We all know two things that affect our health as adults: how we live our lives (diet, exercise, stress reduction, exposure to toxic compounds and the like) and the genetic endowment we got from our parents (genes that raise the risk of cancer, for instance). But over the last few years scientists have begun to recognize a third factor: conditions in the womb during our nine months of gestation.

Now comes more support for this idea. In a new study published today in PLoS Medicine, scientists report that birth size, and in particular birth length, correlates with a woman’s risk of breast cancer in adulthood.

Birth size has long been recognized as a marker of the prenatal environment. In 1999 I wrote the first article in a general publication about the role that the prenatal environment plays in people’s risk of “adult-onset” disorders such as heart disease, stroke, cancer, diabetes and other diseases that we think of as the product of genes or (postnatal) environment. As I said at the time, “The health we enjoy throughout our lives is determined to a large extent by the conditions in which we developed, [conditions that] can program how our liver, heart, kidneys and especially our brain function. It is no exaggeration to call these findings a revolution in the making. The discovery of how conditions in the womb influence the risk of adult disease casts doubt on how much genes contribute to disease (because what scientists classify as a genetic influence may instead reflect gestational conditions) and suggests that adult illnesses long blamed on years of living dangerously (like dining on pizza and cupcakes) instead reflect ‘fetal programming.’ ‘Two years ago no one was even thinking about this,’ says Dr. Matthew Gillman of Harvard Medical School. ‘But now what we are seeing is nothing short of a new paradigm in public health.’"

That paradigm has gotten stronger. In the new study, scientists led by Isabel dos Santos Silva of the London School of Hygiene & Tropical Medicine examined 32 previous studies on the correlation between birth size and breast cancer. That gave them 22,058 cases of breast cancer from a pool of more than 600,000 women. Their conclusion: birth weight is positively associated with breast cancer risk in studies where information on birth size was based on birth records (not in those based on adult self-reports, which are less accurate).

Specifically, every 0.5 kg (about 1 pound) increment in birth weight was associated with about a statistically-significant 7% increase in the risk of breast cancer. Relative to women who weighed 6.6 to 7.7 pounds at birth, those who weighed 8.8 pounds had a 12% greater risk of developing breast cancer. Birth length and head circumference were also associated with an elevated risk: for body length at birth, for instance, the incidence of breast cancer by age 80 is 10%, 10%, 10.4% and 11.5% in those who were in the bottom, second, third and top quarters of birth length, respectively. In other words, the longest baby girls had a 15% greater risk, but that still put them at only 11.5% compared to 10%.

That is certainly not huge. (It’s comparable to the increased risk of breast cancer from drinking alcohol.) Nevertheless, “our study indicates that birth size is a marker of susceptibility to breast cancer in adulthood,” dos Santos said. “The birth size-breast cancer association appeared to be largely independent of known risk factors,” such as diet, pregnancy and nursing. And the association with birth weight held up even after the scientists made statistical adjustments for the woman’s body-mass index in adulthood (obesity is a risk factor for breast cancer), for her mother’s size and other possibly confounding factors. In all, the scientists estimate, large size at birth accounts for about 5% of breast cancers in the U.S. and other developed countries.

In an expert commentary on the study, Pagona Lagiou and Dimitrios Trichopoulos of Harvard University School of Public Health write that it provides “the strongest evidence yet that birth size is a critical determinant of breast cancer risk in adult life.” (Trichopoulos, way back in 1990, suggested that a baby girls’ size at birth might affect her risk of developing breast cancer as an adult, reasoning that in utero exposure to estrogen—which promotes growth—might also primate breast tissue to make it more likely to develop cancer.)

Energy efficiency got a bad name at approximately the moment that a cardigan-wearing President Jimmy Carter gave a televised address to the nation in 1977 and told us all to turn down the thermostats. Ever since, the idea of using less energy has become equated in the public’s mind with sitting in the dark, freezing (or, in summer, broiling) and drinking warm beer—in short, going without.

But the nation’s leading organization of physicists is here to tell you that it doesn’t have to be this way, and that the nation can use less energy to achieve the same (or higher) standard of living and productivity.

