GEN BiotechnologyVol. 2, No. 2 CommentaryFree AccessTo Mars and Beyond: Engineering Life as a Moral DutyChristopher E. MasonChristopher E. Mason*Address correspondence to: Christopher Mason, Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY, 10021, USA, E-mail Address: chm2042@med.cornell.eduDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, New York, USA.Search for more papers by this authorPublished Online:18 Apr 2023https://doi.org/10.1089/genbio.2023.29094.cmaAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail The Martian may not be science fiction much longer, writes the author of The Next 500 Years.The Polaris Dawn mission from SpaceX is set to launch this summer, and it will include some crew members who will also be taking the SpaceX Starship on its first mission in the next year or two in space. This is significant, as the Starship will likely be the first spacecraft to take humans back to the moon and then to the red planet.But if we do finally set foot on Mars, how long can we survive there and what resources (beyond potatoes) would we need to live on Mars long term? To answer such questions, we need to consider how much tweaking, adaptation, and engineering of life will be required (human, microbial, plant, fungal, and otherwise). We will also need to take evolutionary lessons from all creatures, big and small, with us.Related to this goal, nestled in a small bioreactor at Cornell University, New York, under eerie blue LED lights, are some very unusual cells that are prepared for such missions. These cells are chimeras, blending the genes of two different organisms into one. The baseline DNA of the cells is human, but they also contain genes from a tardigrade—a.k.a. the “space bear” as it looks like a tiny bear under the microscope and can survive in the vacuum of space.These special human/tardigrade cells can activate genes from tardigrades, especially when exposed to radiation. In my laboratory, we are using these cells as a model to see if we can increase the tolerance of human cells to space radiation.1 So far, they show an 80% decrease in the amount of damaged DNA when exposed to X-rays. We think it is possible that we can achieve even better results with additional modifications. In the long term, we want to use these lessons to help humans survive the voyage to the moon, Mars, and beyond. To enable us not just to survive, but to thrive.Although innocuous in the form of a cell line, this study raises some significant ethical questions: Should we ever apply such tools and technologies to humans, and if so, when? Also, can we ensure safety across generations and how can we measure the impact? Such questions are the main focus my recent book, The Next 500 Years, where I map out the likely instances where genome modifications are not only possible but are a moral necessity.Ethical EditingAt first glance, the idea of modifying a human genome seems dangerous, a risky gamble that rewrites the fabric of humanity's shared genetic heritage. However, there are ways to make human genome editing safe, selective, and specific to the individual. For example, recent clinical gene-editing treatments using CRISPR show extraordinary promise as a cure for beta-thalassemia and sickle-cell anemia.2 Such approaches involve somatic gene editing, only affecting the cells of the treated individual, and would not be passed on to the next generation. This kind of editing and chimeric cell creation is already endorsed by most medical and professional groups3 and leading to a range of new treatments for cancer, organ transplants, and a growing list of Mendelian disorders, including Duchenne muscular dystrophy.A sharp ethical line is normally drawn at germline editing, wherein such genetic changes are passed onto the next generation. Despite the understandable controversy surrounding the birth of the CRIPSR babies in 2018—covered in detail in recent books such as CRISPR People by Hank Greely and Editing Humanity by Kevin Davies—there may, I believe, be cases where such editing would be morally acceptable, and possibly even required. One example could be to remove suffering for a known serious genetic disease or deleterious trait.This has even happened recently for livestock, in which CRISPR was used to make a laboratory-based version of a naturally occurring gene variant that makes short hair (making the gene-edited cows less susceptible to heat stroke). If a couple was infertile or affected by a serious genetic disease and wanted to have a healthy biological child, they could potentially do so through embryo selection and preimplantation genetic diagnosis; if both parents were homozygous for a recessive mutation, they could alter the germline with genome editing.Notwithstanding the balance of resources to enable such editing versus other social concerns (e.g., many young children are orphans and could be adopted; embryo selection is faster, cheaper, and safer today), the bigger question of reproductive liberty is still pressing. If we have a means to correct heritable genetic diseases to reverse infertility for a couple, even if it creates a modified embryo and those edits are passed onto the next generation, should we tell them they are not allowed to use this technology?An even more striking thought experiment of “positive editing” would be for astronauts traveling to Mars or other planets, as is now on the cards. Given the extremely high radiation risk, we would need to use physical and pharmacological defenses against the radiation, of course, but we should also consider genetic defenses as well. If we had a safe, effective, and comprehensive way to modify the cells in an astronaut's body to prevent DNA damage and the ravages of radiation, why should not we? If a somatic, or even germline, genome editing technology is the best chance