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.
Catching colds may help protect kids from Covid
A new study shows that the immune system's response to colds can help prepare it to defend against COVID-19 - but only in the very young.
A common cold virus causes the immune system to produce T cells that also provide protection against SARS-CoV-2, according to new research. The study, published last month in PNAS, shows that this effect is most pronounced in young children. The finding may help explain why most young people who have been exposed to the cold-causing coronavirus have not developed serious cases of COVID-19.
One curiosity stood out in the early days of the COVID-19 pandemic – why were so few kids getting sick. Generally young children and the elderly are the most vulnerable to disease outbreaks, particularly viral infections, either because their immune systems are not fully developed or they are starting to fail.
But solid information on the new infection was so scarce that many public health officials acted on the precautionary principle, assumed a worst-case scenario, and applied the broadest, most restrictive policies to all people to try to contain the coronavirus SARS-CoV-2.
One early thought was that lockdowns worked and kids (ages 6 months to 17 years) simply were not being exposed to the virus. So it was a shock when data started to come in showing that well over half of them carried antibodies to the virus, indicating exposure without getting sick. That trend grew over time and the latest tracking data from the CDC shows that 96.3 percent of kids in the U.S. now carry those antibodies.
Antibodies are relatively quick and easy to measure, but some scientists are exploring whether the reactions of T cells could serve as a more useful measure of immune protection.
But that couldn't be the whole story because antibody protection fades, sometimes as early as a month after exposure and usually within a year. Additionally, SARS-CoV-2 has been spewing out waves of different variants that were more resistant to antibodies generated by their predecessors. The resistance was so significant that over time the FDA withdrew its emergency use authorization for a handful of monoclonal antibodies with earlier approval to treat the infection because they no longer worked.
Antibodies got most of the attention early on because they are part of the first line response of the immune system. Antibodies can bind to viruses and neutralize them, preventing infection. They are relatively quick and easy to measure and even manufacture, but as SARS-CoV-2 showed us, often viruses can quickly evolve to become more resistant to them. Some scientists are exploring whether the reactions of T cells could serve as a more useful measure of immune protection.
Kids, colds and T cells
T cells are part of the immune system that deals with cells once they have become infected. But working with T cells is much more difficult, takes longer, and is more expensive than working with antibodies. So studies often lags behind on this part of the immune system.
A group of researchers led by Annika Karlsson at the Karolinska Institute in Sweden focuses on T cells targeting virus-infected cells and, unsurprisingly, saw that they can play a role in SARS-CoV-2 infection. Other labs have shown that vaccination and natural exposure to the virus generates different patterns of T cell responses.
The Swedes also looked at another member of the coronavirus family, OC43, which circulates widely and is one of several causes of the common cold. The molecular structure of OC43 is similar to its more deadly cousin SARS-CoV-2. Sometimes a T cell response to one virus can produce a cross-reactive response to a similar protein structure in another virus, meaning that T cells will identify and respond to the two viruses in much the same way. Karlsson looked to see if T cells for OC43 from a wide age range of patients were cross-reactive to SARS-CoV-2.
And that is what they found, as reported in the PNAS study last month; there was cross-reactive activity, but it depended on a person’s age. A subset of a certain type of T cells, called mCD4+,, that recognized various protein parts of the cold-causing virus, OC43, expressed on the surface of an infected cell – also recognized those same protein parts from SARS-CoV-2. The T cell response was lower than that generated by natural exposure to SARS-CoV-2, but it was functional and thus could help limit the severity of COVID-19.
“One of the most politicized aspects of our pandemic response was not accepting that children are so much less at risk for severe disease with COVID-19,” because usually young children are among the most vulnerable to pathogens, says Monica Gandhi, professor of medicine at the University of California San Francisco.
