Of all the sentences you never want to read from scientists running a study of a promising new medical treatment, high on the list has got to be, “the trial was terminated early for futility.”
Yet there it is, describing what happened when researchers assessed a surgical procedure that had “slam dunk” written all over it. The idea was to take patients who had complete blockages of the internal carotid artery, which carries blood to the brain, with the not-surprising result that they had insufficient blood flow to the brain. The patients had also had at least one transient ischemic attack (TIA), or “mini-stroke,” as a result of blood supply to a part of the brain being temporarily reduced or blocked altogether. Half the patients in the study received standard medical treatment, such as aspirin and other anti-clotting drugs plus anti-hypertension drugs, while the other half got the promising surgery: bypassing the blocked carotid, in the neck, with an artery in the scalp. Surely, went the rationale, steering blood around a blockage would lower the subsequent stroke rate. Expectations were high: leaders of the Carotid Artery Occlusion Surgery Study (COSS) projected that there would be 40 percent fewer strokes on the same side as the blockage in patients who had the surgery.
The experimental surgery was nifty but not effective.
Courtesy of Powers, et al., and JAMA
Not so much. In yet another example of how human biology continues to thwart what seems like compelling medical logic (more on which below), the 97 patients receiving the surgery had no fewer strokes than the 98 receiving standard medical care, the COSS team reports in the Journal of the American Medical Association. Things began to go south early. After one month, 14 of the 97 surgery patients had another stroke, compared to 2 of 98 controls. After 2 years, things merely evened out: 20 patients in each group had had a stroke. (A 1985 trial of the surgery had also shown no benefit, in 808 patients.) At that point, the Data Safety Monitoring Board advised halting the trial, which was done in June 2010. (It seems small comfort that if you survived your first month post-surgery without a stroke, your risk of subsequent stroke fell by about 75 percent.) Bypass, concluded the COSS researchers, “provided no additional benefit over medical therapy for preventing recurrent stroke.”
Every few years it seems that the British biologist Steve Jones declares the death of evolution by natural selection in the human species. The logic here is simple even to a schoolboy: evolution requires variation in fitness, and with declining risk by death during our reproductive years humans have abolished the power of selection. But this confuses the symptom for the disease. Death is simply one way that natural selection can occur. Michelle Duggar has 19 children. The average American woman has around two by the end of her reproductive years. It doesn’t take a math whiz to figure out that Michelle Duggar is more “fit” in the evolutionary sense than the average bear. Even without high rates of death, some people have more children than other people, and if those people who have more children than those who do not are different from each other in inherited traits, evolution must occur. Q.E.D.
But you probably shouldn’t be convinced by logic alone. Science requires theory, experiment, and observation. (If you’re talking humans, you can remove the second from the list of possibilities: there are certain unavoidable ethical obstacles to experimenting on human evolution—plus we take far too long to reproduce.) But humans sometimes have something which bacteria can not boast: pedigrees! Not all humans, of course. Like most of the world’s population I don’t have much of a pedigree beyond my great-grandparents’ generation. But luckily for biologists, the Catholic Church has long taken a great interest in life events such as baptism, marriage, and death, and recorded this info parish by parish. With these basic variables, demographers can infer the the rough life histories of many local populations over the centuries. In many European nations, these databases can go more than 10 generations back. And some aspects of human evolution are revealed by these records.
What aspects am I talking about? Reproduction itself. Not only is variation in fitness one of the primary ways by which evolution occurs, but it is also a trait upon which evolution operates! How else are there rabbits which breed like…rabbits, and pandas…which don’t. There is often variation within species for the odds of multiple births, age at first reproduction, and lifespan, depending upon the differences in selection pressures over a population. And that seems to be exactly what occurs in human beings. There is interesting evidence for evolution of reproductive patterns from populations as diverse African pygmies and Finns, but more recently some researchers have been plumbing the depths of the records of the Roman Catholic Church in Quebec, and they’ve come back with gold.
Consider two pandemics: the white-nose syndrome now devastating North American bats and the Black Death that killed a third or more of Europeans in the 14th century. Lethality aside, they may not seem to have much in common. But recent studies suggest they both offer important lessons about understanding that the deadliness of disease organisms is very much a product of the circumstances in which they appear.
Two weeks ago in Nature, a multi-institutional team of U.S. Geological Survey scientists presented conclusive evidence the parasitic fungus that lends white-nose syndrome its name is indeed the cause of the mysterious bat epidemic. The illness came to light in New York in 2006, when cave explorers started finding thousands of little brown bats (and later, other species) dead together in the caves where they spent the winter months, their bodies covered with a white fungus, Geomyces destructans. It has since spread throughout the northeastern U.S., where bat populations have declined on average by 73 percent—which may make it one of the most rapid declines in wildlife populations ever observed. Worse, white-nose syndrome is still on the move, with documented cases in four Canadian provinces and states as far south and west as Tennessee, Missouri, and Oklahoma.
This summer I had the privilege of going to Scifoo, where I met interesting folks and heard about a lot of interesting successes in science. But my story here involves something that was rather less than success. One session was about education, and set itself to address the question, “How can we better motivate youth to enter the sciences and engineering?” As I listened to an influential policymaker, I became more convinced than ever that policymakers really aren’t the people who should be answering this question—they don’t know how to inspire scientists. And it struck me that the preceding session in that very same room, wherein a presenter showed us his mind-searing video taking the viewer on a “flight” through a brain replete with hundreds of thousands of real-data-generated neurons, implicitly had the answer. So did Carl Sagan and his influential PBS show, Cosmos:
The trouble begins with a central term used among those who think about science and technology education. That word is “STEM,” and it is an acronym for “science, technology, engineering and mathematics.” On one level, the term makes perfect sense: there is a core set of technical skills that each of those in STEM must acquire. But there are big differences within the group. Engineers and scientists tend to be different sorts of folks. They require very different sorts of training. And they lead fundamentally different sorts of work lives.
Are the silent viruses within us doing more than we know?
By Laura Kasman, as told to Veronique Greenwood
In the 1970s, doctors noticed that sometimes people with hepatitis B virus infection (HBV) would get suddenly much worse and go into liver failure, and they didn’t know why. But through hard work with what are now antiquated methods, they found out that there was another virus, very different genetically from HBV, but dependent on HBV to spread from person to person. It is called hepatitis D virus or delta agent, and it steals proteins made by HBV to get from cell to cell and victim to victim. The combination of HBV plus hepatitis D is always much more serious than HBV alone, and hepatitis D virus never occurs on its own.
This phenomenon, called viral interference, has been seen in the lab for a while, but it was generally thought to be an artifact with little or no importance in human disease. That’s because we didn’t have the technology to easily find and identify viruses in living people until recently.
The advent of PCR rewrote our understanding of viral interactions, as it did for many areas of biology. We learned that almost everyone has many silent viral infections cooking in them all the time, some that last for life and some that come and go. When the human genome was sequenced, it showed that 8% of the human genome is made up of dormant and disabled retroviruses (the kind of virus that causes AIDS). It’s as if scientists were looking for cockroaches in a big dark room and all we had was a little flashlight. For decades we followed one bug at a time, and it worked and we made progress, so we thought each one was alone. And then with PCR we found the light switch and yikes, they were everywhere! We didn’t notice most of them for so long because they cause no symptoms in most people. Read More