Original black Lab Billy Bean and its puppy clone. (Monni Must)
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."
Basecamp Research is using portable labs like this one to gather samples from ecosystems around the world.
Clark works for Basecamp Research, a biotech company headquartered in London, and his job is to collect samples from ecosystems around the world. By extracting DNA from soil, water, plants, microbes and other organisms, Basecamp is building an extensive database of the Earth’s proteins. While DNA itself isn’t a protein, the information stored in DNA is used to create proteins, so extracting, sequencing, and annotating DNA allows for the discovery of unique protein sequences.
Using what they’re finding in the middle of the Atlantic and beyond, Basecamp’s detailed database is constantly growing. The outputs could be essential for cleaning up the damage done by toxic chemicals and finding alternatives to these chemicals.
Catalysts for change
Proteins provide structure and function in all living organisms. Some of these functional proteins are enzymes, which quite literally make things happen.
“Industrial chemistry is heavily polluting, especially the chemistry done in pharmaceutical drug development. Biocatalysis is providing advantages, both to make more complex drugs and to be more sustainable, reducing the pollution and toxicity of conventional chemistry," says Ahir Pushpanath, who heads partnerships for Basecamp.
“Enzymes are perfectly evolved catalysts,” says Ahir Pushpanath, a partnerships lead at Basecamp. ”Enzymes are essentially just a polymer, and polymers are made up of amino acids, which are nature’s building blocks.” He suggests thinking about it like Legos — if you have a bunch of Lego pieces and use them to build a structure that performs a function, “that’s basically how an enzyme works. In nature, these monuments have evolved to do life’s chemistry. If we didn’t have enzymes, we wouldn’t be alive.”
In our own bodies, enzymes catalyze everything from vision to digesting food to regrowing muscles, and these same types of enzymes are necessary in the pharmaceutical, agrochemical and fine chemical industries. But industrial conditions differ from those inside our bodies. So, when scientists need certain chemical reactions to create a particular product or substance, they make their own catalysts in their labs — generally through the use of petroleum and heavy metals.
These petrochemicals are effective and cost-efficient, but they’re wasteful and often hazardous. With growing concerns around sustainability and long-term public health, it's essential to find alternative solutions to toxic chemicals. “Industrial chemistry is heavily polluting, especially the chemistry done in pharmaceutical drug development,” Pushpanath says.
Basecamp is trying to replace lab-created catalysts with enzymes found in the wild. This concept is called biocatalysis, and in theory, all scientists have to do is find the right enzymes for their specific need. Yet, historically, researchers have struggled to find enzymes to replace petrochemicals. When they can’t identify a suitable match, they turn to what Pushpanath describes as “long, iterative, resource-intensive, directed evolution” in the laboratory to coax a protein into industrial adaptation. But the latest scientific advances have enabled these discoveries in nature instead.
Marlon Clark, a research scientist at Basecamp Research, looks for novel biochemistries in the Azores.
Glen Gowers
Enzyme hunters
Whether it’s Clark and a colleague setting off on an expedition, or a local, on-the-ground partner gathering and processing samples, there’s a lot to be learned from each collection. “Microbial genomes contain complete sets of information that define an organism — much like how letters are a code allowing us to form words, sentences, pages, and books that contain complex but digestible knowledge,” Clark says. He thinks of the environmental samples as biological libraries, filled with thousands of species, strains, and sequence variants. “It’s our job to glean genetic information from these samples.”
“We can actually dream up new proteins using generative AI," Pushpanath says.
Basecamp researchers manage this feat by sequencing the DNA and then assembling the information into a comprehensible structure. “We’re building the ‘stories’ of the biota,” Clark says. The more varied the samples, the more valuable insights his team gains into the characteristics of different organisms and their interactions with the environment. Sequencing allows scientists to examine the order of nucleotides — the organic molecules that form DNA — to identify genetic makeups and find changes within genomes. The process used to be too expensive, but the cost of sequencing has dropped from $10,000 a decade ago to as low as $100. Notably, biocatalysis isn’t a new concept — there have been waves of interest in using natural enzymes in catalysis for over a century, Pushpanath says. “But the technology just wasn’t there to make it cost effective,” he explains. “Sequencing has been the biggest boon.”
AI is probably the second biggest boon.
“We can actually dream up new proteins using generative AI,” Pushpanath says, which means that biocataylsis now has real potential to scale.
Glen Gowers, the co-founder of Basecamp, compares the company’s AI approach to that of social networks and streaming services. Consider how these platforms suggest connecting with the friends of your friends, or how watching one comedy film from the 1990s leads to a suggestion of three more.
“They’re thinking about data as networks of relationships as opposed to lists of items,” says Gowers. “By doing the same, we’re able to link the metadata of the proteins — by their relationships to each other, the environments in which they’re found, the way those proteins might look similar in sequence and structure, their surrounding genome context — really, this just comes down to creating a searchable network of proteins.”
