I called Sarah Putney, the director of the IRB. Sarah had always helped me work through ethical issues in our human work. She had an incredible knowledge of the rules, she loved research, and, perhaps most important, she was a dog person.
I explained what we wanted to do and Sarah immediately seemed to understand.
Getting right to the heart of the matter, she asked, “Who is the subject of the research?”
“The dog.”
“Then this isn’t something the IRB would review,” she replied. “We only review human research.”
“But we have a consent form,” I explained.
“Why?”
I explained that since we were asking people to volunteer their pets for research, it seemed appropriate to explain what we were doing and what the risks were.
All research entails risk. In human research, the spectrum ranges from minimal risk to high. Minimal risk means that the probability and magnitude of harm in the research aren’t greater than what is ordinarily encountered in daily life or during the performance of a routine physical or psychological exam. Anything more than that is considered moderate or high risk. But that is a judgment made by the IRB.
Our human fMRI work is considered minimal risk because we study normal, healthy people, and we don’t give them any drugs. MRI doesn’t use radiation, so it’s considered very safe in and of itself. The main risks to humans are anxiety, because of the tightly enclosed space, and hearing loss from the noise. To limit the risk of a claustrophobic panic attack, subjects are given a button they can press if they want to be removed from the scanner. To protect their hearing, they wear earplugs and earmuffs.
The risks for dogs would be the same, in theory. Dogs have more sensitive hearing, so there might be a greater risk for hearing damage. To minimize that risk, the dogs would need to be trained to wear earmuffs, but I felt that their owners should be aware of all the things that might go wrong, however unlikely. In my opinion, the worst that could happen would be a dog escaping, getting lost or injured in the process.
Because what we were proposing did not meet the definition of human research, no federal law required us to have a consent form. But, as I explained to Sarah, it seemed like the right thing to do. We were about to make a decision that elevated the rights of dogs to the same level as those of our human subjects.
Ever since I started running a research laboratory, I have operated under a simple ethical principle: Do not do any experiments that you wouldn’t be willing to do on yourself or a loved one. This is not a universally shared philosophy. Many scientists do experiments that they would never volunteer for themselves. There is no rule that says you have to. Everyone has their own opinion of the risks and benefits of volunteering for research. The principle of “respect for persons” allows everyone to make their own informed decision to participate in an experiment, including the person running the experiment. But what message would it send if I were unwilling to be a subject in my own experiments? I have had about fifty MRIs over the years. I have no qualms about crawling into one. I would put my kids in an MRI. And my dogs.
After explaining my logic to Sarah, we agreed that the rules governing research on children provided the best model for what we wanted to do. If adults want to participate in research, they simply need to understand the risks and benefits and make an informed decision. Children are different. Not only do they not have the legal standing to make their own decisions, but the rules also recognize that they don’t have the necessary knowledge or experience to understand the risks and benefits.
Research on children is given special scrutiny. If the research is considered minimal risk, then the approval process is pretty much the same as for adults. The main difference is that the parent gives permission and signs the consent form. However, the child must still indicate a willingness to participate, which is called assent. If the research is more than minimal risk, several different factors are weighed, including the relative risk and likely benefit to the child.
Like our human studies, the Dog Project would qualify as minimal risk. So we simply copied a consent form that we had used in one of our previous fMRI studies of children. Wherever the words your child appeared, we replaced them with your dog.
That left the dog itself. Since a dog can’t sign a form, how would we detect the canine equivalent of assent? With a child, assent is usually determined by asking the child. If he is old enough, he can sign a document of assent, which is a child-friendly version of the consent form. But if he is too young to understand or to express himself, the researcher must rely on his behavior. For example, if a mother signs up for a research project with her infant and the baby shows obvious signs of distress, like inconsolable crying, the researcher should interpret this as a sign that the baby doesn’t want to participate, and the experiment should be stopped.
We could do the same thing with dogs and treat them like infant research subjects. If they showed any signs of not wanting to participate, we would stop the experiment. The simplest way to do this would be to dispense with restraints. If a dog didn’t want to be in the MRI scanner anymore, he could simply get out. Same as a human.
Never mind that all previous animal research treated animals as property. Elevating the rights of a dog to that of a human child made both ethical and scientific sense. It was the right thing to do and it would result in better-quality data too. If the dog didn’t want to be in the scanner, the data would be useless anyway. And if he were strapped down, we might not even know that he didn’t want to be there.
With the ethics squared away, it was time to go back to the IACUC with our proposal. The committee was happy with the consent form and pleased that Sarah Putney had helped draft the language. That left just a lineup of university administrators ready to say no.
First up was risk management. The sole purpose of this department is to minimize the chance of anything bad happening. The risk management department looks at research starting with the worst-case scenario. What is the most catastrophic thing that could happen, how would that damage the university’s reputation, and what would it cost the university to defend itself in court?