In a new report, the American Physical Society points out that the United States—with 5% of world population—accounts for 20% of the planet’s annual energy consumption. We pay about $700,000 every minute to foreign countries for oil, and generate more than half of the electricity for our buildings from coal, the worst producer of CO2 emissions. But perhaps the strongest reason for energy efficiency—notice it is not energy conservation, although that would inevitably follow—is that it has worked in the past: in 1975, the first year of U.S. fuel economy standards for cars, the average car got 14 miles per gallon. That rose to 28 mpg for new cars and 22 mpg for new pickup trucks, minivans and SUVs by 1987. The vehicles still got where they were going, and people drove just as much (more, actually)—hence efficiency, not only conservation.

The physicists identify several fat targets for improving efficiency. Every 10% reduction in vehicle weight, which can be done through greater use of high-strength steel, aluminum and composite materials without compromising safety, produces a 6% to 7% increase in fuel economy. Buildings’ use of energy can be reduced 15% to 35% through more efficient insulation, windows and light; eliminating infiltration and duct leakage; upgrading furnaces, boiler and air conditioners; new power supplies that waste less electricity in stand-by or low-power modes; and energy-efficient appliances—all of which pay for themselves in lower utility bills. (Since 1975, Californians have saved more than $30 billion, $2,000 per household, in energy costs thanks to efficiency requirements: the energy needed to cool a new home has fallen by two-thirds, to 800 kWh per year, even though homes are 50% larger than in 1975.)

If you’ve been feeling more than usually guilty about the environment since Tuesday, September 23, there may be a reason: that was the day humans used up all the resources—on cropland, pasture, forests and in fisheries—that nature will provide this year, according to data from the Global Footprint Network, a research group. By the end of the year, we will have used the biological capacity of 1.4 planets, which is only possible, of course, by drawing on the store of resources from previous years.

There’s a lot of research these days aimed at identifying characteristics of cancer cells that make them susceptible to particular treatments, as breast-cancer cells with extra expression of the her2 protein are treatable with Herceptin. Equally important, it seems to me, is identifying cancers that will not respond to standard chemo, which can be hugely debilitating. It would be a great help to patients if doctors could tell before administering a single dose whether the chemo will help.

Now scientists at MIT have shown, in a paper in the online edition of the journal Genes and Development, that 48 specific genes explain a good deal of the variation in whether malignant cells will be killed by chemo.

The old-line chemo drugs, such as those based on platinum compounds such as oxaliplatin, work by damaging DNA. That prevents malignant cells from multiplying. But the MIT scientists find that a group of 48 genes can predict how susceptible a patient is to a toxic compound called MNNG that, like common chemo agents, kills cells by inducing irreparable DNA damage. Which of the 48 genes someone has produces huge variability in response to DNA-damaging compounds. “A cell line from one person would be killed dramatically, while that from another person was resistant to exposure,” said Rebecca Fry, former MIT research scientist and lead author of the paper who is now at the University of North Carolina School of Public Health. “It wasn’t known that cell lines from different people could have such dramatic differences in responses.”

Brace yourself for a spate of stories about how “what you think may affect what you earn,” as the press release from the American Psychological Association puts it. Sounds innocuous. But the "what you think" refers to whether you believe that a woman's place is in the home. “A new study has found that men who believe in traditional roles for women earn more money than men who don’t,” APA continues. There you have it: if you want to rake it in, guys, adopt attitudes that value keeping the little lady barefoot and pregnant.

Before we look at how this conclusion is not exactly supported by the actual study, which I encourage anyone with half an hour or so to read for themselves, it’s only fair to see what the researchers did. Timothy Judge, a management expert at the University of Florida’s Warrington College of Business, and graduate assistant Beth Livingston analyzed data from 12,686 men and women who were interviewed four times between 1979 and 2005; the participants were 14 to 22 when the study began, and 40% of them dropped out or disappeared before the fourth interview. Nonetheless, it's a lot of data, as the researchers report in the September issue of the Journal of Applied Psychology.

At each interview, participants answered questions about their views on gender roles: do you believe a woman’s place is in the home? If a mother works outside the home, are her children more likely to be juvenile delinquents? Should a man be the achiever while the woman takes care of home and family? (Like other studies, this one finds many factors that influence people’s attitudes on all this, including marital status, gender, race, ethnicity, whether they live in a city, religiosity, and whether their parents held traditional views of gender roles. People living in Northeastern cities had less traditional views of gender roles, for instance, as did people whose parents both worked outside the home, while married and religious people had more traditional views.)

