By Katherine Unger Baillie
Forget birthstones and astrological signs; the month in which you were born may carry serious significance for your health.
A research project involving a team from Penn’s Perelman School of Medicine and School of Veterinary Medicine is teasing out a link between birth month and cardiac disease risk, looking at both humans and dogs. The main thrust: Being born in the summer heightens the risk of disease later in life.
“Dogs are more similar to humans than many other animal models,” says Mary Regina Boland, a biostatistician at Penn Medicine. “They’re pets, so they live in the same environment as we do, but they also can naturally develop cardiovascular disease.”
Boland had been examining the link between birth month and heart disease for a few years, relying on electronic health records, but encountered challenges when accounting for biases and disparities reflected in the data. So she turned to another source.
“I started wondering whether there were any animal models that could potentially support this,” Boland says.
Exploring datasets for pet dogs, Boland realized she needed colleagues in the veterinary world to help her navigate. She connected with two veterinary cardiologists at Penn Vet, Anna Gelzer and Marc Kraus. Together, they analyzed datasets from Penn Vet and the Orthopedic Foundation for Animals, an organization that supports research on inherited diseases in pets.
In a study published earlier this year in Scientific Reports, Boland, Gelzer, Kraus, and colleagues found a strong link between birth month and cardiac disease risk in canines: Those born in the summer months were predisposed to developing heart problems, with the risk soaring up to 74 percent higher than expected for dogs born in July.
In that work, as well as prior studies using human health records, researchers pointed fingers at air pollution as a likely culprit for this connection. It’s believed that exposure to fine air particulates—which are at their highest levels in the summer—somehow leads to harmful physiological changes in utero that may not manifest for decades.
Dogs prove a useful parallel subject to humans for these sorts of studies, the researchers note. “Their life spans are shorter, so if they’re going to develop a condition it will show up in a reasonably compressed timeframe compared to humans,” says Kraus.
That project is still in its early stages, but could have a variety of implications for reducing disease risk.
“For dog breeders, it’s pretty easy to control when puppies are born,” says Gelzer. “With June and July having the highest risk for heart disease, we could just advise to breed during months that wouldn’t result in these birthdays.”
When it comes to humans, dictating which month a baby will come into the world is not as straightforward, but insights gleaned from research in dogs have the potential to help uncover the molecular mechanisms that lead to birth-month effects.
For now, the Penn researchers are brainstorming ways to explore those mechanisms, such as statistical deep dives, genomic sequencing, or microbiome analyses, to potentially locate new intervention targets. They’ve also recently begun to explore connections between cancer risk and birth month, collaborating with Penn Vet’s Nicola Mason, a clinician and researcher who has applied immunotherapy approaches to treating cancer in dogs.
“This doesn’t mean there shouldn’t be any more summer babies,” Boland says, “but the findings we generate could be an entry into some very interesting questions about the drivers of these connections.”
By Hannah Kleckner, Penn Vet
Gaunt, stuporous zombie-like deer are stumbling through the American wilderness. Not a product of Hollywood’s imagination, these animals are a very real concern for public health and wildlife officials.
Across the U.S., a growing number of deer are testing positive for chronic wasting disease (CWD), one in a family of rare neurodegenerative diseases that affect humans and animals. Known as prion diseases or transmissible spongiform encephalopathies (TSEs), they include bovine spongiform encephalopathy (BSE), commonly called mad cow disease, Creutzfeldt-Jakob Disease (CJD), variant CJD (vCJD), and more. Symptoms mimic the behaviors of pop culture’s favorite monsters and include extreme thirst and salivation, ataxia, and listlessness, among others.
The diseases are similar and stem from aberrant prion proteins that spark a sponge-like deterioration of the brain. (Penn alumnus Stanley B. Prusiner, C’64 and M‘68, earned the 1997 Nobel Prize for Medicine for discovering prions.)
“The prion protein naturally occurs in animals,” said Perry Habecker, chief of large animal pathology at Penn Vet’s New Bolton Center, which conducts immunohistochemistry tests for CWD and scrapie, another prion disease that affects sheep and goats.
A normal prion is made by cells, consumed by cells, and transported in the body. It never accumulates. “In prion diseases, an abnormal prion sets off a cascade of events when the normal prion has a conformational change,” shared Habecker. “All prions then stick together, and the body cannot get rid of them. The proteins just build up until the buildup translates into a neurological dysfunction of wasting, stupor, and, ultimately, death.”
Death from prion diseases is certain—once the cascade starts, nothing can stop it.
