Counterintuitive experiment may help explain why survivors are more vulnerable to other malignancies

The-Scientist.com, August 2, 2010, by Tina Hesman Saey  —  Being overly protective can backfire. That’s a lesson that many parents have learned and cancer biologists are beginning to recognize.

Killing off damaged cells is supposed to help protect against cancer, but two new studies show that a massive die-off can lead to the disease instead. The findings, published in the August 1 Genes & Development, may have implications for certain types of cancer therapies, including radiation treatment.

Previous research has demonstrated the importance of p53, a protein that acts as a cell’s security system. The protein senses when a cell is under extreme stress, such as that caused by DNA damage, and dispatches other proteins to deal with the problem in several ways. Some of p53’s minions halt cell growth while others attempt to repair the damage. When all else fails, p53 unleashes Puma, a protein that sets in motion a cell-suicide program called apoptosis.

Apoptosis has long been thought to be one of the most important defenses against cancer, perhaps the most important. So researchers fully expected that mice lacking the Puma protein, and thus the ability to kill damaged cells, would be highly susceptible to cancer after radiation treatment. But in science, even when the result seems like a foregone conclusion, the experiment still has to be done.

So two groups of researchers independently tested the ability of mice genetically engineered to lack the Puma protein to withstand repeated rounds of cancer-inducing radiation exposure.

“It seemed a good way to give a Ph.D. student a solid, but not overly exciting paper,” says Andreas Strasser, a cancer biologist at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, who led one of the groups.

Instead of being riddled with cancer, mice lacking Puma “got no tumors at all” after repeated rounds of radiation exposure, Strasser says.

That left researchers with two possibilities: “Either you’ve snuffed up badly, or something exciting is going on,” he says. Repeating the experiment gave the same result; mice lacking Puma seemed impervious to DNA damage caused by radiation. Another group led by Andreas Villunger, a molecular biologist at Innsbruck Medical University in Austria, found the same result independently.

“The fact that this was found by both groups separately gives added credibility” to the result, says Robert Weinberg, a molecular cancer researcher at MIT’s Whitehead Institute for Biomedical Research in Cambridge, Mass.

But mice with intact Puma — which should have been protected against cancer — developed lymphoma after a couple of rounds of radiation. Both groups of researchers traced the source of the lymphoma to overworked stem cells in the bone marrow.

Under normal conditions, radiation causes so much damage to DNA that blood cells can’t cope and turn on Puma’s cell-suicide program. In that way, about 80 percent of mature blood cells die after a massive dose of radiation.

Surviving stem cells have to “first deal with the DNA damage from radiation, and then they have to expand [their numbers] and regenerate like crazy making new blood cells to save the animal from anemia,” says Villunger. The pressure to reproduce many blood cells quickly puts stress on stem cells and may result in mutations that could lead to cancer the next time stem cells have to work that hard.

Stem cells in mice lacking Puma are spared from the heavy work load, because mature cells survive the radiation onslaught. When Strasser’s group killed off mature blood cells in the mice lacking Puma with drugs called glucocorticoids, the mice got lymphoma, indicating that it’s the initial apoptosis-induced die-off of mature cells and subsequent overworking and overstressing of stem cells that causes the cancer.

The results may help explain why children cured of leukemia often develop other types of cancer 20 or 30 years later, Villunger says. About 15 percent of new cancer cases are new types of tumors arising in cancer survivors, he says. That suggests that the tumors could be related to aggressive treatment of the first cancer, and could mean that doctors should reevaluate how hard they should hit tumors with chemotherapy drugs or radiation.

Of course, “how to deal with this in real life with the patient next to you is complicated,” Villunger says. 

WebMD, August 3, 2009, by Lisa Nainggolan,  (New Orleans, Louisiana) — A new review concludes that there is extensive evidence from three decades of research that fish oils, or more specifically the omega-3 polyunsaturated fatty acids (PUFAs) contained in them, are beneficial for everyone [1].

This includes healthy people as well as those with heart disease–including post-MI patients and those with heart failure, atherosclerosis, or atrial fibrillation–say Dr Carl J Lavie (Ochsner Medical Center, New Orleans, LA) and colleagues in their paper published online August 3, 2009 in the Journal of the American College of Cardiology.