On an Azores island, this volcanic opening may harbor organisms that can help scientists identify enzymes for biocatalysis to replace toxic chemicals.
Emma Bolton
Uwe Bornscheuer, professor at the Institute of Biochemistry at the University of Greifswald, and co-founder of Enzymicals, another biocatalysis company, says that the development of machine learning is a critical component of this work. “It’s a very hot topic, because the challenge in protein engineering is to predict which mutation at which position in the protein will make an enzyme suitable for certain applications,” Bornscheuer explains. These predictions are difficult for humans to make at all, let alone quickly. “It is clear that machine learning is a key technology.”
Benefiting from nature’s bounty
Biodiversity commonly refers to plants and animals, but the term extends to all life, including microbial life, and some regions of the world are more biodiverse than others. Building relationships with global partners is another key element to Basecamp’s success. Doing so in accordance with the access and benefit sharing principles set forth by the Nagoya Protocol — an international agreement that seeks to ensure the benefits of using genetic resources are distributed in a fair and equitable way — is part of the company's ethos. “There's a lot of potential for us, and there’s a lot of potential for our partners to have exactly the same impact in building and discovering commercially relevant proteins and biochemistries from nature,” Clark says.
Bornscheuer points out that Basecamp is not the first company of its kind. A former San Diego company called Diversa went public in 2000 with similar work. “At that time, the Nagoya Protocol was not around, but Diversa also wanted to ensure that if a certain enzyme or microorganism from Costa Rica, for example, were used in an industrial process, then people in Costa Rica would somehow profit from this.”
An eventual merger turned Diversa into Verenium Corporation, which is now a part of the chemical producer BASF, but it laid important groundwork for modern companies like Basecamp to continue to scale with today’s technologies.
“To collect natural diversity is the key to identifying new catalysts for use in new applications,” Bornscheuer says. “Natural diversity is immense, and over the past 20 years we have gained the advantages that sequencing is no longer a cost or time factor.”
This has allowed Basecamp to rapidly grow its database, outperforming Universal Protein Resource or UniProt, which is the public repository of protein sequences most commonly used by researchers. Basecamp’s database is three times larger, totaling about 900 million sequences. (UniProt isn’t compliant with the Nagoya Protocol, because, as a public database, it doesn’t provide traceability of protein sequences. Some scientists, however, argue that Nagoya compliance hinders progress.)
“Eventually, this work will reduce chemical processes. We’ll have cleaner processes, more sustainable processes," says Uwe Bornscheuer, a professor at the University of Greifswald.
With so much information available, Basecamp’s AI has been trained on “the true dictionary of protein sequence life,” Pushpanath says, which makes it possible to design sequences for particular applications. “Through deep learning approaches, we’re able to find protein sequences directly from our database, without the need for further laboratory-directed evolution.”
Recently, a major chemical company was searching for a specific transaminase — an enzyme that catalyzes a transfer of amino groups. “They had already spent a year-and-a-half and nearly two million dollars to evolve a public-database enzyme, and still had not reached their goal,” Pushpanath says. “We used our AI approaches on our novel database to yield 10 candidates within a week, which, when validated by the client, achieved the desired target even better than their best-evolved candidate.”
Basecamp’s other huge potential is in bioremediation, where natural enzymes can help to undo the damage caused by toxic chemicals. “Biocatalysis impacts both sides,” says Gowers. “It reduces the usage of chemicals to make products, and at the same time, where contamination sites do exist from chemical spills, enzymes are also there to kind of mop those up.”
So far, Basecamp's round-the-world sampling has covered 50 percent of the 14 major biomes, or regions of the planet that can be distinguished by their flora, fauna, and climate, as defined by the World Wildlife Fund. The other half remains to be catalogued — a key milestone for understanding our planet’s protein diversity, Pushpanath notes.
There’s still a long road ahead to fully replace petrochemicals with natural enzymes, but biocatalysis is on an upward trajectory. "Eventually, this work will reduce chemical processes,” Bornscheuer says. “We’ll have cleaner processes, more sustainable processes.”
In an initial study, Canary analyzed speech recordings with AI and identified early stage Alzheimer’s with 96 percent accuracy.
Arnold was diagnosed sooner than many others. It's important to find out early, when interventions can make the most difference. One promising avenue is looking at how people talk. Research has shown that Alzheimer’s affects a part of the brain that controls speech, resulting in small changes before people show other signs of the disease.
Now, Canary Speech, a company based in Utah, is using AI to examine elements like the pitch of a person’s voice and their pauses. In an initial study, Canary analyzed speech recordings with AI and identified early stage Alzheimer’s with 96 percent accuracy.
Developing the AI model
Canary Speech’s CEO, Henry O’Connell, met cofounder Jeff Adams about 40 years before they started the company. Back when they first crossed paths, they were both living in Bethesda, Maryland; O’Connell was a research fellow at the National Institutes of Health studying rare neurological diseases, while Adams was working to decode spy messages. Later on, Adams would specialize in building mathematical models to analyze speech and sound as a team leader in developing Amazon's Alexa.
