Copying pets is quietly edging us toward human cloning

by Antonio Regalado

When Barbra Streisand disclosed to Variety that she had paid $50,000 to have her dog copied, countless readers discovered for the first time that duplicating pets and other animals is an active commercial industry.

Indeed, for the right price, a company will clone your dog, your horse, or a prize beef bull and hand you a living replica within a few months.

But the report that truly rattled me surfaced shortly afterward. It featured Monni Must, a Michigan-based portrait photographer, who shelled out to duplicate Billy Bean, a Labrador retriever that had once belonged to her eldest daughter, Miya.

Miya had taken her own life a decade earlier. For Must, replicating the aging dog became a method of preserving her daughter's memory and, in her words, "safeguarding" her mourning.

Throughout the cloning process, Must was sent progress reports, among them ultrasound images of the growing fetus. The timeline carried uncanny parallels. The veterinarians picked up the clone's heartbeat on October 11 — Miya's birthday. The puppy arrived in November, the very month Miya ended her life.

"That is a sign. For me, that is a sign that Miya is part of this and aware," Must shared with me.

My internal alarms blared. Must wasn't merely duplicating a pet. She was attempting to hold onto a child she had lost. It bore an unsettling resemblance to an actual human cloning scenario — one in which a grieving mother or father attempts to bring back a son or daughter gone too soon.

I fired off a message to Jose Cibelli, a cloning researcher specializing in animals at Michigan State University: Should we be concerned about human cloning once more?

Cibelli's reply arrived swiftly by email: "Absolutely."

Copying pets is quietly edging us toward human cloning

An unsettling prospect

I first crossed paths with Cibelli a decade and a half ago, during a period when I was among a throng of reporters covering cloning around the clock. At that time, it felt as though someone might attempt to duplicate a human being at any moment. A brash Italian fertility specialist named Antinori claimed he was doing exactly that, while a UFO sect called the Raëlians ran a human cloning venture called Clonaid; their hoax announcement about producing a cloned infant named Eve seemed entirely believable. In 2002, the National Academies rushed out an emergency assessment on the matter.

Yet human cloning never materialized. The explanation is obvious in hindsight. In the fundamental cloning method — the same one used to generate Dolly the sheep in 1996 — researchers extract a whole adult cell and place it inside an egg that has had its own genetic material removed. The embryo that forms is a clone.

However, this approach is woefully inefficient. Across many species, only about one out of every 100 cloned embryos results in a live birth. Some embryos perish in the petri dish. Others deteriorate inside the womb. Of those that make it to birth, a fraction emerge with defects and die shortly after.

It would make you "dread to imagine," a New York Times piece from 2001 noted, "what could go wrong if people were cloned using present-day methods."

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Still, cloning advanced within livestock and companion dogs. The reason is that eggs can be harvested in sufficient quantities, allowing firms to compensate for the technology's built-in wastefulness. Unsuccessful clones simply represent an operational expense.

The underlying causes are better grasped now. For a skin cell to perform as a skin cell, it doesn't require every gene in its arsenal. Plenty are simply switched off. Cloning succeeds at all because an egg possesses a striking talent for switching genes back on through a mechanism known as reprogramming. However, the egg has only a narrow window to accomplish this, and certain genes resist the process.

These stubborn genes — remaining locked and unable to contribute to the embryo's development — are "thought to cause the death of clones," Cibelli explains.

A shift in the landscape

This is also where the latest advances enter the picture. Cibelli directed my attention to the research of Yi Zhang, a stem-cell researcher at Boston Children's Hospital and a Howard Hughes Medical Institute investigator. He explained that Zhang has identified compounds which, when introduced into an egg, can assist in unlocking those silenced genes.

When Zhang added these "modifiers," cloning efficiency jumped significantly — erasing hurdles inherent in mature cells. Zhang initially tested the approach in mice. Previously, roughly 1 percent of cloned embryos produced a live mouse pup; now, he states, the figure climbs to 10 percent.

"The boost in efficiency is enormous," says Zhang, who notes he has submitted a patent tied to the finding.

Zhang subsequently applied the technique to human eggs. Back in 2015, his group enlisted four women to donate eggs harvested from their ovaries. Into those eggs, they introduced skin cells taken from other individuals.

Without the gene-unlocking molecules, the cloned embryos failed to develop properly. With the modifiers, however, roughly a quarter of them developed normally. "Our goal was to eliminate the obstacles in the adult cells," he explains. "The takeaway: we would not have succeeded otherwise."

To be explicit, Zhang has no intention of producing babies. Rather, his purpose in duplicating tiny human embryos is to harvest their stem cells. Referred to as "therapeutic cloning," this approach aims to generate robust embryonic stem cells that genetically match the adult donor — potentially serving as a supply of replacement tissue.

