“Higher animals, Mom?”
I smiled at her attempt to express her liberal, anti-Classist foundation. It was refreshing in its raw form.
TUMBLING SLOWLY
ANIA AND SOFIE sat, side-by-side at the top of the hill. Alert, ears twitching, adjusting to pinpoint each sound. Silently they watched the day flow by, the wind and birds teasing with sporadic flutters. Only the occasional herd of deer in the early evening was worth a bark, and even then, they rarely bolted for the chase. Creatures of habit, their daily routine varied only to match the season. Cooler days shifted their duty to watching squirrels plant future generations of trees. Dog TV. Their view was flowing, as the hill rolled down to the open field, falling off at the creek, and climbing back up from the other bank until it crested above their line of sight. A lone sycamore tree down in the field of green grass gone blonde prepared to mute its leaves to the color of butterscotch. They sat, the two of them side-by-side, lording over their territory, until they were drawn by a human voice.
Mid-September, just as complacency set in, seventeen more dogs died after two dog shows in Maryland and Pennsylvania, and the dog world perked its ears again. As the warm days dissipated and the nights chilled, bold colors emerged. Shades of amber, yellow and red painted the landscape so vibrant that everyone stopped, everyone noticed, and each of us felt the emerging chill and the closing in of the shortened days. As if on cue, the crescendo of the fall palette suddenly shifted to ugly; leaves shriveled and tumbled to the ground en masse. The wind grabbed and swirled them up, tossed them aside where they lay dead and scattered on the ground, composting to dust. The dog leaves too began to fall in droves, stripping the warmth from the hearts of those bonded to their special brand of love. It was cold and bare without them.
The first week of October, on opposite coasts, new incidents at nine more shows loomed ominously. News media called it the “show-dog syndrome,” eager to invent a ratings-grabber headline that was punctuated by tacky graphics; much like they did in the early part of the AIDS epidemic, referring to it as the homosexual-Haitian-hemophiliac disease. The AVMA preferred a symptom-based naming system, flooding the airwaves with Canine Rapid Fading Syndrome—CRFS—which finally won out. As with AIDS, the word “syndrome” was used because it involved a variety of possible symptoms, and it was still not known whether this was caused by an external factor such as a bacterium or virus, or an internal factor like an autoimmune response, or whether it even fit the loose definition of a disease—an abnormal condition of the body or part thereof.
All eyes were on the purebred dog world. Headlines splashed “Only purebred dogs fall victim to CRFS!” and “Genetic defects finally take down purebred dogs.”
One of the quasi-news outlets featured an “expert” who declared, “Well, we’ve been saying this all along. Mutts on average live much longer than purebred dogs. I had one that lived to be seventeen!” Another grabbed her fifteen minutes of fame by declaring, “Those purebreds are so highly inbred, they have all kinds of problems. It’s no surprise to me that they’re getting knocked out by some new disease. Thank goodness we have mixed breeds.”
Though no actual data or studies were ever cited, verification of facts no longer seemed to be the standard for reporting. Meanwhile breed organizations and the scientific community countered in vain that there was no consensus of scientific studies that supported claims of genetic inferiority or susceptibility of purebred dogs. It was moot though—without a known cause, the show dog world was uneasy and under a public microscope.
Conspiracy advocates theorized that terrorists were killing dogs to target the hearts of Americans. That they developed a new virus or agent just for canines. If that was true, they were more cunning than our government could ever imagine. With more than seventy-five million dogs in the US alone, and over 35% of households having a dog, the devastating impact of an attack on our interspecies soul mates would be unimaginable, and brilliant.
Blustery fall days spun leaves in a cyclone of brown. Gray branches and scantily clad trees stood bracing for the winter as the air turned cold. Eighty-six more dogs died. Dog leaves lay in dead piles.
I was in early. So was everyone else.
