Friday, July 30, 2010

The Lyme controversy

This morning at grand rounds, the room was more crowded than I have ever seen it. Every Friday morning, from 8-9 am, a resident or intern presents on a particular topic. People come if they are interested and if they are free. I have seen grand rounds have as few as a dozen people in attendance. There must have been at least fifty today. I have seen rounds where no one asks a question. There were about a dozen questions asked today. The resident closed her talk with a picture of boxing gloves and announced, “This is a controversial topic, so let’s keep our gloves on while we ask questions, okay?” The topic was Lyme disease.

What is Lyme disease?
Lyme disease occurs in humans and dogs, though it presents differently in the two species. (Cats don’t get clinical signs of Lyme.) The disease is caused by a bacteria called Borrelia burgdorferi. The disease is often not serious, with clinical signs like lameness, loss of appetite, and lethargy. These signs are usually resolved after a course of antibiotics, usually doxycycline.

However, Lyme is associated with Lyme nephropathy, a disease of the kidneys which can be fatal. This is a less common outcome, but a very serious one.

Lyme has been studied in laboratory dogs. However, Lyme nephropathy appears to occur most often in Labrador retrievers and golden retrievers; it is possible that they have a genetic predisposition for it. So what we have learned in laboratory dogs (who are almost exclusively Beagles) may or may not apply to retrievers.

Should I vaccinate my dog for Lyme?
This is the first part of the controversy. Different veterinarians have different answers for you.

Some say: Yes! The vaccine is very safe and effective. The possibility of Lyme nephropathy makes any risks associated with vaccination to be well worth taking.

Some say: No! We don’t actually know that Borrelia causes Lyme nephropathy. Some people suspect that it may in fact be associated with the Lyme vaccine. Moreover, 95% of dogs who are exposed to Borrelia never develop any clinical signs. In other words, they never become sick. The few who do develop clinical signs are almost always easily managed with antibiotics. Why take a chance with a vaccine, which may have side effects, when the chances that your dog will develop Lyme nephropathy are so low?

My dog is Lyme positive. Should I treat him with antibiotics?
If your dog shows signs of lameness, fever, lethargy, and has a positive Lyme titer, then definitely he should receive a course of antibiotics. (Of course, a vet will rule out any other likely diagnoses first.)

What if your dog shows no clinical signs? This is the second part of the controversy.

Some say: Yes, the dog should be treated. Otherwise, he is at risk of eventually developing Lyme nephropathy. Best not to risk that.

Some say: No. The likelihood is that the dog will never develop any clinical signs (that he will remain healthy). We don’t actually know, again, that Lyme nephropathy is actually “Lyme” nephropathy. Antibiotics are not 100% safe, and may have side effects. Administration of them may lead to antibiotic resistance. Additionally, most dogs who are treated for Lyme with antibiotics maintain a positive titer for Borrelia after treatment is concluded. In other words, their immune system continues to produce antibodies against the bacteria, suggesting that they still have Borrelia in their systems, despite treatment (though presumably lower levels of it). We may actually be breeding resistant strains of Borrelia in our own dogs by treating unneccessarily. Again, 95% of dogs who have positive Borrelia titers never develop signs of the disease.

It is possible (and probably a good idea) to monitor Lyme-positive dogs by periodically checking their urine for extra protein (“proteinuria”). This is a sign of kidney issues. Even this is up for debate, though, as the test can be expensive and it’s not clear how often it actually catches a problem.

One interesting point made during the discussion at the end of the lecture was from an IDEXX representative. She said that a veterinarian had told her that he routinely treated Lyme-positive dogs, and on re-testing found their Lyme titers to be reduced. A faculty member pointed out in response that as no control group had been tested, it is possible that Lyme-positive dogs see titer reductions after some period of time anyways.

