Medicine

Shooting down cancer

A theory linking the scourge to stem cells may offer new ways of treating this most terrifying of diseases

EVERY age is afraid of plagues. For the most part, such plagues have been infections. The rich world, though, has brought infectious disease under control and, AIDS aside, the memory dims with every generation. Instead, the fear of disease has transferred itself to cancer. How to prevent it, and how to treat it if prevention has failed, fills the health pages of the newspapers. How this or that celebrity won or lost his or her battle with it seems to fill much of the rest.

The military metaphor is not confined to newspapers. It is 37 years since Richard Nixon, then America’s president, declared war on the disease. During that time, the prognosis for cancer patients has got a lot better. Scientists have refined old therapies and found new ones. Moreover, governments have waged a relentless public-health campaign against the biggest cause of cancer—the smoking of tobacco. The war, however, has never looked close to being won. Scan the horizon and there is no sign of a cure.

Nor is there likely to be until the enemy is properly understood. Though luck plays its part in medicine, as it does in warfare, the big breakthroughs usually come from dramatic shifts in understanding. It was not, for example, until Louis Pasteur and Robert Koch proved the connection between germs and infection that doctors realised that to cure such diseases you had to kill the germs. The germ theory of disease made sense of a collection of illnesses that obviously had things in common (a tendency to appear in waves, for example, or to pass from person to person) but were maddeningly different in their details. It took a while, but proof of that theory led to antibiotics that can destroy a whole range of infections.

For cancer, a similar moment of enlightenment may now have arrived (see article). Like infections, cancers have prominent features in common, yet they are bafflingly different in their details. But, borrowing an idea from another part of biology, oncologists are coming to believe that most—possibly all—cancers involve stem cells, or something very like them. They are, in other words, caused and sustained by a small number of cells whose daughters grow into the tissue of a tumour rather as the daughters of healthy stem cells grow into the normal tissues that make up a body.

Patience, s’il vous plaît

This opens new ways of thinking about and treating the cancers. If its stem cells are eradicated, the rest of a tumour may die off. And if the secondary tumours—the truly feared killers in many forms of cancer—are the result of stem cells escaping from a primary tumour, as looks likely, then this knowledge may make them yield more easily to treatment.

This discovery is not a cure. But it does point the way towards one—or, at the least, towards better therapies. Some might be in action soon. For example, it seems that cancer stem cells are less vulnerable to radiation than other cancer cells, because their DNA-repair mechanisms are better. Radiotherapy might thus be made more effective against them by dosing them with existing drugs that inhibit DNA repair. Some existing drugs which are known to interfere with stem cells’ biochemical pathways could be used to attack them selectively.

Other treatments will take far longer—the time needed for clinical trials would see to that and, in any case, a lot more research is in order. And there is the problem of designing drugs that can distinguish between cancer stem cells and those that spin off healthy tissues. But it all looks promising.

Blue sky ahead

The other interesting aspect of the stem-cell link is that it was inspired by work outside the mainstream of the huge cancer-research industry: stem-cell research is now a huge field in its own right. In science you never know where the answer is going to come from. Pasteur found it in a piece of practical science: he was trying to prevent food going off. Charles Darwin, by contrast, found a lead for his theory of natural selection in the whimsical hobby of pigeon fancying, where the birds showed an enormous variety of form and behaviour. And some discoveries happen by accident. Radioactivity came to light a century after the discovery of uranium when Henri Becquerel used uranium salts and photographic plates in the same experiment and found that one fogged the other.

In the 19th century it was commonplace to do an experiment simply to see what would happen. That was, in part, because experimenters were often amateurs who were spending private money. In these days of taxpayer-financed science, most experiments are executed with a pretty clear idea of what the outcome ought to be, especially when they are part of wars and campaigns against this or that. The paradox is that, although such efforts do not eliminate Becquerel-like discoveries, they risk limiting the chances of making them.

This accent on targeted research is understandable. Plenty of the work now done on cancer will be of the targeted sort. The Large Hadron Collider, the huge particle accelerator in Switzerland which was switched on this week (see article), is a grand project that could yield all sorts of discoveries. Yet the easiest way to sell it to politicians was to frame it as a search for a single particle, the Higgs boson.

