New research challenges the popular notion that all commercial breeding kennels are inhumane.
Candace Croney joined the faculty at Purdue University in 2011, thinking her job would focus on the welfare of livestock and poultry in Indiana. With bachelor's, master's, and doctoral degrees in animal sciences, her work until then had centered on sheep, cattle, and pigs. She'd even had the esteemed animal behaviorist Temple Grandin help shape her master's research project.
Croney's research has become the first of its kind in the world—and it's challenging our understanding of how dog breeding is being done.
Then came an email from a new colleague asking Croney to discuss animal welfare with some of Indiana's commercial dog breeders, the kind who produce large quantities of puppies for sale in pet stores.
"I didn't even know the term commercial breeders," Croney says. "I'd heard the term 'puppy millers.' That's pretty much what I knew."
She went to the first few kennels and braced herself for an upsetting experience. She's a dog lover who has fostered shelter mutts and owned one, and she'd seen the stories: large-scale breeders being called cruel and evil, lawmakers trying to ban the sale of commercially bred puppies, and constant encouragement to rescue a dog instead of paying into a greedy, heartless "puppy mill" industry.
But when she got to the kennels, she was surprised. While she encountered a number of things she didn't like about the infrastructure at the older facilities—a lack of ventilation, a lot of noise, bad smells—most of the dogs themselves were clean. The majority didn't have physical problems. No open sores. No battered bodies. Nothing like what she'd seen online.
But still, the way the dogs acted gave her pause.
"Things were, in many regards, better than I thought they would be," Croney says. "Google told me the dogs would be physically a mess, and they weren't, but behaviorally, things were jumping out at me."
While she did note that some of the breeders had play yards for their pups, a number of the dogs feared new people and things like leashes because they hadn't been exposed to enough of them. Some of the dogs also seemed to lack adequate toys, activities, and games to keep them mentally and physically stimulated.
But she was there strictly as a representative of the university to ask questions and offer feedback, no more or less. A few times, she says, she felt like the breeders wanted her to endorse what they were doing, "and I immediately got my back up about that. I did not want my name used to validate things that I could tell I didn't agree with. It was uncomfortable from that perspective."
After sharing the animal-welfare information her colleague had requested, Croney figured that was that. She never expected to be in a commercial kennel again. But six months later, her phone rang. Some of the people she'd met were involved in legislative lobbying, and they were trying to write welfare standards for Indiana's commercial breeders to follow.
In the continuing battle over what is, and is not, a "puppy mill," they wanted somebody with a strong research background to set a baseline standard, somebody who would actually bring objectivity to the breeder-activist conflict without being on one side or the other.
In other words, they wanted Croney's help to figure out not only appropriate enclosure sizes, but also requirements for socialization and enrichment activities—stimulation she knew the dogs desperately needed.
"I thought, crap, how am I not going to help?" she recalls. "And they said, 'Well how long will that take? A couple of weeks? A month?'"
Dr. Croney with Theo, whom she calls "a beloved family member of our research team."
(Photo credit: Purdue University/Vincent Walter)
Six years later, Croney's research remains ongoing. It has become the first of its kind in the world—and it's challenging our understanding of how dog breeding is being done, and how it could and should be done for years to come.
How We Got Here
Americans have been breeding pet dogs in large-scale kennels since World War II. The federal standard that regulates those kennels is the Animal Welfare Act, which President Johnson signed into law in 1966. Back then, people thought it was OK to treat dogs a lot differently than they do today. The law has been updated, but it still allows a dog the size of a Beagle to be kept in a cage the size of a dishwasher all day, every day because for some dogs, when the law was written, having a cage that size meant an improvement in living conditions.
Countless commercial breeders, who are regularly inspected under the Animal Welfare Act, have long believed that as long as they followed the law, they were doing things right. And they've seen sales for their puppies go up and up over the years. About 38 percent of U.S. households now own one or more dogs, the highest rate since the American Veterinary Medical Association began measuring the statistic in 1982.
Consumers now demand eight million dogs per year, which has reinforced breeders' beliefs that despite what activists shout at protests, the breeders are actually running businesses the public supports. As one Ohio commercial breeder—long decried by activists as a "puppy mill" owner—told The Washington Post in 2016, "This is a customer-driven industry. If we weren't satisfying the customer, we'd starve to death. I've never seen prices like the ones we're seeing now, in my whole career."