Then the researchers correlated these views with how much people earned. Bottom line: men with traditional views of gender roles made an average of about $8,500 more per year than their enlightened peers, while women who held traditional views made an average of $1,500 less per year than women with more egalitarian views.

The last finding has a straightforward explanation. If you’re a woman with a job, and if you think you shouldn’t be at work but back home with the kids or hubby, it’s not surprising that, 1) you don’t push yourself to work that hard and get promotions or bonuses or overtime, and 2) you probably didn’t try for a well-paying, high-powered job in the first place if working made you feel guilty.

But how about the men? As they write in the paper, “One straightforward possibility is that traditional gender role orientation advantages men and disadvantages women because traditional men show greater dedication to their work and traditional women show greater dedication to their homes.”

This is as good a place as any to pause and point out the obvious. Although this study is being cast as showing a cause-and-effect relationship between gender-role attitudes and earnings, it proves nothing of the sort: a man who believes in gender equality has the option of working just as hard at his career, and earning a lot, as does a traditionalist. It does not show that egalitarians are doomed to penury.

Similarly, although the researchers say that “traditional men, especially when compared with traditional women or egalitarian individuals, may negotiate their salaries more aggressively and effectively,” that, too, is hardly inevitable or even logical. Guys, if you believe that the little woman has just as much a right to work outside the home as you are, you don't have to slack off on salary demands.

The key to the whole thing, it seems to me, is a little sentence dropped into the paper’s summary (the abstract): “Occupational segregation partly explained these gender differences.” That is, a woman who doesn’t think she should be working—but, perhaps, has to for economic reasons—may “feel uncomfortable in a high-paying, complex job or in those jobs in which she is surrounded by men,” so she chooses to be, say, a secretary rather than an entrepreneur. Similarly, a “keep ‘em barefoot and pregnant” kind of man is probably not going into academia (where the male-female wage gap is small) or teaching (ditto), but is more likely to be drawn to, say, construction, engineering or finance, where the wage gap can be large. As the researchers admit, "traditional men (vs. egalitarian men) and traditional women (vs. egalitarian women) make different occupational choices. . . . For instance, traditional gender role orientations led to higher earnings in male-dominated jobs than in female-dominated jobs, and men were more likely to hold male-dominated jobs.”

So for all you young men out there just entering the work force, let’s be clear: holding egalitarian views does not mean your earnings will inevitably suffer. You have a choice about which fields to enter, and you don't have to check your enlightened views at the office door.

Hard to believe, but Republicans once took the lead in environmental protection and conservation: Richard Nixon proposed the creation of the Environmental Protection Agency and signed the law establishing it in 1970. George Bush (#41) signed an important extension of the Clean Air Act in 1990 and made the U.S. a signatory to the international treaty that paved the way for the Kyoto Treaty on climate change. Theodore Roosevelt pioneered the creation of the country’s national parks.

Then there is today.

In an eye-opening essay in Environment magazine, two scholars examine the partisan divide on the leading environmental issue of the day, global warming. Sociologists Riley E. Dunlap of Oklahoma State University and Aaron M. McCright of Michigan State University trace this to the Reagan administration’s calling environmental regulations a burden on the economy and to the anti-environmental bent of the Republicans who took control of Congress (led by Newt Gingrich) in 1994. But a partisan divide that was originally most apparent among “political elites, such as members of Congress, who tend to be more ideologically polarized than the general public,” has now spread, the authors write. As recently as the mid-1990s Democratic voters supported increased spending on environmental protection at rates only 10 percent higher than self-identified Republicans, but that gap is now a chasm.

To wit:

• 76% of Democrats believe global warming is already happening; 42 percent of Republicans do, according to a Gallup poll. (In 1997, nearly identical percentages of Republicans and Democrats—48 and 52 percent, respectively—said they thought global warming was already happening.)
• Does the press exaggerate the seriousness of global warming? 17% of Democrats say yes; 59% of Republicans do—a gap of 42 points.
• Do most scientists who study climate change agree that it is empirically established? 75% of Dems say yes, compared to 54% of Republicans.
• Is that warming natural or caused by human activities? 72% of Dems say it’s the latter, but only 40% of Republicans do.
• Will global warming pose a serious threat during our lifetime? 49% of Dems say yes, vs. 26% of Republicans.