Like natural selection and germs, the discovery of cancer stem cells illustrates how the most fruitful scientific findings are often not those of individual experiments, however intriguing, but those that organise knowledge into theory. The chemical industry took off within a decade or so of Dmitri Mendeleev’s arrangement of the chemical elements into the periodic table, just as radio communications followed James Clerk Maxwell’s mathematical unification of electricity and magnetism, and antibiotics came after Pasteur and Koch.

With luck, something similar will soon happen in biology in the wake of such things as the Human Genome Project. In retrospect, the discovery of stem cells—cancer stem cells included—may come to be seen as a step in a comprehensive theory of how organisms work. That understanding would be a formidable, if unforeseen, part of the legacy of the war on cancer and an essential part of its mission to save lives.

The “war on terror”

Counting the costs

America's fight against terror, seven years after the September 11th attacks

AT THE most basic level the “war on terror”—a label many reject—over the past seven year has been successful. There has not been an assault on the American mainland since the September 11th attacks, remembered on their anniversary with a visit to “ground zero” by the two candidates for the presidency, Barack Obama and John McCain. But with two American-led wars in the Islamic world, al-Qaeda still thriving in Pakistan and imperfections in homeland security, the war has not been won. Nor will it ever be, in a conventional sense.

Of most concern is the situation in the original base of the September 11th plotters, Afghanistan. Anything like a victory is still a long way off in the theatre of the battle against terror that most resembles a conventional war. America invaded Afghanistan shortly after the 2001 attacks. Yet this week, Admiral Mike Mullen, America’s top military officer, admitted to Congress that “I'm not convinced we're winning it in Afghanistan.”

The Taliban and al-Qaeda continue to mount bold attacks, and American mis-steps—such as operations that result in civilian deaths—continue to hamper the struggle for hearts and minds. Admiral Mullen reckons that America may be “running out of time” in Afghanistan.

Worse, just across the border, Pakistan offers an almost untouchable haven for al-Qaeda. America has begun using aerial drones, and small ground strikes, in the tribal areas, the wild regions along the Pakistani-Afghan border. But this has stirred anger and controversy in Pakistan, where a change of government has hardly added to stability. America pursues al-Qaeda in these areas at the risk of weakening its influence with a crucial ally.

Iraq is a big part of the equation too. America’s top brass now openly admits that, if it had a choice, it would move troops from Iraq to Afghanistan. But the war in Iraq is the main concern for the Bush administration. Thus the latest development, a small shift of troops from Iraq to Afghanistan, will not be enough for the generals in charge of the latter.

Elsewhere, however, the news is less grim. America’s intelligence agencies have revamped themselves extensively to combat terrorism. Insiders say that while anti-American sentiment around the world remains high, co-operation with foreign spy services is good—perhaps the best it has ever been—particularly for those countries who have suffered terrorism since 2001 themselves: Britain, Spain, Morocco, Saudi Arabia, Indonesia and the like. This co-operation has led to a large number of high-profile arrests since 2001, including that of two of the leading organisers of the September 11th attacks.

That is one reason no attack has taken place on American soil since. The other is the tightening of “filters” for terrorists who would hit America's mainland. At every level, terrorist organisations face hurdles: finding recruits, training them, getting them visas into the countries they would attack. It is now much harder to get into America. But there is a price for deterring terror: the new practices have choked the flow of eager foreign workers that has traditionally enriched America's economy. It also hits tourism: a travel-industry lobby group says the country has forgone $140 billion in foreign spending since the attacks.

But if that is a cost Americans are willing to bear for security, the highest price to pay remains the tightening of civil liberties. The Patriot Act, passed in haste after the attacks, has been tweaked but still gives the government sweeping powers of surveillance. And of course America still maintains a legally dubious prison at Guantánamo Bay, a symbol of the ugliest kind of compromise of liberty for security.

Americans retain a strong libertarian streak, and all this has been hard to swallow. The country is still getting used to a world in which its citizens feel vulnerable yet uneasy about what they have given up for better security. Another successful attack could start the panic all over again.

Thursday, September 11, 2008

Pelosi's Gang
Feels the Pressure

By KIMBERLEY A. STRASSEL

Something happened on the way to September.