What do I do?
My dog, Jack, tested positive for Lyme this past spring for the first time. There are indeed plenty of ticks in my back yard (though I do my best to manage them with frequent mowing). His positive Lyme titer means that he has “seen” the disease — been bitten by a tick which carries Borrelia. His immune system has responded appropriately, making antibodies to the bacteria. He shows no clinicial signs; his appetite is excellent, and he is no more lethargic than any other aging golden retriever. I had his urine tested; he has normal protein levels. I have not treated him with antibiotics.

I’m reporting what I learned in this morning’s talk from memory. I hope that I did not misreport any facts, but please take all statements with a grain of salt, as I have only completed two years of veterinary school.

For more information, see:

Links post

Thursday, July 29, 2010

Proposal for organizing science blog networks

I’ve been pondering the questions raised in Dave Munger’s post about how to aggregate science blogs in the absence of one central authority. In the middle of the second chapter of Clay Shirky’s Here Comes Everybody, I realized that there’s no real need for a central authority to aggregate blogs; the tools exist for bloggers to do it themselves. Credit for the solution I’m about to propose goes to my boyfriend, who said “Stop thinking the Diaspora project is the answer; they’re not up and running yet. What about technorati?”

I think it could work. You register your blog with technorati. You tag your blog appropriately. (For many blogging platforms this just means tagging your blog as you usually would, but if technorati doesn’t pull tags automatically from the platform you use, you can explicitly add code to your post that technorati can understand.) If bloggers come to a consensus about shared tag names, readers can then go to the technorati site to get a feed of all recent posts using that tag.

I have been very interested in reading all the commentary about the state of science blogging and its possible future, but I’m having trouble discovering all the posts out there, scattered across so many blogs. I hereby propose (perhaps to an empty room, but why not give it a shot?) that bloggers use the tag “meta-scienceblogging” to tag posts about the ScienceBlogs diaspora, the current state of science blogging, possible futures of science blogging, etc. Register your blogs with technorati (as a side benefit, it should help increase your traffic), and it will aggregate the posts.

I’ve registered this blog and tagged this post. If everything works as it should, posts with this tag from registered blogs will show up at There should even be an associated RSS feed. [ETA: Crankily, I declare that this doesn’t seem to be working for me. Technorati still hasn’t indexed this post under the appropriate tag. Either technorati takes too long to index things (possible) or I did something wrong (also possible). Either way, I don’t think it is the easy-to-use solution I was hoping for.]

I hope this is a useful idea.

Wednesday, July 28, 2010

Links post

Links about science blogging
Links about medicine (sometimes veterinary)
  • Orthopaedics vs anesthesia: “This work is fictional and any resemblance to reality is completely coincidental. No orthopaedic registrars, anaesthetic registrars or patients were harmed during filming.” Video.
  • Position Regarding Dangerous Animal/Dog Legislation (Massachusetts Veterinary Medical Association): the MVMA’s position on breed-specific legislation (e.g., the proposed pit bull ordinance I have been posting links about)

Saturday, July 24, 2010

Breeding healthy Dalmations

The problem

All dog breeds have problems that occur more in that breed than in any other. In the case of Dalmations, the problem is stones — the formation of crystals in their urine. Not every Dalmation gets stones. However, every Dalmation has a high level of uric acid in their urine, which predisposes them to stones. Their kidneys are missing an enzyme which converts uric acid to another substance (allantoin). When the uric acid sits around like that, stones can form.

Just having a urinary bladder full of stones is not always a big deal. However, when the stones get big enough, they can block the outflow of urine. (This happens more often in boy dogs — smaller outflow tube!) This blockage is a veterinary emergency, and may require surgery to correct. Once a blockage is corrected, there is no guarantee that the dog will not form stones again later in its life.

If all Dalmations have unusually high levels of uric acid, why do only some of them develop stones? We aren’t completely sure. It is likely that the levels of uric acid might play a role (more uric acid, more stones). Diet and other environmental factors may also play a role.

Why the obvious solution doesn’t work

So just breed the trait out, right? Find Dalmations with normal uric acid levels, and only breed those dogs.

It turns out that there are no Dalmations with normal uric acid levels. The gene which causes Dalmations to not be able to convert uric acid is located very close to the gene for those distinctive black spots, and was probably bred in when the spots were. You can’t find a normal Dalmation to use to try to breed out this undesirable trait.