Perhaps these gaps are yet another reflection of political polarization, write Dunlap and McCright, including the movement of those who hold one or another belief about climate change to the party that embodies that view, something called “party sorting.”

Interestingly, John McCain has for years taken a position closer to the Democrats, sponsoring legislation (never passed) to control emissions of carbon dioxide. On this issue, write the authors, McCain’s “positions are much closer to Obama’s than they are to almost all of his Republican congressional colleagues. Both McCain and Obama support a mandatory cap on carbon emissions and a high percentage emissions reductions target by 2050 (though Obama’s target is higher). . . . If McCain becomes the next U.S. president, his views on climate change may lead to a shift in the views of some Republicans, but probably not those who have bought into the staunch skepticism of current party elites.” Unless, of course, he defers to his running mate’s interesting views on climate (Sarah Palin does not believe the changes already underway are caused by human activities that add carbon dioxide to the atmosphere) and other scientific issues.

For the couple of decades the Greening Earth Society, a creation of the coal industry, has been happily insisting that the more carbon dioxide we pump into the atmosphere the lusher and more verdant the world will be. As far as climate change goes, their attitude is Alfred E. Neuman’s: what, me worry?

So it is always amusing when even the most straightforward assertions break down. In the climate-change field, one such assertion is that, since plants breathe in carbon dioxide, surely in a world with higher concentrations of CO² plants will flourish and suck up lots of the stuff. We call that a negative feedback. Unfortunately, a study in this week's Nature finds that, after exceptional warming, an ecosystem anchored by a tallgrass prairie actually takes up less carbon dioxide than it did before the warming.

For their study, scientists led by John Arnone of the Desert Research Institute and David Schimel of the National Center for Atmospheric Research turned up the heat in large controlled-environment chambers housing a tallgrass prairie. It was 4 degrees C. (7 degrees F.) warmer than normal. The researchers collected data over four years (the simulated heat wave occurred in year two), and measured what happened to CO2 uptake. Result: warming decreased the ecosystem’s carbon uptake in both the hot year and the following year.

The problem—and plants that absorb less carbon definitely present a problem, since it is carbon uptake that serves as the basis for biomass, otherwise known as food, fuel and fiber—was that the heat triggered a drought in the year it occurred. That suppressed what’s called primary productivity, or how much plants grow as a result of carbon uptake. In all, carbon sequestration fell threefold over the study period of four years. It took two years for carbon uptake to return to what it was pre-heat wave. As the scientists put it, “more frequent anomalously warm years, a possible consequence of increasing anthropogenic carbon dioxide levels, may lead to a sustained decrease in carbon dioxide uptake by terrestrial ecosystems.”

Now, a rise of 4 degrees C. is more than global warming is expected to bring in this century as measured by global median temperatures. But local spikes of that magnitude are in the cards, and already happening. As the world warms, the scientists warn, "an increase in frequency and intensity of anomalously warm years may decrease the ability of terrestrial ecosystems to absorb CO² and store carbon.”

There is no small irony in the finding that warmer conditions cut carbon storage. One of the last great hopes for avoiding dangerous global warming is for plants to suck up more and more of the CO² the industrial world produces. Oh well.

The AP story  on John McCain’s taking a 48-44 lead over Barack Obama included this quite: “My heart sort of runs with McCain and my mind probably tends to run toward Obama,” said David Scorup, 58, a county government official in Othello, Wash. “I think I resonate more with McCain.”

That sent me scurrying for the latest on the power of emotions to sway voters—rational analysis of candidates’ positions and records be damned. I’ve written on the ascendancy of heart over head before, starting with a review in June 2007 of Drew Westen’s book “The Political Brain” and including the Newsweek story in February on how emotions trump reason. Most of the focus has been on how different candidates inspire fear or hope (with the former being more powerful than the latter), or even on how likable they are. But in an essay for the online salon Edge, psychologist Jonathan Haidt of the University of Virginia looks at something that may be even more potent: voters’ gut feelings about candidates’ moral values.

