Research Ethics Talk

And now for something completely different.

*Date and location*: Mon, March 7, 4-6pm, Girvetz 1004

*Speaker*: Prof. Herbert Kroemer

*Abstract*: In early 2002, Bell Labs physicist Hendrick Schoen was considered a rising star in the field of molecular electronics. A little older than 30, Schoen had already authored 90 publications and received a series of prestigious awards. In April 2002, he was being considered for the directorship of the Max Planck Institute for Solid State Research in Stuttgart. In September 2002, he was fired by the Bell Labs and his most prominent papers were withdrawn from publication. What happened? In this talk, Prof. Kroemer will tell us about his role in the investigation on scientific misconduct and discuss issues and repercussions of unethical conduct in research.


To whet your appetite for this talk check out The Rise and Fall of a Physics Fraudster in Physics World. Although this example is from the world of physics the implications for scientific research are very general.

I used to joke with my friends in the physics community that if you want to cleanse your discipline of the worst scientists in it, every three or four years, you should have someone publish a bogus paper claiming to make some remarkable new discovery — infinite free energy or ESP, or something suitably cosmic like that. Then you have it published in a legitimate journal ; it shows up on the front page of the New York Times, and within two months, every bad scientist in the field will be working on it.  Gary Taubes.

Monday funnies

I don't know what made me think of Tim Minchin, I must have seen a reference to him somewhere, but I thought you might enjoy these. Phrases like 'I don't think you're special, I mean you're special but you fall within a bell-curve' probably explain why so many scientists marry other scientists.

Weekend Wildcard

I try to make posts here roughly correspond to what we are covering in class (you don't have to feel quite as restricted) but because I have a life and because it gets hard posting every day I've decided to embrace a concept I dabbled with before - the weekend wildcard. Weekends are open to any posting on any topic of some relevance to the course.

Today is a great example because it pertains to science, the scientific method, how science is done and cards (wild or otherwise). All good fodder for an intro bio class. As some of you may have heard a leading psychology journal is about to publish an article providing evidence for ESP. Even the New York Times is writing about it:
Journal’s Paper on ESP Expected to Prompt Outrage
Some of the experiments are a little odd to say the least:
In another experiment, Dr. Bem had subjects choose which of two curtains on a computer screen hid a photograph; the other curtain hid nothing but a blank screen.
A software program randomly posted a picture behind one curtain or the other — but only after the participant made a choice. Still, the participants beat chance, by 53 percent to 50 percent, at least when the photos being posted were erotic ones. They did not do better than chance on negative or neutral photos.

You can read the actual paper here and a critique here.

The paper was reviewed by 4 referees before being accepted for publication. Should the extraordinary claims have required extraordinary evidence before publication? Should different papers have to meet different standards depending how well they fit our current paradigms? Is the publication of this paper helping or hindering the public perception of science? Is that even an issue scientists should be concerned with?

(I actually lied about having a life, posting here at 11:30 on a Saturday night kind of gives that away, but it does get tricky thinking of something to post every day, especially at the start of the class when we haven't covered very much.)

I don’t know what to believe…

Thanksgiving and Christmas are times where we traditionally meet with family, eat too much and have awkward conversations with relatives we barely know and realize we have very little in common with.

If they find out you are a biologist chances are you'll get asked about topics ranging from global warming to this week's cancer scare. Here's a handy dandy resource for putting people straight about why they shouldn't necessarily believe it when they hear that cell phone towers are killing plants, will cure/cause cancer, or how scientists are all faking global warming. 

Have a safe Thanksgiving.

Texting and Fatal Driving Accidents

Text messages sent per month from hand-held phones increased more than 15-fold from 2002 to 2008. Over the same years the percentage of fatalities in which distracted driving was listed as a possible contributing factor increased from about 12% to nearly 16%.

Based on these data, the authors of a recent report speculate that texting while driving may have contributed to 16,000 additional driving fatalities between 2001 and 2007. The claim was reported in the Los Angeles Times and other papers, but is it true?

There are several problems with this report. First, the authors defined a fatality as caused by driver distraction whenever a distraction was merely listed as present. Other factors such as equipment failure, alcohol, or driver age were not considered. Second, distractions are anything that takes the driver’s attention away from driving, including texting or talking on a hand-held phone, reading an on-board navigation system (also increasingly popular these days), reaching for something, eating, drinking, putting on makeup, etc. Searching for street signs or rubbernecking another accident are also distractions. None of these were factored out in this study.