That breeder, though, is also among leading industry voices who say they understand that public perception of what's acceptable and what's not in a breeding kennel has changed. Regardless of what the laws are, they say, kennels must change along with the public's wishes if the commercial breeding industry is going to survive. The question is how, exactly, to move from the past to the future, at a time when demands for change have reached a fever pitch.
"The Animal Welfare Act, that was gospel. It meant you were taking care of dogs," says Bob Vetere, former head of the American Pet Products Association and now chairman of the Pet Leadership Council. "That was, what, 40 years ago? Things have evolved. People understand much more since then—and back then, there were maybe 20 million dogs in the country. Now, there's 90 million. It's that dramatic. People love their dogs, and everybody is going to get one."
Vetere became an early supporter of Croney's research, which, unbelievably, became the first ever to focus on what it actually means to run a good commercial breeding kennel. At the start of her research, Croney found that the scientific literature underpinning many existing laws and opinions was not just lacking, but outright nonexistent.
"We kept finding it over and over," she says of the literature gaps, citing common but uninformed beliefs about appropriate kennel size as just one example. "I can't find any research about how much space they're supposed to have. People said, 'Yeah, we had a meeting and a bunch of people made some recommendations.'"
She started filling in the research gaps with her team at Purdue, building relationships with dog breeders until she had more than 100 kennels letting her methodically figure out what was actually working for the dogs.
"The measurable successes in animal welfare over the past 50 years began from a foundation in science."
Creating Standards from Scratch
Other industry players soon took notice. One was Ed Sayres, who had served as CEO of the ASPCA for nearly a decade before turning his attention to lobbying efforts regarding the "puppy mill" issue. He recognized that what Croney was doing for commercial breeding mirrored the early work researchers started a half-century ago in the effort that led to better shelters all across America today.
"The measurable successes in animal welfare over the past 50 years began from a foundation in science," Sayres says. "Whether it was the transition to more humane euthanasia methods or how to manage dog and cat overpopulation, we found success from rigorous examination of facts and emerging science."
Sayres, Vetere, and others began pushing for the industry to support Croney's work, moving the goalposts beyond Indiana to the entire United States.
"If you don't have commercial breeding, you have people importing dogs from overseas with no restrictions, or farming in their backyards to make money," Vetere says. "You need commercial breeders with standards—and that's what Candace is trying to create, those standards."
Croney ended up with a $900,000 grant from three industry organizations: the World Pet Association, Pet Food Institute, and the Pet Industry Joint Advisory Council. With their support, she created a nationwide program called Canine Care Certified, like a Good Housekeeping Seal of Approval for a kennel. The program focuses on outcome-based standards, meaning she looks at what the dogs tell her about how well they are doing through their health and behavior. For the most part, beyond baseline requirements, the program lets a breeder achieve those goals in whatever ways work for the dogs.
The approach is different from many legislative efforts, with laws stating a cage must be made three feet larger to be considered humane. Instead, Croney walks through kennels with breeders and points out, for instance, which puppies in a litter seem to be shy or fearful, and then teaches the breeders how to give those puppies better socialization. She helps the breeders find ways to introduce dogs to strangers and objects like umbrellas that may not be part of regular kennel life, but will need to become familiar when the breeding dog retires and gets adopted into a home as a pet. She helps breeders understand that dogs need mental as well as physical stimulation, whether it comes from playing with balls and toys or running up and down slides.
The breeders can't learn fast enough, Croney says, and she remains stunned at how they constantly ask for more information—an attitude that made her stop using the term "puppy mill" to describe them at all.
"Now, full disclosure: Given that all of these kennels had volunteered, the odds were that we were seeing a skewed population, and that it skewed positive," she says. "But if you read what was in the media at the time, we shouldn't have been able to find any. We're told that all these kennels are terrible. Clearly, it was possible to get a positive outcome."
To Buy or Not to Buy?
Today, she says, she's shocked at how quickly some of the kennels have improved. Facilities that appalled her at first sight now have dogs greeting people with wagging tails.
"Not only would I get a dog from them, but would I put my dog there in that kennel temporarily? Yeah, I would."
"The most horrifying thing I learned was that some of these people weren't doing what I'd like to see, not because they didn't care or only wanted money, but because nobody had ever told them," she says. "As it turned out, they didn't know any different, and no one would help them."
For Americans who want to know whether it's OK to get a commercially bred puppy, Croney says she thinks about her own dogs. When she started working with the breeders, there were plenty of kennels that, she says, she would not have wanted to patronize. But now she's changing her mind about more and more of them.
