Misdeeds in the world of science.

You get all busy with work and family and fearing Giblets' plans (while seriously wondering whether Giblets could be a cat), and important bits of news slip by. Like this item about Dr. Eric T. Poehlman at the University of Vermont College of Medicine. From the above-linked ORI press release:

From in or about 1992 to 2000, Dr. Poehlman submitted seventeen (17) research grant applications to federal agencies or departments that included false and fabricated research data. In these grant applications, Dr. Poehlman requested approximately $11.6 million in federal research funding. In most cases, Dr. Poehlman falsified and fabricated research data in the "preliminary studies" sections of grant applications in order to support the scientific basis for and his expertise in conducting the proposed research. Reviewers of these grant applications relied on the accuracy of the "preliminary studies" to determine if a grant should be recommended for award. While many of the grant applications were not awarded, NIH and USDA expended approximately $2.9 million in research funding based on grant applications with false and fabricated research data.

Dr. Poehlman's areas of research in which the fabrication and falsification played a role were fairly important: studies about aging in men and women, menopause, and hormone replacement therapy. Given that it would be helpful to an aging population to know what's going on in these areas, it would be good if one could rely on the data presented in research reports to be accurate rather than made up! In some ways, I find the falsification and fabrication of the "preliminary studies" in the grant applications even more repellant, since Poehlman's convincing fiction may well have resulted in some truly promising studies not being funded when scarce research funding dollars went to Poehlman instead.

Well, Dr. Poehlman can take a break from writing all those grant proposals to federal funding agencies, as he "has agreed to be barred for life from seeking or receiving funding from any federal agency in the future, including all components of the Public Health Service".

Sadly, it's not just scientists asking the feds for money who have been screwing up lately. There are also the scientists in the employ of the federal government who have apparently forgotten that falsification is a no-no.

The scientists in question work for the U.S. Geological Survey, and it would seem they have falsified some data in a safety study. Of the Yucca Mountain project. You know, the one that is supposed to give us a safe place to dump nuclear waste. Except, if one can't trust the reports of the scientists charged to study what is likely to happen at the proposed dump (and, in particular, whether water could seep into it), the whole "safety" question becomes rather more troubling.

Obviously, it's time for someone to step up and put a sexier face on the reality-based community so the wayward scientists will come on back.

Plagiarism vs. Entrapment.

This case is creating quite the buzz in the corner of the blogosphere I've been frequenting. And, it's been getting quite a mixed reaction. (See the comments here and here.)

In a nutshell: a comedian/blogger gets an instant message from a stranger soliciting a 5 page paper (with about 3 references per page) on Hinduism that she would then turn in for a college course. She names a price (but sounds an awful lot like she might stiff the stranger she's soliciting to create the paper). He does the standard Google-enabled cut and paste (with some bits thrown in for humor value, although opinions vary about how successful they are). He delivers the paper. He figures out her full name and the name of her college, and emails the appropriate authorities that this piece of work is about to be turned in under false pretenses.

It seems pretty indisputable to me that this student was WRONG. She's the Mayor of the municipality of Bad Call. The trickier question, ethically speaking, is whether he is in the wrong.

Assuming any of this really happened, of course ...

Discretion, Deception

Today we discussed an animal research case study where the protagonist aired some of her concerns to a (non-scientist) roommate. In our discussion, the question arose as to whether the roommate should actually be counted as an interested party in the situation. After all, she wasn't involved in the research. And, since she wasn't a scientist, she was in no position to assess whether the protocol was reasonable, whether the scientific question was an important one to answer, etc. So, you know ... butt out.

Indeed, one response I've heard to this case is that the protagonist might have an obligation not to discuss her research with outsiders, precisely because an outsider wouldn't really understand. And, not really understanding, an outsider might have a hissy fit about the poor bunnies and their suffering. And, in the throes of the hissy fit, the outsider might get PETA or ALF on the phone, and all of a sudden good science has been shot to hell by militant animal rights activists (or at least by negative public opinion).

But I worry a little about this response. I think there's a danger in only considering one's options in the context of the laboratory (or more precisely, in the context of one's advisor's laboratory). The danger that concerns me in keeping the deliberation inside this bubble is that one can lose sight of the interests that go beyond just getting publishable results. You might start to forget that the public has a stake in your research.