You can’t even breed Dalmations with slightly lower uric acid levels, to try to gradually reduce uric acid levels to a normal level. Their levels are all completely out of the normal range. You would only be able to breed them down to a low abnormal, not into normal range.

In short, there is no way to introduce the “good” version of the gene into the Dalmation breed without doing some gene splicing — or breeding Dalmations to dogs of a different breed.

An alternative solution

A medical geneticist, Dr. Robert Schaible, bred a single Pointer to a Dalmation. He then bred one of their offspring to a Dalmation. He continued breeding back offspring from later generations to Dalmations, selecting for both low uric acid levels and for the things you usually want to see in Dalmations (their particular temperament and coat markings). This project, the Backcross Project, eventually resulted in dogs that are just like purebred Dalmations in all other ways, but have normal uric acid levels — “normal uric acid Dalmations.”

So the problem is solved, right?

Unfortunately, the American Kennel Club (AKC) will not allow the normal uric acid Dalmations to be registered, contending that they are not purebreds. What are the consequences of this decision?
  • Normal uric acid Dalmations cannot be shown in AKC conformation classes. This means that breeders who compete in these classes (based on how a dog looks) will not be willing to breed their dogs to normal uric acid Dalmations. The AKC is hands-down the biggest game in town when it comes to conformation shows. Therefore, the pressure is intense to continue to breed high uric acid (purebred) Dalmations, and in fact that is what is happening today.
  • People who want to own Dalmations just as pets are unlikely to be aware of the existence of normal uric acid Dalmations, or may not have access to one of the very few low normal acid Dalmation breeders. Even though they may never intend to show their dog, or even register it, they will still be more likely to buy a Dalmation with this genetic problem.
What is a purebred, anyway?

Breed registries are relatively recent — within the last hundred years or so. Before then, if it looked like a Dalmation, and so did its parents, it was a Dalmation. At some point, however, breed stud books began to be kept, and they were “closed,” meaning that a dog could only be considered purebred if both its parents had been registered. This prevents breeders from bringing in fresh genes from outside the breed. The selection of those founding dogs that were chosen to be the original Dalmations was necessarily arbitrary. Why shouldn’t new ones be allowed in now?

What you can do

Unfortunately, there is not much that the average dog owner can do about this particular problem; it is in the hands of the AKC and of Dalmation breeders. If you are in the market to buy a Dalmation puppy, you should definitely learn about normal uric acid Dalmations.

On a larger scale, it is important to be aware of what the AKC is and what a “registered” dog is. When people say a dog is “registered,” they usually mean that it has been registered with the AKC. (Other kennel clubs do exist, such as the United Kennel Club, or UKC, which does allow registration of low uric acid Dalmations.) However, AKC registration does not guarantee that the dog is healthy, or even that its breeder put any effort into breeding healthy parents. It means that both parents were registered with the AKC, and absolutely nothing more.

If you are going to buy a puppy, talk to the breeder about what genetic problems the puppy might have, and be sure that the breeder really cares about eliminating those problems from the breed. Don’t settle for the explanation that “all dogs of this breed are likely to have this problem; that’s just the way it is.” Is there a solution that the breeder isn’t taking, because it would cause some change to the breed? If so, think about whether you agree with that choice. In some cases, you may find the choice to be a good one. If not, you may want to reconsider buying a puppy of that breed.

Friday, July 23, 2010

Links post

Tuesday, July 20, 2010

Muzzling the real solution to the problem

Some new legislation has been proposed in Worcester, the city next door to my town. This legislation proposes specific restrictions on pit bulls and their owners. Most importantly, pit bulls would have to be muzzled when out in public, though other restrictions are proposed as well, such as requiring pit bull owners to put signs in their front yards advertising that a pit bull lives there. The local paper has some details.