“We reviewed everything that was published on omega-3 that was clinically important, and the major finding is that there are a tremendous amount of data to support the benefits of omega-3, not just as a nutritional supplement–people have known that for years–but evidence that it prevents and treats many aspects of cardiovascular disease.”

The omega-3 data may not be as impressive or as plentiful as [statin data] but it should be ‘promoted’ to clinicians.

Lavie said he believes physicians are not as familiar with the omega-3 studies as they should be: “Clinicians know the findings of many statin trials even if they do not know all the details–they know that there are a ton of statin data. The omega-3 data may not be as impressive or as plentiful as this, but it should be ‘promoted’ to clinicians.”

Omega-3 PUFA, says Lavie, “is a therapy that clinicians should be considering prescribing to their patients. Not just as something healthy but as something that may actually prevent the next event. In HF, it may prevent death or hospitalization and the same thing post-MI.” He and his colleagues reiterate the advice of the AHA: that those with known CHD or HF eat four or five oily-fish meals per week or take the equivalent in omega-3 supplements; healthy people should consume around two fatty-fish meals per week or the same in supplements.

Most Data on EPA and DHA

In their review, Lavie and colleagues explain that most of the data on omega-3 have been obtained in trials using docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the long-chain fatty acids in this family. The most compelling evidence for cardiovascular benefits comes from four controlled trials of almost 40 000 participants randomized to receive EPA with or without DHA in studies of primary prevention, after MI, and most recently with HF, they note.

[Omega-3 PUFA] is a therapy that clinicians should be considering prescribing to their patients, as something that may actually prevent the next event.

They discuss the results for each specific cardiovascular condition in turn. For CHF, three large randomized trials–the Diet and Reinfarction Trial (DART), the Gruppo Italiano per lo Studio della Sopravvivenza nell’ Infarto Miocardico (GISSI)Prevenzione, and the Japan EPA Lipid Intervention Study (JELIS)–have indicated that omega-3 PUFAs lower CV risk in both the primary- and secondary-prevention settings, they note.

Lavie elaborated, “The benefit is different in different studies but can be as much as 30%.” The effects are seen on total mortality, sudden death, CHD mortality, and cardiovascular mortality.

But there are some studies that have not shown favorable results, although there are generally methodological reasons for this, they say. However, they do flag the most recent study of post-MI patients, OMEGA, which suggests there may not be additional short-term benefit of omega-3 PUFAs in low-risk patients already receiving optimal modern therapy.

There is also evidence of benefit in atherosclerosis and in a wide range of arrhythmias, with the most significant effect and potential benefit seen in “the current epidemic” of AF, note the researchers. But more studies are needed to explore the effects of various doses of omega-3 PUFAs on the primary and secondary reduction of AF and to determine whether the benefits are caused by antiarrhythmic effects, benefits on autonomic tone, or even anti-inflammatory effects, they observe.

Benefit of Fish Oils Also Extend to HF

Recently, the potential benefits of omega-3 PUFAs “have been extended to the prevention and treatment of HF,” say Lavie et al. Although the reduction in events was “only 8% to 9% in the recent GISSI-HF trial, which is not huge,” Lavie admits, “when you think of HF, it’s a very serious disorder, and in GISSI-HF, those patients were treated vigorously for their HF, so they were on good therapy, and adding just one [omega-3 PUFA] pill a day reduced deaths by between 8% and 9%, which is a pretty nice additional benefit.”

But he and his colleagues say further studies are needed to determine the optimal dosing of omega-3 PUFA for different stages of HF and to investigate the underlying mechanisms for the benefits. However, in the meantime, omega-3 PUFA supplements “should join the short list of evidence-based life-prolonging therapies for HF.”

[Omega-3 PUFA supplements] should join the short list of evidence-based life-prolonging therapies for HF.

They also discuss the data on omega-3 PUFAs in hyperlipidemia, noting that the FDA has approved one such supplement for the treatment of very high triglyceride levels.

And they note that more studies are needed to determine the optimal mix of DHA relative to EPA in various populations.

Finally, they state that this review does not focus on the plant-based precursor of EPA, alpha-linolenic acid (ALA), which is found in abundance in flaxseed and to a lesser extent in other plants. But they observe “the overall evidence is much weaker for ALA than for EPA and DHA.”