“The cross-reactivity peaked at age six when more than half the people tested have a cross-reactive immune response,” says Karlsson, though their sample is too small to say if this finding applies more broadly across the population. The vast majority of children as young as two years had OC43-specific mCD4+ T cell responses. In adulthood, the functionality of both the OC43-specific and the cross-reactive T cells wane significantly, especially with advanced age.
“Considering that the mortality rate in children is the lowest from ages five to nine, and higher in younger children, our results imply that cross-reactive mCD4+ T cells may have a role in the control of SARS-CoV-2 infection in children,” the authors wrote in their paper.
“One of the most politicized aspects of our pandemic response was not accepting that children are so much less at risk for severe disease with COVID-19,” because usually young children are among the most vulnerable to pathogens, says Monica Gandhi, professor of medicine at the University of California San Francisco and author of the book, Endemic: A Post-Pandemic Playbook, to be released by the Mayo Clinic Press this summer. The immune response of kids to SARS-CoV-2 stood our expectations on their head. “We just haven't seen this before, so knowing the mechanism of protection is really important.”
Why the T cell immune response can fade with age is largely unknown. With some viruses such as measles, a single vaccination or infection generates life-long protection. But respiratory tract infections, like SARS-CoV-2, cause a localized infection - specific to certain organs - and that response tends to be shorter lived than systemic infections that affect the entire body. Karlsson suspects the elderly might be exposed to these localized types of viruses less often. Also, frequent continued exposure to a virus that results in reactivation of the memory T cell pool might eventually result in “a kind of immunosenescence or immune exhaustion that is associated with aging,” Karlsson says. https://leaps.org/scientists-just-started-testing-a-new-class-of-drugs-to-slow-and-even-reverse-aging/particle-3 This fading protection is why older people need to be repeatedly vaccinated against SARS-CoV-2.
Policy implications
Following the numbers on COVID-19 infections and severity over the last three years have shown us that healthy young people without risk factors are not likely to develop serious disease. This latest study points to a mechanism that helps explain why. But the inertia of existing policies remains. How should we adjust policy recommendations based on what we know today?
The World Health Organization (WHO) updated their COVID-19 vaccination guidance on March 28. It calls for a focus on vaccinating and boosting those at risk for developing serious disease. The guidance basically shrugged its shoulders when it came to healthy children and young adults receiving vaccinations and boosters against COVID-19. It said the priority should be to administer the “traditional essential vaccines for children,” such as those that protect against measles, rubella, and mumps.
“As an immunologist and a mother, I think that catching a cold or two when you are a kid and otherwise healthy is not that bad for you. Children have a much lower risk of becoming severely ill with SARS-CoV-2,” says Karlsson. She has followed public health guidance in Sweden, which means that her young children have not been vaccinated, but being older, she has received the vaccine and boosters. Gandhi and her children have been vaccinated, but they do not plan on additional boosters.
The WHO got it right in “concentrating on what matters,” which is getting traditional childhood immunizations back on track after their dramatic decline over the last three years, says Gandhi. Nor is there a need for masking in schools, according to a study from the Catalonia region of Spain. It found “no difference in masking and spread in schools,” particularly since tracking data indicate that nearly all young people have been exposed to SARS-CoV-2.
Both researchers lament that public discussion has overemphasized the quickly fading antibody part of the immune response to SARS-CoV-2 compared with the more durable T cell component. They say developing an efficient measure of T cell response for doctors to use in the clinic would help to monitor immunity in people at risk for severe cases of COVID-19 compared with the current method of toting up potential risk factors.
In this week's Friday Five: The eyes are the windows to the soul - and biological aging?
Plus, what bean genes mean for health and the planet, a breathing practice that could lower levels of tau proteins in the brain, AI beats humans at assessing heart health, and the benefits of "nature prescriptions"
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on new scientific theories and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the stories covered this week:
- The eyes are the windows to the soul - and biological aging?
- What bean genes mean for health and the planet
- This breathing practice could lower levels of tau proteins
- AI beats humans at assessing heart health
- Should you get a nature prescription?