What's the public's stake? The public would like to benefit from the knowledge the research produced ... which means the public has an interest in the results being accurate. The public is likely involved (at least indirectly) in funding the research, and undoubtedly the public would like that funding to be used effectively ... which means a change in the protocol which might make the results difficult to interpret would be bad. The public (probably) has an interest in minimizing animal suffering ... which means if animal suffering is essential to solve this scientific problem, the public probably deserves an explanation of why the suffering is warranted in this case.

Anytime someone doesn't want to take the time to explain something to me, I get to wondering whether it's because she doesn't have a good explanation to offer.

When the tribe of science makes unilateral decisions about what those in society at large shouldn't worry their pretty little heads about (including how and why animals are used in research), scientists are either denying that the public has a stake, or denying that the public can act in its own interests to defend that stake. Or, I suppose, scientists could recognize that the public has a stake and is competent to defend its interests, but they might have decided that, since the goals of science and the goals of the public are at odds in some fundamental way, they're prepared to screw over the public. Which is probably a better move if you're not taking the public's money.

Getting outside the bubble might actually give you perspective and allow you to think through a decision from the point of view of other stake-holders. I think it's a good idea to explain the inside-the-bubble perspective to the outsider, and it probably doesn't hurt to be discreet about some of the specific details (like which building on campus houses the rabbits). But I think when discretion turns into secrecy, deception is a little to close, and a little too easy.

What I should have said ...

Do you ever have one of those moments, where you start talking about a real-life example that you know connects to some other issue you're discussing, and you know there's an important point to be made about the connection, but you kind of ... coast right by it? (No, it's not a senior moment. Shut up!)

Yesterday, when we were talking about whether animal research was necessary, or useful at all, to answer certain pressing scientific questions, I mentioned the discussion of the body's burden of synthetic chemicals that's been featured in The Argus and on KALW radio. But, of course, I didn't quite make the connection I should have. Let me try now.

The centerpiece of the story was the testing of the members of a Berkeley family to track the levels of various synthetic chemicals found in their blood, hair, and urine. Some of the results were shocking (such as the highest recorded level of a flame-retardant compound in a human being in the blood of the 20-month-old). And of course, while the technology exists to quantify the parts per billion levels of the compounds rather precisely, scientists don't actually know what these levels mean, in the short term or the long term, for the health of these people.

OK, so there's a great scientific question that you might want to answer. And, since we don't know what the heck these chemicals do to humans, it might be quite hard to set up a study with human subjects where we could actually obtain informed consent (since the information ... just isn't there yet). So, let's go to the Mouse House and set up an experiment with animals!

So, here's a reasonable experimental design: Get yourself 200 mice. Set aside a certain number as your control group; they just get to be plain old, unexposed laboratory mice. Take the rest of the mice and break them into (say) three different "treatment" groups: one group gets high exposure to the flame retardant chemical, one mid-level exposure to it, and one low-level exposure. Except for the exposure, the "treatment" groups get the same treatment (food, cages, toys, etc.) as the control-group mice. All the mice get periodic blood tests and have their health assessed in the appropriate mousy ways. They get to live out their days in laboratory luxury, and when they die the cause of death and state of health at time of death will be determined. The effect of the flame retardant exposure on health will be assessed by comparing the "treatment" group mice to the control group mice.

Of course, you might ask why we need to do this with mice. There are plenty of humans out there, apparently, who are already exposed to these compounds. Presumably, to find out the effects of these compounds on human health, we might learn more by tracking the health of the already-exposed humans than by exposing and studying mice. (A mouse is not identical to a human in all relevant respects, after all.)

One problem is that it's much easier to control for all sorts of other possibly relevant variables (like diet, exercise, etc.) working with mice in a lab than it is if you're studying humans running free in the world. (Yes, I know, McDonalds and Starbucks and the persistent push to homogenize American culture are doing their best to help with this, but there's still a good bit of variation in the ways people live.)

Another problem is one that surprised the researchers studying the Berkeley family for the story. Ideally, to determine the effects of the compounds on human health, you'd want to be able to compare the health of people exposed to them to the health of people not exposed to them. And, the researchers could not find any Americans who did not have some of these compounds in them! When they looked on other continents, it was pretty much the same story. In other words, it might be impossible to find an appropriate human control group to find out what the heck these compounds are doing to us.

Thanks, Monsanto and 3M.