All the report really shows is that text-messaging volumes (in and out of cars) and the number of fatal accidents due to all distractions are both going up. The authors call it a correlation, but so what? A correlation does not prove causation. I’m reminded of the example presented by my thesis advisor years ago of the tight correlation between the rise in the number of telephones in the U.S. and the decline in the incidence of tuberculosis. Do telephones prevent tuberculosis? Hardly.

Is texting while driving a problem? Probably yes. Does this paper convince me that texting while driving has caused 16,000 additional fatalities? Sadly, no.

Denialism

Vaccine-autism claims, "Frankenfood" bans, the herbal cure craze: All point to the public's growing fear (and, often, outright denial) of science and reason, says Michael Specter. He warns the trend spells disaster for human progress.

Another of the TED talks. This one raises interesting point about scientific literacy. The time machine question in the first few moments is really rather intriguing. I'd like to see the results from a large sample of people especially if the answers were broken down by age and sex. Actually I'd like to see them broken down by political affiliation too. Oh, and maybe by religious beliefs.

Anciently asexual

Spore-bearing fungal parasites emerge from the digested corpses of three bdelloid rotifers.

Wow, I was just looking around for something to post on and there it is right on the cover of Science this week. Great story and highly relevant to class.

Anciently Asexual Bdelloid Rotifers Escape Lethal Fungal Parasites by Drying Up and Blowing Away

Asexuality has major theoretical advantages over sexual reproduction. An important evolutionary puzzle, therefore, is why exclusively asexual metazoan lineages rarely endure. The Red Queen hypothesis posits that asexuality is rapidly extinguished by relentlessly coevolving parasites and pathogens. If so, any long-lasting asexual lineage must have unusual alternative mechanisms to deal with these biotic enemies. Bdelloid rotifers are freshwater invertebrates that abandoned sexual reproduction millions of years ago. Here, we show that cultured populations of bdelloids can rid themselves of a deadly fungal parasite through complete desiccation (anhydrobiosis) and disperse by wind to establish new populations in its absence. In Red Queen models, spatiotemporal escape can decouple and protect asexuals from coevolving enemies. Thus, our results may help to explain the persistence of the anciently asexual Bdelloidea.

The Neuroscience of Screwing Up

I mentioned this briefly on Tuesday and I may add this as reading for the Biology Colloquium next year but I thought some of you might like to read it. A fascinating discussion of how science is done, how and why we make mistakes and how we interpret them.

Accept Defeat: the Neuroscience of Screwing Up

While the scientific process is typically seen as a lonely pursuit — researchers solve problems by themselves — Dunbar found that most new scientific ideas emerged from lab meetings, those weekly sessions in which people publicly present their data. Interestingly, the most important element of the lab meeting wasn’t the presentation — it was the debate that followed. Dunbar observed that the skeptical (and sometimes heated) questions asked during a group session frequently triggered breakthroughs, as the scientists were forced to reconsider data they’d previously ignored. The new theory was a product of spontaneous conversation, not solitude; a single bracing query was enough to turn scientists into temporary outsiders, able to look anew at their own work.

But not every lab meeting was equally effective. Dunbar tells the story of two labs that both ran into the same experimental problem: The proteins they were trying to measure were sticking to a filter, making it impossible to analyze the data. “One of the labs was full of people from different backgrounds,” Dunbar says. “They had biochemists and molecular biologists and geneticists and students in medical school.” The other lab, in contrast, was made up of E. coli experts. “They knew more about E. coli than anyone else, but that was what they knew,” he says. Dunbar watched how each of these labs dealt with their protein problem. The E. coli group took a brute-force approach, spending several weeks methodically testing various fixes. “It was extremely inefficient,” Dunbar says. “They eventually solved it, but they wasted a lot of valuable time.”

The diverse lab, in contrast, mulled the problem at a group meeting. None of the scientists were protein experts, so they began a wide-ranging discussion of possible solutions. At first, the conversation seemed rather useless. But then, as the chemists traded ideas with the biologists and the biologists bounced ideas off the med students, potential answers began to emerge. “After another 10 minutes of talking, the protein problem was solved,” Dunbar says. “They made it look easy.”

Writing, Reading, and Reviewing Scientific Articles

This coming week in the bio colloquium we're reading an article from the primary literature. To provide general background on the elements of a scientific paper we also handed out "guidelines for writing a scientific paper". To help you think about it from the other end (reviewer vs. writer) you may want to see what guidelines the scientific journals provide their reviewers, that is, what helps us decide whether a paper is "publishable" by a given journal. This is useful in writing (and reading) a paper to see what the "critics" are looking for.

