How Genetic Engineering Could Save the Coral Reefs
Underwater world with corals and tropical fish.
Coral reefs are usually relegated to bit player status in television and movies, providing splashes of background color for "Shark Week," "Finding Nemo," and other marine-based entertainment.
In real life, the reefs are an absolutely crucial component of the ecosystem for both oceans and land, rivaling only the rain forests in their biological complexity. They provide shelter and sustenance for up to a quarter of all marine life, oxygenate the water, help protect coastlines from erosion, and support thousands of tourism jobs and businesses.
Genetic engineering could help scientists rebuild the reefs that have been lost, and turn those still alive into a souped-up version that can withstand warmer and even more acidic waters.
But the warming of the world's oceans -- exacerbated by an El Nino event that occurred between 2014 and 2016 -- has been putting the world's reefs under tremendous pressure. Their vibrant colors are being replaced by sepulchral whites and tans.
That's the result of bleaching -- a phenomenon that occurs when the warming waters impact the efficiency of the algae that live within the corals in a symbiotic relationship, providing nourishment via photosynthesis and eliminating waste products. The corals will often "shuffle" their resident algae, reacting in much the same way a landlord does with a non-performing tenant -- evicting them in the hopes of finding a better resident. But when better-performing algae does not appear, the corals become malnourished, eventually becoming deprived of their color and then their lives.
The situation is dire: Two-thirds of Australia's Great Barrier Reef have undergone a bleaching event in recent years, and it's believed up to half of that reef has died.
Moreover, hard corals are the ocean's redwood trees. They take centuries to grow, meaning it could take centuries or more to replace them.
Recent developments in genetic engineering -- and an accidental discovery by researchers at a Florida aquarium -- provide opportunities for scientists to potentially rebuild a large proportion of the reefs that have been lost, and perhaps turn those still alive into a souped-up version that can withstand warmer and even more acidic waters. But many questions have yet to be answered about both the biological impact on the world's oceans, and the ethics of reengineering the linchpin of its ecosystem.
How did we get here?
Coral bleaching was a regular event in the oceans even before they began to warm. As a result, natural selection weeds out the weaker species, says Rachel Levin, an American-born scientist who has performed much of her graduate work in Australia. But the current water warming trend is happening at a much higher rate than it ever has in nature, and neither the coral nor the algae can keep up.
"There is a big concern about giving one variant a huge fitness advantage, have it take over and impact the natural variation that is critical in changing environments."
In a widely-read paper published last year in the journal Frontiers in Microbiology, Levin and her colleagues put forth a fairly radical notion for preserving the coral reefs: Genetically modify their resident algae.
Levin says the focus on algae is a pragmatic decision. Unlike coral, they reproduce extremely rapidly. In theory, a modified version could quickly inhabit and stabilize a reef. About 70 percent of algae -- all part of the genus symbiodinium -- are host generalists. That means they will insert themselves into any species of coral.
In recent years, work on mapping the genomes of both algae and coral has been progressing rapidly. Scientists at Stanford University have recently been manipulating coral genomes using larvae manipulated with the CRISPR/Cas9 technology, although the experimentation has mostly been limited to its fluorescence.
Genetically modifying the coral reefs could seem like a straightforward proposition, but complications are on the horizon. Levin notes that as many as 20 different species of algae can reside within a single coral, so selecting the best ones to tweak may pose a challenge.
"The entire genus is made up of thousands of subspecies, all very genetically distinct variants. There is a huge genetic diversity, and there is a big concern about giving one variant a huge fitness advantage, have it take over and impact the natural variation that is critical in changing environments," Levin says.
Genetic modifications to an algae's thermal tolerance also poses the risk of what Levin calls an "off-target effect." That means a change to one part of the genome could lead to changes in other genes, such as those regulating growth, reproduction, or other elements crucial to its relationship with coral.
Phillip Cleves, a postdoctoral researcher at Stanford who has participated in the CRISPR/Cas9 work, says that future research will focus on studying the genes in coral that regulate the relationship with the algae. But he is so concerned about the ethical issues of genetically manipulating coral to adapt to a changing climate that he declined to discuss it in detail. And most coral species have not yet had their genomes fully mapped, he notes, suggesting that such work could still take years.
An Alternative: Coral Micro-fragmentation
In the meantime, there is another technique for coral preservation led by David Vaughan, senior scientist and program manager at the Mote Marine Laboratory and Aquarium in Sarasota, Florida.
Vaughan's research team has been experimenting in the past decade with hard coral regeneration. Their work had been slow and painstaking, since growing larvae into a coral the size of a quarter takes three years.
The micro-fragmenting process in some ways raises fewer ethical questions than genetically altering the species.
But then, one day in 2006, Vaughan accidentally broke off a tiny piece of coral in the research aquarium. That fragment grew to the size of a quarter in three months, apparently the result of the coral's ability to rapidly regenerate when injured. Further research found that breaking coral in this manner -- even to the size of a single polyp -- led to rapid growth in more than two-dozen species.
Mote is using this process, known as micro-fragmentation, to grow large numbers of coral rapidly, often fusing them on top of larger pieces of dead coral. These coral heads are then planted in the Florida Keys, which has experienced bleaching events over 12 of the last 14 years. The process has sped up almost exponentially; Mote has planted some 36,000 pieces of coral to date, but Vaughan says it's on track to plant 35,000 more pieces this year alone. That sum represents between 20 to 30 acres of restored reef. Mote is on track to plant another 100,000 pieces next year.
This rapid reproduction technique in some ways allows Mote scientists to control for the swift changes in ocean temperature, acidification and other factors. For example, using surviving pieces of coral from areas that have undergone bleaching events means these hardier strains will propagate much faster than nature allows.
Vaughan recently visited the Yucatan Peninsula to work with Mexican researchers who are going to embark on a micro-fragmenting initiative of their own.
The micro-fragmenting process in some ways raises fewer ethical questions than genetically altering the species, although Levin notes that this could also lead to fewer varieties of corals on the ocean floor -- a potential flattening of the colorful backdrops seen in television and movies.
But Vaughan has few qualms, saying this is an ecological imperative. He suggests that micro-fragmentation could serve as a stopgap until genomic technologies further advance.
"We have to use the technology at hand," he says. "This is a lot like responding when a forest burns down. We don't ask questions. We plant trees."
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.
Listen on Apple | Listen on Spotify | Listen on Stitcher | Listen on Amazon | Listen on Google
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?