Do New Tools Need New Ethics?
Scarcely a week goes by without the announcement of another breakthrough owing to advancing biotechnology. Recent examples include the use of gene editing tools to successfully alter human embryos or clone monkeys; new immunotherapy-based treatments offering longer lives or even potential cures for previously deadly cancers; and the creation of genetically altered mosquitos using "gene drives" to quickly introduce changes into the population in an ecosystem and alter the capacity to carry disease.
The environment for conducting science is dramatically different today than it was in the 1970s, 80s, or even the early 2000s.
Each of these examples puts pressure on current policy guidelines and approaches, some existing since the late 1970s, which were created to help guide the introduction of controversial new life sciences technologies. But do the policies that made sense decades ago continue to make sense today, or do the tools created during different eras in science demand new ethics guidelines and policies?
Advances in biotechnology aren't new of course, and in fact have been the hallmark of science since the creation of the modern U.S. National Institutes of Health in the 1940s and similar government agencies elsewhere. Funding agencies focused on health sciences research with the hope of creating breakthroughs in human health, and along the way, basic science discoveries led to the creation of new scientific tools that offered the ability to approach life, death, and disease in fundamentally new ways.
For example, take the discovery in the 1970s of the "chemical scissors" in living cells called restriction enzymes, which could be controlled and used to introduce cuts at predictable locations in a strand of DNA. This led to the creation of tools that for the first time allowed for genetic modification of any organism with DNA, which meant bacteria, plants, animals, and even humans could in theory have harmful mutations repaired, but also that changes could be made to alter or even add genetic traits, with potentially ominous implications.
The scientists involved in that early research convened a small conference to discuss not only the science, but how to responsibly control its potential uses and their implications. The meeting became known as the Asilomar Conference for the meeting center where it was held, and is often noted as the prime example of the scientific community policing itself. While the Asilomar recommendations were not sufficient from a policy standpoint, they offered a blueprint on which policies could be based and presented a model of the scientific community setting responsible controls for itself.
But the environment for conducting science changed over the succeeding decades and it is dramatically different today than it was in the 1970s, 80s, or even the early 2000s. The regime for oversight and regulation that has provided controls for the introduction of so-called "gene therapy" in humans starting in the mid-1970s is beginning to show signs of fraying. The vast majority of such research was performed in the U.S., U.K., and Europe, where policies were largely harmonized. But as the tools for manipulating humans at the molecular level advanced, they also became more reliable and more precise, as well as cheaper and easier to use—think CRISPR—and therefore more accessible to more people in many more countries, many without clear oversight or policies laying out responsible controls.
There is no precedent for global-scale science policy, though that is exactly what this moment seems to demand.
As if to make the point through news headlines, scientists in China announced in 2017 that they had attempted to perform gene editing on in vitro human embryos to repair an inherited mutation for beta thalassemia--research that would not be permitted in the U.S. and most European countries and at the time was also banned in the U.K. Similarly, specialists from a reproductive medicine clinic in the U.S. announced in 2016 that they had performed a highly controversial reproductive technology by which DNA from two women is combined (so-called "three parent babies"), in a satellite clinic they had opened in Mexico to avoid existing prohibitions on the technique passed by the U.S. Congress in 2015.
In both cases, genetic changes were introduced into human embryos that if successful would lead to the birth of a child with genetically modified germline cells—the sperm in boys or eggs in girls—with those genetic changes passed on to all future generations of related offspring. Those are just two very recent examples, and it doesn't require much imagination to predict the list of controversial possible applications of advancing biotechnologies: attempts at genetic augmentation or even cloning in humans, and alterations of the natural environment with genetically engineered mosquitoes or other insects in areas with endemic disease. In fact, as soon as this month, scientists in Africa may release genetically modified mosquitoes for the first time.
The technical barriers are falling at a dramatic pace, but policy hasn't kept up, both in terms of what controls make sense and how to address what is an increasingly global challenge. There is no precedent for global-scale science policy, though that is exactly what this moment seems to demand. Mechanisms for policy at global scale are limited–-think UN declarations, signatory countries, and sometimes international treaties, but all are slow, cumbersome and have limited track records of success.
But not all the news is bad. There are ongoing efforts at international discussion, such as an international summit on human genome editing convened in 2015 by the National Academies of Sciences and Medicine (U.S.), Royal Academy (U.K.), and Chinese Academy of Sciences (China), a follow-on international consensus committee whose report was issued in 2017, and an upcoming 2nd international summit in Hong Kong in November this year.
These efforts need to continue to focus less on common regulatory policies, which will be elusive if not impossible to create and implement, but on common ground for the principles that ought to guide country-level rules. Such principles might include those from the list proposed by the international consensus committee, including transparency, due care, responsible science adhering to professional norms, promoting wellbeing of those affected, and transnational cooperation. Work to create a set of shared norms is ongoing and worth continued effort as the relevant stakeholders attempt to navigate what can only be called a brave new world.
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.