"I'm just speaking as somebody who loves dogs and wants to make sure I'm not subsidizing anything inhumane or cruel," she says. "Not only would I get a dog from them, but would I put my dog there in that kennel temporarily? Yeah, I would."
She says the most important thing is for consumers to find out how a pup was raised, and how the pup's parents were raised. As with most industries, commercial breeders run the gamut, from barely legal to above and beyond.
Not everyone agrees with Croney's take on the situation, or with her approach to improving commercial breeding kennels. In its publication "Puppy Mills and the Animal Welfare Act," the Humane Society of the United States writes that while Croney's Canine Care Certified program supports "common areas of agreement" with animal-welfare lobbyists, her work has been funded by the pet industry—suggesting that it's impure—and a voluntary program is not enough to incentivize breeders to improve.
New laws, the Humane Society states, must be enacted to impose change: "Many commercial dog breeding operators will not raise their standards voluntarily, and even if they were to agree to do so it is not clear whether there would be any independent mechanism for enforcement or transparency for the public's sake. ... The logical conclusion is that improved standards must be codified."
Croney says that type of attitude has long created resentment between breeders and animal-welfare activists, as opposed to actual kennel improvements. Both sides have a point; for years, there have been examples of bottom-of-the-barrel kennels that changed their ways or shut down only after regulators smacked them with violations, or after lawmakers raised operating standards in ways that required improvements for the kennels to remain legally in business.
At the same time, though, powerful organizations including the Humane Society—which had revenue of more than $165 million in 2018 alone—have routinely pushed for bans on stores that sell commercially bred puppies, and have decried "puppy mills" in marketing and fund-raising literature, without offering financial grants or educational programs to kennels that are willing to improve.
Croney believes that the reflexive demonization of all commercial breeders is a mistake. Change is more effective, she says, when breeders "want to do better, want to learn, want to grow, and you treat them as advocates and allies in doing something good for animal welfare, as opposed to treating them like they're your enemies."
"If you're watching undercover videos about people treating animals in bad ways, I'm telling you, change is happening."
She adds that anyone who says all commercial breeders are "puppy mills" needs to take a look at the kennels she's seen and the changes her work has brought—and is continuing to bring.
"The ones we work with are working really, really hard to improve and open their doors so that if somebody wants to get a dog from them, they can be assured that those dogs were treated with a level of care and compassion that wasn't there five or 10 years ago, but that is there now and will be better in a year and will be much better in five years," she says. "If you're watching undercover videos about people treating animals in bad ways, I'm telling you, change is happening. It is so much better than people realize, and it continues to get even better yet."
Today's podcast guest, Dr. Renee Wegrzyn, directs ARPA-H, a new agency formed last year to spearhead health innovations. Time will tell if ARPA-H will produce advances on the level of its fellow agency, DARPA.
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How will the agency figure out which projects to take on, especially with so many patient advocates for different diseases demanding moonshot funding for rapid progress?
I talked with Dr. Wegrzyn about the opportunities and challenges, what lessons ARPA-H is borrowing from Operation Warp Speed, how she decided on the first ARPA-H project that was announced recently, why a separate agency was needed instead of reforming HHS and the National Institutes of Health to be better at innovation, and how ARPA-H will make progress on disease prevention in addition to treatments for cancer, Alzheimer’s and diabetes, among many other health priorities.
Dr. Wegrzyn’s resume leaves no doubt of her suitability for this role. She was a program manager at DARPA where she focused on applying gene editing and synthetic biology to the goal of improving biosecurity. For her work there, she received the Superior Public Service Medal and, in case that wasn’t enough ARPA experience, she also worked at another ARPA that leads advanced projects in intelligence, called I-ARPA. Before that, she ran technical teams in the private sector working on gene therapies and disease diagnostics, among other areas. She has been a vice president of business development at Gingko Bioworks and headed innovation at Concentric by Gingko. Her training and education includes a PhD and undergraduate degree in applied biology from the Georgia Institute of Technology and she did her postdoc as an Alexander von Humboldt Fellow in Heidelberg, Germany.
Dr. Wegrzyn told me that she’s “in the hot seat.” The pressure is on for ARPA-H especially after the need and potential for health innovation was spot lit by the pandemic and the unprecedented speed of vaccine development. We'll soon find out if ARPA-H can produce gamechangers in health that are equivalent to DARPA’s creation of the internet.