The MSPCA has a brief article about the legislation, with some quotes from one of the sponsors of the bill:

District 5 Councilor William J. Eddy pointed out that over the past three years, only 2 percent of the dogs licensed by the city are pit bulls, while 25 percent of all dog bites over the same period were caused by that breed... “Some will say this is not a (dog) breed problem, but an (dog) owner problem,” Mr. Eddy said. “These are aggressive dogs that can cause great damage. There isn't another breed in Worcester that has that kind of statistics.”

I am one of the people who will say that this is not a dog breed problem, but a dog owner problem. So how do I answer Mr. Eddy?

More bites are caused by pit bulls than by any other breed. Therefore pit bulls are dangerous.

First of all, is it “more bites” or “more reported bites”? Is it possible that people are more likely to report a pit bull bite because of the way the breed is perceived? Is it possible that mixed-breed dogs that bite are assumed to be pit bulls, because it is very hard to tell what is and isn’t a pit bull and because people assume that pits are liable to bite? The National Research Council released a report in 2007 arguing that there is a media bias against pit bulls, and that pit bull bites are more likely to be widely reported than bites involving dogs of other breeds.

But let’s say pits do bite more than other dogs. Is that a problem with the breed, or with perceptions of the breed, and therefore with the kind of people likely to own pits? Pits are the most popular breed used in the underground and illegal sport of dog fighting, for which they are bred and trained. The National Research Council reports that dogs which are not kept as pets, and dogs which are not humanely controlled by their owners, are the dogs which are most likely to bite. Are people more likely to treat pit bulls this way than Labrador retrievers? I think so.

Eddy is further quoted:

“We have a problem in this city and we have an opportunity to address this problem. Frankly, I think it’s long overdue.”
Yes, it is long overdue, and yes, let’s address this problem! (Lucky for Worcester, they have a veterinary school with a behavior department right next door.) So why is BSL (breed specific legislation) a bad answer?

Because it won’t work. This is the really important point! I don’t argue against BSL because I think it’s acceptable for dogs to bite children. I absolutely do not think that is acceptable. But BSL is not the answer. What will BSL actually do?

  • Irresponsible owners who disobey the new muzzle law and are fined may surrender their dogs to a shelter instead of paying the fine. This is what happened in nearby Boston when a muzzle law was enacted there. (Original article in the Boston Herald is behind a pay wall; I linked to a version archived on an anti-BSL site, but don’t be confused by the URL. The article is from a real newspaper.)
  • If the law successfully prevents dog fighters from using pit bulls, there is nothing to stop them from choosing another breed. The law isn’t targeted at dog fighters, however. Having to muzzle their dogs in public shouldn’t be much of a problem for people who don’t generally take their dogs out in public.
  • In fact, there is really no such thing as a pit bull. The term refers to a loose group of dog breeds. Telling what is a “pit bull” and what isn’t has made BSL enforcement somewhat arbitrary in other cities. Take the test, see if you can do it. So this law is likely to be applied to dogs for whom it is not really intended.
But why not just try it? After all:

“We’re not talking about banning this dog; rather what we’re saying is that when you’re out on the public streets, pit bulls should be muzzled,” [Eddy] added.
So what’s the harm?

  • Passing this law will be a Band-aid measure which will make the public think that the problem has been solved. There are some useful ways to address the problem of dog bites, but if this good energy for change is directed into a poorly designed law, there will be no impetus to find real solutions.
  • A muzzle requirement will make it harder for responsible owners to socialize their dogs. How would you react to a muzzled dog which you met on the street? Would you want to pet it, or would you be afraid of it? If you were a dog and every human you met on the street was afraid of you, would you be enthusiastic about meeting new humans? Not to mention the human socialization problem! If your new neighbor had a sign in her front yard proclaiming that a pit bull lived there, would you be as likely to go over to welcome her to the neighborhood with some food? (My neighbors actually did that when I moved in. It was great.)

Dog Zombie, you are so right. I have seen the light. But does that mean we should sit back and do nothing?

I almost always have opinions on what should be done to fix the world!

