Gene Editing of Embryos Is Both Ethical and Prudent
Human cells under a microscope
BIG QUESTION OF THE MONTH: Should we use CRISPR, the new technique that enables precise DNA editing, to change the genes of human embryos to eradicate disease--or even to enhance desirable traits? LeapsMag invited three leading experts to weigh in.
Now that researchers around the world have begun to edit the genes of human embryos with CRISPR, the ethical debate has become more timely than ever: Should this kind of research be on the table or categorically ruled out?
All of us need gene editing to be pursued, and if possible, made safe enough to use in humans. Not only to pave the way for effective procedures on adults, but more importantly, to keep open the possibility of using gene editing to protect embryos from susceptibility to major diseases and to prevent other debilitating genetic conditions from being passed on through them to future generations.
Objections to gene editing in embryos rest on three fallacious arguments:
- Gene editing is wrong because it affects future generations, the argument being that the human germline is sacred and inviolable.
- It constitutes an unknown and therefore unacceptable risk to future generations.
- The inability to obtain the consent of those future generations means we must not use gene editing.
We should be clear that there is no precautionary approach; just as justice delayed is justice denied, so therapy delayed is therapy denied.
Regarding the first point, many objections to germline interventions emphasize that such interventions are objectionable in that they affect "generations down the line". But this is true, not only of all assisted reproductive technologies, but of all reproduction of any kind.
Sexual reproduction would never have been licensed by regulators
As for the second point, every year an estimated 7.9 million children - 6% of total births worldwide - are born with a serious birth defect of genetic or partially genetic origin. Had sexual reproduction been invented by scientists rather than resulting from our evolved biology, it would never have been licensed by regulators - far too inefficient and dangerous!
If the appropriate benchmark for permissible risk of harm to future generations is sexual reproduction, other germline-changing techniques would need to demonstrate severe foreseeable dangers to fail.
Raising the third point in his statement on gene-editing in human embryos, Francis S. Collins, director of the National Institutes of Health, stated: "The strong arguments against engaging in this activity remain … These include the serious and unquantifiable safety issues, ethical issues presented by altering the germline in a way that affects the next generation without their consent."
"Serious and unquantifiable" safety issues feature in all new technologies but consent is simply irrelevant for the simple and sufficient reason that there are no relevant people in existence capable of either giving or withholding consent to these sorts of changes in their own germline.
We all have to make decisions for future people without considering their inevitably absent consent. All would-be/might-be parents make numerous decisions about issues that might affect their future children. They do this all the time without thinking about consent of the children.
George Bernard Shaw and Isadora Duncan were possibly apocryphal exceptions. She, apparently, said to him something like: "Why don't we have a child? With my looks and your brains it cannot fail," and received Shaw's more rational assessment: "Yes, but what if it has my looks and your brains?"
If there is a discernible duty here, it is surely to try to create the best possible child, a child who will be the healthiest, most intelligent and most resilient to disease reasonably possible given the parents' other priorities. This is why we educate and vaccinate our children and give them a good diet if we can. That is what it is to act for the best, all things considered. This we have moral reasons to do; but they are not necessarily overriding reasons.
"There is no morally significant line between therapy and enhancement."
There is no morally significant line that can be drawn between therapy and enhancement. As I write these words in my London apartment, I am bathed in synthetic sunshine, one of the oldest and most amazing enhancement technologies. Before its invention, our ancestors had to rest or hide in the dark. With the advent of synthetic sunshine--firelight, candlelight, lamplight and electric light--we could work and play as long as we wished.Steven Hawking initially predicted that we might have about 7.6 billion years to go before the Earth gives up on us; he recently revised his position in relation to the Earth's continuing habitability as opposed to its physical survival: "We must also continue to go into space for the future of humanity," he said recently. "I don't think we will survive another thousand years without escaping beyond our fragile planet."
We will at some point have to escape both beyond our fragile planet and our fragile nature. One way to enhance our capacity to do both these things is by improving on human nature where we can do so in ways that are "safe enough." What we all have an inescapable moral duty to do is to continue with scientific investigation of gene editing techniques to the point at which we can make a rational choice. We must certainly not stop now.
