Their main shortcoming, their only shortcoming, is that they don’t live long enough. But even that might be a mixed blessing as we would not have a succession of wonderful companions if their lifespan equaled ours. Perhaps we should be grateful that they force us to renew our relationship with them every fifteen or so years, if we are lucky.
I try not to remember those final moments, frantic hours, flashing days, or agonizing weeks when my dogs may have been dying, and that look in their eyes that told me to let go. They are stoic even when in pain, and they will conceal any weakness from the alpha. They will not let you know until it is too late. I try to trust my instincts when I feel that something is off, but sometimes denial is easier to accept when instinct tells you it’s bad, and too often it costs the ultimate price. It is the greatest responsibility in our covenant with a dog. It is also an unparalleled privilege to have to make the decision to let them go
I remember better the stilled silence. Coming home to an empty house where before I was greeted with love. Seeing an empty spot on the couch, feeling cold against my feet on the bed. No dog there when I needed one the most. The loss leaving me wandering an empty house.
If only the dogs could tell us when this whole CRFS thing started, their situation may not have gotten so bad. Maybe we could follow the trail better if we knew the moment they felt something amiss, and maybe we could save them—and so many of their caretakers—from broken hearts.
MYSTERY SOLVED
Dear Dr. Winthrop,
This is my resignation as your technician. I am so very sorry for telling Dr. Kovak about your proposal. I thought she was a friend of yours and when she asked what was new and exciting in the lab, it never occurred to me that she was trying to get inside information.
I have enjoyed working for you, and I will miss everyone in the lab and miss the important work that I had the privilege to do. Thank you for everything you have taught me.
I was able to get a job in the Chemistry Department, even after I explained the reason for my leaving your lab. If you need me to help train a new technician or cover my work until you find someone new, please let me know. I can be reached in Dr. Newman’s lab.
Again, I am so, so sorry. I hope that someday you can forgive me.
Kate
It hadn’t been Perky, or anyone else at Regnum. Kate. I wished she would have come to talk to me. I would have understood; it was an innocent mistake and given how cunning I know Kendal can be, I wouldn’t have put the blame on Kate. Still, one of my own—that stung. I called Kate’s cell phone; she didn’t pick up, though I’m sure she saw my call since she was never without her phone. It was such a shame, I really liked her; I would have let her stay. I left a message on her voice mail. I was sorry too, that she hadn’t come to talk to me, that she had probably been manipulated by Kendal. We could have worked something out. I wished her the best, and told her that if she ever needed a recommendation to let me know. The work she did in the lab would not be overshadowed by this one misstep. She didn’t call back. Neil should have told me it wasn’t one of his team; but did he know?
It took three weeks to hire Haley. Megan got her settled into the routine of feeding the cell lines, and showed her the layout of the lab. Haley came from a family of scientists, so she had been playing with lab equipment since she was a kid. Friendly and inquisitive, Haley was an undergraduate in her second year, majoring in zoology. She came highly recommended by one of my colleagues down the hall who was leaving in the spring to take a tenure track position at another university, and wanted to make sure Haley had a place to finish out her year of work-study. I was happy to help as I’m sure it beats working in the dining hall.
“So Dr. Winthrop, we were just talking in my molecular biology class about evolutionary studies and I was reading up on your work. Why did you start out studying cats and not dogs?”
Megan shook her head and cracked a grin, not looking up.
“Well, I am a dog person—stop rolling your eyes, Jamie—but by a series of right place, wrong time I got handed cats as my project since all the dog work was taken. But it was actually pretty interesting. Besides, I was there to learn how to analyze DNA, not interact with the whole animal.”
“They all look the same on a gel,” Jamie added.
“And cats are a great model for the study of human disease. They have surprisingly similar order to their genes, more so than a lot of other animal groups except primates, and they have a lot of parallel diseases. Like Sandhoff disease; it’s a disease that causes progressive degeneration in nerve cells. Humans and domestic cats both suffer from it.”
“But how does that relate to studying cat evolution?”
“Well, there’s also the need to understand how genes evolve in natural and subsequently domesticated environments, and cats have some pretty interesting evolutionary quirks.”
“Oh yeah, I’ve heard how all cheetahs in the world have the same genes.”
“Pretty much. They have so little diversity in their alleles that in a study done in U.S. zoos and in Africa, the different cheetahs didn’t even reject skin grafts between each other.”
“Skin grafts?”
“Yes, the group of genes that normally make an organism reject something that is not self, were so similar in the cheetahs that they didn’t recognize small areas of skin that were grafted from one animal to another.”
“Wow.”
“It was a pretty remarkable study. It was done back in the 1980s; they couldn’t get away with it nowadays. But based on the results it’s believed that the entire population of cheetahs underwent at least one, if not several bottlenecks, where the population was depleted down to very few individuals from which all current cheetahs descended. As a result, they have almost no genetic diversity, which is critical to facing environmental changes.” I finally rolled a chair over to where she was sitting at the hood plating cells. “Oddly though, the species continues, so they are a really fascinating, naturally occurring population to study.”
