8 ms·

Male Scent May Compromise Biomedical Research

jerf 13y ago
This metaphorically reeks of being the sort of result that in six months will be quietly retracted. But at least there's a mechanism proposed that isn't utterly ludicrous... (See expansion below, which describes why this triggers my BS meter. YMMV, but it's not just "reflexive".)
- groby_b 13y ago
  Please do expand on your thought there. What makes it likely this will be retracted? The experimental set-up seems fairly sound. They controlled for the obvious factors that could influence the outcome. It is somewhat consistent with what we know in other areas - yes, pain is felt less under increased stress, and yes, the presence of other males is a stressor. The interesting part is that it's an inter-species stressor. But then again, testosterone as a male hormone is shared across a lot of species - it's not entirely unreasonable to assume that scent markers might be similar too. So, what makes your BS sensor go off? (I ask in all seriousness. I'm always interested in calibrating my sensor, and it didn't go off for this).
  - jerf 13y ago
    Like I said, and I meant it seriously, it does at least propose a non-silly mechanism that makes sense. But it A: proposes a sweeping result which, if taken seriously, ought to invalidate a lot of other experiments and B: pushes a moderately political button with the gender issue. Neither of those is a disqualifier, but A in particular at least somewhat gets into the realm of "an extraordinary claim that will require extraordinary confirmation". The proposed mechanism would also seem to imply that female hunters don't exist. I would have preferred a proposal that you're inclined to hide your weaknesses around a male in general (lest he either take your woman or harass you in other ways), and the mechanism is likely keyed off of testosterone in general rather than mouse smells in particular, which seems reasonable. My head isn't going to explode if this is established by further experiment. But it's suspicious to me. To siyer's point, impeccably-done research can still come up with coincidental results, unfortunately.
    - sp332 13y ago
      No, the mechanism is increased stress, and it has already been experimentally verified (although I'd like to see it repeated). Mogil has a guess about why that might happen, and it's called out as supposition, not an "extraordinary claim". Other potential explanations include a few male rat-farmers who were rough with the rats, which made the rats edgy around males later in life.
      - CamperBob2 13y ago
        No, the mechanism is increased stress, and it has already been experimentally verified (although I'd like to see it repeated) Until it has been repeated, it has not been verified. That is how experimental science works.
        sp332 13y ago
        Science is repeatable, not repeated. It's not true that one experimental result is meaningless but two are gospel. The first has a probability of being a fluke, and the second reduces that probability, that's all.
        CamperBob2 13y ago
        Indeed, this is true as well. Science isn't the right place to look for absolute certainty. But still, there are some obvious things you can do to increase confidence in a result, and one of those is to get other people to try to reproduce those results.
    - siyer 13y ago
      "and the mechanism is likely keyed off of testosterone in general rather than mouse smells in particular, which seems reasonable." Yes, this is what Figure 1c and 1d of the paper demonstrate. (To be precise, not testosterone, but adrostenone, androstadienone, and 3M2H). "My head isn't going to explode if this is established by further experiment. But it's suspicious to me." Supplementary Fig. 1 and Supplementary Fig. 3 describe replications performed in two other laboratories, one at the University of Alabama, Birmingham, and the other at another laboratory at McGill. Look, I'm all for scientific skepticism, and it's true that there's a lot of low-powered stuff out there. However, papers are best evaluated on what they actually say (which, incidentally, is why open-access/archiving is important), rather than on a filtered impression of what a press release says. If you'd like a copy of the paper, let me know, I'd be happy to send you a pdf.
- siyer 13y ago
  This is just reflexive HN negativity. As a pain researcher who's completely unaffiliated with the group that did this work, I find this to be an excellent paper - carefully done, with good controls, standard sample sizes for the field, and sensible assays. People interested in more of the details can read the Nature Methods article here: http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.2935.html http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth... It also fits into a long history of work out of the Mogil lab about the limitations in our current assays for pain. It's worth noting that this is by no means an easy problem. Pain is inherently subjective, and measuring and quantifying it in humans is difficult, let alone in rodents. The only way forward is more work like this - that carefully quantifies the sources of potential bias and error in our assays, and proposes solutions for how to get around them. Edited to add: Vox has a good interview with Mogil that goes more into this. You can read it here: http://www.vox.com/2014/4/28/5653444/mice-get-stressed-out-from-men#interview http://www.vox.com/2014/4/28/5653444/mice-get-stressed-out-f...
  - CamperBob2 13y ago
    I'll take the liberty of rephrasing jerf's comment: this is the sort of paper I'll be more likely to believe after it's been reproduced by multiple labs. Until then, I'd just as soon not even be told about it. It sounds too much like any number of "xxx affected by cell phone radiation!!1!!" results that historically have given rise to much panic, intense discussion, and clicking of links, but have never, ever, ever proven to be consistently replicable. At some point, skepticism and even a bit of "HN negativity," as you put it, becomes the most rational response to initial reports of such phenomena.
    - siyer 13y ago