“When gut feelings are present, dispassionate reasoning is rare,” he writes—something every political psychologist I’ve spoken to this election year agrees with. “Feelings come first and tilt the mental playing field on which reasons and arguments compete,” he continues. “If people want to reach a conclusion, they can usually find a way to do so. The Democrats have historically failed to grasp this rule, choosing uninspiring and aloof candidates who thought that policy arguments were forms of persuasion.”

The Democrats, as Haidt sees it, have really blown it by thinking that morality is about fairness, equality, individual rights and other manifestations of how people treat one another and how society treats individuals. In fact, he writes, morality “is also about binding groups together, supporting essential institutions, and living in a sanctified and noble way. When Republicans say that Democrats ‘just don’t get it,’ this is the ‘it’ to which they refer.” And nothing arouses voters’ passions more strongly than morals and, especially, the perception that the other guy's are just plain wrong.

Haidt’s alternative definition of morality is “any system of interlocking values, practices, institutions, and psychological mechanisms that work together to suppress or regulate selfishness and make social life possible.” That means favoring self-control over self-expression, duty over rights, and loyalty to one’s groups over concerns for people different from you (racism, anyone?).

Many people have a gut instinct favoring policies that do this, such as by producing social cohesion and downplaying the rights of the individual (sex? abortion?) for the good of the group (intact nuclear families?). How many is “many”? According to Haidt, “one of the main reasons that so many Americans voted Republican over the last 30 years [is that] they honestly prefer the Republican vision of a moral order to the one offered by Democrats. . . . Conservative positions on gays, guns, god, and immigration must be understood as means to achieve one kind of morally ordered society. When Democrats try to explain away these positions . . . they err, they alienate, and they earn the label ‘elitist’.”

The plain fact is that many voters—we’ll see on November 4 if it’s “most” voters—value loyalty and respect for authority above values that liberals (mistakenly) think are synonymous with morality, such as fairness and caring for the less fortunate. (You can test which values you hold dearest at www.YourMorals.org.) Read Haidt’s essay, and you’ll be less puzzled about why working-class voters so often make election-day choices that go against their economic self-interest, the “what’s the matter with Kansas?” conundrum.

Now that Americans are hanging around virtual worlds almost as much (it seems) as the real one, research on how we behave in places like Second Life and how things like our choice of avatar spills over into the real world is heating up. As I described in a column last February, players who had super-attractive avatars have an exaggerated view of their real-world appearance and act accordingly. For instance, they believe that especially attractive men or women whose faces they’re shown from an online dating site would be interested in them. (When you have a more realistic view of your attractiveness, you dial down your expectations.) Now a study finds an uglier side to avatars: they display racist attitudes just as real people in the real world do.

In the experiment that Paul W. Eastwick and Wendi L. Gardner of Northwestern University describe in a paper called “Is It a Game? Evidence for Social Influence in the Virtual World,” published online in the journal Social Influence, one avatar asked another if he would teleport to Duda Beach (one of the sites in the virtual world There.com) with her and let her take a screenshot of him. (The him’s and her’s are interchangeable here; the scientists used male and female avatars in various permutations.)

The avatar was more likely to agree if that request had been preceded by a more unreasonable one: teleporting to 50 locations with her to take screenshots. That would have required about two hours of teleporting and traveling—an unreasonable request. When the one-beach request was presented alone, players were less likely to say okay.

What seems to happen—and this is true in real life as well—is that when you reject one request, and the requester then makes a second, more moderate one, you reciprocate what you perceive as her “concession” by going from brushing her off to acquiescing.

Then the scientists gave the avatar making the request dark skin. While white avatars got about 20 percent more of those they asked to agree to the modest request after the unreasonable one, the increase for the dark-toned avatars was only 8 percent. Even when the avatars modified what they were asking, players still mostly brushed them off.

Again back in the real world, decades of psychology studies have shown that whether or not someone agrees to a request under these experimental conditions—and also in real life—depends on whether they think the requester is worthy of impressing, For dark-skin avatars, apparently, the answer is, not so much. I should add that the players knew they were part of a psych study; not even that had a significant effect on (let's just say it) racism.