At the end of a 2015 summit where I spoke about this issue, the renowned Harvard geneticist George Church noted that gene editing "opens up the possibility of not just transplantation from pigs to humans but the whole idea that a pig organ is perfectible…Gene editing could ensure the organs are very clean, available on demand and healthy, so they could be superior to human donor organs."
"We know for sure that in the future there will be no more human beings and no more planet Earth."
We know for sure that in the future there will be no more human beings and no more planet Earth. Either we will have been wiped out by our own foolishness or by brute forces of nature, or we will have further evolved by a process more rational and much quicker than Darwinian evolution--a process I described in my book Enhancing Evolution. Even more certain is that there will be no more planet Earth. Our sun will die, and with it, all possibility of life on this planet.As I say in my recent book How to Be Good:
By the time this happens, we may hope that our better evolved successors will have developed the science and the technology needed to survive and to enable us (them) to find and colonize another planet or perhaps even to build another planet; and in the meanwhile, to cope better with the problems presented by living on this planet.
Editor's Note: Check out the viewpoints expressing condemnation and mild curiosity.
Gene Transfer Leads to Longer Life and Healthspan
In August, a study provided the first proof-of-principle that genetic material transferred from one species to another can increase both longevity and healthspan in the recipient animal.
The naked mole rat won’t win any beauty contests, but it could possibly win in the talent category. Its superpower: fighting the aging process to live several times longer than other animals its size, in a state of youthful vigor.
It’s believed that naked mole rats experience all the normal processes of wear and tear over their lifespan, but that they’re exceptionally good at repairing the damage from oxygen free radicals and the DNA errors that accumulate over time. Even though they possess genes that make them vulnerable to cancer, they rarely develop the disease, or any other age-related disease, for that matter. Naked mole rats are known to live for over 40 years without any signs of aging, whereas mice live on average about two years and are highly prone to cancer.
Now, these remarkable animals may be able to share their superpower with other species. In August, a study provided what may be the first proof-of-principle that genetic material transferred from one species can increase both longevity and healthspan in a recipient animal.
There are several theories to explain the naked mole rat’s longevity, but the one explored in the study, published in Nature, is based on the abundance of large-molecule high-molecular mass hyaluronic acid (HMM-HA).
A small molecule version of hyaluronic acid is commonly added to skin moisturizers and cosmetics that are marketed as ways to keep skin youthful, but this version, just applied to the skin, won’t have a dramatic anti-aging effect. The naked mole rat has an abundance of the much-larger molecule, HMM-HA, in the chemical-rich solution between cells throughout its body. But does the HMM-HA actually govern the extraordinary longevity and healthspan of the naked mole rat?
To answer this question, Dr. Vera Gorbunova, a professor of biology and oncology at the University of Rochester, and her team created a mouse model containing the naked mole rat gene hyaluronic acid synthase 2, or nmrHas2. It turned out that the mice receiving this gene during their early developmental stage also expressed HMM-HA.
The researchers found that the effects of the HMM-HA molecule in the mice were marked and diverse, exceeding the expectations of the study’s co-authors. High-molecular mass hyaluronic acid was more abundant in kidneys, muscles and other organs of the Has2 mice compared to control mice.
In addition, the altered mice had a much lower incidence of cancer. Seventy percent of the control mice eventually developed cancer, compared to only 57 percent of the altered mice, even after several techniques were used to induce the disease. The biggest difference occurred in the oldest mice, where the cancer incidence for the Has2 mice and the controls was 47 percent and 83 percent, respectively.
With regard to longevity, Has2 males increased their lifespan by more than 16 percent and the females added 9 percent. “Somehow the effect is much more pronounced in male mice, and we don’t have a perfect answer as to why,” says Dr. Gorbunova. Another improvement was in the healthspan of the altered mice: the number of years they spent in a state of relative youth. There’s a frailty index for mice, which includes body weight, mobility, grip strength, vision and hearing, in addition to overall conditions such as the health of the coat and body temperature. The Has2 mice scored lower in frailty than the controls by all measures. They also performed better in tests of locomotion and coordination, and in bone density.
