The First Cloned Monkeys Provoked More Shrugs Than Shocks
A few months ago, it was announced that not one, but two healthy long-tailed macaque monkeys were cloned—a first for primates of any kind. The cells were sourced from aborted monkey fetuses and the DNA transferred into eggs whose nuclei had been removed, the same method that was used in 1996 to clone "Dolly the Sheep." Two live births, females named Zhong Zhong and Hua Hua, resulted from 60 surrogate mothers. Inefficient, it's true. But over time, the methods are likely to be improved.
The scientist who supervised the project predicts that cloning, along with gene editing, will result in "ideal primate models" for studying disease mechanisms and drug screening.
Dr. Gerald Schatten, a famous would-be monkey cloner, authored a controversial paper in 2003 describing the formidable challenges to cloning monkeys and humans, speculating that the feat might never be accomplished. Now, some 15 years later, that prediction, insofar as it relates to monkeys, has blown away.
Zhong Zhong and Hua Hua were created at the Chinese Academy of Science's Institute of Neuroscience in Shanghai. The Institute founded in 1999 boasts 32 laboratories, expanding to 50 labs in 2020. It maintains two non-human primate research facilities.
The founder and director, Dr. Mu-ming Poo, supervised the project. Poo is an extremely accomplished senior researcher at the pinnacle of his field, a distinguished professor emeritus in Biology at UC Berkeley. In 2016, he was awarded the prestigious $500,000 Gruber Neuroscience Prize. At that time, Poo's experiments were described by a colleague as being "innovative and very often ingenious."
Poo maintains the reputation of studying some of the most important questions in cellular neuroscience.
But is society ready to accept cloned primates for medical research without the attendant hysteria about fears of cloned humans?
By Western standards, use of non-human primates in research focuses on the welfare of the animal subjects. As PETA reminds us, there is a dreadful and sad history of mistreatment. Dr. Poo assures us that his cloned monkeys are treated ethically and that the Institute is compliant with the highest regulatory standards, as promulgated by the U.S. National Institutes of Health.
He presents the noblest justifications for the research. He predicts that cloning, along with gene editing, will result in "ideal primate models" for studying disease mechanisms and drug screening. He declares that this will eventually help to solve Parkinson's, Huntington's and Alzheimer's disease.
But is society ready to accept cloned primates for medical research without the attendant hysteria about fears of cloned humans? It appears so.
While much of the news coverage expressed this predictable worry, my overall impression is that the societal response was muted. Where was the expected outrage? Then again, we've come a long way since Dolly the Sheep in terms of both the science and the cultural acceptance of cloning. Perhaps my unique vantage point can provide perspective on how much attitudes have evolved.
Perhaps my unique vantage point can provide perspective on how much attitudes have evolved.
I sometimes joke that I am the world's only human cloning lawyer—a great gig but there are still no clients.
I first crashed into the cloning scene in 2002 when I sued the so-called human cloning company "Clonaid" and asked in court to have a temporary guardian appointed for the alleged first human clone "Baby Eve." The claim needed to be tested, and mine was the first case ever aiming to protect the rights of a human clone. My legal basis was child welfare law, protecting minors from abuse, negligence, and exploitation.
The case had me on back-to-back global television broadcasts around the world; there was live news and "breathless" coverage at the courthouse emblazoned in headlines in every language on the planet. Cloning was, after all, perceived as a species-altering event: asexual reproduction. The controversy dominated world headlines for month until Clonaid's claim was busted as the "fakest" of fake news.
Fresh off the cloning case, the scientific community reached out to me, seeing me as the defender of legitimate science, an opponent of cloning human babies but a proponent of using cloning techniques to accelerate ethical regenerative medicine and embryonic stem cell research in general.
The years 2003 to 2006 were the era of the "stem cell wars" and a dominant issue was human cloning. Social conservative lawmakers around the world were seeking bans or criminalization not only of cloning babies but also the cloning of cells to match the donor's genetics. Scientists were being threatened with fines and imprisonment. Human cloning was being challenged in the United Nations with the United States backing a global treaty to ban and morally condemn all cloning -- including the technique that was crucial for research.