“You would think when you’re wandering around this fantasyland, operating outside of the normal laws of time, space and gravity and meeting all types of strange characters, that you might behave differently,” Eastwick said. “But people exhibited the same type of behavior, and the same type of racial bias, that they show in the real world all the time,” where people are more uncomfortable with minorities and less likely to help them.

With all the ways cancer cells can elude chemotherapies (as well as radiation, for some of the same reasons: radiation damages DNA, but malignant cells activate DNA-repair mechanisms), it may seem a miracle that anyone beats cancer. Yet clearly, millions of people do; some living with it for decades, others having no detectable malignancies by the end of treatment. What gives?

I put this question to Keith Block, an innovative oncologist who runs the Block Center for Integrative Cancer Treatment in Evanston, Illinois, and who is also the director of Integrative Medical Education at the University of Illinois College of Medicine, editor-in-chief of the journal Integrative Cancer Therapies, and scientific director of the Institute for Integrative Cancer Research & Education. As you can tell from the names of the programs Block is involved in, he practices integrative care: he uses all of the standard chemo and radiation treatments, but supplements those with a program of fitness, diet and mind-spirit interventions (stress reduction, improving sleep and the like).

The goal of the latter is not only to make getting through treatment less torturous (Block's diet and natural supplement programs include steps to reduce nausea, for instance), but also—primarily, I should say—to improve patients’ chance of surviving. Many, many patients with cancer actually die not from failure of an organ that cancer has attacked, but from things such as embolisms (clots in the lung, often thrown off by a tumor), pneumonia (from a weakened immune system), sepsis and wasting—in short, secondary consequences of the cancer. Patients with, say, lung cancer who die of an embolism are usually categorized as dying of their cancer—that’s how the hospital classified them when they entered, and that’s how it classifies them when they leave—so these causes of death don’t show up in cancer mortality data. But Block believes that targeting them could significantly extend survival, and in patients who do make it, the reason may be that their internal "terrain," or microenvironment, is hostile to cancer.

Block calls his program Life Over Cancer, and he has some strong ideas about why some people truly beat cancer. In addition to warding off these secondary causes of death, he says, the key factor is making a patient’s internal microenvironment—the biochemical milieu around cancer cells—hostile to malignant cells. Block’s program is aimed at doing that, so that rogue cells that split off from the primary tumor, and that are the chief reasons patients relapse and, too often, die, never take hold. “We have almost completely ignored the environment that cancer sits in,” he told me, “and put all our bullets toward the cancer itself, even when it’s clear that the microenvironment matters.”

That started to become apparent in the early 1980s, with hints that the presence of inflammatory molecules (as in diabetics who also have cancer) meant a poor prognosis. In the 1990s came evidence that the higher a lung-cancer patient’s blood sugar, the worse the prognosis—again, because something about glucose supports the proliferation of cancer cells, and inflammation seems to make cancer cells less vulnerable to chemo and radiation.

In the magazine story this week, I wrote about several leading oncology researchers who couldn’t get funding for one or another innovative idea (including those that eventually led to Gleevec and Herceptin). Block has had similar experiences. “You get funded by NCI for very narrowly-focused research,” he noted. “The problem is, that’s not biological reality.” There have been no large, controlled studies of these complicated interactions between aspects of the internal microenvironment and the march of malignancy.

Despite hints from small studies that breast-cancer patients, for instance, can cut their risk of dying of their disease by 50 percent if they stay fit and are not overweight, says Block, ‘there was almost no funding in this area in the 1980s and 1990s,” and little more now.

Instead, the support goes to research aimed at finding the next chemo. “This kind of focus reflects the magic-bullet mindset of cancer care,” says Block. “We’re so focused on the single defect or disruption [that can mortally wound a cancer cell] because it’s easy to do that research. The Achilles heel mindset, that if you hit cancer in one place the whole thing will come tumbling down, is why we haven’t gotten further.”

Studies that do not fit the Achilles heel paradigm are especially tough to get funded. Block gives the example of pairing the herb astragalus with the mainline chemo drug oxaliplatin, which seems to improve survival in lung-cancer patients. A 2006 analysis of 34 clinical trials of herbal formulas containing astragalus found a 34 percent improvement in the response to chemotherapy and 33 percent reduction in the risk of death among patients receiving astragalus. Yet don't expect to see a large-scale, definitive study of this or any other herbal anytime soon. 