Although we said “dog,” I think risk management heard “Cujo,” after Stephen King’s fictional rabid Saint Bernard. Worst-case scenario: dog escapes, runs amok on campus, bites student, student gets rabies and dies. Because we would not be scanning at Yerkes, the dogs would have to be under control at all times, particularly when they were being transported to the MRI scanner at the Emory University Hospital. Fortunately, the MRI room had a door leading directly to the outside of the building. We could walk the dogs right up to the door without having to go through crowded corridors. Risk management liked that. It minimized the chance of inadvertent human contact. On the inside, there were three doors between the MRI room and the rest of the hospital, so there was no chance a dog was going to escape once inside the scanner room.
Next up was employee health. Working with animals created an occupational hazard. What if somebody on the research team was allergic to dogs? Could the dogs leave dander in the MRI that would cause a reaction in someone who went in the scanner afterward? The solution to the first question was for all members of the lab to certify that they were not allergic to dogs. Most of the team had dogs, so this wasn’t a problem. To deal with the dog dander, we would dispose of the linens and wipe down the scanner with disinfectant.
The only remaining hurdle was the biosafety office. The biosafety officer was also concerned about rabies. She suggested that the research team receive preventive rabies vaccinations. Never mind that there have been no cases of human rabies in the United States resulting from a domestic dog bite in the last decade. Because all the volunteer dogs in our study would have proof of vaccination, the chances of contracting rabies from them would be essentially zero. The risks from the vaccine were far greater. The preventive rabies vaccination requires three shots over a month, and 50 to 75 percent of people receiving it get mild to moderate side eff
ects, including headaches, nausea, dizziness, abdominal pain, and fever. No thanks. After being confronted with this data from the CDC, the biosafety office backed down and agreed that the risks from vaccination were greater than the risks of contracting rabies from a domestic dog.
With the final administrative hurdle cleared, the army of lawyers signed off on the Dog Project. We received approval to initially study up to ten dogs. If things went well, we could seek approval for more dogs after that.
Now we just had to find some subjects.
8
The Simulator
WITH THE ISSUE OF where to scan the dogs out of the way, we could turn our attention to acclimating the dogs to the MRI. This meant that we would have to build an MRI simulator.
The entire project hinged on a dog’s ability to hold its head still while in the scanner. But training a dog to hold its head still was going to be the easy part. Doing it in an MRI was a different story. The interior of the MRI scanner is six feet long and less than two feet in diameter. Many people don’t like being stuck in a coffin-sized tube. Fortunately, dogs aren’t like humans, and many breeds actually like to be in small spaces. Callie, being of the terrier family, had no such fears and loved to tunnel under ivy and into holes. Even so, all the dogs that were going to participate in the study would need to be trained to go into a tube of the exact dimensions of the MRI. Once they were acclimated to the tube, they would then have to be trained to put their head into the head coil. The coil, which is nicknamed the “birdcage” because of the resemblance, is even smaller than the MRI tube. The dog would need to shimmy its body and head into the center of the birdcage.
The second, more difficult aspect of the MRI was the noise. MRIs are loud. When performing a functional scan, the MRI sounds like a machine gun. At nearly 100 decibels, being in an MRI is like standing next to a leaf blower. Although not terribly painful for humans, dogs have more sensitive hearing, and we worried about damaging their ears. Also, many dogs are just plain afraid of loud noises. It would do no good to scan the brain of an anxious, frightened dog. Not only would we need to find dogs with a calm temperament, we would still need to get them used to the noise. The simulator had to mimic this key aspect of the MRI procedure.
It is commonly believed that dogs have more sensitive hearing than humans. But how much more? At the low end, humans can hear frequencies of about 8 Hz, which sounds like a very deep vibration. The high end is limited to about 20,000 Hz. This range tends to shrink with age, with the high frequencies being lost to ear damage from loud noises over the years. Most human speech is in the 300 to 3,000 Hz range. The first investigation of dogs’ hearing was done in the 1940s. But because sound-generation technology was limited at the time, the scientists couldn’t generate very high frequencies, and they couldn’t determine the dogs’ upper frequency range. It wasn’t until the 1980s that technology could reliably generate high-frequency tones. In the 1990s, an even more sophisticated technique was developed. This technique measures electrical responses in the part of the dog’s brain that responds to sound. These brainstem auditory evoked responses, or BAERs, are also used in humans. Today, most scientists agree that dogs can hear tones up to about 60,000 Hz, well beyond the human range.
The actual MRI scanner makes a wide variety of sounds. These noises originate from what are called the gradient magnets. There are two types of magnetic fields in an MRI. The main field is produced by the miles of superconducting wire that are wrapped around the bore. The main field never changes and is always on. The gradients are much smaller magnetic fields that are constantly changing during a scan. By switching the gradients on and off, we can select specific locations in the brain. A gradient can be switched on by running electrical current through it, which activates the magnetic field. The sudden inrush of electricity causes the magnet to expand slightly, and this rapid expansion causes a pressure wave inside the MRI, which we hear as a loud banging. The exact noise that it makes depends on the type of scan being performed and whether it is a structural or a functional MRI.