  • The AVMA (American Veterinary Medical Association) put together a task force on dog bite prevention which, in 2001, published a lovely article titled “A community approach to dog bite prevention.” This article has some specific suggestions for how communities should handle the problem, including both suggestions for prevention (controlling loose dogs, educating of animal control officers), and suggestions for how to handle bite incidents (having a protocol which includes reporting of the bite and follow-up investigation).
  • Sue Sternberg (who is well known in the shelter community) is promoting a “Lug Nuts” program, in which teens who might otherwise participate in dog fighting are encouraged to instead enter their dogs in pulling competitions. What a creative idea for redirection! Extra points to Sternberg for working within the parameters of the problem instead of supporting rules passed down from on high.
  • I think people need consequences. People need to be fined if their dogs are aggressive in public. Dog aggression needs to be taken seriously before bites happen, and no matter what breed is involved (“punish the deed, not the breed”). And laws against dog fighting need to be actively enforced.
My final message to Mr. Eddy: You have hold of an important issue. Please take steps to address it wisely. The solution you have proposed will be successful only in winning you votes, not in reducing dog bites. There are better ways. Find one.

Sunday, July 18, 2010

Seeing it their way

This weekend, I attended a seminar with Patricia McConnell, Ph.D., CAAB. The “CAAB” after her name means that Dr. McConnell is a behavior specialist who works clinically with dogs who have behavior problems. (The difference between a behaviorist with a Ph.D. and one with a D.V.M. is sort of like the difference between a psychologist with a Ph.D. and a psychiatrist with an M.D.) She is a great public speaker, and if you are interested in this kind of thing and have a chance to go hear her, I highly recommend the experience.

Dr. McConnell spoke about why we have reason to believe that dogs have many emotions similar to ours. She showed some fascinating pictures and videos of canine body language and talked about how to interpret it. And she worked with two dogs, demonstrating both classical and operant conditioning as tools for helping fearful dogs become more comfortable.

One specific part of the day serves, for me, to illustrate some skills I’d particularly like to learn, and they weren’t dog training skills. McConnell showed the audience video recordings of a dog with a resource-guarding problem being trained using an aggressive dominance-based approach. Resource-guarding dogs don’t like to give up their possessions. My dog doesn’t much like to give up his toys either, but he never growls or tries to bite when I take them away, and that is the difference between a dog who has a resource guarding problem and one who does not. So the danger when you’re working (or just interacting) with a dog like this is that you might get bitten.

Now, this was an audience of dog people. We all knew a lot about dog body language (and had learned more over the course of the previous few hours). As we watched the video, we were all flinching repeatedly, anticipating that the dog was going to bite, based on his body language. The woman in the video clearly wasn’t seeing what we were seeing and did not perceive any danger, even putting her face next to the dog’s mouth several times (yikes).

There was a lot going on in this bit of the seminar. First of all, a lot of trainers and behaviorists would have taken the opportunity to mock the woman on the video for her lack of understanding of the situation. There is one dog trainer whose book and seminars I otherwise very much enjoy, but who seems unable to refrain from shaming the clients she works with when they appear to know less about dog training than she does. Instead, McConnell emphasized what a good job this woman had done. She did exactly the right thing: she took her dog to a trainer, and she followed the trainer’s instructions to the letter. She was the ideal client. It would be very easy for someone who knew more to get caught up in anger about how an inappropriate training method was making things worse for the dog. It is so important, and so difficult, to instead see things from the other person’s point of view, and this was a great example of doing just that.

Secondly, rather than just focusing on teaching us about dog body language (preaching to the choir), McConnell repeatedly pointed out specific ways in which the general public tends to miss some messages that dogs give us. It’s rewarding but not useful to just fine-tune the abilities all day of a group of people who are already self-selected to be pretty good dog trainers. It’s much more useful to help them learn to see what the problems are in the community of dogs and humans around them. Maybe if more dog trainers knew what information the public was missing about how to read their dogs, they would do a better job of instructing people who come to puppy class. (I am not bashing trainers! Lots of them do a spectacular job. But we can all do better, because too many people get bitten, even by their own dogs.)