Here, you might think that this would seal the deal for the mice -- if we can set up an appropriate mouse control group, this is our best bet to get a definitive answer about the effects of these compounds. But there are a couple of potential problems. For one, it's entirely possible that all the mice have these compounds in them already, too. (The researchers for the story didn't check.) If they do, there's no clean way to set up a mouse control group either.

If American laboratory mice screen negative for all these compounds, though, it might point to a fundamental problem with this animal model. Because the fact that all the humans in the country (and beyond) seem to have these compounds in them points to their prevalence in our environment: in the food and water, in the air, in the dust, in the building materials, etc. Laboratory mice are not getting certain kinds of exposure that humans are (e.g., they don't generally smoke, or wear nail polish, or use shampoo or lotion, or disposable diapers, etc., etc.); but many of the humans whose blood contains these compounds haven't exposed themselves in these ways either. This would seem to indicate that these compounds are ubiquitous in our environment. And the laboratories the mice are raised in are not entirely sealed off from that environment. So, if the mice that have been exposed to the same environment seem not to show the presence of these compounds in their blood, urine, and hair, that would seem to indicate that the mouse's body either doesn't take up these compounds, or that it has some process for getting rid of them quickly. In other words, we'd already have good reason to think the mouse body responds differently to these compounds than does the human body. And this might be good reason to worry that studies of these compounds on mice wouldn't tell us what we need to know about exposure to these compounds on humans.

Looks like it's time to come up with a better experimental approach to this question. Anyone?

Animals and Research

Way back, during my misspent scientific youth (although not quite this far back), I was involved in a research project that used rats. Many, many rats.

We were doing diabetes research. Specifically, we were looking at the effects an aldose reductase inhibitor had on certain diabetes-related conditions, like cataracts and neuropathy. This was primarily a physiological question: what happens in a diabetic if you inhibit the conversion of glucose to other compounds? And, there just didn't seem to be a good way to really answer this question without in vivo studies.

So, the rats.

The first relevant fact is that all the rats we used were given diabetes (or a condition close enough to diabetes to serve as a good animal model), some by injection with a compound that knocked out the pancreas, others via a diet packed with galactose. What this means is that life was not super for our control groups. The experimental groups got treated with the promising compound, at various doses, for various lengths of time. But then, they got "sacrificed" so their lenses, kidneys, and caudal arteries could be extracted and analyzed. (Of course, the control group rats were sacrificed, too, so we could use their lenses, kidneys, and caudal arteries for comparison.)

As a student researcher in the lab, I never had to sacrifice the rats or do the extractions, but I was there (because I had to be to prepare the tissue samples). The first time I was on the team for tissue harvest day, I felt rather dizzy and had to sit in the hall with my head between my knees for awhile. I was told that this was a very common reaction ... and that I'd get over it. For the most part, I did.

There were particular parts of my job in the lab that did not evoke great sympathy for the rats from me. For example, cleaning the "metabolic cages". Besides tissue samples, we collected urine samples from the rats for analysis. You really can't get a rat to pee in a cup, so, metabolic cages are designed to collect the urine as the rat urinates. They are nasty to clean. Still, I wouldn't say that they're so nasty that the being making the mess automatically deserves to have its eyeballs pulled out.

Also, the P.I. made a point of telling me that it cost more per day to maintain one of our laboratory rats under IRB-approved conditions than it did to feed a person in India ... which, I suppose, was meant to reassure me that the rats were receiving excellent care, but instead made me really worry about the well-being of the people in India.

Did the benefits of this research outweigh the costs?

The costs, in terms of number of rats sacrificed and their quality of life before they were sacrificed, was significant. Then again, short of going right to testing on humans, it seems to me animal testing was the only way to answer the questions we were trying to answer. And these questions are pretty significant for the health and well-being of people with diabetes, since they went right to the heart of the dominant approach to treatment (controlling glucose level). If it was not the glucose level but rather the levels of the compounds produced from the glucose that led to the serious complications of diabetes, then controlling the conversion of compound would seem a more promising approach to treatment. The animal model seemed like a good one -- the control group diabetic rats developed the same kinds of complications as did humans with diabetes. So, on the whole, I felt like this research was probably defensible.

Of course, I was involved in this research back in 1986-1987. Now, the incidence of Type-II diabetes, especially among children, is exploding. And, it makes me think that if I were doing this research today, I might feel differently about whether using and sacrificing so many experimental rats was justified. The reason for this is that most indications are that the explosion of Type-II diabetes is caused by lifestyle -- poor diet and lack of exercise. In other words, it should be totally avoidable!