“Now we’re learning about the use of microsatellites and DNA analysis, but you didn’t have those techniques back then, right? I’d love to hear how you think those studies compare to those done now.”
Megan looked up at her with pleading eyes. I know she was trying to rescue her from the emerging lecture.
“Well, there have been so many advances since my day. When I was doing my graduate work –”
“Back when the dinosaurs roamed the Earth,” Jamie said.
“And DNA was just a figment of Crick’s imagination,” Megan added.
“And Darwin was still throwing up on the Beagle,” Jamie said, being Jamie.
I waited until they were finished.
“As I was saying before those who depend on me for their employment so rudely interrupted, there are thirty-seven species in Family Felidae. Lots of work preceded mine, so I was simply applying the most modern laboratory tools to confirm what most folks using morphology had already determined from fossils and by comparing the structural variation between species.”
“Modern at the time,” Jamie pointed out.
“Don’t you have some sequences to compare?” I said, shooing him away.
“But morphology can be deceiving,” Haley observed.
“Correct, morphology can be deceiving. Just look at the skull of a Yorkie compared to a bulldog and you would be hard pressed to say they were the same species.”
“But you don’t see that in domestic cats. They’re pretty much all the same.”
“True. There’s not a lot of mystery within the domestic cat when it comes to grouping them as one species, and within the Felidae there are some pretty obvious groupings, like the big cats—lions, tigers, leopards, jaguars—all of them group well together on one evolutionary branch based on morphology and confirmed by genetics. But there are a lot of smaller wild cats like those making up the domestic cat lineage—European wildcat, African wildcat, jungle cat, sand cat—that don’t easily separate out from o
ther small cats like the Pallas’ cat, fishing cat, and flat-headed cat that branch off from the domestic cat lineage.”
“I don’t think I’ve heard of most of those.”
“Neither had I when I started. I used the ‘ancient’ technique of protein electrophoresis to see if I could resolve some of the ambiguities,” I said, giving Jamie a ‘don’t you dare’ glare.
“Did you?” Haley asked.
“Sort of.” I shrugged. “It solidified the close relationship between the cheetah and puma, which though they occur continents apart today, show similarities based on fossils found in North America. There has been a lot of work since mine that has added to the consensus evolutionary tree of the Felidae. Truthfully, I haven’t kept track of all of it,” I confessed. “I found it interesting to watch it come together and it was cool to confirm their relationships based on a control. We used the hyena as the outgroup since it’s a species that is equally distant to all of the cats.”
“So the hyena in the cat family?”
“No, it is actually in its own family, but closer to the cats than the dog family. So it should and did show up with equal genetic difference to all the cats.”
“Cool.”
“There are a bunch of other cool things used to figure out cat evolution.” I continued since she was still eager, or at least appeared to be. “Cats group similarly with respect to purring versus roaring. The prevailing theory is that this is due to the ossification of the hyoid bone. Smaller cats have a more rigid hyoid bone better supporting the tongue and larynx, allowing them to purr, and this change occurred in a common ancestor. The smaller cats also group based on endogenous retroviruses.”
“Retrovirus, isn’t that what AIDS is? “
“Yes, and herpes, and chicken pox. Retroviruses are viruses that insert into the host’s DNA to make more copies of themselves. The retro part refers to the fact that they are RNA-based, not DNA, and they bring their own set of tools, like their own enzymes, to make the cell’s processes work to assemble a complete virus.”
“So the same retroviruses are found in all members of the domestic cat lineage?”
“Correct, but the operative word is endogenous. AIDS and herpes are EXogenous retroviruses, meaning they originate outside the host, and are essentially a parasite on that host. An ENdogenous virus is one that has been incorporated into the host’s DNA so long ago that it no longer functions, and has become an inert—most of the time—part of the host’s genome.”
Jamie and Megan jointly rolled their eyes. They had suffered through this story many times before.
“Some species within the Felidae have a set of similar viral sequences that appear in their genome. These sequences are likely from an ancient retrovirus that became non-functional by losing part of its sequence, but remain forever embedded in the cat’s DNA. It occurred millions of years ago as the lineage evolved, so all the modern cat species branching from that common ancestor have the same sequences.”
“Wow, that’s unique, isn’t it?”
“Sort of. The two that occur in the Felidae are only seen in those species within the domestic cat branch, but as far as endogenous ancient viruses go, we see the same thing in primates, as well as in many other mammals. Since they were pretty well described before, they weren’t important in my work. But endogenous viruses are often used in tissue culture labs to stimulate cells to grow.”
“I thought you said they’re no longer functional.”
“In general they are, but some of them have the ability to stimulate cell growth. You know how the cells you are growing start to die off after several passages, or generations?”
“Yes! That’s so frustrating!”
“Well some endogenous retroviruses, when added to the media used to feed cells growing in culture, somehow immortalize the cells, and keep them growing generation after generation.”
“That’s lit!”
“Uh, okay.” I was clearly behind on my lingo. “But like I said, I didn’t study them. For my work, mitochondrial DNA was the key to figuring out how all the cats were related.”
