Your Beloved Pet Is Old. Should You Clone It?
Melvin was a special dog. A mixture of Catahoula and Doberman with black and tan markings, he was the office greeter, barking hellos to everyone who visited the Dupont Veterinary Clinic in Lafayette, Louisiana, which is owned by his human companions, Dr. Phillip Dupont and his wife, Paula. The couple say he's the best dog they ever owned.
When Melvin passed away, having two identical replicas helped ease the couple's grief.
He seemed to have an uncanny knack for understanding what they were saying, he could find lost car keys in tall grasses and the Duponts trusted him so much they felt comfortable having him babysit their grandson unattended in the backyard.
So when the 75-pound canine turned 9 and began to show signs of age, the Duponts sent off some of his skin cells to a lab in South Korea, the Sooam Biotech Research Foundation, to have him cloned. The Duponts toured the South Korean facilities and were satisfied that the animals were being treated well. While the first cloned puppy died from distemper, the second attempt produced two healthy animals—which the couple named Ken and Henry. When Melvin did pass away nearly two years later, in 2014, having two identical replicas helped ease the couple's grief. Even though it cost about $70,000 to clone Melvin, it was well worth it. "Melvin gave us a lot of pleasure," says Paula Dupont, "and this was less than the price of a new Land Cruiser."
As the technology improves, costs will tumble, making pet cloning more affordable for the mainstream.
The news has been filled recently with stories of celebrities such as Barbra Streisand or billionaire Barry Diller and his fashion icon wife, Diane von Furstenberg, spending big bucks to preserve their beloved pets—a practice New York magazine called "a laughable, extravagant waste of money." But cloning Fido isn't just for the ultra-wealthy anymore. Texas-based ViaGen now offers a domestic cloning service that will replicate Lassie for $50,000 and Garfield's kittens for a mere $25,000. While the exact number of cloned pets isn't known, the South Korean company says it has cloned about 800 pets while ViaGen has cloned about 100 cats and dogs. And as the technology improves, costs will tumble, making it more affordable for the mainstream, says Ron Gillespie, who heads PerPETuate, a Massachusetts-based outfit that collects and cryo preserves pet DNA, and works closely with ViaGen.
Even if the animals are genetic twins, biologists say, there are no guarantees their personalities will match, too.
While replicating Fido is becoming more feasible, should you? Animal rights organizations like The Humane Society and PETA are sharply critical of the practice, which is largely unregulated, and think it's outrageous to spend $50,000 or more to preserve Fluffy's genetic makeup when millions of cats and dogs are languishing in shelters and millions more are euthanized every year. And even if the animals are genetic twins, biologists say, there are no guarantees their personalities will match, too. Like humans, dogs' personalities are influenced by their environment and there are always variations in how the genes are expressed--although the Duponts say that Ken and Henry seem more like Melvin every day. "Their personalities are identical," says Paula.
Clones Ken and Henry, with Dr. Dupont and 10-year-old Melvin. Though all three dogs are genetic twins, their markings differ because the environment can influence how genes are expressed.
Still, the loss of a beloved pet can be incredibly painful, and in some cases, cloning can help deal with deep psychological wounds. When Monni Must's daughter died suddenly at age 28, the Michigan-based photographer adopted her child's black Lab, Billy Bean. As the dog got older and frailer, Must realized she couldn't handle losing her last link to her daughter—so she ponied up $50,000 to have the animal cloned. "I knew that I was falling apart," Must told Agence France-Presse. "The thought of Billy dying was just more than I could handle."
But these heated disputes miss what bioethicists believe is the real ethical dilemma—the fate of the female animals that provide the eggs and gestate the cloned puppies. "This issue tends to get framed as 'it's their personal choice, it's their money and they can do what they want with it,'" says Jessica Pierce, a bioethicist and author of Run, Spot, Run: The Ethics of Keeping Pets. "But this whole enterprise has all this collateral damage and behind-the-scenes impacts that people ignore. No one is talking about the dogs who are sacrificing themselves for this indulgence, and are suffering and being tormented just to have your clone."
"Even in the best-case scenarios, the cloned pet may go through several rounds of failed reproductive attempts—failed pregnancies, still births, and deformities."
Animal cloning, of course, is not new. Dolly, the sheep, made her debut in 1996 as the first cloned mammal. In 2005, Korea's Sooam Biotech cloned the first dog, and cloning horses and cows has become almost routine. Typically, the cloning process for dogs is fairly uncomplicated. It entails the use of a group of female dogs whose hormones are artificially manipulated with drugs to promote them to produce eggs. The eggs are then surgically harvested from donor dogs' ovaries. The immature eggs are stripped of their genetic information and then the pet's DNA is fused with the egg. When the embryo begins to develop, it is then transplanted to the womb of a surrogate dog.