It wasn't until 2015 that they decided to make use of the fit between their backgrounds. ““We established Canary Speech in 2017 to build a product that could be used in multiple languages in clinical environments,” O'Connell says.
The need is growing. About 55 million people worldwide currently live with Alzheimer’s, a number that is expected to double by 2050. Some scientists think the disease results from a buildup of plaque in the brain. It causes mild memory loss at first and, over time, this issue get worse while other symptoms, such as disorientation and hallucinations, can develop. Treatment to manage the disease is more effective in the earlier stages, but detection is difficult since mild symptoms are often attributed to the normal aging process.
O’Connell and Adams specialize in the complex ways that Alzheimer’s effects how people speak. Using AI, their mathematical model analyzes 15 million data points every minute, focusing on certain features of speech such as pitch, pauses and elongation of words. It also pays attention to how the vibrations of vocal cords change in different stages of the disease.
To create their model, the team used a type of machine learning called deep neural nets, which looks at multiple layers of data - in this case, the multiple features of a person’s speech patterns.
“Deep neural nets allow us to look at much, much larger data sets built out of millions of elements,” O’Connell explained. “Through machine learning and AI, we’ve identified features that are very sensitive to an Alzheimer’s patient versus [people without the disease] and also very sensitive to mild cognitive impairment, early stage and moderate Alzheimer's.” Based on their learnings, Canary is able to classify the disease stage very quickly, O’Connell said.
“When we’re listening to sublanguage elements, we’re really analyzing the direct result of changes in the brain in the physical body,” O’Connell said. “The brain controls your vocal cords: how fast they vibrate, the expansion of them, the contraction.” These factors, along with where people put their tongues when talking, function subconsciously and result in subtle changes in the sounds of speech.
Further testing is needed
In an initial trial, Canary analyzed speech recordings from phone calls to a large U.S. health insurer. They looked at the audio recordings of 651 policyholders who had early stage Alzheimer’s and 1018 who did not have the condition, aiming for a representative sample of age, gender and race. They used this data to create their first diagnostic model and found that it was 96 percent accurate in identifying Alzheimer’s.
Christian Herff, an assistant professor of neuroscience at Maastricht University in the Netherlands, praised this approach while adding that further testing is needed to assess its effectiveness.
“I think the general idea of identifying increased risk for cognitive impairment based on speech characteristics is very feasible, particularly when change in a user’s voice is monitored, for example, by recording speech every year,” Herff said. He noted that this can only be a first indication, not a full diagnosis. The accuracy still needs to be validated in studies that follows individuals over a period of time, he said.
Toby Walsh, a professor of artificial intelligence at the University of New South Wales, also thinks Canary’s tool has potential but highlights that Canary could diagnose some people who don’t really have the disease. “This is an interesting and promising application of AI,” he said, “but these tools need to be used carefully. Imagine the anxiety of being misdiagnosed with Alzheimer’s.”
As with many other AI tools, privacy and bias are additional issues to monitor closely, Walsh said.
Other languages
A related issue is that not everyone is fluent in English. Mahnaz Arvaneh, a senior lecturer in automatic control and systems engineering at the University of Sheffield, said this could be a blind spot.
“The system may not be very accurate for those who have English as their second language as their speaking patterns would be different, and any issue might be because of language deficiency rather than cognitive issues,” Arvaneh said.
The team is expanding to multiple languages starting with Japanese and Spanish. The elements of the model that make up the algorithm are very similar, but they need to be validated and retrained in a different language, which will require access to more data.
Recently, Canary analyzed the phone calls of 233 Japanese patients who had mild cognitive impairment and 704 healthy people. Using an English model they were able to identify the Japanese patients who had mild cognitive impairment with 78 percent accuracy. They also developed a model in Japanese that was 45 percent accurate, and they’re continuing to train it with more data.
The future
Canary is using their model to look at other diseases like Huntington’s and Parkinson’s. They’re also collaborating with pharmaceuticals to validate potential therapies for Alzheimer’s. By looking at speech patterns over time, Canary can get an indication of how well these drugs are working.
Dave Arnold and his wife dance at his nephew’s wedding in Rochester, New York, ten years ago, before his Alzheimer's diagnosis.
Dave Arnold
Ultimately, they want to integrate their tool into everyday life. “We want it to be used in a smartphone, or a teleconference call so that individuals could be examined in their home,” O’Connell said. “We could follow them over time and work with clinical teams and hospitals to improve the evaluation of patients and contribute towards an accurate diagnosis.”
Arnold, the patient with early stage Alzheimer’s, sees great promise. “The process of getting a diagnosis is already filled with so much anxiety,” he said. “Anything that can be done to make it easier and less stressful would be a good thing, as long as it’s proven accurate.”