“And that’s DNA that is separate from the DNA in the nucleus.”
“Correct. I love how what I only learned in graduate school has become common knowledge for undergraduates or even in high school.”
“Exactly! We keep trying to tell you how much harder it is for us these days since we have so much more to learn!” Megan playacted exhaustion.
“Ignore them. Mitochondrial DNA—or mtDNA—is small and simple. In most mammals it has only thirty-seven genes, and is relatively well conserved within a species but at the same time is variable enough to show differences between species. Similar to how endogenous viral sequences may have become part of another species’ genome, the theory on mitochondria and why they have their own DNA is that they were once a separate organism, probably a bacterium, that formed a mutually beneficial relationship inside another cell.”
Jamie stuck his head in. “It’s a very romantic story.”
I felt my lecture ending. “Over time, they simply became a single entity. The bacteria became the mitochondria, which produce all the energy for the cell to use, and still retains its own DNA. The host cell contributes the building blocks—glucose and amino acids to keep it functioning.”
“So why is it so well conserved within a species?”
“For one thing there is no recombination. The genome is inherited wholly intact, and as the genes are few and specific, they can’t handle a lot of mutation. The combination of these two features means that any genetic change is very telling.” Gasping for my last breath I continued, “Also, with rare exceptions, it’s maternally inherited and this straight line of inheritance makes it a great tool to track the evolutionary history of populations.”
“How does that happen?” she asked. “I mean, the maternal inheritance?”
“Well, mitochondria exist in most cells, including the egg and the sperm, and there are usually many copies per cell. However, in the sperm, they are all in the tail so they can produce the energy the sperm need to swim. But since the tail falls off at fertilization and only the head enters the egg, none of the paternal mtDNA is transferred.”
Jamie closed the lecture. “What a poignant ending for all that hard work.”
“We can continue this later,” I assured Haley.
Megan loudly whispered behind my back, “Trust me, you haven’t heard the last of this.”
I smiled. My indoctrination had been successful, despite the heckling.
Epidemiology is the search for the source of a disease. The science of epidemiology combines slick, TV-worthy forensic medicine with the intricate, less glamorous field of statistics. Data are collected, maps are overlaid, patterns emerge, connections are made. But it’s the statistically significant correlations that hold the key. The Centers for Disease Control and Prevention—CDC—in Atlanta, Georgia, is the US’—and possibly the world’s—premier hub for epidemiologists. These scientists have played major roles in piecing together the spread of AIDS from patient zero in the 1980s, tracing the trail of anthrax attacks in the early 2000s, and isolating the sources during threats of human epidemics like SARS and Ebola.
But finding the source differs greatly from finding the cause. Finding the cause is often a progression of fits and starts, following up on hopeful leads, revisiting dead ends, and gut feelings about that oddity that you observed last week that makes you rethink your whole approach. Clinical symptoms can distract from the process, as an organism’s defense system may overreact and mask the initial or underlying response that is the important clue.
The interplay of epidemiology and identifying a disease’s cause is important, since knowing the routes and rates of transmission can help zero in on the causative agent. But it can still take years to pinpoint the actual cause and even longer to find a prevention or cure. Symptoms of HIV infection were known as far back as 1920. It is believed to have been picked up by humans who ate chimpanzees; the di
scovery that it was transmitted by bodily fluids supported the theory that it was caused by a virus. Still, it took nearly ten years after it emerged in the US before the actual virus was identified, and decades later we still wait and hope for a vaccine and cure.
Any scientific discovery is the result of many contributors, Nobel Prize work included, building upon an accumulation of data until the scientifically significant aha moment. It takes a village—a scientific village. The scientific publication announcing the discovery of the gene for cystic fibrosis, the most common human genetic disease—listed twenty-three authors.
THE DEAD OF WINTER
ANIA LAY on her back, legs spider-like in all directions, spotlighted by the sun radiating through the window, twitching, sound asleep, as I downed my first dose of caffeine. Ancestral genes retained in her species granted her the ability to fall asleep anywhere, anytime, secure in the comfort that she sat at the top of the food chain.
She woke and rose unhurriedly. Like pastry dough gently pulled between two hands, a stretch glided from the tips of her front paws up her neck through her arching back, and flowing through her extended back legs. She stepped out and shook from nose to tail; invigorated by slumber, she locked eyes with me, her tail wiggled, and her face brightened.
Being alone with a dog was like being alone and still feeling loved. That feeling you got when someone you love wrapped their arms around you on a cool, sunny Saturday when you had nothing to do and could simply exhale the world away. She came to me, put her head on my lap, and turned slightly to rub the sleep away. I rubbed her neck and her muzzle, and she kissed my face. “Guess I should get moving, huh?” I asked. For a moment she too seemed to want to take in the feeling, but then she shook it off and beckoned me to the day with a toss of her head. I unfolded myself from the warmth of my cushy robe, stood and stretched as she has taught me to do, and bent down opening my arms to welcome her in our morning embrace.
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