at survival, does it then become medically necessary, and thus the most ethical path?Many might disagree and raise concerns about the accuracy of the technology for genome editing, which is nascent and still being improved. However, this is a tactical consideration, not a moral one; these questions should be distinct. Recent methods such as prime editing can enable new DNA targets to be corrected and reduce errors (as the method avoids the double-strand DNA breaks caused by CRISPR-Cas9). Moreover, as genome editing methods continue to improve, their off-target mutation rates may be indistinguishable from background mutations that occur in cells naturally.To the EpigenomeThere are other options worth considering that do not require genome editing at all, which can instead create temporary changes to gene functions. These “epigenome editing” methods change how genes are activated or repressed, without directly changing the genetic code in the cells (“epi” is Greek for “on top” of the genome). These new clinical and cellular modifying tools are analogous to turning on and off a light switch, instead of breaking open the walls and rewiring the electrical circuits.There are now at least five companies actively working on therapeutic methods for epigenome editing (Chroma Medicine, Tune Therapeutics, Navega Therapeutics, Sangamo Therapeutics, and Encoded Therapeutics). Hundreds of millions of dollars have been invested in the past few years to accelerate their work. All of these tools might one day be applied to keep astronauts safe in flight, just as well as patients on Earth.Yet, beyond the therapeutic uses, there are larger existential ethical issues that drive the likely need for such applications of genome and epigenome editing: survival and stewardship. As far as we know, humans alone possess an awareness of the possibility of any species' extinction and of the Earth's finite life span. Humans alone comprehend the extinction-level events (e.g., asteroid collisions) that have already occurred and decimated life on at least five previous occasions in the Earth's history.Thus, we are the only species that can actively assess the risks of (and prevent) extinction, not only for ourselves but for all other organisms on this planet, plus any others that we may find in the future. There is no other species in the universe, as far as we know, that can leverage the frailty of mortality into an intergenerational stability of sentience. Humans alone can project estimates of risk for loss of life into the future, across entire ecosystems, and preserve them.Of course, we have not been ideal stewards of life so far across history, but we have only had global communication systems for a few decades, and the ability to act on them (e.g., solving the hole in the ozone layer) is also relatively recent. Our moral duties have not yet expanded to this new planetary-scale capacity, but the time is now. The past year (2022) set the record for the most number of missions and objects launched into space, and more missions than ever are planned for the coming years, which can be the guide of a pan-species, pan-generational sense of duty.Extinction AwarenessThe proposed missions to other planets, as well as ideas for genetic and planetary-scale engineering, are a necessary duty for humanity and a logical consequence of our unique cognitive and technological capabilities. Life is fragile in the universe, and as far as we know, unique to our planet. If engineering life is the only means by which we can ensure life survives, then it becomes a duty of humanity to employ such methods.Most duties in life are personalized, such as a duty toward country, religion, ideology, or even family. For me, there was one duty that was permanently activated the moment it was understood: “extinction awareness”—and the duty to avoid extinction. This duty was one that could not be absolved once it was understood, like a tattoo on the brain. A person can ignore, delay, or complain they do not have the resources or the power to affect the change, but the responsibility remains nonetheless to effectively all humans, even if the challenge is vast.Some of this work is already happening with the Revive and Restore project, where the latest tools and methods in cell and genome engineering are being used to clone endangered species, nurture them back to health, and improve their immune systems to increase their odds of survival.4 The very tools of technology that once imperiled us can now be used to preserve, protect, and maintain life. These tools can even be used to “resurrect” life that already fell extinct, as with ambitious plans to bring back the woolly mammoths at Colossal Biosciences (cofounded by George Church) to help mitigate climate change. However, just as the depletion of a species from an ecosystem could have devastating effects, bringing a version back into the modern ecosystem could also have unforeseen undesirable impact. Similar to all clinical trials, field trials, and new medicines, this study will need to be done carefully slowly, with extensive oversight.Nonetheless, the duty to the universe, and to all life, is something that will always hold true for us, as well as for any subsequent species or entity (made of any matter, including some artificial intelligences) that realizes this responsibility of prevention extinction and caring for the complexity and rarity of life. This duty enables, for the first time, a tiny piece of the universe to keep the universe's creations sustained, protected, and thriving.We finally have the tools to survive on Earth without disease, to ensure sustained presence in space, and to be protected en route to Mars. These are not just tools of a biotechnological revolution—they are the tools of a moral duty to Life itself, past, present, and future.