      My point is more that there are differing levels of the prior probability of a study being true. Yes, 'xxx affected by cell phones' stories are bunk, however, those stories tend not to be published in Nature Methods, tend not to come out of highly respected laboratories, and tend not to have voluminous documentation and results, with 9 Supplementary Figures. I've been reading this paper closely over the past 30 minutes, it's important enough that I'm sure it'll be heavily discussed at conferences and meetings this year. I can't think of a single thing that these researchers could have done that they haven't done. They've approached the question carefully, looked into a ton of second-order explanations and effects, and provided a plausible discussion of how and why they see their effects.
- anigbrowl 13y ago
  This metaphorically reeks I see what you did there.
- nuser 13y ago
  Your comment reeks of being the sort of claim that you will pretend you never made if nothing changes, but you will hold up as evidence of your incredible knowledge of it isn't. There's literally nothing of value in your comment (unsurprising, as nearly all of your comments are just you restarting your tired and dullheaded Libertarian beliefs). You're upvoted solely because HN is a shithole that was long ago ruined by nontrepreneurs like you.
- sesqu 13y ago
  This particular study seems fairly solid, but the linked one about a cardboard cutout appears contradictory. The comment about predators seems careless, in that light, but the person making the comment has clearly been theorizing about the effect for a while. So I don't expect the study to be retracted, but I expect half a dozen more papers and then a theory that will be eventually debunked in favor of a more politically convenient one.
dang 13y ago
The original title seems both linkbaity and misleading, so we changed it. If anyone can suggest a better title, please do. Edit: Ok, since most people who commented don't agree that it was a bad title, we changed it back.
- deleted 13y ago
  [deleted]
- TazeTSchnitzel 13y ago
  Which? 'Male Scent May Compromise Biomedical Research' seems better than 'Experimenter gender is a confounding factor in lab animal research', but which was the original?
  - anigbrowl 13y ago
    Yeah, the 'male scent' (original) title is better. When I read 'Experimenter gender' I was expecting to read an article about some sort of gender-originated cognitive bias.
    - deleted 13y ago
      [deleted]
  - dnautics 13y ago
    actually should be "experimenter sex". Gender is a social term.
- siyer 13y ago
  The current changed title is overbroad, it's certainly not shown by this study that experimenter sex is an issue in all animal research. I would simply suggest the title of the paper itself: "Olfactory exposure to males, including men, causes stress and related analgesia in rodents". It's fairly straightforward, and not as jargon-filled as scientific titles go.
- ars 13y ago
  A suggestion: When you make such changes please write in your comment what the old and new titles were.
pwrfid 13y ago
This could certainly be plausible. Fairly rigorous studies. Just needs to be repeated in other labs
VikingCoder 13y ago
Richard Feynman spoke specifically to this point in his Cargo Cult Science piece: http://neurotheory.columbia.edu/~ken/cargo_cult.html http://neurotheory.columbia.edu/~ken/cargo_cult.html "That is the experiment that makes rat-running experiments sensible, because it uncovers that clues that the rat is really using-- not what you think it's using. And that is the experiment that tells exactly what conditions you have to use in order to be careful and control everything in an experiment with rat-running."
- Balgair 13y ago
  First, thank you. I have been looking for this for years! Now i have something to search for to find the paper. I worked in a rat lab for a while that tried testing smells. It was impossible to get data, but sure enough, the professor insisted that stuff was there and published weak papers that were rejected thoroughly. We had about 15 rats and at least 50 major variables to test, if not more confounding variables. I used to read PhD comics as a salve, and then realized that it was a shield. So many grad students feel so badly precisely because they know that the science is crap and no-one will read it anyway because we all know it is crap[0][1]. The rule is getting to be; If the P-value is at 0.05, flip a coin; heads I read it, tails I eat lunch. This isn't just isolated to the ivory tower either. The public sees this and not just from friends and family. These back and forth studies screaming 'coffee is a super-food' and then 'coffee is poison' are an example. They give the public an impression that we scientists don't have a clue. And, true, we may not, but allowing the press to scream these things for funding and publicity's sake is a tragedy of the commons. Yes, I know, you can't expect everything to be perfect. But what we have is so very far from that (and yes, I know, China or India are waaay worse). Still, to see in the grad student's eyes that they know the last 6 years were total crap is tragic, especially when the professor insists it isn't to new students and older ones know they can do nothing to persuade the new ones differently. [0]http://www.economist.com/news/briefing/21588057-scientists-think-science-self-correcting-alarming-degree-it-not-trouble http://www.economist.com/news/briefing/21588057-scientists-t... [1]https://en.m.wikipedia.org/wiki/John_P._A._Ioannidis https://en.m.wikipedia.org/wiki/John_P._A._Ioannidis
  - kennywinker 13y ago
greenyoda 13y ago
This kind of response by lab animals to stressors in their environment reminds me of the "Rat Park"[1] experiment, in which rats who were stressed out from being kept isolated in small cages (rats are social animals) had a tendency to become addicted to morphine, but those who lived in a pleasant environment did not. [1] https://en.wikipedia.org/wiki/Rat_park https://en.wikipedia.org/wiki/Rat_park
- vanderZwan 13y ago
  BTW, Stuart McMillen made an excellent comic about Rat Park. I think it may have been linked on HN before, but just in case: http://www.stuartmcmillen.com/comics_en/rat-park/ http://www.stuartmcmillen.com/comics_en/rat-park/