Therapeutic cloning isn't a fresh concept. Cibelli himself pioneered the effort (unsuccessfully) fifteen years back. When it flopped, researchers pivoted to alternative methods of generating stem cells by reprogramming skin cells directly in the laboratory. Abruptly, however, cloning for stem cell production is no longer the far-fetched notion it once seemed. With greater efficiency, physicians might realistically employ it to generate compatible tissue for patients who can pay, Zhang notes. He is launching a venture called NewStem to begin stockpiling cloned stem cells.

"Earlier, it was conceivable in theory, but you'd need enormous numbers of eggs, so it was impractical," Zhang says. "Now, given the efficiency, it's achievable."

Primate duplicates

We can now fabricate cloned human embryos fairly reliably. Could we push further and nurture those embryos into a child? A hint surfaced in January 2018, when scientists in China duplicated our primate relatives — monkeys — for the very first time. Images of two adorable baby primates, Zhong Zhong and Hua Hua, rapidly circulated globally.

Qiang Sun and Mu-ming Poo | Chinese Academy of Sciences | Cell Press

What had enabled the Chinese team where every prior monkey cloning effort had stumbled? The answer: they had employed Zhang's efficiency-boosting compounds.

Not every hurdle has been cleared. The Chinese researchers produced the animals using skin cells sourced from an aborted monkey fetus. However, two additional clones, generated from an adult animal's cells, perished soon after delivery. Little information is available explaining those two deaths. But it's reasonable to assume incomplete reprogramming of the adult cells played a role.

From Zhang's perspective, attempting to clone a person would remain reckless, unworkable, and unlawful. Despite the improved efficiency, he points out that the Chinese researchers relied on 63 surrogate mothers and 417 eggs to produce two monkey clones. Picture trying to organize that many human surrogates and egg contributors.

"No society would tolerate that," Zhang states. "On the flip side, if you're asking whether efficiency can be improved further, the answer is yes. My conclusion is that ultimately, from a technical standpoint, human cloning will become feasible."

Drivers behind cloning

Producing a human clone isn't solely a technical puzzle. You'd also require a purpose, specialists prepared to assist, and funding to bankroll the endeavor.

Finding deep-pocketed risk-takers might be the simplest piece. In March, the CBS show 60 Minutes broadcast a segment featuring La Dolfina, an Argentinian polo team whose members all ride replicas of an identical horse. The businessman behind the horse cloning operation, Texas entrepreneur D. Alan Meeker, informed CBS that he had "been approached by some of the wealthiest individuals on earth to clone a human being." Meeker said he had turned them down. His rationale: nobody would explain why they wanted a clone.

Yet we are aware of one motivation — possibly the most compelling of all. During my phone conversation with Must, the photographer, she described her anguish over her daughter's suicide.

Must had inherited Miya's dog, Billy Bean, and told me the notion of cloning struck her abruptly, years afterward, as the dog approached age 14. "I worried that everyone would forget Miya, that I would forget Miya," Must recalled. "I sensed I was about to lose the dog, and I was genuinely breaking down. The idea hit me like a flash: oh my God, I'm going to clone her. I was simply desperate."

Labrador retriever Billy Bean alongside her clone, Gunni. Photo courtesy of Monni Must

Must eventually hired a veterinarian to gather a skin tissue sample from the dog and forwarded it to a firm called PerPETuate. For a $1,300 charge, PerPETuate establishes a cell culture from a pet's skin and preserves the cells in liquid nitrogen for potential future cloning. The service essentially offers an affordable method of safeguarding an animal's DNA while you weigh whether to commit to the full $50,000 cloning expense. PerPETuate's founder Ron Gillespie reports he is preserving frozen tissue from dogs, cats, and even a lion belonging to a Mexican zoo. Must isn't the only individual to have cloned a dog connected to a deceased child, he says. The company, however, will not process human cells. Not from grieving parents or anybody else.

"We've fielded numerous inquiries," Gillespie says. "I tell them we don't offer that. And when people insist on knowing where they could get it done, I say 'I'm not sure.' I simply shut it down entirely. One of the biggest criticisms we encounter is that this will pave the way for human cloning, and people are strongly against that, myself included."

Billy Bean's cells were ultimately dispatched to ViaGen Pets, a Texas-based outfit offering cloning services. In September 2017, Must was informed that cloned Billy Bean embryos had been implanted into a canine surrogate. Two months afterward, she collected the new puppy. The dog "possesses a genuine spirit and embodies everything my daughter represented — playful, outgoing, compassionate, and people are drawn to her," she says. "I feel I still have that physical, tangible bond and not merely a spiritual one."

I eventually posed the question to Must: Would she have cloned Miya given the opportunity?

She replied that it's a question without an answer for her. "When you lose a child, you are not in a healthy state. You are not in any position to think clearly," she says.

Indeed, she acknowledges that people thought she had "gone off the deep end" when she decided to clone the dog. "It was an especially desperate move on my part. My other daughters believed I had gone crazy," she says. "But it succeeded. It is somewhat frightening to contemplate the implications."

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