Here is the link for reviewers for the journal, Ecology:
http://esapubs.org/esapubs/reviewers.htm

Also informative is the "Reviewers Information Pack" (http://www.nxtbook.com/nxteu/elsevier/reviewersinfopack/) for everything you might want to know about the review process for journal articles. This is provided by Elsevier, which publishes Developmental Biology, and hundreds of other journals (http://www.elsevier.com/wps/find/journal_browse.cws_home)

Here's their reviewers' home page:
http://www.elsevier.com/wps/find/reviewershome.reviewers

Monkey-Man

Kathy pointed me to an interesting editorial in Nature today about the recent fossil primate discovery I mentioned here last week.

The article, entitled Media Frenzy, has the subhead:

A hyped-up fossil find highlights the potential dangers of publicity machines.

Take a look at the original paper in PLoS ONE, Nature's original report and today's editorial.

Do you agree with Nature's assertion that:
In principle, there is no reason why science should not be accompanied by highly proactive publicity machines. But in practice, such arrangements introduce conflicting incentives that can all too easily undermine the process of the assessment and communication of science.

Do you think the authors of the original paper did anything wrong?
Do you think the journalists who covered the story have been accurate in their reporting?

(The image above, which is from Nature's original report, is called 'monkey-man.jpg'. This is exactly the sort of misleading hype that Nature is railing against!)

Correlation Versus Causation

According to a study of the nearly 140,000 women who were enrolled in the Women’s Health Initiative, women who breast-fed their babies had a lower risk of developing heart disease and diabetes later in life than women who did not breast-feed their babies. The headline of the New York Times article about the research read “Breast-Feeding Benefits Mothers, Study Finds”. Is this a correct summary of the research?

The answer is “NO”! This is a classic case of the common misunderstanding about the relationship between correlation and causation. Yes, there is a clear correlation between breast-feeding and a lower risk of diabetes and heart disease later in life, according to the study. But that is not proof that the act of breast-feeding is what reduces the risk. What if women who breast-fed their children are just more health conscious overall throughout life? What if they exercise more often, or have healthier diets?

A more correct headline would be “Breast-Feeding May Benefit Mothers, Study Suggests”. Indeed, the article itself goes on to say that some experts are cautioning that an association (between breast-feeding and health benefits) does not prove a causal relationship, and that more research would be needed to determine the exact cause of the effect (lower risk).

Robot Scientist

If you've been in a research lab you can't have failed to notice not only how much expensive looking equipment there often is, but how much of it is linked together these days. Lots of machinery either comes with a computer or is later linked to one in the lab to automate data entry.

It's only a couple of steps from there to linking together all your equipment, adding in some simple algorithms for how the scientific process works, and you can go hang out on a beach whilst your lab equipment does its own experiments.

Sounds a bit futuristic? Nope, a recent paper in Science entitled 'The Automation of Science' describes just such a scenario. Scientists in England developed a robot named Adam to identify genes involved in yeast metabolism. Adam formulates hypotheses about the origins of enzymes for which scientists have been unable to identify the encoding genes. The robot then plans and executes experiments to test its hypotheses--selecting yeast mutants from a collection, incubating cells, and measuring their growth rates. Adam came up with 20 hypotheses about genes encoding 13 enzymes, 12 of which it confirmed.

There's a commentary on the paper in Science, the story was picked up by the media, but the best comment is in a New Scientist report:

'Will Bridewell, an artificial intelligence researcher at Stanford University in Palo Alto, California, says Adam is operating only at the level of a graduate student. '

The hype of science

Kathy sent me a link to this article at TheScientist.com - The hype of science Leading journals including Science and Nature are exaggerating research novelty. You will need to register to read the article but there's no cost.

When original and interesting research is distorted to garner additional attention, both the work in question and previous studies can be shortchanged. Here, I will describe a recent and notable case from the journal Science in which the perceived novelty and importance of a study were significantly enhanced.

Florigen - found and not found

From Science magazine's list of the 'Breakthrough's of the year' in 2005:

In August three groups of plant molecular biologists finally pinned down the identity of florigen, a signal that initiates the seasonal development of flowers. The signal is the messenger RNA of a gene called FT. When days get long enough, this RNA moves from leaves to the growth tip, where the FT protein interacts with a growth tip-specific transcription factor, FD.

However if you click on the original article then you may notice the sentence 'This article has been retracted.'