Recommendations for Omega-3 Consumption

Mirroring recommendations from the AHA, European Society of Cardiology, and WHO, Lavie and colleagues recommend that healthy people consume at least 500 mg per day of EPA/DHA–equal to around two fatty-fish meals per week–and that those with known CHD or HF get 800 to 1000 mg per day EPA/DHA.

Asked by heartwire whether people should try to consume more fish or alternatively take supplements, Lavie says: “If somebody really were eating salmon and tuna and mackerel and sardines, and they were doing that several times a week, then they wouldn’t need to be taking a supplement. But in the US, at least, very few people are going to eat the therapeutic doses of fatty fish.”

Other good reasons to take supplements include the fact that they have usually had impurities, such as mercury, removed, he notes.

If people are trying to improve their consumption of oily fish, they could take supplements only on the days they were not eating such fish or every other day to try to get up to the recommended amount of omega-3 PUFAs, Lavie says.

But he warns that regimens that are too complex might result in underconsumption: “I would tend to think that most people are getting very little omega-3 PUFAs in the diet. There’s no harm in taking extra–the only negative of extra is the calories. I don’t think anyone thinks now that fish oil is doing any harm.”

Lavie has been a consultant and speaker for Reliant, Pfizer, Bristol-Myers Squibb, and Sanofi-Aventis and is a speaker receiving honoraria from and on the speaker’s bureau of GlaxoSmithKline, Abbott, and Solvay. Disclosures for the coauthors are listed in the paper.

Medscape.com, by Laurie Barclay MD, August 2, 2010 — Intake of processed meat and its components is linked to increased risk for bladder cancer, according to the results of the large, prospective National Institutes of Health–AARP Diet and Health Study reported online August 2 in Cancer.

“Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs),” write Leah M. Ferrucci, PhD, from the National Cancer Institute in Rockville, Maryland, and colleagues. “The authors comprehensively investigated the association between meat and meat components and bladder cancer.”

Among 300,933 men and women who completed a validated food-frequency questionnaire, there were 854 cases of transitional cell bladder cancer identified during 7 years of follow-up. Using quantitative databases of measured values, the investigators estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat, and they calculated total dietary nitrate and nitrite based on literature values.

For the fifth quintile vs the first quintile of red meat consumption, hazard ratio (HR) for bladder cancer was 1.22 (95% confidence interval [CI], 0.96 – 1.54; P for trend = .07). For the fifth vs first quintile of the HCA 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), HR was 1.19 (95% CI, 0.95 – 1.48; P for trend = .06). These HRs showed a borderline statistically significant increased risk for bladder cancer. There were also positive associations in the top quintile for total dietary nitrite (HR, 1.28; 95% CI, 1.02 – 1.61; P for trend = .06) and nitrate plus nitrite intake from processed meat (HR, 1.29; 95% CI, 1.00 – 1.67; P for trend = .11).

“These findings provided modest support for an increased risk of bladder cancer with total dietary nitrite and nitrate plus nitrite from processed meat,” the study authors write. “Results also suggested a positive association between red meat and PhIP and bladder carcinogenesis.”

Limitations of this study include lack of data on urination frequency and bladder infections and only limited data on beverage intake.

“Our findings highlight the importance of studying meat-related compounds to better understand the association between meat and cancer risk,” senior author Amanda J. Cross, PhD, also from the National Cancer Institute, said in a news release. “Comprehensive epidemiologic data on meat-related exposures and bladder cancer are lacking; our findings should be followed up in other prospective studies.”

The Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, supported this study in part.

Cancer. Published online August 2, 2010.

PharmaLive.com, August 2, 2010  —  Despite a volatile year in terms of M&As and product lawsuits, overall U.S. pharmaceutical sales continue to grow. However, some of the top-selling prescription medicines are set to lose patent protection during 2010 and 2011. Manufacturers and marketers of these products are taking advantage of their remaining patented months and lofty sales status by continuing to penetrate emerging regions and marketing their products’ additional indications.

Many of the best-selling prescription medicines are relying on foreign markets to boost sales. Advair/Seretide generated worldwide pound sales growth of 20% (or 5% growth at constant exchange rates) in 2009, with strong sales increases coming from emerging markets (21%) and Japan (79%).

Lipitor hangs on to best-selling reign

Lipitor, the world’s top-selling prescription drug from 2001 through 2009, produced global sales of $12.54 billion last year. The cholesterol reducer lost its U.S. basic product patent in March 2010 and the patent specifically covering its enantiomeric form expires during June 2011.