- dnautics 13y ago
  this one, too, and this one is really confounding because the LAW requires animals to be handled at RT. http://www.nature.com/news/chilly-lab-mice-skew-cancer-studies-1.14190 http://www.nature.com/news/chilly-lab-mice-skew-cancer-studi...
cmyr 13y ago
Their conclusion that "Male odors seemed to act like painkillers" seems like only one of several possible interpretations? My first reaction was that the possible presence of other male mammals provided a selection bias for individuals who displayed less pain. Amongst individuals of the same species, showing pain would be a sign of weakness, obviously, but it might be a similar marker for possible predators. So perhaps all the animals are feeling the same discomfort, but those who sense other males are less willing to perform their discomfort behaviourally?
- Jemaclus 13y ago
  The article addresses this: > Further testing showed that the rodents exposed to male odors were actually feeling less pain, rather than simply hiding the pain they were in. The male aroma ramped up their stress levels, which deadened the hurt. “It’s really astounding that such a robust effect could have been missed for so many years,” Mogil says. Though, to be fair, they don't go into detail about how exactly they determined that the rodent was "actually feeling less pain"...
  - Blahah 13y ago
    It's properly addressed in the actual paper [0]: True SIA should be accompanied by decreased immediate-early gene expression in the pain-processing neurons of the spinal cord dorsal horn; we observed a dramatic (≥50%) decrease in Fos protein–positive neurons in mice injected with zymosan and exposed to male but not female experimenters or shirts (Kruskal-Wallis test statistic: 12.0, degrees of freedom = 4, P < 0.05; Fig. 2d). Much is known about the neurochemistry of SIA, which exists in opioid (naloxone-reversible9), non-opioid (cannabinoid-1 (CB1) receptor–mediated10) and mixed opioid/non-opioid11 forms. The male experimenter SIA seen here was found to be the latter, as it was blocked (observer × drug interaction: F3,56 = 2.8, P < 0.05) by the broad-spectrum opioid receptor antagonist naloxone (1 mg per kg body weight (mg/kg); P < 0.05), by the inverse CB1 receptor agonist AM-251 (10 mg/kg; P < 0.05) and by a combination of the two drugs (P < 0.01), at doses not affecting pain sensitivity per se (Fig. 2e). In other words, pain in mice is associated with a particular protein binding neurons in a particular part of the brain. The researchers showed that in mice handled by men, the proportion of those neurons bound by the pain-associated protein was significantly decreased, supporting the hypothesis that male-handled mice are actually experiencing less pain. http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.2935.html http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth...
anon4 13y ago
Maybe researchers should then just always use suits, or at least put on a clean shirt each time before getting close to the rat cages and handling them.
- veew 13y ago
  Or maybe awful men need to step aside and let others run things. They always ruin everything anyway.
- judk 13y ago
  You are being down voted because people are amusingly misinterpreting the kind of "suit" you meant
return0 13y ago
Maybe this affects only certain kinds of experiments. There is a reason why only male mice are used in experiments and why scents (peppermint) is usually used to denote context.
- Balgair 13y ago
  To elaborate, male rodents are typically used because they do not go through estrus[0] [0]https://en.wikipedia.org/wiki/Estrous_cycle https://en.wikipedia.org/wiki/Estrous_cycle
Alex3917 13y ago
There is a great video about these sorts of effects called Lullaby For A Mouse: http://vimeo.com/33803995 http://vimeo.com/33803995 The basic gist is that most research done on mice (and other animals) is complete crap: - Almost all laboratory mice are morbidly obese and get little to no exercise. - They're all starved of social contact. - The variations in the daily schedule of the researchers mess with their circadian systems. - The results vary enormously based on how the researchers treat the animals. The title comes from the fact that one of the researchers started singing to his mice in order to get better results.
- thinkpad20 13y ago
  I worked in a laboratory with mice for about two years after college. * None of our mice were morbidly or even slightly obese (I know because I had to cut them open). * The mice lived in groups of up to 6 in a cage, which I don't know how it compares to their normal situation, but it's not "starved of social contact." * I don't remember how we dealt with the mice's circadian rhythms, but I think that we had the lights on timers for this. * Research is inherently subject to variation. There might be compelling reasons why results would vary based on how researchers treat their animals, but I think it would depend a lot on what kind of experiments were being performed. Stating that in a blanket fashion, I think, is misleading. Biological science is just plain hard, and many experiments fail, often with no clear explanation why. That someone could get frustrated enough to start singing to their animals is not an indication that mouse research is inherently flawed. At the end of the day, a vast quantity of scientific knowledge is owed to mouse research. Denouncing it as "[mostly] complete crap" is just plain false.
  - hoggle 13y ago
    It's good that the lab you worked in had good standards in place but can you be sure this is the case for most labs?
singlsrv0x99fa 13y ago
Why inflict pain instead of pleasure ? From my experience experiments on animal subjects tend to focus on negative responses. Beside specifically testing negative agents, is there a logical reason for this approach ? Why not measure attraction instead of avoidance ? Do mice exhibit visible joyful facial expressions vs the grimacing this article describes ? It sounds silly, but couldn't we measure how much we delight the mice ?
brortao 13y ago