After the first author (T.H.) left the Umeå Plant Science Centre for another position, analysis of his original data revealed several anomalies. It is apparent from these files that data from the real-time RT-PCR were analyzed incorrectly. Certain data points were removed, while other data points were given increased weight in the statistical analysis. When all the primary real-time RT-PCR data are subjected to correct statistical analysis, most of the reported significant differences between time points disappear. Because of this, we are retracting the paper in its entirety.

In new experiments, we have reproduced the floral induction caused by a heat-shock induction of FT in a single leaf, but we have failed to detect movement of the transgenic FT mRNA from leaf to shoot apex. We therefore retract the conclusion that FT mRNA is part of the floral inductive signal moving from leaf to shoot apex.

Curious. After 70 years of elusivity (is that a word?) Florigen is not ready to give in yet.

HIV/AIDS Incidence Revised Upward

The number of new HIV infections per year in the United States has been grossly underestimated for the past 20 years, according to an article published in today’s Journal of the American Medical Association (“Estimation of HIV Incidence in the United States.” JAMA 300:520-529, August 6, 2008.) The new estimate for HIV incidence is 56,300 new cases in 2006, 40% higher than previously reported by the CDC. The new data also show that the incidence of HIV has not declined at all since 1991, in sharp contrast to the previously estimated 50% decline since that time (compare Figure 1 in the JAMA article with Figure 9.24 in Human Biology, 5th ed., taken from official CDC data available at the time.) The total number of people living with HIV/AIDS is also expected to be revised upward, but those numbers will not be available until later this year.

How could the numbers have been so far off? For one, the new data are based on better testing methods that more precisely differentiate new HIV infections from long-standing ones. In addition, HIV infection rates are notoriously hard to come by, especially back in time. Even the new estimates are based on extrapolations using data from only 22 states. The CDC does the best it can do with limited data; the rest is an educated estimate.

Officials emphasize that this does not mean that there actually were more new cases of HIV – rather, we now have better estimates of the actual rates of new infection that existed at the time, regardless of whether or not they were accounted for. Nevertheless, some Democrats are criticizing the Bush administration for not doing enough to combat HIV/aids in this country. Senator Waxman of California released a statement last week in which he pointed out that the CDC budget for prevention has actually shrunk by 19% since 2002, and that the president recently requested a reduction in funding for HIV prevention at the CDC. Given that the incidence of HIV has not declined at all over the past 15 years, Senator Waxman may have a valid concern.

Students may react with a "So what are we supposed to believe, when even scientists can't get it right?" attitude. They'll need convincing that this kind of "flip-flop", as it would derisively be labeled in politics, is actually a normal part of a healthy scientific process.

Why We Believe Anecdotal Evidence

Why do many people persist in believing that certain vaccinations may cause autism, despite the fact that there has never been any scientific evidence to support such a claim? Why is it that we continue to be suckers for all kinds of vague, unsubstantiated health claims for various herbs and food supplements? Michael Shermer, publisher of Skeptic magazine, thinks he’s found a reason. He hypothesizes that our willingness to believe in anecdotal evidence over objective data is hard-wired into our brains as a consequence of evolution. He argues that making a false positive error (believing that "A" leads to "B" when actually it does not) usually has no consequences – if you believe that a fruit is poisonous, choosing not to eat it only leaves you hungry. On the other hand, making a false negative error (failing to believe that "A" leads to "B" when in fact it actually does) can kill you - if you eat a poisonous fruit you may die.

What do you think? Read Mr. Shermer’s one-page opinion column in the August issue of Scientific American (“Wheatgrass Juice and Folk Medicine”, Scientific American August 2008, p. 42) and judge for yourself. This article might be a useful supplement for Chapter 1, Human Biology, 5th ed.

Gardasil and Irresponsible Journalism

Last Monday the CBS Early Show ran a story about a 14-year-old girl named Jenny who is now nearly completely paralyzed by a degenerative mucle disease of unknown cause. It just so happens that she received Gardasil, the vaccine against human papillomavirus (HPV) 15 months ago, like so many other girls her age. Her parents spoke to CBS News with the hope that coverage of Jenny’s plight would help them find “comparables” - other patients with the same symptoms, so that her doctors could discern the actual cause of her disease. Nevertheless, CBS chose to run the online story with the more sensationalist headline, “HPV Vaccine Linked to Teen’s Paralysis?” (CBSNews.com, July 7).

Four days later, FOX news went one step further with a story entitled “HPV Vaccine Blamed for Teen’s Paralysis” (foxnews.com, July 11).