Other proposals in integrative care have also been dead on arrival. In 1997 Block and his colleagues proposed a study on the effects of vegetarian diets in breast cancer. In 2002 they proposed one on an integrated program of diet/fitness/stress reduction for prostate cancer patients. In 2006, they proposed studying how fish oils affect the microenvironment. In 2007, they proposed a pilot study of a diet/exercise/stress management program for breast cancer patients receiving chemotherapy. In every case, no go, even though preliminary studies suggested that these interventions might make a big difference in patients' microenvironment and therefore on their chancer of surviving cancer.

“They did not receive funding for a variety of reasons,” Block told me, “but mainly they were considered too ambitious--an obvious problem with multi-dimensional interventions, at least for reviewers who are accustomed to study designs that are very simple, one dimensional and reductionistic) We have had a number of conversations with staff members at NIH who explained that they are very reluctant to fund studies that involve complex or multi-component interventions because they are considered difficult to interpret scientifically.”

Block continued: “The fact is, our research system is great at studying what we know how to do easily. But it does not necessarily get us the results we need. So, instead of changing the system, we stick with it and keep repeating it over and over and over again.”

This week’s story paints a fairly bleak picture of cancer therapy 37 years after the start of the war on cancer, but as I spoke to some of the nation’s leading oncologists about their memories of when they first entered the field, I was struck by two things: the real progress that has been made since 1971, and their remarkable ability to remain hopeful in the face of a disease that, 1,500 times a day (that's how many people in the U.S. will die of cancer every day this year), reminds them that cancer keeps winning far too many battles.

David Johnson of Vanderbilt-Ingram Cancer Center was in medical school in 1971, the year Richard Nixon declared war on cancer in his State of the Union speech. Oncology wasn’t even recognized as a medical specialty, Johnson recalled to me. “Cancer wasn’t something you talked about much, except to note that it existed and that patients didn’t do well,” he said.

The first cancer patient Johnson had as a young resident was a man with small-cell lung cancer. “It was so rapidly progressive,” he said. “Patients might live a few weeks without treatment. I remember preparing for my presentation to the attending physician, spending hours in the library to learn everything I could about this disease. As we moved down the hallway to this patient’s room, I became increasingly anxious. I’ll never forget it as long as I live: I began, saying 'Mr. So-and-so is a 63-year old man with a diagnosis of small-cell lung cancer . . . ' And the attending shook his hand in my face: ‘this is not a disease for which we have a lot to offer; let’s move on.’”

Johnson’s initial reaction, he recalled to me, was that he was off the hook as far as presenting the case went. But then he felt mounting frustration. “I said to myself, wait a minute, why isn’t there something we can do for this man?” Johnson told me. “It influenced my thinking about cancer from then on. The whole idea of going to medical school was to help people. If doctors can’t do anything, there’s something wrong with this picture.”

By the mid-1970s, oncologists had made some progress against the liquid cancers, as they’re called—leukemias and lymphomas—and had shown that giving chemotherapy after a women with breast cancer has had a mastectomy increases the chance that she’ll remain cancer-free and survive. “For solid tumors, there was a presumption that the cytotoxic drugs used in leukemia would also work,” Johnson recalled, “but these cancers didn’t respond as well. The reason leukemias are vulnerable [to chemo agents that barely lay a glove on solid tumors] is that the disruption in the signaling pathways aren’t as complex as they are in solid tumors: there are maybe one or two in leukemias compared to 20 or 40 in solid tumors.”

That was the most common refrain I heard as I spoke to one after another oncologist about why, as one put it to me, the dumbest cancer is smarter than the most brilliant oncologist: cancer cells can use any of dozens if not scores of biochemical pathways to proliferate and spread. Stop one and the cells turn on a different one, kind of like squeezing a balloon squashes it here but just makes it bulge out somewhere else.

