a list. The question is, what can be done with it? Jeremy Rich, a neurologist at Duke University in Durham, North Carolina, has one idea. He created mice that had human glioblastoma tumours, a form of brain cancer, growing in them. Then he treated these mice with radiation (the standard therapy for such cancer in people). He found that the cancer stem cells were more likely to survive this treatment than the other cells in the tumour. That turned out to be because, although all the tumour cells suffered equal amounts of DNA damage from the radiation, the stem cells were better able to repair this damage. When he treated the mice simultaneously with radiation and with a drug that interferes with DNA repair, however, the stem cells no longer had an advantage. They were killed by the radiation along with the other cells.

If that result applies to people as well as rodents, it opens up a whole avenue of possibility. In fact, Dr Rich is now in negotiations with several companies, with a view to testing the idea in humans. That “if” is a real one, though. A mouse is not a human being.

Indeed, the stem-cell hypothesis is often criticised for its reliance on animal models of disease. Some researchers worry that the experiments used to identify putative cancer stem cells are too far removed from reality—human tumour cells do not naturally need to survive in mice—and thus may not reflect human cancer biology at all.

Proponents of the hypothesis are alive to that concern, but they think that the same pattern has been seen so often in so many different cancers that it is unlikely to be completely wrong. The practical test, though, will be whether the hypothesis and ideas that emanate from it, such as Dr Rich’s combination therapy, actually help patients survive.

Searching for the suspects

As a step towards discovering whether they do, William Matsui, an oncologist at Johns Hopkins University School of Medicine in Baltimore, looked for cancer stem cells in pancreatic-tumour samples taken from nearly 300 patients. His team found that patients whose tumours did contain such stem cells survived for an average of 14 months. Those whose tumours lacked them survived for 18 months.

That finding is consistent with the idea that cancer stem cells contribute to the most aggressive forms of the disease, though it does not prove they cause tumours in the first place. And although the absence of detectable stem cells in some tumours may be seen as casting doubt on the whole idea, it may instead be that they are too rare to be easily detected. If the stem-cell idea is confirmed, it may help doctors and patients choose how to treat different tumours. Those with detectable stem cells might be candidates for aggressive chemical and radiation therapies, while those without might best be treated with the surgeon’s knife alone.

Breast-cancer researchers are also testing the stem-cell hypothesis in the clinic. Jenny Chang’s group at Baylor College of Medicine, in Texas, took samples of tumours from women before and after standard chemotherapy. When they counted the cells in the tissue they found that the proportion of stem cells in a tumour increased after treatment. That suggests the chemotherapy was killing the non-stem tumour cells and leaving the stem cells behind. When the group repeated the experiment using a modern drug called Tykerb that blocks what is known as the HER2 pathway, they got a different result. HER2 is a gene which encodes a protein that acts as a receptor for molecules called growth factors which, as their name suggests, encourage cell growth and proliferation. After the HER2-blocking treatment, cancer stem cells formed the same proportion of the residual tumour as beforehand. That suggests they, too, were being clobbered by the new treatment. It is probably no coincidence that another drug, Herceptin, which also goes after HER2, is one of the few medicines that is able to prolong the lives of people with advanced cancer.

Illustration by Noma Bar

The stem-cell hypothesis has also changed the way people do basic research. For example, over the past few years cancer researchers have been grinding up pieces of tumour and using what are known as gene-expression microarrays to work out which genes are active in them. However, if the hypothesis is correct, this approach will probably yield the wrong result, because the crucial cells make up but a small part of a tumour’s bulk and the activity of their genes will be swamped by that of the genes of the more common non-stem cells. The answer is to isolate the stem cells before the grinding starts.

This approach has already yielded one important finding. When Dr Chang used microarrays to study gene expression in the CD44-positive cells from breast tumours, she noticed that they did not look like those of the epithelial cells that make up the bulk of such a tumour. Epithelial cells are immobile, grow in “cobblestone” patterns and produce proteins that help them stick together. The gene expression of the putative stem cells, however, resembled that of a mesenchymal cell. Mesenchymal cells rarely stick together. Indeed, they are mobile and are able to slip through the matrix of proteins that holds epithelial cells together.