Show links:
ARPA-H - https://arpa-h.gov/
Dr. Wegrzyn profile - https://arpa-h.gov/people/renee-wegrzyn/
Dr. Wegrzyn Twitter - https://twitter.com/rwegrzyn?lang=en
President Biden Announces Dr. Wegrzyn's appointment - https://www.whitehouse.gov/briefing-room/statement...
Leaps.org coverage of ARPA-H - https://leaps.org/arpa/
ARPA-H program for joints to heal themselves - https://arpa-h.gov/news/nitro/ -
ARPA-H virtual talent search - https://arpa-h.gov/news/aco-talent-search/
Dr. Renee Wegrzyn was appointed director of ARPA-H last October.
Tardigrades can completely dehydrate and later rehydrate themselves, a survival trick that scientists are harnessing to preserve medicines in hot temperatures.
Formulating biologics to withstand drying and hot temperatures has been the holy grail for pharmaceutical researchers for decades. It’s a hard feat to manage. “Biologic pharmaceuticals are highly efficacious, but many are inherently unstable,” says Thomas Boothby, assistant professor of molecular biology at University of Wyoming. Therefore, during storage and shipping, they must be refrigerated at 2 to 8 degrees Celsius (35 to 46 degrees Fahrenheit). Some must be frozen, typically at -20 degrees Celsius, but sometimes as low -90 degrees Celsius as was the case with the Pfizer Covid vaccine.
For Covid, fewer than 73 percent of the global population received even one dose. The need for refrigerated or frozen handling was partially to blame.
The costly cold chain
The logistics network that ensures those temperature requirements are met from production to administration is called the cold chain. This cold chain network is often unreliable or entirely lacking in remote, rural areas in developing nations that have malfunctioning electrical grids. “Almost all routine vaccines require a cold chain,” says Christopher Fox, senior vice president of formulations at the Access to Advanced Health Institute. But when the power goes out, so does refrigeration, putting refrigerated or frozen medical products at risk. Consequently, the mRNA vaccines developed for Covid-19 and other conditions, as well as more traditional vaccines for cholera, tetanus and other diseases, often can’t be delivered to the most remote parts of the world.
To understand the scope of the challenge, consider this: In the U.S., more than 984 million doses of Covid-19 vaccine have been distributed so far. Each one needed refrigeration that, even in the U.S., proved challenging. Now extrapolate to all vaccines and the entire world. For Covid, fewer than 73 percent of the global population received even one dose. The need for refrigerated or frozen handling was partially to blame.
Globally, the cold chain packaging market is valued at over $15 billion and is expected to exceed $60 billion by 2033.
Adobe Stock
Freeze-drying, also called lyophilization, which is common for many vaccines, isn’t always an option. Many freeze-dried vaccines still need refrigeration, and even medicines approved for storage at ambient temperatures break down in the heat of sub-Saharan Africa. “Even in a freeze-dried state, biologics often will undergo partial rehydration and dehydration, which can be extremely damaging,” Boothby explains.
The cold chain is also very expensive to maintain. The global pharmaceutical cold chain packaging market is valued at more than $15 billion, and is expected to exceed $60 billion by 2033, according to a report by Future Market Insights. This cost is only expected to grow. According to the consulting company Accenture, the number of medicines that require the cold chain are expected to grow by 48 percent, compared to only 21 percent for non-cold-chain therapies.
Tardigrades to the rescue
Tardigrades are only about a millimeter long – with four legs and claws, and they lumber around like bears, thus their nickname – but could provide a big solution. “Tardigrades are unique in the animal kingdom, in that they’re able to survive a vast array of environmental insults,” says Boothby, the Wyoming professor. “They can be dried out, frozen, heated past the boiling point of water and irradiated at levels that are thousands of times more than you or I could survive.” So, his team is gradually unlocking tardigrades’ survival secrets and applying them to biologic pharmaceuticals to make them withstand both extreme heat and desiccation without losing efficacy.
Boothby’s team is focusing on blood clotting factor VIII, which, as the name implies, causes blood to clot. Currently, Boothby is concentrating on the so-called cytoplasmic abundant heat soluble (CAHS) protein family, which is found only in tardigrades, protecting them when they dry out. “We showed we can desiccate a biologic (blood clotting factor VIII, a key clotting component) in the presence of tardigrade proteins,” he says—without losing any of its effectiveness.