Of course, it's not that simple, especially if you're a little kid. You eat what you're fed. Can you help it if your parents get your food from a fast-food restaurant or the snack aisle? How are you supposed to exercise when your neighborhood isn't safe enough for you to be out playing unsupervised (and there are no adults to supervise you because they're working multiple jobs or commuting long distances) and your school doesn't have funding for gym class? How the heck are you supposed to secure, on your own, the conditions required to avoid the avoidable Type-II diabetes?

Yet, I can't help but feel someone bears some responsibility here, and that that person or persons ought to be asked to bear some of the cost in addressing the problem that an animal study might be asked to solve. No, I'm not suggesting research on fast food executives ... not yet, anyway. But if their personal benefits (profits and the like) are tied to the conditions that create the problem, shouldn't these people also bear some responsibility for solving the problem? Do the rats have to do all the heavy lifting here?

Face transplants

I heard a story on the radio the other day about new research in face transplantation. Yes, transplanting a whole face.

It seems that your standard skin-grafting reconstructive surgery doesn't work so well on faces. Faces have lots of little muscles, and the skin can stretch and contort in all sorts of ways that your mother threatened would become permanent if done too often. People who require facial reconstruction because of serious burns and the like standardly undergo scores of surgeries, none of which usually do a satisfactory job.

The option that's being explored experimentally is transplanting entire faces (skin plus underlying tissue) from cadavers. Of course, doing this requires the removal of the skin and underlying tissue of the face recipient, leaving the facial muscles.

So, without even getting into the new identity-theft possibilities this might open up, there is some question of how ethical this kind of medical procedure could be.

The risks are pretty extreme. If you reject a skin graft, they can take it off and try again. If you reject a whole face, taking it off leave you with no face to fall back on. What kind of back-up would we want the doctors to have in place if the first face transplant for patient X fails? A second face available to transplant (and a third, and a fourth)? Extensive skin grafts ready to go? (How will the success of this more standard approach to reconstruction be affected by the full face removal that precedes an attempted face transplant?) Something else?

The big ethical question here is whether the likely benefits of the procedure outweigh the potential risks. And just how to measure this is the puzzle. For the burn victim, a successful face transplant might be like winning the lottery -- the last surgery you need to have a face that functions fully (and doesn't necessarily mark you forever as a burn victim). Of course, this sets aside issues like the effects of the non-rejection medications you'd have to be on for the rest of your life. But, like the lottery, the likelihood of success might be very, very small. Given the expected payout when the odds of success are very small, is it rational to undertake the risk (especially of less risky treatments are available and well-understood)?

But, I can imagine a burn victim arguing that this is an instance where, given full information about the potential risks, the potential benefits, their anticipated probabilities, and the available alternatives, she ought to be able to decide whether to gamble on this new procedure. Mortality and morbidity are not the only factors that matter to her. Being able to be done with surgery might be a real benefit. Being able to go through life with a face that looks and functions like a face might feel like the biggest benefit at all. Who should tell the burn victim that she can't rationally decide it's worth risking everything else for that?

If it happens, I imagine the doctors will develop a wicked-good waiver of liability!

Dealing with uncertainties

If we knew everything there was to know, choices would be fairly easy. But, we don't, so they usually aren't. So, the trick is to figure out good ways to act in the face of uncertainties.

I have no idea whether there's a good general approach to take to this problem, but I know what I would want people to do (and would do myself) in certain specific situations.

Is driving while talking on a cell phone dangerous? Some studies seem to indicate so (even for hands-free models). Presumably, some folks (maybe even folks not in the employ of a cell phone company) think there is some uncertainty in these findings ... because even people who are aware of these studies seem to drive while talking on their phones! But, in the face of uncertainty here, I'd prefer that drivers err on the side of caution!

How real is reality TV? Could these people actually be as stupid/narcissitic/toadying/drunk as they appear to be in this show? Unless the editing is really obvious, there will be some uncertainty about this. (Yes, even if you're one of the people in the reality show -- Omarosa? Trishelle? I'm looking at you!) When in doubt? Assume that Mark Burnett's crack editing team may have at least altered the magnitude.

The lottery -- somebody has to win it! Sure, it's not impossible that you'll win the lottery, so you can't be certain that you won't. But you probably shouldn't be buying the major appliances on the basis of the non-impossibility of winning.

(Yes, it's the petty stuff today. It doesn't mean it's not relevant.)