Walking into the lab, one was blinded by the bright, ceiling-to-bench windows on the opposite wall, and it took a moment to adjust and focus on the two rows of black granite lab benches running perpendicular to the window, each with open shelves stacked with supplies. The tissue culture and chemical hoods lined the right-side entry wall, the left housed bright chrome wire shelves of clean and sterile glassware, and loosely arranged boxes of pipettes, beakers, well plates, and bags of microtubes. My office was carved out of the far-left windowed corner.
I headed to my space, dumped my bag and walked back into the lab to the giant whiteboard on the wall next to the door. Megan, Jamie, and Kate all stopped what they were doing and waited for me to speak. Normally exuding confidence and a sense of invincibility, they looked more like hopeful but worried dogs watching the ritual of their human packing the car.
“I guess you’ve all been listening to last night’s news,” I said, uncapping a marker. “We need to do some major brainstorming.”
“You think we can get some funding to work on this?” Kate asked. Though she wasn’t a graduate student, she knew that even a technician’s position required successive funding through “soft” grant money.
“I don’t know. I don’t even know if we even want to work—”
“We have to work on this!” Megan interrupted.
Jamie and Kate jumped in “Yeah!” “We can’t ignore this!” “This is going to be very big, and cool!”
“Okay folks, then anyone got any ideas on what angle we might explore? One that won’t take away from our Addison’s work? There’s a lot of competition for the samples from the dogs, and limited funding, and not very many clues on what needs to be researched.” I cleared the scribbles from the whiteboard that filled the wall by the door. “Let’s start with what we know.”
“It affects only purebred dogs.” Jamie remarked blandly.
“Oh dear Lord, really?” I said, giving him my best incredulous teenage act. “What anti-purebred group have you joined? You want to rephrase that?”
It was a pet peeve of mine when someone jumped to a conclusion based on simple association. We called it the pantyhose-cancer connection. Since most people who get breast cancer wear pantyhose, then it must mean that pantyhose cause breast cancer, right? No. There’s a huge difference between association, correlation, and cause.
Jamie cringed. “Sorry. So far, only purebred dogs have been affected and—”
“Only dogs at dog shows have been affected, thus only purebred dogs at dog shows have been exposed,” Megan interjected, rocketing to the front of her class.
“Or so we think,” Jamie said. “We don’t know if there are isolated cases here and there that aren’t noticed because they don’t have an obvious connection.”
Good point. I drew a big circle labeled dog shows, and a smaller inner circle, purebreds. “What else?”
Kate joined in. “They haven’t found signs of poison, have they?”
I drew a line down the center of the board. “I haven’t seen any reports, but I’m not sure they’ve ruled out anything.” Megan and Jamie shook their heads in agreement. “Okay, we’ll put that over here in the possible, but out of our bailiwick column. But that brings up a good point. Since our research is geared towards genetic research, what’s a plausible explanation for why we think the cause might be caused by something live—a bacteria, virus, or fungi.”
Crickets.
“Come on guys, think about the three possible transmission routes—inhalation, injection, or ingestion.”
“Well if it was injection, wouldn’t there have been some evidence?” Kate asked.
“I don’t mean injection with a needle. Bloodborne diseases like HIV can be transmitted by coming in contact with the blood stream through open cuts or sores, whi
ch is considered injection. But I think you’re right, someone would have seen evidence of injection as show dogs are so carefully groomed.” I sat down on a stool. “Look, it’s likely that a lot of proposals will involve looking for a DNA or protein signature from the causative agent, which is also what we will do. But what might set us apart is if we can demonstrate some due diligence by suggesting possible sources and thus routes of infection that would support looking for telltale signs of a foreign organism.” I could see them bracing for my lecture. “Back in the 70s when the first known outbreak of Legionnaires disease occurred it took almost six months to identify a bacterium as the causative agent. That was after chasing all kinds other potential causes—including toxins and viruses—from a myriad of sources until it was found in the air conditioning system. They didn’t know what they were looking and the shotgun approach didn’t help quell the panic. We have an advantage here in that there were multiple venues and we can look for commonalities of potential sources and routes.” They still didn’t look convinced. ‘So if this is a live agent, what are the potential sources? Think about where the incidents took place.”