Medicine of the Year – Humira

Abbott Laboratories’ prize biologic product, Humira, generated a 21.4% increase in sales for the year. Including Eisai’s sales in Japan, Humira produced a total of $5.56 billion in sales, placing ninth among all prescription products worldwide, four places higher than in 2008. In early 2010, Humira became the first biologic approved in Japan for the treatment of plaque psoriasis and psoriatic arthritis. The product is awaiting approval in Japan for Crohn’s disease and ankylosing spondylitis. Abbott executives expect Humira’s strong growth to continue as penetration rates in key therapeutic areas remain low, particularly outside the United States. Humira is expected to become the No. 1 product in 2012 with sales of $8.28 billion, and will retain its top spot until 2016 when sales could exceed $10 billion.

by Paul Greenberg

Catch of the Day

By SAM SIFTON

FOUR FISH – Book Review of…

…The Future of the Last Wild Food by Paul Greenberg

The New York Times, August 2, 2010  —  In the late fall of 2009, bluefin tuna came inshore along the New Jersey coast and began to crash the surface of the ocean, chasing bait. For days, fast, open fishing boats played run-and-gun with them across the waters near Deal and Asbury Park, not 30 miles from New York City as the gannet flies.

These were not giant bluefin, the 1,000-pound bullet trains so prized by the Japanese that they might sell for $100,000 or more. Those are almost gone now, as Paul Greenberg points out in his important and stimulating new book, “Four Fish,” which takes as its subject the global fisheries market and the relationship humans have with tuna, cod, sea bass and salmon. Giant bluefin tuna have been overharvested here and abroad as they travel north and south, east and west, heedless of international borders or treaties, their population hovering on the brink of total collapse.

These tuna were instead their progeny’s progeny, fish of merely 75 or 150 pounds, the shape of huge, iridescent footballs. They are graceful as ballet dancers, and as strong, some of “the wildest things in the world,” as Greenberg calls them.

A fishing guide I know well was out there and got a client close enough to a small pod of tuna to cast to it. The client got his fish, which is his own story. And a few hours later, my friend, driving north through Brooklyn with five pounds of ruby­-red tuna belly resting on ice in the back of his car, called me to ask if I had any soy sauce.

I was newly installed as the restaurant critic of The New York Times and had spent the previous few months on a surreptitious tour of some of the city’s best restaurants. I had been eating stupendously well. But nothing I had eaten that summer and fall prepared me for the taste of this tuna that late afternoon, for the intense blast of flavor and rich, creamy fattiness delivered by a cut of truly fresh otoro — supreme tuna belly, in the parlance of the sushi bar — not yet four hours old.

Nothing I had ever eaten could have. The bluefin tuna you get at restaurants, even the best ones, has been flash-frozen and thawed, is days — or weeks — old, has traveled thousands and thousands of miles. In a bite of that absolutely fresh tuna from New Jersey, I experienced a taste of truly wild food, a majestic flavor, something incredibly rare.

And as it melted on my tongue and receded into memory, I felt guilt and doubt and fear. Will my children, who demurred in eating the fish that day, ever have a chance to eat bluefin tuna? Will their children? Will anyone? Should they? What are we really to do with these fish?

Greenberg, a journalist who has contributed to The New York Times Magazine, has constructed a book that, even as it lays out the grim and complicated facts of common seas ravaged by separate nations, also manages to sound a few hopeful and exciting notes about the future of fish, and with it, the future of civilizations in thrall to the bounty of the sea.

The point of the book comes down to the push and pull of our desire to eat wild fish, and the promise and fear of consuming the farmed variety. As Greenberg follows his four species, and our pursuit of them, farther and farther out into the ocean, he posits the sense of privilege we should feel in consuming wild fish, along with the necessity of aquaculture.

Along the way, Greenberg raises real-life ethical questions of the sort to haunt a diner’s dreams, the kind of questions that will not be easily answered by looking at the Monterey Bay Aquarium’s seafood-watch card. In truth, he shows, there is rarely such a thing as a good wild fish for any of us to eat, at least not if all of us eat it.