I think this serves as a good example of (one of) the issues with animal testing. The scientist in this article doesn't think that we need to "redo decades of animal research", but it certainly casts doubt on previous results. In general, testing on animals isn't effective. Considering the amount of suffering it inflicts on animals, I'm not sure that it's morally defensible. The British Union for the Abolition of Vivisection has a [good resource][1] on the issues. [1]: http://buav.org/humane-science/key-criticisms/ http://buav.org/humane-science/key-criticisms/
tokenadult 13y ago
The hypothesized mechanism is very interesting. Perhaps mice vary their behavioral response to pain depending on how safe it is to express distress from pain. VikingCoder has already given the definitive comment: further controlled experiments will tease out how important this effect is over what range of behaviors. There are many, many, many kinds of mouse experiments (I am currently doing reading on behavior genetics research on learning and intelligence and fear and aggression in mouse model organisms), and some will be more influenced by what the interesting preliminary report here suggests than others. See the book How Genes Influence Behavior[1] for a fascinating description of how we can learn about human behavior by studying mouse behavior (and even by studying fruit fly behavior!). [1] http://global.oup.com/academic/product/how-genes-influence-behavior-9780199559909;jsessionid=D71B0EC416B75938EC3C4BB81BDB7183?cc=us&lang=en& http://global.oup.com/academic/product/how-genes-influence-b...
josephschmoe 13y ago
It's clearly not just the male scent, because it gets cancelled out by the female scent. There's obviously more to this.
- Balgair 13y ago
  Huh? How can scents be canceled out?
  - cevn 13y ago
    In the original article, the effect that the male scent had on the mice was cancelled out by the female scent also being present - not sure of the actual mechanism, but it's not the actual 'scents cancelling out'
ChrisNorstrom 13y ago
2 Theories: 1) It's the brain's way of telling the body: "Another male is nearby, do not show weakness or submission because that male may try to dominate you and you may end up getting into a fight or dying." I'd assume this evolutionary response would only work for same species scents. Apparently it works between species. Men have a tendency not to get into fights with confident men. 2) During a fight with another male, the mind needs to ignore pain in order to continue on and win the fight. In all species, males who didn't have this trait lost battles, died, and did not pass on their genes. Males who had this mutation didn't let the pain get to them, went on to win the fight, lived, reproduced, and passed on these characteristics.
- serf 13y ago
  a theory I had : perhaps due to past generations of male experimenters, mice have developed a central nervous system which deadens pain in the expectation of a painful experiment when exposed to male scents.
  - vectorpush 13y ago
    What would be the selective advantage of pain resistance in the context of a lab environment? It seems to me like the rodent's chance of passing on it's genes would have no correlation with resistance to pain.
    - serf 13y ago
      That's a good question. We know that pain stresses the nervous system, and that it also increases incidence of depression. Both pain and depression lower survival chances, as they both increase the chances for negative effects on the host such as sudden weight fluctuation, abnormal sleep cycles, and uncoordinated muscle control. I have not worked in such a lab setting, so i'm unsure if any of the mice that survive experimentation are exterminated or repurposed. If repurposed, one can imagine that a pain-reduction schema would be useful in such environments for the sake of species proliferation. Mice/rats better suited to the pain thresholds required of them would eat better, sleep better, and ultimately breed more. Again, just an armchair theory and little more.
neurobro 13y ago
It sounds like each test involved the same person both giving injections and sitting in the room. I wonder if they can somehow mechanically inject the irritant without human involvement. Then they could have male/female participants sit in the room without knowing if any animals are present. This would help distinguish whether the rodents were reacting to a general difference in scents, or males and females give off different signals when handling rodents.
bambax 13y ago
> “It’s a primordial response,” he says. “If you smell a solitary male nearby, chances are he’s hunting or defending his territory.” If you’re in pain, you’re showing weakness. I don't know about those results, but this explanation sounds preposterous: it doesn't work if you're hunted down by a lioness (which does the hunting while the male lion sleeps); it also doesn't work if you're spotted from the air by an eagle (which is one the main hazards if you're a small rodent). Why does every behavior has to be explained in terms of survival, we'll never know. Stephen Jay Gould was so good at debunking those easy explanations; how I miss him.
- fit2rule 13y ago
  Lions hunt alone. Lionesses usually hunt in packs.
fit2rule 13y ago
This is like the "Heartbleed" backdoor of the medical industry .. how many previously-though-defensible studies are now trash because of this? Its mind-boggling, to be honest ..
MyGod 13y ago
"Mogil’s group discovered that this gender distinction alone [...]" It's sex, not gender distinction. Gender - what you identify as, sex - what you are. Males that identify as females would still throw their test off. Yah, nipicking. And call me paranoid, but this seems to have agenda....
Allower 13y ago
We can only account for variables we can imagine, this is why science is so often proving itself wrong.
joeevans1000 13y ago
Wow. I didn't really know there was an 'animal grimace scale'. I have to say, after googling that a minute ago, I have actually become an superfluous animal testing opponent, after having suspected animal testing was done excessively. I dare you to google it. These researchers... what assholes.