“We already have dog shows,” Jamie said.
“Where these took place,” I prompted.
“You mean the convention center,” Megan said.
“Yes. What are some variables connected with each venue?”
“Environmental factors!” Kate shouted. Jamie’s hand shot up for a high five.
“Right, such as . . .”
“Air, water,” Jamie said. “Inhalation and ingestion.”
“Ventilation systems, like with Legionella.” Megan added. “But I guess I just don’t see how this is helpful. Both viruses and bacteria can be inhaled. Anthrax, the flu. So what does it matter if we think it was harbored in the ventilation systems and inhaled as an airborne particle? Besides, this is way out of our line of research. What could these possibly have to do with dog genetics and Addison’s?”
“You’re right, it’s a huge leap, and out of our area of expertise.” I was starting to agree with the futility of perusing this line of thinking. “I was just hoping that if we could suggest a plausible route of transmission, we could better justify asking for funding to research to screen DNA, as opposed to doing more toxicology screenings. If we found out something like . . . like they used the same manufacturer’s substrate in their dog relief area at the shows, like shredded mulch, we might be able suggest that it is more likely a bacterium or a virus. We could then offer to include screening our Addison’s samples as a large pool of non-CRFS controls thus cover some of the cost of processing our samples that can be used for other purposes. Kill lots of little birdies with one big boulder.”
“Or dogs with one,” Jamie added.
We all shot him a look.
Advancing technologies like shotgun sequencing allow scientists to rapidly sort through sequence data from short pieces of DNA, which is made up of four compounds—adenine (A), guanine (G), cytosine (C), and thymine (T)—and use computer algorithms to match those with a known sequence of interest, such as the dog genome, which consists of over two billion base pairs. The trouble is, for diseases such as Addison’s, it’s likely that the genetic change that causes it is very small, and different forms of the disease may be due to mutations at several different locations, as with cystic fibrosis. We knew we were looking for a very small change because the dogs survive, often functioning normally for the first few years of their life. If it were a more dramatic change, they would have never survived after birth. Such a small change is similar to natural variation in many genes, and thus there is a lot of noise in the analysis.
Since Addison’s is likely inherited, we needed to look at DNA from a lot of related animals, affected and not, as well as unrelated animals, to observe a pattern of tiny changes, and match these to pedigree of related animals that are being studied to determine the disease inheritance. The world of breeders and owners with Addison’s dogs had rallied to the cause, and we slowly worked through the freezers full of samples from them. As we knew this would likely take years of research, it was daunting to think how far we had yet to go with CRFS.
We spent the next two hours brainstorming and Internet searching. The venues didn’t seem to have any matching characteristics—several shows were held at county fairgrounds in dusty indoor arenas on grounds used for everything from 4H shows with chickens, horses, and other barnyard animals, to Irish and Polish festivals, to monster truck rallies. One was at a retired elementary school that was rented out for art shows, kids’ day, and dog and cat and even rabbit shows to keep the venue alive. And then there was the Balistar show held at the Gardens, as in Madison Square, sharing the venue with rock concerts, sports competitions, and kids’ extravaganzas. No common thread between them except the dog show.
We researched each of the cases, the breeds, the other scarce information available on pathology reports, and the disease progression. Some of it had to be pulled from news reports, but much of it was available through websites established by the AKC, the AVMA, US Department of Agriculture, and the Centers for Disease Control, or CDC, who were now involved over growing concern that CRFS might make the jump to humans. Each had a different focus, each with a different dataset.
Throughout the day, in between spinning DNA, loading gels, and combing through computer readouts of combinations of ATGCs, we filled the board with more circles, lines, and x’s, zeroing in on any connections we might follow. The most important observations, like so much in science, were the negatives.