Scientists and patients were touting the cloning technique as a major biomedical breakthrough because cells could be created as direct genetic matches from a specific donor.
At the same time, scientists and patients were touting the cloning technique as a major biomedical breakthrough because cells could be created as direct genetic matches from a specific donor.
So my organization organized a conference at UN headquarters to defend research cloning and all the big names in stem cell research were there. We organized petitions to the UN and faxed 35,000 signatures to the country mission. These ongoing public policy battles were exacerbated in part because of the growing fear that cloning babies was just around the corner.
Then in 2005, the first cloned dog stunned the world, an Afghan hound named Snuppy. I met him when I visited the laboratories of Professor Woo Suk Hwang in Korea. His minders let me hold his leash -- TIME magazine's scientific breakthrough of the year. He didn't lick me or even wag his tail; I figured he must not like lawyers.
Tragically, soon thereafter, I witnessed firsthand Dr. Hwang's fall from grace when his human stem cell cloning breakthroughs proved false. The massive scientific misconduct rocked the nation of Korea, stem cell science in general, and provoked terrible news coverage.
Nevertheless, by 2007, the proposed bans lost steam, overridden by the advent of a Japanese researcher's Nobel Prize winning formula for reprogramming human cells to create genetically matched cell lines, not requiring the destruction of human embryos.
After years of panic, none of the recent cloning headlines has caused much of a stir.
Five years later, when two American scientists accomplished therapeutic human cloned stem cell lines, their news was accepted without hysteria. Perhaps enough time had passed since Hwang and the drama was drained.
In the just past 30 days we have seen more cloning headlines. Another cultural icon, Barbara Streisand, revealed she owns two cloned Coton de Tulear puppies. The other weekend, the television news show "60 Minutes" devoted close to an hour on the cloned ponies used at the top level of professional polo. And in India, scientists just cloned the first Assamese buffalo.
And you know what? After years of panic, none of this has caused much of a stir. It's as if the future described by Alvin Toffler in "Future Shock" has arrived and we are just living with it. A couple of cloned monkeys barely move the needle.
Perhaps it is the advent of the Internet and the overall dilution of wonder and outrage. Or maybe the muted response is rooted in popular culture. From Orphan Black to the plotlines of dozens of shows and books, cloning is just old news. The hand-wringing discussions about "human dignity" and "slippery slopes" have taken a backseat to the AI apocalypse and Martian missions.
We humans are enduring plagues of dementia and Alzheimer's, and we will need more monkeys. I will take mine cloned, if it will speed progress.
Personally, I still believe that cloned children should not be an option. Child welfare laws might be the best deterrent.
The same does not hold for cloning monkey research subjects. Squeamishness aside, I think Zhong Zhong and Hua Hua will soon be joined by a legion of cloned macaques and probably marmosets.
We humans are enduring plagues of dementia and Alzheimer's, and we will need more monkeys. I will take mine cloned, if it will speed the mending of these consciousness-destroying afflictions.
Scientific revolutions once took centuries, then decades, and now seem to bombard us daily. The convergence of technologies has accelerated the future. To Zhong Zhong and Hua Hua, my best wishes with the hope that their sacrifices will contribute to the health of all primates -- not just humans.
DNA- and RNA-based electronic implants may revolutionize healthcare
Implantable electronic devices can significantly improve patients’ quality of life. A pacemaker can encourage the heart to beat more regularly. A neural implant, usually placed at the back of the skull, can help brain function and encourage higher neural activity. Current research on neural implants finds them helpful to patients with Parkinson’s disease, vision loss, hearing loss, and other nerve damage problems. Several of these implants, such as Elon Musk’s Neuralink, have already been approved by the FDA for human use.