Johnson specializes in lung cancer, as did a few oncologists I spoke to, and every one of them was remarkable for his or her unflagging optimism against an implacable foe (lung cancer is the nation’s leading cancer killer). In Johnson’s case, he remembers vividly the first baby steps toward fighting this disease, in the mid-1970s and early 1980s,when some of the DNA-breaking drugs such as methotrexate shrank tumors. But as would become clear even with the much-ballyhooed targeted therapies, shrinking a tumor does not mean cure or even, necessarily, long-term remission.

“The more recalcitrant tumors have redundant systems to let them escape from what we throw at them,” Johnson told me. “In lung cancer, each cell has multiple abnormalities, and one cell might be next to one with eight different abnormalities. These solid tumors have the capacity to elude the various therapies we throw at them. A solid tumor goes away on an x-ray, and then it comes back: you’d have to be a functional moron not to realize that the cancer cell has figured out how to get around the therapy.”

The goal is to keep throwing different therapies at the cancer, choosing the therapies so that they target the precise proliferation pathways the cancer is using. “We are truly within a few years of being able to profile tumors so that I can say to a patient, ‘we shouldn’t use this drug on you, because it won’t help, but we should use this one,’” Johnson said.

When I asked Johnson how he felt about critics who say we have made embarrassingly little headway against cancer since 1971, he said, “I don’t know any investigator or clinician who’s satisfied with the progress that’s been made.”

The fact that cancers elude chemotherapy so often raises the obvious question: how does anyone go into remission and stay there, truly beating cancer? Some ideas on that tomorrow.

Mea culpa: Lab Notes was missing in action last week because I couldn’t tear myself away from interviewing oncologists for the story in this week’s magazine [] about the war on cancer. I wanted to chart the progress that has been made against the disease in the 37 years since Richard Nixon launched the war on cancer, and that meant talking to researchers and clinicians who have been in trenches for several decades. 

Their stories were heartbreaking, not only for the patients they lose but for the missed opportunities.

Gerold Bepler, chief of the division of thoracic oncology (that’s lung cancer) at H. Lee Moffitt Cancer Center, started his Ph.D. thesis on Hodgkin’s lymphoma in 1980 and then turned to lung cancer as a post-doctoral fellow. He recalled that the big breakthroughs in lung-cancer chemotherapy 25 years ago let patients with small-cell lung cancer survive a year instead of six-to-eight weeks, as had been the case before cisplatinin and other drugs were developed. “With non-small-cell lung cancer,” he recalls, “the response rate was much lower, maybe 15 to 20 percent, and it had remarkable toxicity. You wondered, were you really helping people if you made them so sick for the little extra time that you kept them alive?”

“The next breakthroughs were anti-nausea drugs in the mid-1980s to early 1990s. Cisplatinin became much easier to give. I remember people throwing up for a week at a time, before these drugs, when they got chemo once every three weeks. Suddenly, with the anti-nausea drugs, chemo became tolerable,” Bepler told me.

And what counts as progress against lung cancer? In the 1990s, 14 to 15 percent of patients lived at least five years. Today, Bepler said, 16 to 17 percent do. “It’s a very small number, and we are far, far, far from being able to cure this disease.”

Why is it so tough to treat? “Lung cells have developed mechanisms to cope with genotoxic stress,” Bepler told me. That means that the chemo drugs that act by damaging DNA, so that malignant cells cannot replicate, eventually stop working: the cancer cells turn on DNA-repair mechanisms or other pathways that render the chemo agents useless.

Like so many of the scientists I interviewed, Bepler points to many missed opportunities over the 37 years of the war on cancer. In his case, he proposed a study in the mid-1990s in which researchers would have taken samples of lung cancers, analyzed and stored them, and then determined which molecular profiles predicted response to which existing or future chemo drugs. “I struggled to get NCI [National Cancer Institute] approval,” Bepler said. “What gets funded depends on what people think at the time is hot, or in. I’ve served on NCI study sections [those are the panels of, usually, outside scientists who review grant proposals and score them, determining which get funded] so I can see it from both perspectives. When you start reading the applications, you are automatically drawn to the ones perceived to be interesting,” sometimes losing sight of the fact that the goal here is to treat cancer and not (only) discover cool things about the molecular biology of cancer. “In my case, people thought the idea couldn’t be implemented in patients because they didn’t think patients would be willing to have repeated biopsies,” which is what would have been required to match their tumor to a particular chemo drugs.