We still needed a physical mockup of the scanner to train the dogs in. Many universities that house MRIs for brain research have mock scanners. There are many situations where it makes sense to train people in the scanner before actually scanning their brains. Brain-imaging studies of children, for example, must first teach kids to lie still in the scanner by using a simulator. Because the MRI can be frightening, it is very helpful to allow children to get used to the environment before they go into the real scanner.
It isn’t surprising that a few companies have cropped up to sell mock scanners. The price tag, however, is steep. When we embarked on the Dog Project, the going rate for a mock scanner was about $40,000. Since we had no funding, this wouldn’t be practical. Besides, I couldn’t see spending so much money for what amounted to an empty tube with a few speakers inside to simulate the noise.
But how much of the real MRI would we need to simulate? Did we need something that could fill an entire room, like the real scanner? Or could we get away with a simple tube? After all, the dog was going to be inside only the scanner.
Mark came to the hospital to check out the MRI facility and determine how much of the actual MRI we would need to simulate for dog training. He hopped up on the patient table and lay down, putting his head in the birdcage. With the press of a button, the table glided into the center of the magnet. A quick thumbs-up indicated he was good to go. We went through a few quick brain scans so that Mark could get an idea of the types of noises and how loud they were.
Mark came out of the scanner with a big grin on his face and proclaimed, “This is completely doable.”
“Do you think we need a mockup of the entire scanner?” I asked.
“No, just the patient table and the tube will be fine.”
This was good news, because we were going to have to build the simulator ourselves. The mock scanner would have three elements: a tube to simulate the inside of the scanner; an exact model of the birdcage, which the dog would have to shimmy into; and a sound system to play recordings of the scanner noise at the appropriate loudness.
I was looking forward to this. Constructing a simulator would let me dust off some woodworking equipment that had been lying dormant in the garage. It’s fun to build stuff.
To simulate the inside of the scanner, we needed a tube of the right diameter. The MRI bore measured sixty centimeters, or two feet, in diameter—larger than any tubing you would find at your local hardware store. That is, however, a common diameter of concrete pillars used in the construction of buildings. These pillars are made by pouring concrete into molds sold under the trade name Sonotube. Andrew made a few calls to construction supply houses around Atlanta and soon located a twelve-foot-long, two-foot-wide Sonotube.
“Do they sell it by the foot?” I asked him.
“Nope,” Andrew replied. “We have to buy the whole piece.”
“How much?”
“About a hundred bucks.”
“How long is the MRI bore again?”
“Six feet.”
“This is great,” I said. “We can do this NASA style.”
Andrew looked puzzled.
“In the old days,” I explained, “NASA always launched two spacecraft for their missions. The reason was that most of the cost of a project was in the design and development. Once those were achieved, the added cost of a second spacecraft was minimal. Plus, it added a level of protection if one craft failed. If we need to buy twelve feet of Sonotube, we might as well just cut it in half and build two simulators. We’ll give one to Mark to use at CPT, and I can keep one at home to test on Callie.”
Building the main tube didn’t require much beyond cutting the Sonotube in half. Andrew and I found everything else we needed at the local Home Depot. We bought two folding tables to mount the tubes on. A sheet of plywood and some lumber would serve as the patient table inside the tube. We did the construction in my garage on a Saturday.
Even though t
he result looked nothing like an actual MRI scanner on the outside, the important part for the dog was the interior of the tube. Andrew had obtained all the measurements from the real scanner. All we had to do was duplicate the height and width of the patient table when fully inserted into the MRI bore. To test it, we took turns crawling into the simulator. We both agreed it felt just as claustrophobic as the real thing.
Andrew and I building the MRI simulator.
(Helen Berns)
Building a mockup of the birdcage was a little more complicated. It is a peculiar shape, a cylinder about a foot long and a foot in diameter. Because it lies on its side, the cylinder rests in a cradle that attaches to the patient table inside the MRI tube. Andrew took exact measurements of the real coil and made a full-scale tracing of the ends of the birdcage. We transferred the tracings to some plywood and used a jigsaw to cut out exact replicas of the ends of the coil. Wood dowels were used to simulate the cage of the coil and also to hold the ends of the birdcage together. We bent a thin sheet of plywood into a semicircle and glued it inside the whole construction. For humans, this would form the cradle where the head rests. The dogs would need to shimmy their whole body into the coil and assume a sphinx position.
Callie kept a respectable distance from the simulator. She wasn’t afraid of it, but she wasn’t treating it like a toy either.
Just for fun, I tried to coax her into the tube, but she wanted nothing to do with it. Even with a dog treat inside, she still wouldn’t go in. The whole thing was just too foreign. Plus, it was elevated on a table, and she did not like being placed on a table. Too much like a visit to the vet.
How Dogs Love Us: A Neuroscientist and His Adopted Dog Decode the Canine Brain Page 7