Yet, pacemakers, neural implants, and other such electronic devices are not without problems. They require constant electricity, limited through batteries that need replacements. They also cause scarring. “The problem with doing this with electronics is that scar tissue forms,” explains Kate Adamala, an assistant professor of cell biology at the University of Minnesota Twin Cities. “Anytime you have something hard interacting with something soft [like muscle, skin, or tissue], the soft thing will scar. That's why there are no long-term neural implants right now.” To overcome these challenges, scientists are turning to biocomputing processes that use organic materials like DNA and RNA. Other promised benefits include “diagnostics and possibly therapeutic action, operating as nanorobots in living organisms,” writes Evgeny Katz, a professor of bioelectronics at Clarkson University, in his book DNA- And RNA-Based Computing Systems.
While a computer gives these inputs in binary code or "bits," such as a 0 or 1, biocomputing uses DNA strands as inputs, whether double or single-stranded, and often uses fluorescent RNA as an output.
Adamala’s research focuses on developing such biocomputing systems using DNA, RNA, proteins, and lipids. Using these molecules in the biocomputing systems allows the latter to be biocompatible with the human body, resulting in a natural healing process. In a recent Nature Communications study, Adamala and her team created a new biocomputing platform called TRUMPET (Transcriptional RNA Universal Multi-Purpose GatE PlaTform) which acts like a DNA-powered computer chip. “These biological systems can heal if you design them correctly,” adds Adamala. “So you can imagine a computer that will eventually heal itself.”
The basics of biocomputing
Biocomputing and regular computing have many similarities. Like regular computing, biocomputing works by running information through a series of gates, usually logic gates. A logic gate works as a fork in the road for an electronic circuit. The input will travel one way or another, giving two different outputs. An example logic gate is the AND gate, which has two inputs (A and B) and two different results. If both A and B are 1, the AND gate output will be 1. If only A is 1 and B is 0, the output will be 0 and vice versa. If both A and B are 0, the result will be 0. While a computer gives these inputs in binary code or "bits," such as a 0 or 1, biocomputing uses DNA strands as inputs, whether double or single-stranded, and often uses fluorescent RNA as an output. In this case, the DNA enters the logic gate as a single or double strand.
If the DNA is double-stranded, the system “digests” the DNA or destroys it, which results in non-fluorescence or “0” output. Conversely, if the DNA is single-stranded, it won’t be digested and instead will be copied by several enzymes in the biocomputing system, resulting in fluorescent RNA or a “1” output. And the output for this type of binary system can be expanded beyond fluorescence or not. For example, a “1” output might be the production of the enzyme insulin, while a “0” may be that no insulin is produced. “This kind of synergy between biology and computation is the essence of biocomputing,” says Stephanie Forrest, a professor and the director of the Biodesign Center for Biocomputing, Security and Society at Arizona State University.
Biocomputing circles are made of DNA, RNA, proteins and even bacteria.
Evgeny Katz
The TRUMPET’s promise
Depending on whether the biocomputing system is placed directly inside a cell within the human body, or run in a test-tube, different environmental factors play a role. When an output is produced inside a cell, the cell's natural processes can amplify this output (for example, a specific protein or DNA strand), creating a solid signal. However, these cells can also be very leaky. “You want the cells to do the thing you ask them to do before they finish whatever their businesses, which is to grow, replicate, metabolize,” Adamala explains. “However, often the gate may be triggered without the right inputs, creating a false positive signal. So that's why natural logic gates are often leaky." While biocomputing outside a cell in a test tube can allow for tighter control over the logic gates, the outputs or signals cannot be amplified by a cell and are less potent.
TRUMPET, which is smaller than a cell, taps into both cellular and non-cellular biocomputing benefits. “At its core, it is a nonliving logic gate system,” Adamala states, “It's a DNA-based logic gate system. But because we use enzymes, and the readout is enzymatic [where an enzyme replicates the fluorescent RNA], we end up with signal amplification." This readout means that the output from the TRUMPET system, a fluorescent RNA strand, can be replicated by nearby enzymes in the platform, making the light signal stronger. "So it combines the best of both worlds,” Adamala adds.