Combining on-the-ground and on-the-ocean reporting from the Yukon to Greece, from the waters of Long Island Sound to the Mekong Delta, along with accounts of some stirring fishing trips, Greenberg makes a powerful argument: We must, moving forward, manage our oceans so that the fish we eat can exist both in aquacultural settings and within the ecosystems of wild oceans.

Wild fish were once everywhere, of course, in such numbers as to astound. (And still, Greenberg reports, the current global catch of wild fish measures 170 billion pounds a year, “the equivalent in weight to the entire human population of China.”) Wild fish seemed to be, as Greenberg puts it, “a crop, harvested from the sea, that magically grew itself back every year. A crop that never required planting.”

Once, Greenberg writes, as many as 100 million Atlantic salmon larvae hatched every year in the upper reaches of the Connecticut River and eventually made their way south to Long Island Sound, and north from there to Greenland before returning to the Berkshire foothills to spawn. Dams, overfishing and more dams still have taken their grim toll on their descendants. Today, every piece of Atlantic salmon you’ll find at your local supermarket or fishmonger, smoked into lox, wrapped around mock crabmeat, or lying flat and orange against crushed ice, is farmed. As Greenberg explains clearly and well, the process by which that farming is undertaken threatens the future of what wild salmon remain here and in the Pacific. The amount of wild fish needed to feed farmed salmon, the threat of farmed salmon escaping and crossbreeding with wild salmon stocks, the rise of pollution from the farms themselves — when it comes to the business of domesticating salmon, Greenberg writes, “we should have chosen something else.”

Of course we did choose something else, some of us. That fish is sea bass — branzino, as it’s mostly called on restaurant menus now — a species that once thrived in the wild along the coast of Europe, throughout the Mediterranean Sea and through the Strait of Gibraltar, along the western coasts of Portugal, Spain and France, north to England. No more, though the farmed version is a success story of ample proportions, as anyone who spends more nights than not in white-tablecloth restaurants can tell you.

Greenberg’s accounting of the 2,000-year process of learning to farm sea bass, “one that involved the efforts of ancient Roman fishermen, modern Italian poachers, French and Dutch nutritionists, a Greek marine biologist turned entrepreneur, and an Israeli endocrinologist,” reads in parts like the treatment for a Hollywood film, a toga epic in fishy smell-o-vision.

And cod? As Greenberg writes, it fueled the American economy in its early days, and good parts of the European one, too. A five-foot wooden carving of the fish hangs from the ceiling in the Massachusetts State House, to celebrate its place in the region’s history.

But industrial fishing of these tremendous and once common animals, by fishermen the world over, has led to terribly depleted stocks and closed fishing grounds — and, Greenberg reports, to a turn toward wild Alaskan pollock to fill our desire for firm, white-fleshed fish to make fish sticks and battered-fish sandwiches, and from there toward farmed Vietnamese tra and African tilapia.

These shifts, of course, come with their own nightmares and possibilities, their own showcases of human frailty in the face of commerce, greed and hunger. Greenberg’s reporting lays these out with care.

The story of the bluefin tuna, meanwhile, is one of the great tragedies of the modern age. This magnificent creature, once mostly shunned by the world’s cooks and diners for its bloody flesh unsuitable for human consumption, now teeters almost on the edge of extinction, principally because the world’s nations cannot agree to the one measure that will guarantee its future: a total ban on its commercial harvest, in all waters.

“The passion to save bluefin is as strong as the one to kill them,” Greenberg writes, “and these dual passions are often contained within the body of a single fisherman.” “Four Fish” is a marvelous exploration of that contradiction, one that is reflected in the stance and behavior of all nations that fish. It is a necessary book for anyone truly interested in what we take from the sea to eat, and how, and why.

Sam Sifton is the restaurant critic for The Times.

GoogleNews.com, FORBES.com, August 2, 2010  —  In the 33 months since the launch of Amazon’s Kindle platform, sales of Kindle e-books have surpassed sales of hardcover books. Amazon CEO Jeff Bezos predicts that e-book sales will surpass paperback sales within the next 12 months, and combined hardcover and paperback sales soon after that. This despite the fact that the 600,000 titles in the Kindle bookstore represents only a fraction of Amazon’s inventory.