jerf 13y ago

This metaphorically reeks of being the sort of result that in six months will be quietly retracted. But at least there's a mechanism proposed that isn't utterly ludicrous... (See expansion below, which describes why this triggers my BS meter. YMMV, but it's not just "reflexive".)

groby_b 13y ago
Please do expand on your thought there. What makes it likely this will be retracted? The experimental set-up seems fairly sound. They controlled for the obvious factors that could influence the outcome. It is somewhat consistent with what we know in other areas - yes, pain is felt less under increased stress, and yes, the presence of other males is a stressor. The interesting part is that it's an inter-species stressor. But then again, testosterone as a male hormone is shared across a lot of species - it's not entirely unreasonable to assume that scent markers might be similar too. So, what makes your BS sensor go off? (I ask in all seriousness. I'm always interested in calibrating my sensor, and it didn't go off for this).
- jerf 13y ago
  Like I said, and I meant it seriously, it does at least propose a non-silly mechanism that makes sense. But it A: proposes a sweeping result which, if taken seriously, ought to invalidate a lot of other experiments and B: pushes a moderately political button with the gender issue. Neither of those is a disqualifier, but A in particular at least somewhat gets into the realm of "an extraordinary claim that will require extraordinary confirmation". The proposed mechanism would also seem to imply that female hunters don't exist. I would have preferred a proposal that you're inclined to hide your weaknesses around a male in general (lest he either take your woman or harass you in other ways), and the mechanism is likely keyed off of testosterone in general rather than mouse smells in particular, which seems reasonable. My head isn't going to explode if this is established by further experiment. But it's suspicious to me. To siyer's point, impeccably-done research can still come up with coincidental results, unfortunately.
  - sp332 13y ago
    No, the mechanism is increased stress, and it has already been experimentally verified (although I'd like to see it repeated). Mogil has a guess about why that might happen, and it's called out as supposition, not an "extraordinary claim". Other potential explanations include a few male rat-farmers who were rough with the rats, which made the rats edgy around males later in life.
    - CamperBob2 13y ago
      No, the mechanism is increased stress, and it has already been experimentally verified (although I'd like to see it repeated) Until it has been repeated, it has not been verified. That is how experimental science works.
      - sp332 13y ago
        Science is repeatable, not repeated. It's not true that one experimental result is meaningless but two are gospel. The first has a probability of being a fluke, and the second reduces that probability, that's all.
        CamperBob2 13y ago
        Indeed, this is true as well. Science isn't the right place to look for absolute certainty. But still, there are some obvious things you can do to increase confidence in a result, and one of those is to get other people to try to reproduce those results.
  - siyer 13y ago
    "and the mechanism is likely keyed off of testosterone in general rather than mouse smells in particular, which seems reasonable." Yes, this is what Figure 1c and 1d of the paper demonstrate. (To be precise, not testosterone, but adrostenone, androstadienone, and 3M2H). "My head isn't going to explode if this is established by further experiment. But it's suspicious to me." Supplementary Fig. 1 and Supplementary Fig. 3 describe replications performed in two other laboratories, one at the University of Alabama, Birmingham, and the other at another laboratory at McGill. Look, I'm all for scientific skepticism, and it's true that there's a lot of low-powered stuff out there. However, papers are best evaluated on what they actually say (which, incidentally, is why open-access/archiving is important), rather than on a filtered impression of what a press release says. If you'd like a copy of the paper, let me know, I'd be happy to send you a pdf.
siyer 13y ago
This is just reflexive HN negativity. As a pain researcher who's completely unaffiliated with the group that did this work, I find this to be an excellent paper - carefully done, with good controls, standard sample sizes for the field, and sensible assays. People interested in more of the details can read the Nature Methods article here: http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.2935.html http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth... It also fits into a long history of work out of the Mogil lab about the limitations in our current assays for pain. It's worth noting that this is by no means an easy problem. Pain is inherently subjective, and measuring and quantifying it in humans is difficult, let alone in rodents. The only way forward is more work like this - that carefully quantifies the sources of potential bias and error in our assays, and proposes solutions for how to get around them. Edited to add: Vox has a good interview with Mogil that goes more into this. You can read it here: http://www.vox.com/2014/4/28/5653444/mice-get-stressed-out-from-men#interview http://www.vox.com/2014/4/28/5653444/mice-get-stressed-out-f...
- CamperBob2 13y ago
  I'll take the liberty of rephrasing jerf's comment: this is the sort of paper I'll be more likely to believe after it's been reproduced by multiple labs. Until then, I'd just as soon not even be told about it. It sounds too much like any number of "xxx affected by cell phone radiation!!1!!" results that historically have given rise to much panic, intense discussion, and clicking of links, but have never, ever, ever proven to be consistently replicable. At some point, skepticism and even a bit of "HN negativity," as you put it, becomes the most rational response to initial reports of such phenomena.
  - siyer 13y ago
    My point is more that there are differing levels of the prior probability of a study being true. Yes, 'xxx affected by cell phones' stories are bunk, however, those stories tend not to be published in Nature Methods, tend not to come out of highly respected laboratories, and tend not to have voluminous documentation and results, with 9 Supplementary Figures. I've been reading this paper closely over the past 30 minutes, it's important enough that I'm sure it'll be heavily discussed at conferences and meetings this year. I can't think of a single thing that these researchers could have done that they haven't done. They've approached the question carefully, looked into a ton of second-order explanations and effects, and provided a plausible discussion of how and why they see their effects.
anigbrowl 13y ago
This metaphorically reeks I see what you did there.
nuser 13y ago
Your comment reeks of being the sort of claim that you will pretend you never made if nothing changes, but you will hold up as evidence of your incredible knowledge of it isn't. There's literally nothing of value in your comment (unsurprising, as nearly all of your comments are just you restarting your tired and dullheaded Libertarian beliefs). You're upvoted solely because HN is a shithole that was long ago ruined by nontrepreneurs like you.
sesqu 13y ago
This particular study seems fairly solid, but the linked one about a cardboard cutout appears contradictory. The comment about predators seems careless, in that light, but the person making the comment has clearly been theorizing about the effect for a while. So I don't expect the study to be retracted, but I expect half a dozen more papers and then a theory that will be eventually debunked in favor of a more politically convenient one.

dang 13y ago

The original title seems both linkbaity and misleading, so we changed it. If anyone can suggest a better title, please do. Edit: Ok, since most people who commented don't agree that it was a bad title, we changed it back.

deleted 13y ago
[deleted]
TazeTSchnitzel 13y ago
Which? 'Male Scent May Compromise Biomedical Research' seems better than 'Experimenter gender is a confounding factor in lab animal research', but which was the original?
- anigbrowl 13y ago
  Yeah, the 'male scent' (original) title is better. When I read 'Experimenter gender' I was expecting to read an article about some sort of gender-originated cognitive bias.
  - deleted 13y ago
    [deleted]
- dnautics 13y ago
  actually should be "experimenter sex". Gender is a social term.
siyer 13y ago
The current changed title is overbroad, it's certainly not shown by this study that experimenter sex is an issue in all animal research. I would simply suggest the title of the paper itself: "Olfactory exposure to males, including men, causes stress and related analgesia in rodents". It's fairly straightforward, and not as jargon-filled as scientific titles go.
ars 13y ago
A suggestion: When you make such changes please write in your comment what the old and new titles were.

pwrfid 13y ago

This could certainly be plausible. Fairly rigorous studies. Just needs to be repeated in other labs

VikingCoder 13y ago

Richard Feynman spoke specifically to this point in his Cargo Cult Science piece: http://neurotheory.columbia.edu/~ken/cargo_cult.html http://neurotheory.columbia.edu/~ken/cargo_cult.html "That is the experiment that makes rat-running experiments sensible, because it uncovers that clues that the rat is really using-- not what you think it's using. And that is the experiment that tells exactly what conditions you have to use in order to be careful and control everything in an experiment with rat-running."

Balgair 13y ago
First, thank you. I have been looking for this for years! Now i have something to search for to find the paper. I worked in a rat lab for a while that tried testing smells. It was impossible to get data, but sure enough, the professor insisted that stuff was there and published weak papers that were rejected thoroughly. We had about 15 rats and at least 50 major variables to test, if not more confounding variables. I used to read PhD comics as a salve, and then realized that it was a shield. So many grad students feel so badly precisely because they know that the science is crap and no-one will read it anyway because we all know it is crap[0][1]. The rule is getting to be; If the P-value is at 0.05, flip a coin; heads I read it, tails I eat lunch. This isn't just isolated to the ivory tower either. The public sees this and not just from friends and family. These back and forth studies screaming 'coffee is a super-food' and then 'coffee is poison' are an example. They give the public an impression that we scientists don't have a clue. And, true, we may not, but allowing the press to scream these things for funding and publicity's sake is a tragedy of the commons. Yes, I know, you can't expect everything to be perfect. But what we have is so very far from that (and yes, I know, China or India are waaay worse). Still, to see in the grad student's eyes that they know the last 6 years were total crap is tragic, especially when the professor insists it isn't to new students and older ones know they can do nothing to persuade the new ones differently. [0]http://www.economist.com/news/briefing/21588057-scientists-think-science-self-correcting-alarming-degree-it-not-trouble http://www.economist.com/news/briefing/21588057-scientists-t... [1]https://en.m.wikipedia.org/wiki/John_P._A._Ioannidis https://en.m.wikipedia.org/wiki/John_P._A._Ioannidis
- kennywinker 13y ago

greenyoda 13y ago

This kind of response by lab animals to stressors in their environment reminds me of the "Rat Park"[1] experiment, in which rats who were stressed out from being kept isolated in small cages (rats are social animals) had a tendency to become addicted to morphine, but those who lived in a pleasant environment did not. [1] https://en.wikipedia.org/wiki/Rat_park https://en.wikipedia.org/wiki/Rat_park

vanderZwan 13y ago
BTW, Stuart McMillen made an excellent comic about Rat Park. I think it may have been linked on HN before, but just in case: http://www.stuartmcmillen.com/comics_en/rat-park/ http://www.stuartmcmillen.com/comics_en/rat-park/
dnautics 13y ago
this one, too, and this one is really confounding because the LAW requires animals to be handled at RT. http://www.nature.com/news/chilly-lab-mice-skew-cancer-studies-1.14190 http://www.nature.com/news/chilly-lab-mice-skew-cancer-studi...

cmyr 13y ago

Their conclusion that "Male odors seemed to act like painkillers" seems like only one of several possible interpretations? My first reaction was that the possible presence of other male mammals provided a selection bias for individuals who displayed less pain. Amongst individuals of the same species, showing pain would be a sign of weakness, obviously, but it might be a similar marker for possible predators. So perhaps all the animals are feeling the same discomfort, but those who sense other males are less willing to perform their discomfort behaviourally?

Jemaclus 13y ago
The article addresses this: > Further testing showed that the rodents exposed to male odors were actually feeling less pain, rather than simply hiding the pain they were in. The male aroma ramped up their stress levels, which deadened the hurt. “It’s really astounding that such a robust effect could have been missed for so many years,” Mogil says. Though, to be fair, they don't go into detail about how exactly they determined that the rodent was "actually feeling less pain"...
- Blahah 13y ago
  It's properly addressed in the actual paper [0]: True SIA should be accompanied by decreased immediate-early gene expression in the pain-processing neurons of the spinal cord dorsal horn; we observed a dramatic (≥50%) decrease in Fos protein–positive neurons in mice injected with zymosan and exposed to male but not female experimenters or shirts (Kruskal-Wallis test statistic: 12.0, degrees of freedom = 4, P < 0.05; Fig. 2d). Much is known about the neurochemistry of SIA, which exists in opioid (naloxone-reversible9), non-opioid (cannabinoid-1 (CB1) receptor–mediated10) and mixed opioid/non-opioid11 forms. The male experimenter SIA seen here was found to be the latter, as it was blocked (observer × drug interaction: F3,56 = 2.8, P < 0.05) by the broad-spectrum opioid receptor antagonist naloxone (1 mg per kg body weight (mg/kg); P < 0.05), by the inverse CB1 receptor agonist AM-251 (10 mg/kg; P < 0.05) and by a combination of the two drugs (P < 0.01), at doses not affecting pain sensitivity per se (Fig. 2e). In other words, pain in mice is associated with a particular protein binding neurons in a particular part of the brain. The researchers showed that in mice handled by men, the proportion of those neurons bound by the pain-associated protein was significantly decreased, supporting the hypothesis that male-handled mice are actually experiencing less pain. http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.2935.html http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth...

anon4 13y ago

Maybe researchers should then just always use suits, or at least put on a clean shirt each time before getting close to the rat cages and handling them.

veew 13y ago
Or maybe awful men need to step aside and let others run things. They always ruin everything anyway.
judk 13y ago
You are being down voted because people are amusingly misinterpreting the kind of "suit" you meant

return0 13y ago

Maybe this affects only certain kinds of experiments. There is a reason why only male mice are used in experiments and why scents (peppermint) is usually used to denote context.

Balgair 13y ago
To elaborate, male rodents are typically used because they do not go through estrus[0] [0]https://en.wikipedia.org/wiki/Estrous_cycle https://en.wikipedia.org/wiki/Estrous_cycle

Alex3917 13y ago

There is a great video about these sorts of effects called Lullaby For A Mouse: http://vimeo.com/33803995 http://vimeo.com/33803995 The basic gist is that most research done on mice (and other animals) is complete crap: - Almost all laboratory mice are morbidly obese and get little to no exercise. - They're all starved of social contact. - The variations in the daily schedule of the researchers mess with their circadian systems. - The results vary enormously based on how the researchers treat the animals. The title comes from the fact that one of the researchers started singing to his mice in order to get better results.

thinkpad20 13y ago
I worked in a laboratory with mice for about two years after college. * None of our mice were morbidly or even slightly obese (I know because I had to cut them open). * The mice lived in groups of up to 6 in a cage, which I don't know how it compares to their normal situation, but it's not "starved of social contact." * I don't remember how we dealt with the mice's circadian rhythms, but I think that we had the lights on timers for this. * Research is inherently subject to variation. There might be compelling reasons why results would vary based on how researchers treat their animals, but I think it would depend a lot on what kind of experiments were being performed. Stating that in a blanket fashion, I think, is misleading. Biological science is just plain hard, and many experiments fail, often with no clear explanation why. That someone could get frustrated enough to start singing to their animals is not an indication that mouse research is inherently flawed. At the end of the day, a vast quantity of scientific knowledge is owed to mouse research. Denouncing it as "[mostly] complete crap" is just plain false.
- hoggle 13y ago
  It's good that the lab you worked in had good standards in place but can you be sure this is the case for most labs?

singlsrv0x99fa 13y ago

Why inflict pain instead of pleasure ? From my experience experiments on animal subjects tend to focus on negative responses. Beside specifically testing negative agents, is there a logical reason for this approach ? Why not measure attraction instead of avoidance ? Do mice exhibit visible joyful facial expressions vs the grimacing this article describes ? It sounds silly, but couldn't we measure how much we delight the mice ?