These organic-based systems could detect cancer cells or low insulin levels inside a patient’s body.
The TRUMPET biocomputing process is relatively straightforward. “If the DNA [input] shows up as single-stranded, it will not be digested [by the logic gate], and you get this nice fluorescent output as the RNA is made from the single-stranded DNA, and that's a 1,” Adamala explains. "And if the DNA input is double-stranded, it gets digested by the enzymes in the logic gate, and there is no RNA created from the DNA, so there is no fluorescence, and the output is 0." On the story's leading image above, if the tube is "lit" with a purple color, that is a binary 1 signal for computing. If it's "off" it is a 0.
While still in research, TRUMPET and other biocomputing systems promise significant benefits to personalized healthcare and medicine. These organic-based systems could detect cancer cells or low insulin levels inside a patient’s body. The study’s lead author and graduate student Judee Sharon is already beginning to research TRUMPET's ability for earlier cancer diagnoses. Because the inputs for TRUMPET are single or double-stranded DNA, any mutated or cancerous DNA could theoretically be detected from the platform through the biocomputing process. Theoretically, devices like TRUMPET could be used to detect cancer and other diseases earlier.
Adamala sees TRUMPET not only as a detection system but also as a potential cancer drug delivery system. “Ideally, you would like the drug only to turn on when it senses the presence of a cancer cell. And that's how we use the logic gates, which work in response to inputs like cancerous DNA. Then the output can be the production of a small molecule or the release of a small molecule that can then go and kill what needs killing, in this case, a cancer cell. So we would like to develop applications that use this technology to control the logic gate response of a drug’s delivery to a cell.”
Although platforms like TRUMPET are making progress, a lot more work must be done before they can be used commercially. “The process of translating mechanisms and architecture from biology to computing and vice versa is still an art rather than a science,” says Forrest. “It requires deep computer science and biology knowledge,” she adds. “Some people have compared interdisciplinary science to fusion restaurants—not all combinations are successful, but when they are, the results are remarkable.”
In today’s podcast episode, Leaps.org Deputy Editor Lina Zeldovich speaks about the health and ecological benefits of farming crickets for human consumption with Bicky Nguyen, who joins Lina from Vietnam. Bicky and her business partner Nam Dang operate an insect farm named CricketOne. Motivated by the idea of sustainable and healthy protein production, they started their unconventional endeavor a few years ago, despite numerous naysayers who didn’t believe that humans would ever consider munching on bugs.
Yet, making creepy crawlers part of our diet offers many health and planetary advantages. Food production needs to match the rise in global population, estimated to reach 10 billion by 2050. One challenge is that some of our current practices are inefficient, polluting and wasteful. According to nonprofit EarthSave.org, it takes 2,500 gallons of water, 12 pounds of grain, 35 pounds of topsoil and the energy equivalent of one gallon of gasoline to produce one pound of feedlot beef, although exact statistics vary between sources.
Meanwhile, insects are easy to grow, high on protein and low on fat. When roasted with salt, they make crunchy snacks. When chopped up, they transform into delicious pâtes, says Bicky, who invents her own cricket recipes and serves them at industry and public events. Maybe that’s why some research predicts that edible insects market may grow to almost $10 billion by 2030. Tune in for a delectable chat on this alternative and sustainable protein.
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Further reading:
More info on Bicky Nguyen
https://yseali.fulbright.edu.vn/en/faculty/bicky-n...
The environmental footprint of beef production
https://www.earthsave.org/environment.htm
https://www.watercalculator.org/news/articles/beef-king-big-water-footprints/
https://www.frontiersin.org/articles/10.3389/fsufs.2019.00005/full
https://ourworldindata.org/carbon-footprint-food-methane
Insect farming as a source of sustainable protein
https://www.insectgourmet.com/insect-farming-growing-bugs-for-protein/
https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/insect-farming
Cricket flour is taking the world by storm
https://www.cricketflours.com/
https://talk-commerce.com/blog/what-brands-use-cricket-flour-and-why/
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.