Jamie came to me after lunch. “So I looked at the transmission rates. It doesn’t appear to be highly contagious. There are a hundred and fifteen suspected cases, with over four thousand dogs attending the shows with the dead dogs.”
“Can we maybe call them the victims or something less gut-punching, please?” Megan asked.
Jamie shook his head, but seemed to acquiesce. “There also don’t seem to be any reported cases of dogs returning home to pass on CRFS to other dogs in their homes and kennels.”
Since breeders tend to have a number of dogs at one time, often including puppies—very expensive puppies—I knew this would be a major source of relief in the community.
“So if they didn’t get it through direct contact with a sick dog, maybe it was airborne,” Megan suggested.
I thought about that a moment. “That would make sense. Dogs’ noses are like vacuum cleaners. Something could easily be sucked up. I doubt it was by ingestion since handlers are fairly vigilant about not letting their dogs eat off the floor. So, yes, I’d guess inhalation too. One thing, though—we can’t say anything about its virulence.”
“Why is that?” Kate asked. “Virulence is the strength of a pathogen to cause a disease, right?” I nodded. “So since we know that the dogs died really fast, wouldn’t it be considered highly virulent?”
“Possibly,” I said. “But what we don’t know is whether the dogs that died were the only ones exposed. If that were the case, I agree that CRFS would be highly virulent. But what if lots of dogs were exposed, but only a few got it? That could certainly be the case at a big show like Balistar.”
Megan jumped in excitedly. “So how about we see if we can look at a larger population of dogs that attended the shows, get samples from some that died, and some that were fine, and as controls, from others that were nowhere near the show? If it is a virus or bacteria, we might find a genetic trail, or an odd protein that doesn’t belong.”
“Good idea,” I said, “but we still need to focus in on what we’re looking for. Since we already have a bunch of Addison’s and control groups that we’ve run genetic variants and pathway analysis on we can use some of those and the same screening tools on any dog show samples we can get. Adding our data to Balistar’s would show that we’re sharing the costs.”
“You think that’s an issue?” Jamie asked.
“Added value is always the catchphrase. If anyone comes close to proposing the same thing, at le
ast we’ll have that,” I said, though I hated even the concept of competing science based on price.
By seven, we had fleshed out an idea for a proposal. Even Kate stayed beyond her normal working hours, caught up in the intrigue of chasing clues. I sent her home, and the others finished up their lab work while I went to my computer to search for funding opportunities. Two hours later Jamie’s big puppy-dog eyes woke me from my electronic trance.
“You want me to stay and help?”
“No, I’m good. Megan still here?”
He motioned over his shoulder. “She’s packing up. Probably pissed that she didn’t beat me to offering you help,” he whispered.
“Stop. Don’t poke the bear, Jamie.”
“Yes boss, but it’s so fun to razz her.” Jamie pushed aside my computer bag clearing a small space for him to sit on my only guest chair. “I really do want to help,” he said. “We both do.” He smiled. “You know it’s after nine. You sure I can’t help you at least do some searches?”
“Actually, I found some grant opportunities. They’re pretty straightforward. The awardees will have access to samples collected from a large number of victims as well as other dogs from shows whose owners donated samples in the hope it would help. I’m going to go through their application requirements a few more times and head home. But thanks.”
“Okay. Good night.”
“See you tomorrow,” I said. He hoisted his backpack and turned.
“Bye, see you bright and early tomorrow!” Megan called out, joining him.
Jamie really needed to give her a break. Megan had an amazing talent for making things work at the bench. She could isolate the smallest unique sequence of DNA and duplicate any technique in the literature. If she couldn’t duplicate it, then the author had omitted a critical step. Jamie teased her like a relentless brother, telling her that she was so good at the bench because women were so good at domestic work, like cooking. He wasn’t a chauvinist by any means, but instead was always trying to get her to lighten up and self-promote her awesome talent.
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