Reading The Emperor of All Maladies, Siddhartha Mukherjee’s “biography of cancer” from last year, one is struck by both the long and short history of cancer. Descriptions of breast cancer can be found as long ago as an Egyptian papyrus dated to 2500 BC and ancient Greek histories, and tumors have been found in thousand-year-old mummified remains from Peru. But the idea of cancer as a treatable disease is barely a hundred years old, and as recently as the 1940’s, clinicians could do little more than help patients die from the disease as comfortably as possible. Despite these deep historical roots, Mukherjee chooses to start his book in 1947, with Sidney Farber’s first experiments on chemotherapy for children with leukemia.

From there, the pace of the “war on cancer” (though not known by that phrase until 1971’s National Cancer Act) accelerates rapidly, as chemotherapy, radiation and surgical protocols were improved through scientific inquiry. Progress in understanding and treating cancer no doubt seemed incremental as it was happening, and even today some still question its overall success. But Mukherjee’s skillful portrayal presents an astonishing difference in the experience of cancer patients only 50 years apart - from being hidden in out-of-the way wards because of the hopelessness of their condition, to the ultra-modern cancer centers of today offering targeted treatments that offer the promise of a cure, if not yet a certainty.

But stumbling blocks still exist in the scientific progress against cancer. One place where reinforcements are desperately needed is at the level of clinical cancer trials, where the true benefits of laboratory discoveries are put to the test in a human population. While there is no shortage of ideas for new cancer therapies, clinical trials have struggled due to insufficient accrual of patients. Though 25,000 to 30,000 patients are enrolled in cancer trials each year, they only represent 3 to 5 percent of all U.S. adult cancer patients,  Richard Schilsky, professor of medicine and chief of hematology/oncology, wrote in a commentary for Science Translational Medicine last week.

“Despite various attempts to remedy the accrual problem, such as awareness campaigns, establishment of clinical trial registries, and the development of search engines to match patients to trials, annual enrollment on cooperative group clinical trials has remained essentially unchanged throughout the past decade,” he writes. As a result, “up to 40% of cooperative group phase III trials have failed to complete accrual and closed without achieving study endpoints, wasting the contribution of those patients willing to enroll in the trial.”

There are plenty of barriers against getting cancer patients into appropriate trials, Schilsky says. Many are institutional - physicians outside of the academic world may not have dedicated research staffs than can help coordinate patients, deal with regulations and insurance issues, and fill out the extensive paperwork. To circumvent these issues, some doctors would rather write off-label prescriptions for drugs being tested in a clinical trial, getting the potential benefits of the drug without the logistical commitments. On the other side, patients may not be aware of the trials available to them, or may misunderstand the purpose of a clinical trial.

The new era of molecular medicine could raise some of these obstacles even higher or knock them down, Schilsky writes. In 2001, the drug Gleevec ushered in the age of smarter drugs that directly interfere with the cause of the disease, rather than general features of tumor growth. Testing these types of drugs requires new types of trials, with more biospecimens (blood, tumor tissue, DNA) collected from patients and tighter rules about who is eligible for the experiments. Classifying broad cancers into more specific subtypes may eventually improve treatment effectiveness, but in the short term could make testing those treatments even more difficult.

“The challenge is that many patients may need to be screened if the biomarker used for patient selection is of low prevalence in the tumor type under study,” Schilsky writes.

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CREDIT: ADAPTED BY P. HUEY/SCIENCE

The public perception of science in action typically involves a person in a white coat pouring brightly-colored fluids in and out of test tubes. Sure, a little bit of that does go on in a laboratory. But before the glassware is broken out, a lot of less glamorous stuff has to happen. Every experiment is built on a foundation of reading - devouring the scientific literature that came before you and keeping up with the pile of new journals from your field that arrive on a weekly basis.

Once upon a time - say the 17th century - it was possible for a scientist to keep up with the flow of science because there were only a couple dozen of people contributing to it. Today, University of Chicago sociologist James Evans and professor of medicine Andrey Rzhetsky estimate, a cancer biologist is confronted with millions of relevant journal articles within their field, with thousands more added every month. Obviously, there’s no way for a mere mortal to keep up with that kind of reading list, much less keep an eye on other fields to inspire creative ideas.

In last week’s issue of Science, Evans and Rzhetsky suggest a potential substitute to handle this impossible task: the computer. Appearing the same day as Gary An’s pitch for using computer models to test hypotheses, Evans and Rzhetsky’s piece is an argument for using computers to generate those hypotheses by boiling down the unreadable avalanche of scientific literature into promising questions.

“During Newton’s time, a scientist could read everything that was published, at least in English,” Rzhetsky, a senior fellow of the University’s Computation Institute, told Wired’s Brandon Keim in an interview. “That’s just not an option anymore. We can’t deal with all this information.”

But the answer is not to just simply plug data into a computer with zero context and hope for promising treatments to pop out the other end, Rzhetsky told Keim, deploying an excellent film reference as a metaphor.

“In the movie Memento, a man has only a short-term memory. Every 15 minutes has to reconstruct causal relationships. He observes people talking to him, and doesn’t know who’s a friend and who’s a foe. That’s my metaphor for abandoning hypothesis and context,” Rzhetsky said.

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In a rare though hardly surprising development, two evolution researchers at the University of Chicago have the top two books in the “Evolution” category at amazon.com. (It’s hardly surprising because the university’s graduate program in ecology and evolutionary biology is consistently ranked the best in the nation… end of gratuitous plug.) The #1 bestseller in the category is Neil Shubin’s “Your Inner Fish,” and #2 is Jerry Coyne’s new hardcover, “Why Evolution Is True.”

Now it’s turned into a well-nigh Darwinian struggle to see who can claim and keep the top spot, with Jerry openly yearning to wrest away Neil’s bestseller mojo.

In truth they’re both fine books with very different audiences, and Science Life is shamelessly exploiting both authors. We’ve already run interviews with Neil on misconceptions about evolution and other topics, and soon we’ll have a dialogue with Jerry about the links between biology and ideology. For a preview, check out Jerry’s recent essay in The New Republic on why efforts to reconcile evolution and religion are doomed to fail. I disagree with him on some points, including the minor issue of whether God exists. But he’s certainly right that a religion that takes evolution seriously might look very different from the religious views that most believers hold. I wrote about the same subject for the Chicago Tribune magazine last year, complete with a colorful description of Jerry’s own de-conversion experience.

UPDATE: Now Jerry is in the lead, and Neil is second. The Botany Pond grudge match continues…

I sat down yesterday with Robert Richards, author of “The Meaning of Evolution,” to talk about Darwin’s cultural influences and his place in history. Richards gave a very nice explanation of how deeply Darwin was influenced by John Milton’s “Paradise Lost.”

When [Darwin] was on The Beagle, he carried Milton’s “Paradise Lost” with him everywhere. He read the poem incessantly. And of course it’s the story of death and suffering - man’s fall. But man’s fall is a necessary prerequisite for the coming of the savior, and the production of life more abundantly, a new kind of life. And if you read those last paragraphs [in "The Origin of Species"], it looks as though Darwin is trying to justify suffering and death. How do you do it? Death and suffering are justified because of the production of the higher animals, life more abundantly. A life leading to the production of the highest animal, namely us, with our moral sentiments.

Darwin’s theory has been so successful that we sometimes overlook the extent to which it was a product of his time, and his distinct way of seeing the world. This link to “Paradise Lost” casts the evolutionary process as something tragic, yet containing the seed of great beauty.