It was in July that Chris Van Hollen, head of the Democrats' House campaign operation, predicted this year would prove "another big-wave election" for his party -- a repeat of 2006 when Democrats gained 31 seats. Barack Obama's "50-state strategy" was supposed to secure both the White House and blowout gains in Congress. At the recent Democratic convention, Majority Leader Steny Hoyer bragged his party had 75 pick-up opportunities.

M.E. Cohen

Or maybe not. Slowly, without much notice, the political landscape has changed. House Republicans are getting traction on issues like energy and reform, and a boost from a newly energized McCain-Palin ticket. An even bigger problem for Democrats is that Nancy Pelosi's liberal governing has put her own vaunted freshmen at risk in their conservative districts.

Some Republicans now cautiously predict they might keep losses to the single digits. Some Democrats morosely agree.

One big shift is in the way voters are looking at Republicans. The GOP brand may still stink, but has lost at least some of its odor. Republicans have closed the gap in polls that ask whether voters are more likely to go for a generic Republican or a generic Democrat -- and in some cases reversed it. New polls also show a real majority of voters in today's GOP-held districts would prefer to keep a Republican in office.

That last number is especially key for the two-dozen open seats Republicans are actively defending. The conventional wisdom was that mass GOP retirements would guarantee a Republican rout, and it's true the party will lose some long-held districts that are now trending left. Then again, this passing of the old guard has held an upside. It's allowed the party to field fresh faces at a time of anti-incumbent mania.

These younger candidates have seized on the energy issue, and embraced John McCain's promise to reform the GOP on earmarks, spending and entitlements. Free of the party's baggage, they've rejuvenated conservative voters and intrigued independents.

Nine-term California Republican John Doolittle was headed to defeat, thanks to a corruption investigation. He instead retired, and today's Republican candidate is state Sen. Tom McClintock, an ardent fiscal conservative. Should he and like-minded newbies win, they will bolster the party's reform wing.

Democrats still hold the cards, but face a possible reckoning. The Democratic leadership got smart in 2006, running conservative Democrats who picked off unpopular Republicans in conservative districts. Yet that same leadership has proceeded to govern in a way that has made many of those freshmen vulnerable in their first re-election. Of the 20 most competitive Democratic seats, 16 are held by newcomers.

If you want to know why Mrs. Pelosi is so eager to now talk energy, this is it. Wisconsin's Steve Kagen, who in 2006 won a district that went 55% for George W. Bush, is getting hammered by his GOP opponent, John Gard, for his party's refusal to pass drilling legislation. Republican Lynn Jenkins is accusing Kansas freshman Nancy Boyda of casting the deciding vote for Congress to go on August recess instead of dealing with high gas prices. Mrs. Pelosi has meanwhile forbade her party from signing a petition to bring GOP drilling legislation to the floor; Republicans are making her power over freshmen Democrats an issue.

The newcomers are also getting knocked for their party's failed promise to reform spending and earmarks. Pennsylvania's Chris Carney (whose district went 60% for Mr. Bush) is up against GOP reformer Chris Hackett. Mr. Hackett has taken a no-earmark pledge, and turned Mr. Carney's pork into a central theme. He's been getting an assist from media attention on the neighboring district of 12-term Democrat Paul Kanjorski, who may lose his seat over an earmark scandal.

What's really hurting freshmen are votes on which their leadership demanded unity. Some are getting hit for a Democratic vote to eliminate secret ballots in union elections, which has tarred candidates with the stench of a special-interest labor agenda. Some are getting hit for Mrs. Pelosi's resolution condemning the Iraq surge. Some, in particular Democrats who belong to the Blue Dog coalition, are getting hit for their votes to raise taxes or increase spending.

As for Mr. Obama's 50-state game, many freshman Dems are too worried about being tarred with his liberal stances to even risk being seen with him. Republicans are also encouraged by the new enthusiasm Sarah Palin has injected into the McCain campaign. They are hoping for better turnout, and for voters to follow historic patterns by voting largely down the ticket line.

Republicans continue to fret that their better fortunes are tied to gas prices, and that as they fall, they'll "lose" the energy issue, and their appeal to voters. Possibly. But if there's a lesson in all this -- for both parties -- it's that voters are responding to promises to break with the Washington same-old, same-old. That's a message that will resonate no matter the price of oil.