The researchers mixed the tardigrade protein with the blood clotting factor and then dried and rehydrated that substance six times without damaging the latter. This suggests that biologics protected with tardigrade proteins can withstand real-world fluctuations in humidity.
Furthermore, Boothby’s team found that when the blood clotting factor was dried and stabilized with tardigrade proteins, it retained its efficacy at temperatures as high as 95 degrees Celsius. That’s over 200 degrees Fahrenheit, much hotter than the 58 degrees Celsius that the World Meteorological Organization lists as the hottest recorded air temperature on earth. In contrast, without the protein, the blood clotting factor degraded significantly. The team published their findings in the journal Nature in March.
Although tardigrades rarely live more than 2.5 years, they have survived in a desiccated state for up to two decades, according to Animal Diversity Web. This suggests that tardigrades’ CAHS protein can protect biologic pharmaceuticals nearly indefinitely without refrigeration or freezing, which makes it significantly easier to deliver them in locations where refrigeration is unreliable or doesn’t exist.
The tricks of the tardigrades
Besides the CAHS proteins, tardigrades rely on a type of sugar called trehalose and some other protectants. So, rather than drying up, their cells solidify into rigid, glass-like structures. As that happens, viscosity between cells increases, thereby slowing their biological functions so much that they all but stop.
Now Boothby is combining CAHS D, one of the proteins in the CAHS family, with trehalose. He found that CAHS D and trehalose each protected proteins through repeated drying and rehydrating cycles. They also work synergistically, which means that together they might stabilize biologics under a variety of dry storage conditions.
“We’re finding the protective effect is not just additive but actually is synergistic,” he says. “We’re keen to see if something like that also holds true with different protein combinations.” If so, combinations could possibly protect against a variety of conditions.
Commercialization outlook
Before any stabilization technology for biologics can be commercialized, it first must be approved by the appropriate regulators. In the U.S., that’s the U.S. Food and Drug Administration. Developing a new formulation would require clinical testing and vast numbers of participants. So existing vaccines and biologics likely won’t be re-formulated for dry storage. “Many were developed decades ago,” says Fox. “They‘re not going to be reformulated into thermo-stable vaccines overnight,” if ever, he predicts.
Extending stability outside the cold chain, even for a few days, can have profound health, environmental and economic benefits.
Instead, this technology is most likely to be used for the new products and formulations that are just being created. New and improved vaccines will be the first to benefit. Good candidates include the plethora of mRNA vaccines, as well as biologic pharmaceuticals for neglected diseases that affect parts of the world where reliable cold chain is difficult to maintain, Boothby says. Some examples include new, more effective vaccines for malaria and for pathogenic Escherichia coli, which causes diarrhea.
Tallying up the benefits
Extending stability outside the cold chain, even for a few days, can have profound health, environmental and economic benefits. For instance, MenAfriVac, a meningitis vaccine (without tardigrade proteins) developed for sub-Saharan Africa, can be stored at up to 40 degrees Celsius for four days before administration. “If you have a few days where you don’t need to maintain the cold chain, it’s easier to transport vaccines to remote areas,” Fox says, where refrigeration does not exist or is not reliable.
Better health is an obvious benefit. MenAfriVac reduced suspected meningitis cases by 57 percent in the overall population and more than 99 percent among vaccinated individuals.
Lower healthcare costs are another benefit. One study done in Togo found that the cold chain-related costs increased the per dose vaccine price up to 11-fold. The ability to ship the vaccines using the usual cold chain, but transporting them at ambient temperatures for the final few days cut the cost in half.
There are environmental benefits, too, such as reducing fuel consumption and greenhouse gas emissions. Cold chain transports consume 20 percent more fuel than non-cold chain shipping, due to refrigeration equipment, according to the International Trade Administration.
A study by researchers at Johns Hopkins University compared the greenhouse gas emissions of the new, oral Vaxart COVID-19 vaccine (which doesn’t require refrigeration) with four intramuscular vaccines (which require refrigeration or freezing). While the Vaxart vaccine is still in clinical trials, the study found that “up to 82.25 million kilograms of CO2 could be averted by using oral vaccines in the U.S. alone.” That is akin to taking 17,700 vehicles out of service for one year.
Although tardigrades’ protective proteins won’t be a component of biologic pharmaceutics for several years, scientists are proving that this approach is viable. They are hopeful that a day will come when vaccines and biologics can be delivered anywhere in the world without needing refrigerators or freezers en route.