That the success of the Kindle is good news for Amazon should go without saying. But it represents a remarkable environmental advance as well. The publishing industry in the U.S. felled roughly 125 million trees and generated vast amounts of wastewater. And, of course, physical books have to be transported by trucks, which generate carbon emissions, exacerbate congestion, increase traffic fatalities and cause wear-and-tear on already overburdened roads. One assumes that Bezos didn’t have the environment foremost in mind when he pushed the Kindle concept forward, yet he’s arguably done more to fight climate change by threatening hardcovers and paperbacks with extinction than any number of environmental activists.

The Kindle is a beautiful example of the phenomenon visionary architect and futurist Buckminster Fuller called “ephemeralization,” in which human societies use fewer raw materials to accomplish tasks as they grow more advanced. The rise of Zipcar is another perfect example. Whereas many city-dwellers might have once owned an automobile for the sole purpose of occasionally ferrying groceries from supermarket to apartment building, those same city-dwellers can now rely on a low-cost car-sharing service. Over the next decade an ever larger share of these automobiles will be built of ultradurable, ultralight carbon fiber, which will further lighten the environmental load of driving.

A more ephemeral economy places heavier emphasis on taste, identity and friendship. As we grow more affluent, we place heavier emphasis on consumption than on production. We choose our partners not on the basis of who will prove the best breadwinner but rather on who will be the most congenial company. In a similar vein, we’re more likely to choose where we live on the basis of amenities. The most important amenity is increasingly the presence of like-minded people or, more prosaically, people who like to consume the same things and experiences.

The rapid rise of location-based services on the Web–including Foursquare, Gowalla, Latitude and Loopt, among many others–is rooted in the powerful promise of a real world that can be indexed and organized as cleanly and coherently as Google has indexed and organized the Web. A tool like Foursquare allows you to “check-in” to your favorite businesses, allowing friends to know when you’re in a particular dive bar and how often you go. And local business owners, in turn, get a better sense of who they’re serving and how they can serve their customers better. These are the kind of metrics and insights that have fueled the explosive growth of Amazon and other successful e-commerce firms.

Entrepreneur Mark Cuban recently caused considerable consternation by envisioning a world in which people will never have to actively check in. Rather, everyone will be monitored by video cameras that will use sophisticated facial recognition software and a vast database of Facebook profile photos to pinpoint the identities of everyone in a crowd. This will allow your local eatery to give you a personalized greeting, and a menu that only lists the foods it knows you love. Many argue that this is profoundly unlikely, as the mass public will object to being monitored so closely. Yet the rapid proliferation of CCTV suggests otherwise. If passive check-in offers consumers tangible benefits, it seems likely that the vast majority will happily accept the death of anonymity, with the holdouts finding themselves on the margins of society.

Despite the ravaging effects of high unemployment, the ephemeralization of the economy continues unabated. Facebook, with 500 million members worldwide, might be the most vivid illustration of ephemeralization–a large and growing business that, apart from a few server farms and a few cubicle farms, has few tangible assets–and it has recently teamed up with Amazon to make Amazon’s recommendations more “social.”

If I had to make a bet on which company would define the ephemeralization era, it would be Amazon and not Facebook. Facebook sees itself as a “social utility,” an infrastructure that will remake the Web. But Facebook sufers from a fatal flaw. People cultivate an identity on Facebook by carefully selecting likes and dislikes, which might or might not reflect reality. Amazon, in contrast, knows exactly where you spend your money, thus giving it a more intimate portrait of the real you. A marriage of Amazon and Facebook would create an unstoppable juggernaut.

On its own, however, Amazon has proven to be a wily innovator that eschews the spotlight while hoovering up billions of dollars in commercial transactions–$6.57 billion in the second quarter of 2010 at $0.45 earnings per share, to be precise. Though Amazon is often accused of having an intensely secretive culture, Bezos has been shrewd about letting Kindle e-books be sold on any platform, including Apple’s iPad.

Though Amazon is primarily a retailer, it has pursued a number of other business opportunities that seem likely to expand in the years and decades to come, including Amazon Web Services, which allows other companies to rent a portion of Amazon’s vast computing power, and Mechanical Turk, an artificial artificial intelligence program that allows would-be employers to hire workers a small task at a time. In a small way Amazon has already paved the way towards becoming a service provider rather than just a seller of physical goods, creating a platform that allows power sellers, Web startups and countless others to make real money. Rest assured, the company that brought us the Kindle has many more innovations up its sleeve.