brortao 13y ago

I think this serves as a good example of (one of) the issues with animal testing. The scientist in this article doesn't think that we need to "redo decades of animal research", but it certainly casts doubt on previous results. In general, testing on animals isn't effective. Considering the amount of suffering it inflicts on animals, I'm not sure that it's morally defensible. The British Union for the Abolition of Vivisection has a [good resource][1] on the issues. [1]: http://buav.org/humane-science/key-criticisms/ http://buav.org/humane-science/key-criticisms/

tokenadult 13y ago

The hypothesized mechanism is very interesting. Perhaps mice vary their behavioral response to pain depending on how safe it is to express distress from pain. VikingCoder has already given the definitive comment: further controlled experiments will tease out how important this effect is over what range of behaviors. There are many, many, many kinds of mouse experiments (I am currently doing reading on behavior genetics research on learning and intelligence and fear and aggression in mouse model organisms), and some will be more influenced by what the interesting preliminary report here suggests than others. See the book How Genes Influence Behavior[1] for a fascinating description of how we can learn about human behavior by studying mouse behavior (and even by studying fruit fly behavior!). [1] http://global.oup.com/academic/product/how-genes-influence-behavior-9780199559909;jsessionid=D71B0EC416B75938EC3C4BB81BDB7183?cc=us&lang=en& http://global.oup.com/academic/product/how-genes-influence-b...

josephschmoe 13y ago

It's clearly not just the male scent, because it gets cancelled out by the female scent. There's obviously more to this.

Balgair 13y ago
Huh? How can scents be canceled out?
- cevn 13y ago
  In the original article, the effect that the male scent had on the mice was cancelled out by the female scent also being present - not sure of the actual mechanism, but it's not the actual 'scents cancelling out'

ChrisNorstrom 13y ago

2 Theories: 1) It's the brain's way of telling the body: "Another male is nearby, do not show weakness or submission because that male may try to dominate you and you may end up getting into a fight or dying." I'd assume this evolutionary response would only work for same species scents. Apparently it works between species. Men have a tendency not to get into fights with confident men. 2) During a fight with another male, the mind needs to ignore pain in order to continue on and win the fight. In all species, males who didn't have this trait lost battles, died, and did not pass on their genes. Males who had this mutation didn't let the pain get to them, went on to win the fight, lived, reproduced, and passed on these characteristics.

serf 13y ago
a theory I had : perhaps due to past generations of male experimenters, mice have developed a central nervous system which deadens pain in the expectation of a painful experiment when exposed to male scents.
- vectorpush 13y ago
  What would be the selective advantage of pain resistance in the context of a lab environment? It seems to me like the rodent's chance of passing on it's genes would have no correlation with resistance to pain.
  - serf 13y ago
    That's a good question. We know that pain stresses the nervous system, and that it also increases incidence of depression. Both pain and depression lower survival chances, as they both increase the chances for negative effects on the host such as sudden weight fluctuation, abnormal sleep cycles, and uncoordinated muscle control. I have not worked in such a lab setting, so i'm unsure if any of the mice that survive experimentation are exterminated or repurposed. If repurposed, one can imagine that a pain-reduction schema would be useful in such environments for the sake of species proliferation. Mice/rats better suited to the pain thresholds required of them would eat better, sleep better, and ultimately breed more. Again, just an armchair theory and little more.

neurobro 13y ago

It sounds like each test involved the same person both giving injections and sitting in the room. I wonder if they can somehow mechanically inject the irritant without human involvement. Then they could have male/female participants sit in the room without knowing if any animals are present. This would help distinguish whether the rodents were reacting to a general difference in scents, or males and females give off different signals when handling rodents.

bambax 13y ago

> “It’s a primordial response,” he says. “If you smell a solitary male nearby, chances are he’s hunting or defending his territory.” If you’re in pain, you’re showing weakness. I don't know about those results, but this explanation sounds preposterous: it doesn't work if you're hunted down by a lioness (which does the hunting while the male lion sleeps); it also doesn't work if you're spotted from the air by an eagle (which is one the main hazards if you're a small rodent). Why does every behavior has to be explained in terms of survival, we'll never know. Stephen Jay Gould was so good at debunking those easy explanations; how I miss him.

fit2rule 13y ago
Lions hunt alone. Lionesses usually hunt in packs.

fit2rule 13y ago

This is like the "Heartbleed" backdoor of the medical industry .. how many previously-though-defensible studies are now trash because of this? Its mind-boggling, to be honest ..

MyGod 13y ago

"Mogil’s group discovered that this gender distinction alone [...]" It's sex, not gender distinction. Gender - what you identify as, sex - what you are. Males that identify as females would still throw their test off. Yah, nipicking. And call me paranoid, but this seems to have agenda....

Allower 13y ago

We can only account for variables we can imagine, this is why science is so often proving itself wrong.

joeevans1000 13y ago

Wow. I didn't really know there was an 'animal grimace scale'. I have to say, after googling that a minute ago, I have actually become an superfluous animal testing opponent, after having suspected animal testing was done excessively. I dare you to google it. These researchers... what assholes.