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."
In a recent research trial, patients with Parkinson's disease reported that their symptoms had improved after stem cells were implanted into their brains. Martin Taylor, far right, was diagnosed at age 32.
For years, there's been little improvement in the standard treatment. Patients are typically given the drug levodopa, a chemical that's absorbed by the brain’s nerve cells, or neurons, and converted into dopamine. This drug addresses the symptoms but has no impact on the course of the disease as patients continue to lose dopamine producing neurons. Eventually, the treatment stops working effectively.
BlueRock Therapeutics, a cell therapy company based in Massachusetts, is taking a different approach by focusing on the use of stem cells, which can divide into and generate new specialized cells. The company makes the dopamine-producing cells that patients have lost and inserts these cells into patients' brains. “We have a disease with a high unmet need,” says Ahmed Enayetallah, the senior vice president and head of development at BlueRock. “We know [which] cells…are lost to the disease, and we can make them. So it really came together to use stem cells in Parkinson's.”
In a phase 1 research trial announced late last month, patients reported that their symptoms had improved after a year of treatment. Brain scans also showed an increased number of neurons generating dopamine in patients’ brains.
Increases in dopamine signals
The recent phase 1 trial focused on deploying BlueRock’s cell therapy, called bemdaneprocel, to treat 12 patients suffering from Parkinson’s. The team developed the new nerve cells and implanted them into specific locations on each side of the patient's brain through two small holes in the skull made by a neurosurgeon. “We implant cells into the places in the brain where we think they have the potential to reform the neural networks that are lost to Parkinson's disease,” Enayetallah says. The goal is to restore motor function to patients over the long-term.
Five patients were given a relatively low dose of cells while seven got higher doses. Specialized brain scans showed evidence that the transplanted cells had survived, increasing the overall number of dopamine producing cells. The team compared the baseline number of these cells before surgery to the levels one year later. “The scans tell us there is evidence of increased dopamine signals in the part of the brain affected by Parkinson's,” Enayetallah says. “Normally you’d expect the signal to go down in untreated Parkinson’s patients.”
"I think it has a real chance to reverse motor symptoms, essentially replacing a missing part," says Tilo Kunath, a professor of regenerative neurobiology at the University of Edinburgh.
The team also asked patients to use a specific type of home diary to log the times when symptoms were well controlled and when they prevented normal activity. After a year of treatment, patients taking the higher dose reported symptoms were under control for an average of 2.16 hours per day above their baselines. At the smaller dose, these improvements were significantly lower, 0.72 hours per day. The higher-dose patients reported a corresponding decrease in the amount of time when symptoms were uncontrolled, by an average of 1.91 hours, compared to 0.75 hours for the lower dose. The trial was safe, and patients tolerated the year of immunosuppression needed to make sure their bodies could handle the foreign cells.
Claire Bale, the associate director of research at Parkinson's U.K., sees the promise of BlueRock's approach, while noting the need for more research on a possible placebo effect. The trial participants knew they were getting the active treatment, and placebo effects are known to be a potential factor in Parkinson’s research. Even so, “The results indicate that this therapy produces improvements in symptoms for Parkinson's, which is very encouraging,” Bale says.
Tilo Kunath, a professor of regenerative neurobiology at the University of Edinburgh, also finds the results intriguing. “I think it's excellent,” he says. “I think it has a real chance to reverse motor symptoms, essentially replacing a missing part.” However, it could take time for this therapy to become widely available, Kunath says, and patients in the late stages of the disease may not benefit as much. “Data from cell transplantation with fetal tissue in the 1980s and 90s show that cells did not survive well and release dopamine in these [late-stage] patients.”
Searching for the right approach
There's a long history of using cell therapy as a treatment for Parkinson's. About four decades ago, scientists at the University of Lund in Sweden developed a method in which they transferred parts of fetal brain tissue to patients with Parkinson's so that their nerve cells would produce dopamine. Many benefited, and some were able to stop their medication. However, the use of fetal tissue was highly controversial at that time, and the tissues were difficult to obtain. Later trials in the U.S. showed that people benefited only if a significant amount of the tissue was used, and several patients experienced side effects. Eventually, the work lost momentum.
“Like many in the community, I'm aware of the long history of cell therapy,” says Taylor, the patient living with Parkinson's. “They've long had that cure over the horizon.”
In 2000, Lorenz Studer led a team at the Memorial Sloan Kettering Centre, in New York, to find the chemical signals needed to get stem cells to differentiate into cells that release dopamine. Back then, the team managed to make cells that produced some dopamine, but they led to only limited improvements in animals. About a decade later, in 2011, Studer and his team found the specific signals needed to guide embryonic cells to become the right kind of dopamine producing cells. Their experiments in mice, rats and monkeys showed that their implanted cells had a significant impact, restoring lost movement.
Studer then co-founded BlueRock Therapeutics in 2016. Forming the most effective stem cells has been one of the biggest challenges, says Enayetallah, the BlueRock VP. “It's taken a lot of effort and investment to manufacture and make the cells at the right scale under the right conditions.” The team is now using cells that were first isolated in 1998 at the University of Wisconsin, a major advantage because they’re available in a virtually unlimited supply.
Other efforts underway
In the past several years, University of Lund researchers have begun to collaborate with the University of Cambridge on a project to use embryonic stem cells, similar to BlueRock’s approach. They began clinical trials this year.
A company in Japan called Sumitomo is using a different strategy; instead of stem cells from embryos, they’re reprogramming adults' blood or skin cells into induced pluripotent stem cells - meaning they can turn into any cell type - and then directing them into dopamine producing neurons. Although Sumitomo started clinical trials earlier than BlueRock, they haven’t yet revealed any results.
“It's a rapidly evolving field,” says Emma Lane, a pharmacologist at the University of Cardiff who researches clinical interventions for Parkinson’s. “But BlueRock’s trial is the first full phase 1 trial to report such positive findings with stem cell based therapies.” The company’s upcoming phase 2 research will be critical to show how effectively the therapy can improve disease symptoms, she added.
The cure over the horizon
BlueRock will continue to look at data from patients in the phase 1 trial to monitor the treatment’s effects over a two-year period. Meanwhile, the team is planning the phase 2 trial with more participants, including a placebo group.
For patients with Parkinson’s like Martin Taylor, the therapy offers some hope, though Taylor recognizes that more research is needed.
BlueRock Therapeutics
“Like many in the community, I'm aware of the long history of cell therapy,” he says. “They've long had that cure over the horizon.” His expectations are somewhat guarded, he says, but, “it's certainly positive to see…movement in the field again.”
"If we can demonstrate what we’re seeing today in a more robust study, that would be great,” Enayetallah says. “At the end of the day, we want to address that unmet need in a field that's been waiting for a long time.”
Editor's note: The company featured in this piece, BlueRock Therapeutics, is a portfolio company of Leaps by Bayer, which is a sponsor of Leaps.org. BlueRock was acquired by Bayer Pharmaceuticals in 2019. Leaps by Bayer and other sponsors have never exerted influence over Leaps.org content or contributors.