However, cloning can have a high failure rate. When South Korea's Sooam Biotech lab cloned the first dog in 2005, there were 1000 failures—which means that number of eggs were fertilized and began to gestate, but at some point their development failed. And this figure doesn't include the number of dogs born with deformities serious enough that they are incompatible with life and need to be euthanized. "Even in the best-case scenarios, the cloned pet may go through several rounds of failed reproductive attempts—failed pregnancies, still births, and deformities," says Insoo Hyun, a bioethicist at Case Western Reserve University in Cleveland. "You can't do just one egg and one transfer. That won't happen. There is no guarantee that the very first time you will have a healthy animal. They're not miracle workers and you can't fight biology."
"You just have to let your pet go. It's all part of the experience."
But Ron Gillespie, who's been in the animal breeding business for decades, thinks these fears are overblown and that cloning is similar to the selective breeding that goes on all the time with cattle and even with champion racehorses. "We're really the victim of a lot of misinformation and misunderstanding," he says. "Right now, on average, we're dealing with three dogs: two that supply eggs and one to carry the embryo to term."
Still, this debate skirts the hard realities: dogs and cats simply have shorter lifespans than humans, and ethicists and animal rights activists believe there are better ways to deal with that grief. "You just have to let your pet go," says Hyun. "It's all part of the experience."
Scientists aim to preserve donkeys, one frozen embryo at a time
Every day for a week in 2022, Andres Gambini, a veterinarian and senior lecturer in animal science at the University of Queensland in Australia, walked into his lab—and headed straight to the video camera. Trained on an array of about 50 donkey embryos, all created by Gambini’s manual in vitro fertilization, or IVF, the camera kept an eye on their developmental progress. To eventually create a viable embryo that could be implanted into a female donkey, the embryos’ cells had to keep dividing, first in two, then in four and so on.
But the embryos weren’t cooperating. Some would start splitting up only to stop a day or two later, and others wouldn’t start at all. Every day he came in, Gambini saw fewer and fewer dividing embryos, so he was losing faith in the effort. “You see many failed attempts and get disappointed,” he says.
Gambini and his team, a group of Argentinian and Spanish researchers, were working to create these embryos because many donkey populations around the world are declining. It may sound counterintuitive that domesticated animals may need preservation, but out of 28 European donkey breeds, 20 are endangered and seven are in critical status. It is partly because of the inbreeding that happened over the course of many years and partly because in today’s Western world donkeys aren’t really used anymore.
“That's the reason why some breeds begin to disappear because humans were not really interested in having that specific breed anymore,” Gambini says. Nonetheless, in Africa, India and Latin America millions of rural families still rely on these hardy creatures for agriculture and transportation. And the only two wild donkey species—Equus africanus in Africa and Equus hemionus in Asia—are also dwindling, due to losing their habitats to human activities, diseases and slow reproduction rates. Gambini’s team wanted to create a way to preserve the animals for the future. “Donkeys are more endangered than people realize,” he says.
There’s much more to donkeys' trouble though. For the past 20 or so years, they have been facing a huge existential threat due to their hide gelatin, a compound derived from their skins by soaking and stewing. In Chinese traditional medicine, the compound, called ejiao, is believed to have a medicinal value, so it’s used in skin creams, added to food and taken in capsules. Centuries ago, ejiao was a very expensive luxury product available only for the emperor and his household. That changed in the 1990s when the Chinese economy boomed, and many people were suddenly able to afford it. “It went from a very elite product to a very popular product,” says Janneke Merkx, a campaign manager at The Donkey Sanctuary, a United Kingdom-based nonprofit organization that keeps tabs on the animals’ welfare worldwide. “It is a status symbol for gift giving.”
Having evolved in the harsh and arid mountainous terrains where food and water were scarce, donkeys are extremely adaptable and hardy. But the Donkey Sanctuary documented cases in which an entire village had their animals disappear overnight, finding them killed and skinned outside their settlement.
The Chinese donkey population was quickly decimated. Unlike many other farm animals, donkeys are finicky breeders. When stressed and unhappy, they don’t procreate, so growing them in large industrial settings isn’t possible. “Donkeys are notoriously slow breeders and really very difficult to farm,” says Merkx. “They are not the same as other livestock like sheep and pigs and cattle.” Within years the, the donkey numbers in China dropped precipitously. “China used to have the largest donkey population in the world in the 1990s. They had 11 million donkeys, and it's now down to less than 3 million, and they just can't keep up with the demand.”