This is biased journalism at its worst. Who exactly is blaming Gardasil for Jenny’s disease - Fox News? In fact the Fox News article is full of errors. For one, the article attributes to Jenny’s parents a statement made by a spokesperson for Merck, Gardasil’s manufacturer. In addition, the article uses the word “casually” in place of “causally”. For the record, what a Merck spokesperson actually said was, “We’re aware of this case and based on the facts that we’ve received, the information doesn’t suggest that this event was causally associated with vaccination.”

On their blog site on July 7 (see www.jenjensfamily.blogspot.com), the parents expressed disappointment with the CBS news coverage, saying “The family believes that there may be a link between Jenny’s health and the HPV vaccination……” “But, there is no medical consensus on whether this hypothesis is stronger than other possible explanations.”

Jenny’s parents are obviously scientifically literate. They know how to distinguish between a hypothesis and a scientifically justifiable conclusion. As you’re discussing the importance of being scientifically literate in your classroom, Jenny’s parents’ blog site and the two news articles would make interesting topics for discussion.

One final thought: Do you think that the biased news coverage of Gardasil could be intentional, given that conservatives don’t like the idea of a vaccine against a sexually transmitted disease being given to young girls? What do your students think?

Cell Phones and Brain Cancer

First, someone says (again) that cell phones may cause brain cancer. Then the FDA reports that there is no convincing evidence that cell phones are a health risk. (See “Experts Revive Debate Over Cellphones and Cancer”, The New York Times online, June 3, 2008.) What’s a consumer to believe?

This is a good example of the limitations of the scientific method, and why it is sometimes hard to know the truth. Regarding the first statement, yes, cell phones may cause brain cancer (and then again, they may not.) As for the second statement, it is true that there is still no scientifically convincing evidence that cell phones are a health risk. (but again, that doesn’t mean they aren’t!)

Why is it so hard to find the truth? First, brain cancers are so rare that one would have to study literally hundreds of thousands of people. Second, to do the scientific study properly, a controlled study would need to be done in which the lives of hundreds of thousands of people would have to be strictly controlled. It can’t be done. Third, no one has used cell phones for 50 years, so potential long-term effects won’t show up for awhile. And fourth, modern phones emit much less energy than the older models did.

What can we do? We can study those few patients with brain cancer and ask questions – questions about health habits, including past cell phone use. Self-reports by patients are notoriously unreliable, of course, so it may take hundreds of such studies before we consider the evidence “convincing”. We don’t need to panic, but we need to be watchful of the changing state of knowledge regarding cell phones and cancer.

You might remind your students that a similar question came up in the 1950s when smoking was actively encouraged – does smoking cause lung cancer? Who could have known that nearly sixty years later the rates of lung cancer in persons over 65 would be more than five times the rates of that same age group in 1950?!

Texas Blocks 'Creation Science' Master's Degree

The Texas Higher Education Coordinating Board voted unanimously last month not allow the Institute for Creation Research (ICR) to grant online Master of Science degrees in science education. The ICR makes no secret of the fact that it supports a literal interpretation of the Bible, including the creation of Earth in six days.

“Religious belief is not science,” said the state’s commissioner of Higher education in recommending to the board that they disallow the ICR application. He added, “Science and religious belief are surely reconcilable, but they are not the same thing.”

AIDS Vaccine Tests Halted

Two trials of promising AIDS vaccines have been halted in recent months because the vaccines didn't work. Worse yet, they may have nearly doubled the subjects’ chances of contracting AIDS. It’s an enormous setback for the AIDS vaccine, and no one saw it coming.

The National Institutes of Health, which funded the two studies, will be meeting this week to reexamine its entire AIDS vaccine program, currently funded at nearly $500 million per year. But the findings from the two halted vaccine trials were so disastrous that scientists now seriously doubt that an AIDS vaccine could be ready in the next few decades. It may depend on whether any new hypotheses come out of the new findings, and whether (and how much) NIH decides to fund AIDS vaccine research in the future. No one is giving up just yet, but an AIDS vaccine has certainly proved to be a more difficult challenge than was expected. Way back in 1984, federal officials predicted that an AIDS vaccine would be ready in three years.

See an article available online in The Washington Post March 21 entitled “Vaccine Failure Is Setback in AIDS Fight”. The article could be used as a springboard for a class discussion about the process of scientific inquiry; how new hypotheses are oftentimes developed out of the failure of old ones. You can almost see that happening in the speculation in the article about the causes of the vaccine’s failure.