McConnell’s well-known book, The Other End of the Leash, tries to help people see things from the point of view of their dogs. But she is also good at trying to help people see things from the point of view of other people, and that’s invaluable. Hmm. Where should I go to school to learn that skill?

(For more on McConnell, try her books, The Other End of the Leash or For the Love of a Dog, or read her blog. You can also download old episodes of her radio show, Calling All Pets, to listen to her demonstrate her lovely verbal judo, in which she is able to basically tell callers that they are completely mistaken, without in any way making them feel bad.)

Tuesday, July 13, 2010

Why do other measurements of stress suck worse than cortisol?

After an overwhelming number of requests (2) for a sequel to my post Why cortisol sucks as a measurement of stress, I am obliging. The fact that I am in the middle of writing this particular section of my thesis and need some high-level perspective on it might also have something to do with it. So: why do other measurements of stress suck worse than cortisol?

When I left you, you were trying to design a study of stress in hospitalized dogs using cortisol as your marker of psychological distress. You were confounded by the fact that cortisol measures both psychological and physiological distress, and that it varies a lot between individuals. I haven’t been around to keep an eye on you lately, so you have started investigating other approaches to measuring stress other than cortisol.

Cortisol is a messenger used by the HPA (hypothalamic-pituitary-adrenal) axis, for the brain to send a message about stress levels out to the body, for the body to pass that message along to the organs that need to change their operations as a result, and for the body to then report back to the brain that the message has been received, so the brain can stop yelling about it. There are multiple levels in this axis; cortisol comes from the bottom-most level, the adrenals. Why not go up one level, to the pituitary? It is actually in the brain, so it is closer to the source of the message and might be less distorted by the game of telephone.

The hormone that the pituitary gland releases as part of the HPA axis is ACTH (adrenocorticotropic hormone, or “the hormone that makes the adrenal cortex change”). ACTH causes cortisol release. Why don’t you measure ACTH release directly? Unfortunately, ACTH can only be measured in the blood; it doesn’t get into the saliva. (Or urine, hair, or feces, three other places you can go to get an estimate of cortisol levels.) The owners of your hospitalized dogs aren’t going to be happy if you tell them you need to draw blood from their dogs for your study. And remember, you’d have to draw the blood pretty quickly in order to get it before the brain mounted a stress response as a result of having a needle stuck into the body. Cortisol levels change in under three minutes. I don’t actually know how long it takes ACTH levels to change, but I will hazard a guess that since they are farther up the telephone chain, they change faster.

What about farther down the chain? CBG (corticosteroid binding globulin, a.k.a. transcortin) is a protein that carries cortisol around in the blood. The body uses CBG as a way of regulating the stress response. When there is less CBG, cortisol is more able to jump inside cells and do its work. OK, no one actually uses CBG to measure stress levels, because we have no real idea how it works. But it is a very cool system that I’m really curious about. And stress researchers would do well to remember that it is there. If the dogs you are studying are very sick, they might not be able to make as much CBG as a healthy dog would, and that would affect their cortisol levels.

That pretty much exhausts using the HPA. Luckily there is an entire second axis for you to mine: the SAM (sympatho-adrenomedullary) axis. This is the series of chemicals that regulate the well-known “fight or flight” response. This particular game of telephone includes adrenaline (epinephrine), the effects of which which many people enjoy abusing when they go on roller coasters. This axis works much more quickly than the HPA. If you hear a sudden loud noise, you will get an adrenaline rush within a second. So you can try to measure adrenaline levels in the blood, but there is just no way you will be able to get the blood out fast enough to not have the stress of the needle (damn needle) affecting them. If you had a very controlled population of animals, with catheters already placed that they were used to, so that you could draw out blood without stressing them, that might work, assuming you could catch the animals without stress. (Catch a mouse without stressing it: difficult. Catch a dog without stressing it: actually, when I went into the runs with the hospitalized dogs I was studying, they definitely experienced eustress, or happy stress.)