That finding is important because mobile cells are more likely to escape from a tumour and form secondary cancers elsewhere in the body. Once such secondaries are established, successful treatment is much harder. And the CD44-positive cells also expressed genes that are important for stem-cell self-renewal, particularly one called Notch that controls the flow of chemical signals within a cell.

Researchers at OSI Pharmaceuticals, a firm that makes a drug called Tarceva, found a similar pattern in lung cancer. Several years ago, they started looking for gene-expression patterns that correlated with response to Tarceva. They found that tumours with a pattern that resembled epithelial cells were sensitive to the drug. By contrast, those that had a mesenchymal pattern were not. They hypothesised that as tumours develop, some of their cells actually switch from a sticky, epithelial state to a mobile, mesenchymal one. This epithelial-to-mesenchymal transition, or EMT, is well known to biologists who study embryonic development, but OSI’s results, and those of other researchers, suggest that cancers may have hijacked it for their own use.

Robert Weinberg, a molecular biologist at the Massachusetts Institute of Technology, and his colleagues have come to the same conclusion but they have taken the hypothesis one step further. They think that tumour cells which have undergone EMT have acquired many of the characteristics of cancer stem cells. Experiments in his laboratory, employing a variety of animal models of breast cancer, suggest that communication between tumour cells and surrounding non-cancerous support cells can lead some of the cancer cells to undergo EMT.

That is intriguing. If this transition really can be induced in tumour cells, then any of them might be able to become a cancer stem cell. So it may be that the fundamentalist version of the stem-cell hypothesis is wrong, and the stem cells are a result of a cancer, rather than its cause. That could be another reason why Dr Matsui found that pancreatic cancers do not always seem to contain stem cells.

Dr Weinberg is sensitive to this point, and is cautious when talking about these experiments. He refers to the cells that have undergone EMT as “having the qualities of stem cells” but avoids actually calling them cancer stem cells. If his idea is correct, though, it means that finding drugs which block the signals that induce EMT could reduce the stem-cell population and prolong the survival of the patient. It also means that both the epithelial cells and the mesenchymal ones will have to be attacked. And OSI is now testing a drug that does just that.

Notch up a victory?

Breast-cancer researchers, too, are testing drugs that hit molecular targets highlighted by cancer-stem-cell studies. Merck, for example, has turned to a drug it originally developed to treat Alzheimer’s disease. Although this drug, code-named MK0752, did not slow that disease, it does block activity of Notch, the stem-cell self-renewal gene, and might thus be an appropriate weapon against breast-cancer stem cells. Dr Chang and Dr Wicha have started a clinical trial which uses MK0752 in combination with standard chemotherapy. By the end of the year they hope to have some idea of whether the combination kills cancer cells in human tumours.

Attacking Notch is a high-risk approach, because this gene is used by healthy stem cells as well as cancerous ones; healthy organs as well as tumours could be damaged. Some researchers are therefore taking a different tack and looking for drugs that hit only the unhealthy stem cells. Craig Jordan, a biologist at the University of Rochester Medical Centre, in New York state, is one such. He has discovered that a chemical called parthenolide, found in feverfew, a medicinal plant, kills AML stem cells. Normal stem cells, however, seem to be able to tolerate the drug without difficulty. The reason is that the leukaemia cells are reliant on a biochemical pathway that parthenolide blocks, whereas normal stem cells are not. If all goes well, a trial to test the safety of a modified form of parthenolide will start in a few months.

If the safety issues can be dealt with—and most researchers think they can—then attacking cancer stem cells really could help patients survive. If, that is, the stem-cell hypothesis is correct.

At the moment, scientists being scientists, few are willing to be anything other than cautious. They have seen too many past cures for cancer vanish in a puff of smoke. The proof needs to come from patients—preferably with them living longer. But if the stem-cell hypothesis is indeed shown to be correct, it will have the great virtue of unifying and simplifying the understanding of what cancer is. And that alone is reason for hope.

(from The Economist)