Gorbunova’s results show that a gene artificially transferred from one species can have a beneficial effect on another species for longevity, something that had never been demonstrated before. This finding is “quite spectacular,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study.
Just as in lifespan, the effects in various organs and systems varied between the sexes, a common occurrence in longevity research, according to Austad, who authored the book Methuselah’s Zoo and specializes in the biological differences between species. “We have ten drugs that we can give to mice to make them live longer,” he says, “and all of them work better in one sex than in the other.” This suggests that more attention needs to be paid to the different effects of anti-aging strategies between the sexes, as well as gender differences in healthspan.
According to the study authors, the HMM-HA molecule delivered these benefits by reducing inflammation and senescence (cell dysfunction and death). The molecule also caused a variety of other benefits, including an upregulation of genes involved in the function of mitochondria, the powerhouses of the cells. These mechanisms are implicated in the aging process, and in human disease. In humans, virtually all noncommunicable diseases entail an acceleration of the aging process.
So, would the gene that creates HMM-HA have similar benefits for longevity in humans? “We think about these questions a lot,” Gorbunova says. “It’s been done by injections in certain patients, but it has a local effect in the treatment of organs affected by disease,” which could offer some benefits, she added.
“Mice are very short-lived and cancer-prone, and the effects are small,” says Steven Austad, a biologist at the University of Alabama at Birmingham. “But they did live longer and stay healthy longer, which is remarkable.”
As for a gene therapy to introduce the nmrHas2 gene into humans to obtain a global result, she’s skeptical because of the complexity involved. Gorbunova notes that there are potential dangers in introducing an animal gene into humans, such as immune responses or allergic reactions.
Austad is equally cautious about a gene therapy. “What this study says is that you can take something a species does well and transfer at least some of that into a new species. It opens up the way, but you may need to transfer six or eight or ten genes into a human” to get the large effect desired. Humans are much more complex and contain many more genes than mice, and all systems in a biological organism are intricately connected. One naked mole rat gene may not make a big difference when it interacts with human genes, metabolism and physiology.
Still, Austad thinks the possibilities are tantalizing. “Mice are very short-lived and cancer-prone, and the effects are small,” he says. “But they did live longer and stay healthy longer, which is remarkable.”
As for further research, says Austad, “The first place to look is the skin” to see if the nmrHas2 gene and the HMM-HA it produces can reduce the chance of cancer. Austad added that it would be straightforward to use the gene to try to prevent cancer in skin cells in a dish to see if it prevents cancer. It would not be hard to do. “We don’t know of any downsides to hyaluronic acid in skin, because it’s already used in skin products, and you could look at this fairly quickly.”
“Aging mechanisms evolved over a long time,” says Gorbunova, “so in aging there are multiple mechanisms working together that affect each other.” All of these processes could play a part and almost certainly differ from one species to the next.
“HMM-HA molecules are large, but we’re now looking for a small-molecule drug that would slow it’s breakdown,” she says. “And we’re looking for inhibitors, now being tested in mice, that would hinder the breakdown of hyaluronic acid.” Gorbunova has found a natural, plant-based product that acts as an inhibitor and could potentially be taken as a supplement. Ultimately, though, she thinks that drug development will be the safest and most effective approach to delivering HMM-HA for anti-aging.
A new study provides key insights in what causes Alzheimer's: a breakdown in the brain’s system for clearing waste.
In recent years, researchers of Alzheimer’s have made progress in figuring out the complex factors that lead to the disease. Yet, the root cause, or causes, of Alzheimer’s are still pretty much a mystery.
In fact, many people get Alzheimer’s even though they lack the gene variant we know can play a role in the disease. This is a critical knowledge gap for research to address because the vast majority of Alzheimer’s patients don’t have this variant.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman