Evolution suffers Kansas setback

From BBC News:Darwin_afp203body

The US state of Kansas has approved science standards for public schools that cast doubt on evolution. The Board of Education’s vote, expected for months, approved the new language criticising evolution by 6-4. Proponents of the change argue they are trying to expose students to legitimate scientific questions about evolution. Critics say it is an attempt to inject creationism into schools, in violation of the constitutional separation between church and state. The decision is part of an ongoing national debate over the teaching of evolution and intelligent design. The theory of intelligent design holds that the universe is so complex that it must have been created by a higher power.

Tuesday’s vote was the third time in six years that the Kansas board has rewritten standards with evolution as the central issue.

More here.

Engrossed in a World of Political Idealism

From The New York Times:

Most television dramas play with the question “what if?” NBC’s “West Wing” revels in “if only….”

Sunday’s live presidential debate was the quintessence of wishful writing. Two intelligent, principled candidates tossed aside debate rules and went at each other full throttle on live television, debating everything from immigration and energy policy to foreign debt relief.

The world hates us, and even Americans deplore the sorry state of political discourse in their country. But only the uninformed or disingenuous complain about the quality of American television. It has a variety and breadth that no other nation can match. For every offensive reality series or inane daytime talk show, there are comedies and dramas that reach far higher in a single episode than most movies or Broadway shows.

More here.

November 8, 2005

Uncool Cities

From London and Berlin to Sydney and San Francisco, civic authorities agree that the key to urban prosperity is appealing to the ‘hipster set’ of gays, twentysomethings and young creatives. But the only evidence for this idea comes from the dot-com boom of the late 1990s—and that time is over.”

Joel Kotkin in Prospect Magazine:

Yet rather than address serious issues like housing, schools, transport, jobs and security, mayors and policy gurus from Berlin and London to Sydney and San Francisco have adopted what can be best be described as the “cool city strategy.” If you can somehow make your city the rage of the hipster set, they insist, all will be well.

New Orleans, the most recent victim of catastrophic urban decline, is a case in point. Once a great commercial hub, the city’s economic and political elites have placed all their bets on New Orleans becoming a tourist and culture centre. Indeed, just a month before the disaster, city leaders held a conference that promoted a “cultural economy initiative” strategy for attracting high-end industry. The other big state initiative was not levee improvement but a $450m expansion for the now infamous convention centre.

This rush to hipness has its precedents, perhaps even in Roman festivals or medieval fairs. But in the past, most cities did not see entertainment as their main purpose. Rome was an imperial seat; Manchester, Berlin, Chicago and Detroit foundries of the industrial age; London, New York, and later Tokyo, global financial centres.

More here.

terror bill could turn academics into criminals

Polly Curtis and Matthew Taylor in The Guardian:

The Association of University Teachers says the new offences of encouraging or training for terrorism could effectively outlaw an ethics debate about political violence, or a chemistry lesson.

“The major problem is you don’t need proof that you are intending to encourage terrorism,” says Jonathan Whitehead, the AUT’s head of parliamentary and public affairs. “And on the training law, the definition is anyone who ‘knows or suspects’ that the training could be used for terrorist purposes. Lecturers will have to start having suspicions about their students.”

Now Universities UK, which represents vice-chancellors, has taken up the issue, alongside the AUT and Sconul. Vivienne Stern, public affairs advisor to Universities UK, says: “The bill is unacceptably wide and will, in our view, expose academic staff and librarians – and by virtue of that the university management – to the risk of committing criminal offences during their standard work.”

More here.

petah coyne

Picksimg_large_4

Returning to the SculptureCenter, host of her breakthrough debut in 1987, the queen of mixed media brings nearly two decades of prolific creation full circle. Laboriously constructed from hair, wax, chicken wire, silk, hay, tar, ribbon, and myriad other materials, her trademark hanging, spreading, or climbing tangles, lumps, and clumps—simultaneously repulsive and gorgeous—stage encounters with delicacy and ponderousness, purity and dreck. With fourteen large-scale sculptures and eight dreamlike black-and-white photographs on view, this nineteen-year survey promises the quintessential Coyne experience.

from Artforum.

The Literary Darwinists

D. T. Max in the New York Times Magazine:

For the common reader, “Pride and Prejudice” is a romantic comedy. His or her pleasure comes from the vividness of Austen’s characters and how familiar they still seem: it’s as if we know Elizabeth and Darcy. On a more literary level, we enjoy Austen’s pointed dialogue and admire her expert way with humor. For similar reasons, critics have long called “Pride and Prejudic” a classic – their ultimate (if not well defined) expression of approval.

But for an emerging school of literary criticism known as Literary Darwinism, the novel is significant for different reasons. Just as Charles Darwin studied animals to discover the patterns behind their development, Literary Darwinists read books in search of innate patterns of human behavior: child bearing and rearing, efforts to acquire resources (money, property, influence) and competition and cooperation within families and communities. They say that it’s impossible to fully appreciate and understand a literary text unless you keep in mind that humans behave in certain universal ways and do so because those behaviors are hard-wired into us. For them, the most effective and truest works of literature are those that reference or exemplify these basic facts.

More here.

Houston Hip-Hop

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In the fall of 1991, an unusual song found its way onto the radio. It was called “Mind Playing Tricks on Me,” and was performed by a Houston hip-hop trio called Geto Boys. A slow, mournful plaint, “Mind” relied on long, harmonically complex guitar samples—a departure from the short horn bursts and rapid drums then dominating hip-hop. If the song had an antecedent, it was the blues, not music you might have heard in a disco. Geto Boys—Scarface, Bushwick Bill, and Willie D—had deep, unmistakably Southern voices, and their lyrics didn’t celebrate or protest anything. “Mind” is an unsettling song, its opening couplets freighted with anxiety: “At night I can’t sleep, I toss and turn. / Candlesticks in the dark, visions of bodies being burned. / Four walls just staring at a nigger. / I’m paranoid, sleeping with my finger on the trigger.” For several months, “Mind” was on the radio all the time. Then Geto Boys—and Southern hip-hop—seemed to disappear. In the fourteen years since “Mind” was released, the band has showed up again on the Billboard pop charts only twice, most recently in 1996.

more from Sasha Frere-Jones at The New Yorker here.

Gender divide in getting the joke

From BBC:Laughing203

The latest study used sophisticated scans to monitor the brains of 10 men and 10 women as they watched 70 black-and-white cartoons. The researchers found similarities between the way that male and female brains respond to humour. But some brain regions were activated more in women, including both the left prefrontal cortex and the mesolimbic reward centre. The researchers say their findings suggest women place a greater emphasis on the language of humour, possibly employing a more analytical approach. They also believe that the women in the study were less likely to expect the cartoons to be funny – so when they were, their pleasure centre lit up with greater intensity than their male counterparts.

More here.

Down for the Count

From The New York Times:Babbon

Today animals sleep in many different ways: brown bats for 20 hours a day, for example, and giraffes for less than 2. Sleep was once considered unique to vertebrates, but in recent years scientists have found that invertebrates likes honeybees and crayfish sleep, as well. The most extensive work has been carried out on fruit flies. “They rest for 10 hours a night, and if you keep them awake longer, they need to sleep more,” said Dr. Giulio Tononi, a psychiatrist at the University of Wisconsin. Discovering sleep in vertebrates and invertebrates alike has led scientists to conclude that it emerged very early in animal evolution – perhaps 600 million years ago.

Scientists have offered a number of ideas about the primordial function of sleep. Dr. Tononi believes that it originally evolved as a way to allow neurons to recover from a hard day of learning. “When you’re awake you learn all the time, whether you know it or not,” he said. Learning strengthens some connections between neurons, known as synapses, and even forms new synapses. These synapses demand a lot of extra energy, though. “That means that at the end of the day, you have a brain that costs you more energy,” Dr. Tononi said. “That’s where sleep would kick in.”

More here.

Gaza: A Dubai on the Mediterranean

Sara Roy in the London Review of Books:

Last April President Bush said that Israel’s withdrawal from Gaza would allow the establishment of ‘a democratic state in the Gaza’ and open the door for democracy in the Middle East. The columnist Thomas Friedman was more explicit, arguing that ‘the issue for Palestinians is no longer about how they resist the Israeli occupation in Gaza, but whether they build a decent mini-state there – a Dubai on the Mediterranean. Because if they do, it will fundamentally reshape the Israeli debate about whether the Palestinians can be handed most of the West Bank.’

Embedded in these statements is the assumption that Palestinians will be free to build their own democracy, that Israel will eventually cede the West Bank (or at least consider the possibility), that Israel’s ‘withdrawal’ will strengthen the Palestinian position in negotiations over the West Bank, that the occupation will end or become increasingly irrelevant, that the gross asymmetries between the two sides will be redressed. Hence, the Gaza Disengagement Plan – if implemented ‘properly’ – provides a real (perhaps the only) opportunity for resolving the conflict and creating a Palestinian state. It follows that Palestinians will be responsible for the success or failure of the Plan: if they fail to build a ‘democratic’ or ‘decent mini-state’ in Gaza, the fault will be theirs alone.

More here.

Gigantic Apes Coexisted with Early Humans, Study Finds

Bjorn Carey in LiveScience:

051107_giant_ape_01A gigantic ape standing 10 feet tall and weighing up to 1,200 pounds lived alongside humans for over a million years, according to a new study.

Fortunately for the early humans, the huge primate’s diet consisted mainly of bamboo.

Scientists have known about Gigantopithecus blackii since the accidental discovery of some of its teeth on sale in a Hong Kong pharmacy about 80 years ago. While the idea of a giant ape piqued the interest of scientists – and bigfoot hunters – around the world, it was unclear how long ago this beast went extinct.

Now Jack Rink, a geochronologist at McMaster University in Ontario, has used a high-precision absolute-dating method to determine that this ape – the largest primate ever – roamed Southeast Asia for nearly a million years before the species died out 100,000 years ago during the Pleistocene period. By this time, humans had existed for a million years.

More here.

Can the C.I.A. legally kill a prisoner?

Jane Mayer in The New Yorker:

051114mast_1_13166f_p198After September 11th, the Justice Department fashioned secret legal guidelines that appear to indemnify C.I.A. officials who perform aggressive, even violent interrogations outside the United States. Techniques such as waterboarding—the near-drowning of a suspect—have been implicitly authorized by an Administration that feels that such methods may be necessary to win the war on terrorism. (In 2001, Vice-President Dick Cheney, in an interview on “Meet the Press,” said that the government might have to go to “the dark side” in handling terrorist suspects, adding, “It’s going to be vital for us to use any means at our disposal.”) The harsh treatment of Jamadi and other prisoners in C.I.A. custody, however, has inspired an emotional debate in Washington, raising questions about what limits should be placed on agency officials who interrogate foreign terrorist suspects outside U.S. territory.

This fall, in response to the exposure of widespread prisoner abuse at American detention facilities abroad—among them Abu Ghraib; Guantánamo Bay, in Cuba; and Bagram Air Base, in Afghanistan—John McCain, the Republican senator from Arizona, introduced a bill in Congress that would require Americans holding prisoners abroad to follow the same standards of humane treatment required at home by the U.S. Constitution.

More here.

November 7, 2005

Dispatches: Divisions of Labor

This Wednesday, graduate students at New York University will begin a strike with the intention of forcing NYU’s administration to bargain with their chosen collective agent, the union UAW/Local 2110.  (Full disclosure: I am one such, and will be participating in this action.)  This situation has been brewing for months, as the union’s contract with NYU, dating to 2001, expired in August.  That contract was something of a historic event, since it recognized the right to unionize of graduate students at a private university, for the first time in U.S. history.  That decision was helped along by a (non-binding) arbitration by the National Labor Relations Board, which ruled that NYU graduate students were workers in addition to being students.  Owing to turnover in the Board, however, and the Bush administration’s appointment of anti-labor replacement members, the Board has since reversed its precedent-setting decision in reference to a similar dispute at Brown University.  Though this is not a binding decision, and NYU is under no compulsion to derecognize its graduate student union, this is exactly what it has done, albeit while attempting to produce the impression that they tried and failed to come to an agreement. 

In actuality, the administration did not come to the bargaining table until August, at which point they issued a ultimatum to the graduate student union, insisting that they agree to a severely limited ‘final offer’ in forty-eight hours.  Made in bad faith, this offer was of course rejected, as it would have been impossible even to organize a vote of union members in the span allotted.  But it did allow President John Sexton and his administration to claim to have made an offer and been refused, which they have lost no opportunity to repeat in a series of inflammatory emails and letters to the student community.  Last week, in the wake of the union’s announcement that members had voted by approximately eighty-five to fifteen percent in favor of striking, the university administration sent yet another such communique, this time from Provost David McLaughlin, with the subject line ‘UAW votes to disrupt classes.’  Strategically, the administration seems to believe that by avoiding all reference to graduate students, and instead identifying the source of ‘trouble’ as ‘Auto Workers,’ the undergraduates and larger community might be convinced that the strike is simply the deluded power grab of a few dissatisfied individuals in league with an extraneous group.  Yet the transparency of the university’s rhetoric has had the opposite effect: undergraduates and faculty alike have been radicalized in support of graduate students.  My own students, for instance, have been extremely understanding, comprehending perfectly that graduate students’ teaching, for which a paycheck is received, tax and social security having been withheld, is work.

Politics, it is said, makes curious bedfellows.  One such pairing has occurred as a result of the current NYU situation.  The physicist Alan Sokal is best known for his 1996 article, published in Social Text, attempting to expose the spurious nature of references to math and science in the work of high theorists such as Derrida and Lacan.  His article, which purported to demonstrate twentieth-century physics’ confirmation of the anti-realism of post-structuralist theory, was duly accepted and published in a special issue of the journal on ‘Science Wars.’  After his revelation that the article was a ‘hoax,’ a small repeat of the two cultures conflagration ensued.  Responses abounded, including a rebuttal from Andrew Ross, professor of American Studies at NYU and the co-editor of the issue.  The entire episode has received its most detailed accounting and most rigorous intellectual genealogy (tracing the roots of this debate back to the development of logical positivism) in an article by yet another NYU professor, John Guillory.  That piece, ‘The Sokal Affair and the History of Criticism,’ is well worth reading, not least for its clarification that the stakes in the two cultures debate are not necessarily related to one’s position vis-a-vis ‘postmodernism’ or cultural studies, which, as Guillory convincingly demonstrates, has no fixed relation to particular political stances.  The current labor strife at NYU reconfirms this analysis, as Sokal and Ross find themselves on the same side of the barricades as members of Faculty Democracy, the faculty organization urging the NYU administration to bargain with the graduate student union.

Sokal has written this clear-eyed summary (to which Robin previously linked) of the issues involved, and his commonsensical tone is a much-appreciated palliative in the midst of rhetorically overheated statements issuing from many quarters.  Perhaps most importantly (and most ironically for someone who has been lambasted as an ‘unreconstructed’ leftist), Sokal points out that the paternalism of the administration’s position should be rejected.  Whether or not one considers the graduate students to be right in their cause, he points out, their democratically decided resolution to collectivize in order to negotiate contracts should be respected.  Sokal’s distaste for the increasingly rapid transformation of the university into an institutional substitute for parental duties (and a remedial solution to the decrepitude of public high school education) is one I share.  I would add that the current impasse is more a matter of structural conflict than of political sympathy.  Private universities as they exist today depend on a pyramidal structure: a large number of graduate students at the bottom of the labor force are needed to perform much of undergraduate teaching, while at the top of the pyramid are ever fewer tenured faculty.  Even these can be further divided into ‘stars’ who command greatly disproportionate income while having few teaching responsibilities, and the lower order of adjunct professors who perform much of the remedial education in such subjects as composition.  This system necessarily produces many more credentialed Ph.D.’s than the labor market can employ at the higher levels, which in turn means that many graduate students spend years teaching for a pittance without making it to the security of a tenured position.  Hence the pressure on this beleaguered strata to unionize, so as to ensure a modicum of stability of salary and benefits. 

Though they are a transient class, passing through degree programs, as opposed to a permanent workforce, graduate students have thus come to bear a very large portion of the daily labor of teaching undergraduates.  Interestingly, what the commotion about this strike has appeared to ignite at NYU is a debate about collectivism.  While many are fully willing to grant a certain ethical status to the picket line, and so defer to the right to strike that has been the hallmark victory of the labor movement, the union’s opponents (be they faculty or students) tend to retreat to personal responsibility as the ground on which to base such decisions.  Thus does American individualism reappear in the debate, as usual licensing those for whom ethical imperatives are always imposed from without, rather than perceived from within.  Combined with the detached, analytical impulse that intellectual work requires, this produces a strong ideological propensity for members of this particular class of workers to dissent from counting themselves as part of a collective organization, with the exception, of course, of their belonging to the university itself.  Membership in the university, however, is mystified by the institution’s self-image as the social location outside of or beyond corporate culture and other more baldly hierarchical sites of work.  That the intellectual and editorial freedom that the university trumpets as its role to protect might conflict with the conditions under which that freedom is maintained is a paradox that remains all too often unclear to the participants in this debate.  Whether the temptation to fall back on just this founding myth of the university will prove to be the union movement’s undoing, we shall discover in the days and weeks ahead.

Dispatches:

Local Catch
Where I’m Coming From
Optimism of the Will
Vince Vaughan…Eve Sedgwick
The Other Sweet Science
Rain in November
Disaster!
On Ethnic Food and People of Color
Aesthetics of Impermanence

Rx: The War on Cancer

I will also ask for an appropriation of an extra $100 million to launch an intensive campaign to find a cure for cancer, and I will ask later for whatever additional funds can effectively be used. The time has come in America when the same kind of concentrated effort that split the atom and took man to the moon should be turned toward conquering this dread disease. Let us make a total national commitment to achieve this goal. America has long been the wealthiest nation in the world. Now it is time we became the healthiest nation in the world.–-President Richard M. Nixon in his 1971 State of the Union address.

I. THE SITUATION AT PRESENT

The famous Greek doctor and the author of the Hippocratic oath defined cancer as a disease which spreads out to grab parts of the body like “the arms of a crab”. What proves fatal for the victim is the spread of the cancer cells beyond the site of origin, and in this sense, it was a thousand years later that Avicenna of Baghdad, noticed that “a tumor grows slowly and invades and destroys neighboring tissues”. Faithful to its name in more ways than could possibly have been anticipated by Hippocrates, the disease which has launched the $200 billion “War on Cancer” in America continues to spread, invading the lives of almost every family. Based on available data, there were 10.9 million new cases of cancer worldwide, 6.7 million deaths, and 24.6 million persons who had been diagnosed with cancer in the previous five years. Like in many other areas, unfortunately the USA is leading this one as well. More than 1.5 million Americans develop cancer each year claiming some 563,700 lives, killing more Americans in 14 months than the combined toll of all wars the nation has ever fought (a new cancer is diagnosed every 30 seconds in the United States, about 1,540 dying each day from their disease). A look at the worldwide incidence of cancer raises some puzzling issues, especially related to the unexpectedly high incidence of cancers in the USA:

Clip_image001

If we ascribe the increased incidence solely to the aging of the population, then why is the incidence so much higher in the USA than in some of the developed countries where life expectancy is comparable? On the other hand, if lifestyle is more important as suggested by the association of smoking and cancers of the lung, then why is this incidence not equally high in countries where people smoke at least as much as in the USA? One answer could be that the smokers in countries such as South America or India do not live long enough to develop cancer. However, the incidence of lung cancer in Sweden with an average life expectancy of 80.3 years is less than half of that in the USA which has a life expectancy of 77.4 years ((22 versus 55.7 per 100,000 respectively) even though 22% adults smoke in both countries. This suggests that lifestyles may be important, but that smoking may not be the only important factor.

Table 1. Approximate incidences of daily smoking among adults in different geographic areas.

Sweden

Europe

Eastern
Europe

the Middle
East

Turkey

The rest of
Asia

South
Amerika

Africa

Man

 

22

46

60

41

63

44-54

40

29

Female

24

26

28

8

24

4-7

21

4

 

Källa: Tobacco Alert. Geneva: World Health Organization, Programme on Substance, 1996

Clip_image001_1

The idea that genetic predisposition to cancer may have something to do with these high American numbers has been largely laid to rest by the experience of the Japanese who immigrated to America. Both the incidence of cancer, as well as the types of cancer, were quite different between the fresh immigrants and their American counterparts, however these differences disappeared in the second generation Japanese Americans who adopted the local lifestyle.

II. PROBLEMS IN THE FIGHT AGAINST CANCER

President Nixon declared the War on Cancer 34 years ago using the 100 words which stand as an epigraph for this essay. Acknowledging the fact that the tools necessary to accomplish the task were missing, the mandate was to invest money in research and apply the results to reduce the incidence, morbidity and mortality from cancer. After spending approximately $200 billion (if we add up the taxes, industry support etc) since 1971 on this war, 150,855 experimental studies on mice and publication of 1.56 million papers, the results can best be summarized in this one graph:

Clip_image001_2

While deaths from heart disease have declined significantly in the last 30 years, the percentage of Americans dying from cancer, save for those with Hodgkin’s, some leukemias, carcinomas of the thyroid and testes, and some childhood cancers, is about the same as in 1950. For the last twelve years, there is a 1% decline annually in cancer mortality. Early detection has had some significant impact, but once the cancer has spread, the outcome has generally not changed for the last half a century.

As someone who has been directly involved in cancer research since 1977, and obsessed by it for longer, I am a first hand witness to the by now familiar cycles of high expectation and deflating disappointments which have been its hallmark for the last three decades. Because the stakes are so high, both in terms of life-death issues as well as the staggering nature of the finances involved, emotions tend to run high on all sides. In this, and a series of subsequent essays, I would like to summarize some of the rather obvious reasons why this war on cancer has not manifested the anticipated, tangible signs of victory so far, as well as the dramatic gains that have been achieved at the scientific level as a result of this unprecedented investment in basic science. I hope that at the end of it all, you will be able to view the score-card dispassionately and declare a winner.

  • Even though President Nixon, and subsequent administrations have continued to invest heavily in cancer research, the dedicated budget for the National Cancer Institute alone rocketing up to more than seven billion this year, the monies are not being spent as wisely as they could be. For example, the funding agencies tend to reward basic research being performed in Petri dishes and mouse models that bear little relevance for humans, 99% investigators using xenografts. Imagine the exceedingly contrived scenario of achieving a “cure” in a severely immune-compromised animal injected locally with human tumor cells and then treated with a strategy being tested. Is it a surprise when the results cannot be reproduced in humans? Basic cancer research may one day be successful at identifying the signaling pathways that determine malignant transformation, however, it will be a long time before the entire process of cancer initiation, clonal expansion, invasion, and metastases is understood, especially in the context of the highly complex, poorly understood micro-environment in which the seed-soil interaction is occurring. Using this approach, an effective therapy for cancer can only be developed essentially after we understand how life works. Can our cancer patients afford to wait that long? Isn’t the history of medicine replete with examples of cures obtained years, decades, and even centuries before the mechanism of action was fully understood for these cures? What about digitalis, aspirin, cinchona, vaccination? Another problem with the funding is that the basic scientists have encouraged each other to focus on defining the earliest molecular events even though >90% cancers kill through expansion and metastasis, 92% of the ~9,000 grants awarded last year having no mention of the word metastasis.
  • There is an odd love-hate relationship that has developed between Academia and the Pharmaceutical industry. On the one hand, major research and development (R&D) efforts by industry, conducted under great secrecy, result in the identification of potentially useful novel agents which nonetheless must ultimately be tested in humans. Credible clinical trials in human subjects are conducted by academic oncologists. On the other hand, advances being made in the laboratories of academic researchers need the partnership of industry for commercial and widespread application. This forces the Industry and Academia to become reluctant bedfellows. Roughly 350 cancer drugs are in clinical trials now.
  • In order for a drug to show efficacy, FDA demands that it be tested first in animal models that are not relevant to humans. To make matters worse, when the drugs are approved for human trials, they can only be tested in terminally ill patients. Many agents that would be effective in earlier stages of the disease are therefore thrown out like the baby with the bathwater. Finally, the end point sought in most drug trials even in end stage patients, continues to be a significant clinical response. Very few, if any, surrogate markers are used to gauge the biologic effects of the drugs. The surrogate or bio-markers include proteins being produced by the abnormal genes, as well as processes and pathways that distinguish cancer cells from normal cells such as formation of new blood vessels or angiogenesis. If a drug does not produce the desired clinical end point, it is then likely to be abandoned completely, even though its biologic activity could be harnessed for more effective use in combination with other agents.
  • As the internet dotcom bubble burst in the 90s, the bi-technology industry was the big winner since some of the best minds in the country made lateral moves and began to invest their talents in this area. The striking change over the last decade in the pharmaceutical industry has been its ability to attract and retain high caliber academic scientists and clinical investigators. Even with this vital infusion, it takes 12-14 years and a prohibitive ~800 million dollars for a pharmaceutical company to get a new drug approved, most of the money having been raised from the private sector which is clamoring for a profit. Following the arduous R&D process and the tedious, time consuming and labor intensive animal studies, by the time a clinical trial is undertaken in human subjects, the stakes are already too high and companies may have to be struggling to demonstrate the tiniest statistical benefits over each other’s products.
  • The catch phrase today is “Trageted Therapies”; the concept that a convergence of science and advanced technologies will illuminate the cumulative molecular mechanisms that ultimately produce cancer, and this will lead to an objective drug design to pre-empt or reverse the cancer process. Except for the drug Gleevec developed against Chronic Myeloid Leukemia (CML), a rare type of leukemia in which single gene mutation underlies the pathology, all other Targeted therapies so far have met with modest successes. For example, the recently approved Erbitux and Avastin for cancer of the colon and rectum improved survival by 4.7 months when given in conjunction with chemotherapy. Even in the area of targeted therapies, the efforts are frequently scattered. Academia, Industry and Institutions such as the NCI, FDA, CDC, EPA, DOD etc are not coordinating their resources efficiently. For example, hundreds of researchers across the nation are performing gene expression and proteomic experiments, diluting the number of specific cancers examined for potential targets instead of developing organized collaborative studies.
  • Research on such topics as epidemiology, chemo-prevention, diet, obesity, life-styles, environment, and nutrition is woefully under-funded.

III. WHAT SHOULD BE DONE TO FIGHT THE WAR MORE EFFECTIVELY

“Stomach cancer has disappeared for reasons nobody knows and lung cancer has rocketed upward for reasons everyone knows,” says John Cairns, a microbiologist now retired from the Harvard School of Public Health. To win this war, some steps that need to be taken are rather apparent while others remain to be carefully debated and planned. For the vast majority of cases, no “cause” can be identified, but cancer is presently believed to be triggered by a combination of genetic predisposition and lifestyle factors such as diet and occupation. Consequently, chances of developing cancer can be significantly reduced by not smoking, adopting a healthier lifestyle, and proper nutrition. Focus is needed in improving methods for early detection, on treating precancerous conditions, (the dysplasias, metaplasias), and on understanding the reasons for susceptibility to the malignant process in individuals and families.

Where research is concerned, man must remain the measure of all things. Human tumors rather than mouse models should be studied directly. To harness rapidly evolving fields like nanotechnology, proteomics, immunology, and bioinformatics, and focus them on serving the cause of the cancer patient, we must insist on collaboration between government institutions (NCI, FDA, CDC, DOD etc), academia and industry. In the case of the Human Genome Project, collaboration was the key to the rapid mapping. The same concerted effort needs to be invested now in sequencing mutations in hundreds of freshly obtained human cancers of all types, a venture which has been proposed as the Cancer Genome Project. It is a well known fact that all those machines and robotics developed worldwide for sequencing the human genome are either sitting idle or being used for sequencing the genomes of microorganisms and fruit flies. They would serve a far better purpose by being employed in sequencing several hundred breast, lung, colon and prostate cancers to identify the most common mutations. Identification of specific mutations will lead to the discovery of seminal signaling pathways unique to organ specific malignant cells which can then serve as therapeutic targets. Given that nature is highly parsimonious, it is likely that some of these pathways would be redundant as was the case with Gleevec. This drug was developed specifically to inhibit the tyrosine kinase of the Abl gene, and has proved to be effective in producing remissions in >97% CML patients. However, it has now been discovered that patients with gastro-intestinal stromal tumors or GIST can also respond to this drug as the cells use the same tyrosine kinase blocked by Gleevec. More recently, thyroid papillary cancers, subsets of patients with other bone marrow disorders (for example those showing translocations between chromosomes 5 and 12) and even cases of as different a disease as pulmonary hypertension, have been found to respond to Gleevec. What this proves is that some key pathways are likely to be present in cancers or even diseases across organs, and their identification could deliver unexpected benefits.

Cancer is a multi-step process that involves initiation, expansion, invasion, angiogenesis and metastasis. Each stage of the disease may offer a variegated set of targets, thereby making the one drug, “magic bullet” approach only feasible in a handful of cancers where single mutations underlie the malignant process (as described above for CML and Gleevec). A critical lesson from developing successful therapy for AIDS is that three drugs targeting the same virus had to be used before effective control of its replication was achieved. Similarly, multiple targets must be attacked at the same time in the cancer cell. The “seed and soil” approach where drugs act on both the malignant cells and their microenvironment would be preferred over those targeting either in isolation. For example, a drug that blocks a key deregulated intracellular signaling pathway and checks the malignant cell’s perpetual proliferation can be combined with an anti-angiogenic drug which stops the formation of new blood vessels and arrests the invasion of tissues by the tumor. The objective choice of agents would require the practice of evidence-based medicine, and this is what the government institutions should be rewarding the investigators for. Many effective therapies directed against components of the seed and soil, are already available, but researchers are only allowed to use one investigational agent at a time, and that too in patients with advanced disease. This stilted and almost self-defeating approach needs to be abandoned. Patients who already have a diagnosis of cancer cannot afford to wait.

I am optimistic that in the next few years, given the power and sheer velocity of the evolving bio-technology, the very fundamentals of cancer research and treatment will have undergone cataclysmic changes. It may not be possible to cure cancer within the next decade, but, in the words of the NCI Director, Dr. Andrew von Eschenbach, it may very well be possible to “transform cancer into chronic, manageable diseases that patients live with – not die from”.

November 6, 2005

The Semiotics of a Leaf

Carl Zimmer in his blog, The Loom:

LeafA new autumn has brought another burst of red and yellow leaves. And it has also brought an interesting new idea about why trees put on this show every year.

In recent years, scientists have been roughly divided into two camps when it comes to autumn leaves. One camp holds that autumn colors are just part of preparations for winter. The other holds that the colors are a warning to insects to stay away.

The warning hypothesis came from the late biologist William Hamilton. He pointed out that trees fight off insect larvae with toxins. A more vigorous tree could produce more toxins than a weaker one. It could also produce more vibrant colors in the fall by producing more pigment molecules. (The red in leaves is created by molecules called anthocyanins, for example). Perhaps a tree could send a message to insects looking for a place to lay their eggs: stay away from me or I’ll kill your kids in the spring.

More here.

Force (as in F = ma) as a cultural concept

David Schoonmaker reviews The Best American Science Writing 2005, edited by Alan Lightman, in American Scientist:

Frank Wilczek’s scientific achievements are certainly familiar to me, but his popular writing was not. In “Whence the Force of F=ma?” the Nobelist explores his long-standing problem with the left-hand side of Newton’s second law. It had never occurred to me how insubstantial the concept of force is, so I was intrigued to learn that thinkers like Wilczek have been questioning its value to physics as a concept for more than a century. No less than Bertrand Russell titled the 14th chapter of his book The ABC of Relativity “The Abolition of Force.” Wilczek notes that “the concept of force is conspicuously absent from our most advanced formulations of the basic laws. It doesn’t appear in Schrödinger’s equation, or in any reasonable formulation of quantum field theory, or in the foundations of general relativity.”

Wilczek then gets to the nub of his concern: “If F=ma is formally empty, microscopically obscure, and maybe even morally suspect, what’s the source of its undeniable power?” His answer is that force is more a cultural concept than a physical one. “F=ma by itself does not provide an algorithm for constructing the mechanics of the world. The equation is more like a common language, in which different useful insights about the mechanics of the world can be expressed.”

Score one for risk taking. Frank Wilczek’s insights are worthy and clearly presented, and his prose is lively and engaging. I look forward to reading more from him.

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Michel Houellebecq, literary rock star

Andrew Hussey in The Guardian:

Michel_houellebecq_kikaIt is just before nine on a Friday morning in Edinburgh and a thin, faint rain is falling outside the Scottish Poetry Library in Crichton’s Close, a short step from the tourist tat of the Royal Mile. This is where I meet French novelist and poet Michel Houellebecq, who is squatting on the building’s concrete steps, hunched up in a large black anorak against the drizzle, sucking hard on the first of a long line of cigarettes.

With his pinched face and shambling gait, he is, to say the least, an incongruous figure; he looks more like a local wino than a world-famous man of letters. But Houellebecq, 47, is the nearest thing to a literary superstar France has produced in recent years. His books have been translated into 36 languages and recent film deals have made him a multi-millionaire. He is in Edinburgh to attend a conference which is being held in his honour by the University of St Andrews to coincide with the publication of his new novel, and which has attracted distinguished scholars and critics from all over the Western world.

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Holmes & his commentators

Theodore Dalrymple in The New Criterion:

Cw20sherlock20holmes20rwbAccording to Hazlitt, if we wish to know the force of human genius, we have only to read Shakespeare, but if we wish to know the futility of human learning, we have only to read his commentators.

Something similar might almost be said —almost, but not quite—of Sherlock Holmes and his commentators. The gulf is not nearly as great as that between Shakespeare and his critics, of course, but if literary genius is required in order to create a mythological world that is more real and alluring to readers than any reality itself, that once read is never forgotten, that for a century has inspired the devotion of the literary and the unliterary unlike, and that is vastly and innocently entertaining without being wholly devoid of instruction, then Conan Doyle had such genius to a very considerable degree.

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A chilling diagnosis of how the war on terrorism has been waged thus far

From The Washington Post:

Attack “We are losing,” warn Daniel Benjamin and Steven Simon on the opening page of The Next Attack . In this chilling new book, they argue that the United States has, in the years since 9/11, frittered away more time than it took to win World War II: The Bush administration has plunged into a war of choice in Iraq that played into Osama bin Laden’s hands and produced “an extraordinary amount of wheel-spinning” instead of shoring up America’s domestic defenses. Meanwhile, the public’s attention has wandered, and the jihadist movement has weathered the loss of its Afghan haven and recast itself into new, more supple forms. “Even in his most feverish reveries,” the authors write, bin Laden could not “have imagined that America would stumble so badly.”This book’s Iraq chapters come as a glum reminder that, all too often, the debate over whether to invade Iraq was hermetically sealed off from the wider question of how best to destroy al Qaeda — as an organization, a network, a brand and an ideology. Even the administration’s critics (and human-rights-minded liberal hawks like George Packer) rarely talked about a potential war’s opportunity cost — about the range of urgent, attainable counterterrorism tasks that would be left undone because Washington had chosen to make the Iraq gamble its top post-9/11 priority.

And there is plenty to do.

More here.