To keep the ejiao conveyor going, some producers turned to the illegal wildlife trade. Poachers began to steal and slaughter donkeys from rural villages in Africa. The Donkey Sanctuary documented cases in which an entire village had their animals disappear overnight, finding them killed and skinned outside their settlement. Exactly how many creatures were lost to the skin trade to-date isn’t possible to calculate, says Faith Burden, the Donkey Sanctuary’s director of equine operations. Traditionally a poor people’s beast of burden, donkey counts are hard to keep track of. “When an animal doesn't produce meat, milk or eggs or whatever edible product, they're often less likely to be acknowledged in a government population census,” Burden says. “So reliable statistics are hard to come by.” The nonprofit estimates that about 4.8 million are slaughtered annually.
During their six to seven thousand years of domestication, donkeys rarely got the full appreciation for their services. They are often compared to horses, which doesn’t do them justice. They’re entirely different animals, Burden says. Built for speed, horses respond to predators and other dangers by running as fast as they can. Donkeys, which originate from the rocky, mountainous regions of Africa where running is dangerous, react to threats by freezing and assessing the situation for the best response. “Those so-called stubborn donkeys that won’t move as you want, they are actually thinking ‘what’s the best approach,’” Burden says. They may even choose to fight the predators rather than flee, she adds. “In some parts of the world, people use them as guard animals against things like coyotes and wolves.”
Scientists believe that domestic donkeys take their origin from Equus africanus or African wild ass, originally roaming where Kenya, Ethiopia and Eritrea are today. Having evolved in the harsh and arid mountainous terrains where food and water were scarce, they are extremely adaptable and hardy. Research finds that they can go without water for 72 hours and then drink their fill without any negative consequences. Their big jaws let them chew tough desert shrubs, which horses can’t exist on. Their large ears help dissipate heat. Their little upright hooves are a perfect fit for the uneven rocky or other dangerous grounds. Accustomed to the mountain desert climate with hot days and cold nights, they don’t mind temperature flux.
“The donkey is the most supremely adapted animal to deal with hostile conditions,” Burden says. “They can survive on much lower nutritional quality food than a cow, sheep or horse. That’s why communities living in some of the most inhospitable places will often have donkeys with them.” And that’s why losing a donkey to an illegal skin trade can devastate a family in places like Eritrea. Suddenly everything from water to firewood to produce must be carried by family members—and often women.
Workers unloading donkeys at the Shinyanga slaughterhouse in Tanzania. Fearing a future in which donkeys go extinct, scientists have found ways to cryopreserve a donkey embryo in liquid nitrogen.
TAHUCHA
One can imagine a time when worldwide donkey populations may dwindle to the point that they would need to be restored. That includes their genetic variability too. That’s where the frozen embryos may come in handy. We may be able to use them to increase the genetic variability of donkeys, which will be especially important if they get closer to extinction, Gambini says. His team had already created frozen embryos for horses and zebras, an idea similar to a seed bank. “We call this concept the Frozen Zoo.”
Creating donkey embryos proved much harder than those of zebras and horses. To improve chances of fertilization, Gambini used the intracytoplasmic sperm injection or ICSI, in which he employed a tiny needle called a micropipette to inject a donkey sperm into an egg. That was a step above the traditional IVF method, in which the egg and a sperm are left floating in a test tube together. The injection took, but during the incubating week, one after the other, the embryos stopped dividing. Finally, on day seven, Gambini finally spotted the exact sight he was hoping to see. One of the embryos developed into a burgeoning ball of cells.
“That stage is called a blastocyst,” Gambini says. The clump of cells had a lot of fluids mixed within them, which indicated that they were finally developing into a viable embryo. “When we see a blastocyst, we know we can transfer that into a female.” He was so excited he immediately called all his collaborators to tell them the good news, which they later published in the journal of Theriogenology.
The one and only embryo to reach that stage, the blastocyst was cryopreserved in liquid nitrogen. The team is waiting for the next breeding season to see if a female donkey may carry it to term and give birth to a healthy foal. Gambini’s team is hoping to polish the process and create more embryos. “It’s our weapon in the conservation ass-enal,” he says.
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
Too much of this ingredient leads to autoimmune diseases, new research shows. Here's how to cut back.
For more than a century, doctors have warned that too much salt in your diet can lead to high blood pressure, heart disease and stroke - and many of the reasons for these effects are well known. But recently scientists have been looking deeper, into the cellular level, and they are finding additional reasons to minimize sodium intake; it is bad for immune cells, creating patterns of gene expression and activity seen in a variety of autoimmune diseases such as multiple sclerosis, lupus, rheumatoid arthritis, and type-1 diabetes.