You can also measure adrenaline levels in pee! This turns out not to be useful, though. Adrenaline levels go up and down, as we’ve said, very quickly, in response to individual stressors. Pee collects all those changes and averages them out over however many hours (say six). So this approach is definitely not good for measuring responses to specific stressors, like a sudden loud noise. It might be better at measuring something longer term (hey, like the response to being in a hospital!) but initial studies haven’t shown it to work very well at that, either. Adrenaline is just the most interesting when you can map it as it goes up and down, not when you have to look at an average and guess about what was smoothed out.

What about the other end of the SAM? When you get an adrenaline rush, you have some physical changes. Among many other things, your heart rate gets faster. Can you measure that? Well, again, good luck measuring that in a dog without having the excitement of interacting with a human confound your measurement! And heart rate is very sensitive to physical changes; you might be measuring whether the dog is standing up versus lying down, rather than its level of distress.

It turns out that what is a better way to measure physiologic changes from SAM activation is heart rate variability. Your heart rate normally speeds up a little when you breathe in, and slows down a little when you breathe out. (I actually did notice this in a dog once, in a lab where I was supposed to be learning how to find abnormal heart rhythms, and I had to call a vet over to ask if it was actually normal, because it sounded so weird once I noticed it.) When you are stressed (physically or psychologically), this variability goes away. This is not a bad way to measure stress, but you can’t measure it with a stethoscope; you have to hook up equipment to the dog in the form of a little vest with a monitor attached. This is expensive (too expensive for you to use, because your project is on a shoestring budget!). You would also have to get the dog used to the vest, so that you were sure you wouldn’t be measuring stress from having clothing on when the dog is used to being naked. It is therefore not a good measurement for hospitalized dogs on their first day in the hospital, but it is a good measurement for some studies. It’s best when used in conjunction with cortisol, so that the two measurements can catch each other’s mistakes.

That uses up the SAM, but there is a system that is the opposite of the SAM. When your body is not in “fight or flight” mode, it is in “rest and digest” mode. This mode is regulated by the parasympathetic branch of the ANS (autonomic nervous system). (The SAM is the sympathetic branch of the ANS.) Can you measure parasympathetic activity? It should increase when stress decreases, and vice versa. It turns out that when your body is thinking it’s time to rest and digest, it releases a digestive protein into your saliva, known as α-amylase. This protein is useful for pre-digesting carbohydrates. More α-amylase suggests less stress. And it’s even in the saliva, so it can be measured non-invasively! You are very excited until you find a paper from the 1950s (I am not kidding) which is the last time anyone bothered to look for α-amylase in dog saliva. Dogs don’t make it. Because they are not meant to eat lots of carbs? Oh wait, this isn’t a post about nutrition.

(For those of you who say “OK, but what about measuring stress via α-amylase in humans?” — I didn’t delve any deeper into this one after I learned it wasn’t useful in dogs. My guess is that it suffers from similar problems to measuring cortisol: it measures more than just [lack of] distress. It also has been less widely used than cortisol, so we understand its pitfalls less. This would be another good measurement to use as a complement to measuring cortisol. If you want to use it in humans, read lots studies that have used it before you commit.)

So much for the ANS. But you know that increases in stress cause decreases in parts of the immune system. In fact, that’s partly why we care about stress in hospitalized dogs — stressed dogs may not heal as quickly or as well. Can we measure the immune system?

We can. Your saliva normally contains a kind of antibody called IgA. This presumably provides a first line of defense against the bugs on your food. When you are stressed, you make less of it. (At a guess, this is because when you’re running from a lion, you’re not likely to be eating. You’re more likely to be getting bitten, so your immune system needs to focus on defenses against open wounds instead of microbes in food.) Salivary IgA is known as “sIgA.” Can you measure that in dogs? You can, and it is being fairly widely used in humans, in fact. Only some initial work has been done on it in dogs, though. It seems to be prey to some of the same issues cortisol is — varying regularly throughout the day, varying irregularly between individuals — so it’s not yet clear if it’s really a better option. It might be a good way to go for a long term project. For something short, though, it might be better to stick with what is well-understood.