“Prions are the first ‘infectious agent’ that don’t have DNA in them,” said Habecker. “We know about viruses, bacteria, protozoa, fungi, but prions can infect and cause disease and not really reproduce themselves in a way that a bacteria, fungus, protozoa, or virus would with DNA. So, we don’t have a way to stop or reverse the diseases.”
Species to Species to Species
Therein lies the fear of widespread, uncontainable prion outbreaks. There is no known treatment for humans or animals. And prion diseases are, in some cases, transferrable among species.
Many of us remember the outbreak of mad cow disease in the United Kingdom for its impact on the cattle industry and threat to human life. At the epidemic’s peak in Britain, almost 1,000 cases were reported each week and eventually totaled in the death of nearly 180,000 cattle from 1986-2001.
The outbreak also claimed human lives. Since 1996, 231 people in 12 countries, including the UK, France, the U.S., and Canada, have died from its variant, vCJD. It’s widely believed humans contract vCJD from eating meat from cattle infected by mad cow disease.
And while national occurrences of CJD have increased from 260 to 481 cases between 2002-2015, the Centers for Disease Control and Prevention (CDC) is not linking CJD to CWD or any other animal-originated prion diseases.
Zombie Deer Are Here
Mad cow disease is no longer an imminent public health issue; scrapie, according to Habecker, is “pretty much under control;” and kuru, another human-form prion disease, has essentially been eradicated. But CWD weighs on the minds of hunters, deer farmers, wildlife experts, and public health officials.
As of January 2018, the disease had been detected in free-ranging and captive deer and elk in 22 states and two Canadian provinces.
“CWD originated from captive deer in Colorado,” explained Habecker. It was first recognized in the 1960s. “Over the years, deer breeders shuffled infected deer between farms and hunting preserves, redistributing the disease throughout the country.”
Perry Habecker of Penn Vet’s New Bolton Center helps lead a surveillance program that includes tests for the prion-transmitted infection chronic wasting disease.
In 2012, CWD made its first showing in Pennsylvania at a captive deer facility. This year, the number of infected deer is large enough that the Pennsylvania Game Commission has designated four parts of the state as Disease Management Areas. Hunting, feeding, and transporting deer is restricted in these areas. And samples of brain or spinal cord tissues is tested from every deer killed by hunters, as well as from road kill and deer culled by the Game Commission.
Although some evidence exists that CWD has zoonotic potential, “as far as we know it is not a threat to humans” said Habecker. He referenced tests in squirrel monkeys and macaques. Researchers found squirrel monkeys inoculated with brain tissue from a CWD infected deer acquired the disease.
Macaques, evolutionarily closer to humans than squirrel monkeys, were found unsusceptible in one study but susceptible in another. Researchers are also currently exploring whether the disease transplants from deer to plant life—and if so what the implications are.
Penn Vet on the Frontline
On the frontline of CWD, Penn Vet tests non-captive, hunter-killed deer in Pennsylvania. Additionally, it tests deer for several Northeastern states. Habecker screens nearly 1,000 samples a year with technology called an Autostainer that examines about 200 specimens at a time.
With the School’s services for the Pennsylvania Animal Diagnostic Laboratory System, a partnership among Penn Vet, the Pennsylvania Department of Agriculture, and Penn State University, the pathology team also keeps a close watch for other emerging threats to animals and food sources.
Penn Vet faculty not only provide vital diagnostic information, they contribute to the control and eradication of infectious diseases. For example, New Bolton Center was instrumental in developing an avian flu surveillance program after a 1983-84 avian flu outbreak necessitated the death of more than 17 million birds. In the last two subsequent outbreaks of avian flu alone, Penn Vet was instrumental in preventing nearly $5 billion in damages.
As a monitor of CWD, Habecker is concerned, although he’s not ready yet to raise a red flag. “We haven’t reached a tipping point, though we are monitoring the situation closely.”
Even if experts are not linking upticks of human prion diseases to a rise in CWD in deer, research demonstrating the transmission of the disease from venison to monkeys has heightened the CDC’s attention. The agency continues to watch for human CWD, investigating unusual cases of human prion disease and cases in people with increased risk of exposure to chronic wasting disease.
For the foreseeable future, however, Habecker advised, “When neighbors bring a gift of venison they’ve killed, go ahead and eat it. If they’re eating it, you’re probably safe to eat it too.” You will not, he reassured, join the walking dead.
Hannah is the communications specialist for Penn Vet’s New Bolton Center.