Salt is a major part of the ocean from which life evolved on this planet. We carry that legacy in our blood, which tastes salty. It is an important element for conducting electrical signals along nerves and balancing water and metabolites transported throughout our bodies. We need to consume about 500 milligrams of salt each day to maintain these functions, more with exercise and heavy sweating as that is a major way the body loses salt. The problem is that most Americans eating a modern western diet consume about 3400 milligrams, 1.5 teaspoons per day.
Evidence has been accumulating over the last few years that elevated levels of sodium can be harmful to at least some types of immune cells. The first signal came in monocytes, which are immune cells that travel to various tissues in the body, where some of them turn into macrophages, a subset of white blood cells that can directly kill microorganisms and make chemical signals that bring other types of immune cells into play.
Two years ago, Dominik N. Müller from the Max-Delbrueck-Center in Berlin, Germany and Markus Kleinewietfeld, an immunologist at Hasselt University in Belgium, ran a study where they fed people pizza and then measured their immune cell function. “We saw that in any monocytes, metabolic function was down, even after a single salty meal,” Kleinewietfeld says. It seemed to be the cellular equivalent of the sluggish feeling we get after eating too much. The cells were able to recover but more research is needed to answer questions about what dose of sodium causes impairment, how long the damage lasts, and whether there is a cumulative effect of salt toxicity.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations.
The latest series of experiments focused on a type of T cell called T regulatory cells, or Tregs. Most T cells release inflammatory mediators to fight pathogens and, once that job is done, Tregs come along to calm down their hyperactive brethren. Failure to do so can result in continued inflammation and possibly autoimmune diseases.
In the lab, Kleinewietfeld and his large team of international collaborators saw that high levels of sodium had a huge effect on Tregs, upregulating 1250 genes and downregulating an additional 1380 genes so that they looked similar to patterns of gene expression seen in autoimmune diseases.
Digging deeper, they found that sodium affected mitochondria, the tiny organelles inside of cells that produce much of its energy. The sodium was interfering with how the mitochondria use oxygen, which resulted in increased levels of an unstable form of oxygen that can damage cell function. The researchers injected those damaged Tregs into mice and found that they impaired the animals' immune function, allowing the inflammation to continue rather than shutting it down.
That finding dovetailed nicely with a 2019 paper in Nature from Navdeep Chandel's lab at Northwestern University, which showed in mice that inhibiting the mitochondrial use of oxygen reduced the ability of Tregs to regulate other T cells. “Mitochondria were controlling directly the immunosuppressive program, they were this master regulator tuning the right amount of genes to give you proper immunosuppression,” Chandel said. “And if you lose that function, then you get autoimmunity.”
Kleinewietfeld's team studied the Treg cells of humans and found that sodium can similarly decrease mitochondrial use of oxygen and immunosuppressive activity. “I would have never predicted that myself,” Chandel says, but now researchers can look at the mitochondria of patients with autoimmune disease and see if their gene expression also changes under high salt conditions. He sees the link between the patterns of gene expression in Tregs generated by high salt exposure and those patterns seen in autoimmune diseases, but he is cautious about claiming a causal effect.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations. He says a high salt diet could also have an indirect effect on immune function through the way it affects the gut microbiome and the molecules made by microbes when they break down food. But the research results are too preliminary to say that for sure, much less parse out the role of salt compared with other possible factors. “It is still an exciting journey to try to understand this field,” he says.
Additionally, it is difficult to say precisely how this research in animals and human cell cultures will translate into a whole human body. Individual differences in genetics can affect how the body absorbs, transports, and gets rid of sodium, such that some people are more sensitive to salt than are others.
So how should people apply these research findings to daily life?
Salt is obvious when we sprinkle it on at the table or eat tasty things like potato chips, but we may be unaware of sodium hidden in packaged foods. That's because salt is an easy and cheap way to boost the flavor of foods. And if we do read the labeled salt content on a package, we focus on the number for a single serving, but then eat more than that.
Last September, the U.S. Food and Drug Administration (FDA) began a process to update labels on the content of food, including what is meant by the word “healthy” and how food manufacturers can use the term. Many in the food industry are resisting those proposed changes.
Chandel cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker.
Until labels are updated, it would be prudent to try to reduce sodium intake by cutting down on packaged foods while making your own food at home, where you know just how much salt has been added. The Mayo Clinic offers guidance on how to become more aware of the sodium in your diet and eat less of it.
Chandel thinks many people will struggle with minimizing salt in their diets. It’s similar to the challenge of eating less sugar, in that the body craves both, and it is difficult to fight that. He cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker. “Dietary antioxidants have failed in just about every clinical trial, yet the public continues to take them,” Chandel says. But he is optimistic that research will lead us to a better understanding of how Tregs function, and uncover new targets for treating autoimmune diseases.