Are there any other ways to measure immune system function as it relates to stress? As I said, your immune system reorients when it thinks you’re running from a lion, to protect against open wounds. It does this in part by packing the blood full of a kind of white blood cell called a neutrophil. Neuts are the first line of defense against microbes coming in through open wounds. You can measure their ratio to another kind of white blood cell, a lymphocyte, to measure stress. A greater N : L (neutrophil : lymphocyte) ratio implies greater stress levels. In some ways, this is a really great measure of stress, because it takes a little while — an hour or so — for the N : L ratio to change after a stressor. So when dogs first come in to the hospital, if you can get blood right away, you could actually measure their unstressed baseline. A later blood sample could provide a comparison. Then you could ignore all that annoying individual variability, because you would be measuring the difference pre- and post-stressor in the same individual. I would have loved to have use this measurement.

But, as always, good luck getting an owner to consent to not one but two unnecessary blood draws. I am not sure I would have felt good about adding that much stress to an already stressed dog’s hospital visit, either. For a different kind of study, this might be a really good option, though as always, it measures the effects of multiple systems, so there is going to be some extra variability to account for.

And that is why, though cortisol is a really appalling way to try to measure stress (looking at my salivary cortisol data right now, I keep saying “why does anyone use this hormone?!”), it is still the most widely used approach. As we learn more about how all these systems interact, it is possible that some day we will develop a method of taking multiple kinds of measurements and basically triangulating distress. Or maybe we’ll develop hand-held fMRI scanners and be able to directly measure activation of specific parts of the brain. For now, we are stuck with spit.

Thursday, July 8, 2010

Links post

  • The Chicken Project: Hope: La Vida Locavore has been writing about her project to convince her town to legalize ownership of chickens. I could explain why chickens make great pets (and more useful ones than dogs), but she does it so much better.
  • How to win a Nobel Prize: fail, persist, iterate (Ars Technica)
  • A treat by any other name... (Dog Star Daily): Some great philosophy of dog training. Do you know the difference between treats and reinforcement?
  • Out with the old, in with the noobs (Pet Connection): The new veterinary interns are starting around now. My old roommate is starting her internship this month, too. This is a nice overview of what a veterinary internship is, and why (and why not) someone might choose to do one.
  • PLoS ONE: Is a High Impact Factor a Blessing or a Curse? (The Scholarly Kitchen): insights on open access publishing, and how it will handle increasing popularity
  • The Third Reviewer: a blog of anonymous reviews of peer-reviewed literature. This seems to me to be a great way to get feedback on journal articles, in a way that hasn’t been well supported before. We’ll see how the experiment goes.

Recommendations to bloggers participating in the diaspora

In the wake of Pepsigate (the appearance of a corporate blog by PepsiCo at the esteemed site), science bloggers are leaving in droves, citing conflict of interest.

I would really hate to see the loss of as a site where science bloggers come together. If they are scattered to the winds, I think that loss of community would be sad, especially in this time when science blogging is doing so well at finding its feet and beginning to significantly supplement traditional science journalism as a way to communicate science to non-scientists. had begun some really interesting intiatives, like Ask a Science Blogger, that work best with a central authority.

What’s the right answer? The scene reminds me of a kerfluffle in the fanfiction community a few years ago. (Tell me I’m not the only science blogger who likes to read fanfiction!) The response of the fanfiction community was to come together and build their own organization (The Organization for Transformative Works, or OTW) and their own archive for their work (The Archive of Our Own, or AO3).

So, participants in the diaspora, if I had my way, you would all come together and find a way to continue your community through a non-profit effort. You don’t necessarily need to have all your blogs on the same site, as the fanfiction folks chose to do. You would only need a central place which organized your blogs. It would provide links to blogs that were good enough to be considered part of your group, just as people have to apply to join today. It would organize things like “Ask a science blogger” and have group RSS feeds. And it would be non-profit, so conflict of interest would not be an issue.

That’s my take on the matter. Good luck to all who are searching for new blog homes.