How Genetic Engineering Could Save the Coral Reefs
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."
Bivalent Boosters for Young Children Are Elusive. The Search Is On for Ways to Improve Access.
It’s Theo’s* first time in the snow. Wide-eyed, he totters outside holding his father’s hand. Sarah Holmes feels great joy in watching her 18-month-old son experience the world, “His genuine wonder and excitement gives me so much hope.”
In the summer of 2021, two months after Theo was born, Holmes, a behavioral health provider in Nebraska lost her grandparents to COVID-19. Both were vaccinated and thought they could unmask without any risk. “My grandfather was a veteran, and really trusted the government and faith leaders saying that COVID-19 wasn’t a threat anymore,” she says.” The state of emergency in Louisiana had ended and that was the message from the people they respected. “That is what killed them.”
The current official public health messaging is that regardless of what variant is circulating, the best way to be protected is to get vaccinated. These warnings no longer mention masking, or any of the other Swiss-cheese layers of mitigation that were prevalent in the early days of this ongoing pandemic.
The problem with the prevailing, vaccine centered strategy is that if you are a parent with children under five, barriers to access are real. In many cases, meaningful tools and changes that would address these obstacles are lacking, such as offering vaccines at more locations, mandating masks at these sites, and providing paid leave time to get the shots.
Children are at risk
Data presented at the most recent FDA advisory panel on COVID-19 vaccines showed that in the last year infants under six months had the third highest rate of hospitalization. “From the beginning, the message has been that kids don’t get COVID, and then the message was, well kids get COVID, but it’s not serious,” says Elias Kass, a pediatrician in Seattle. “Then they waited so long on the initial vaccines that by the time kids could get vaccinated, the majority of them had been infected.”
A closer look at the data from the CDC also reveals that from January 2022 to January 2023 children aged 6 to 23 months were more likely to be hospitalized than all other vaccine eligible pediatric age groups.
“We sort of forced an entire generation of kids to be infected with a novel virus and just don't give a shit, like nobody cares about kids,” Kass says. In some cases, COVID has wreaked havoc with the immune systems of very young children at his practice, making them vulnerable to other illnesses, he said. “And now we have kids that have had COVID two or three times, and we don’t know what is going to happen to them.”
Jumping through hurdles
Children under five were the last group to have an emergency use authorization (EUA) granted for the COVID-19 vaccine, a year and a half after adult vaccine approval. In June 2022, 30,000 sites were initially available for children across the country. Six months later, when boosters became available, there were only 5,000.
Currently, only 3.8% of children under two have completed a primary series, according to the CDC. An even more abysmal 0.2% under two have gotten a booster.
Ariadne Labs, a health center affiliated with Harvard, is trying to understand why these gaps exist. In conjunction with Boston Children’s Hospital, they have created a vaccine equity planner that maps the locations of vaccine deserts based on factors such as social vulnerability indexes and transportation access.
“People are having to travel farther because the sites are just few and far between,” says Benjy Renton, a research assistant at Ariadne.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. When the boosters first came out she expected her toddler could get it close to home, but her husband had to drive Charlee four hours roundtrip.
This experience hasn’t been uncommon, especially in rural parts of the U.S. If parents wanted vaccines for their young children shortly after approval, they faced the prospect of loading babies and toddlers, famous for their calm demeanor, into cars for lengthy rides. The situation continues today. Mrs. Smith*, a grant writer and non-profit advisor who lives in Idaho, is still unable to get her child the bivalent booster because a two-hour one-way drive in winter weather isn’t possible.
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited.
Protect Their Future (PTF), a grassroots organization focusing on advocacy for the health care of children, hears from parents several times a week who are having trouble finding vaccines. The vaccine rollout “has been a total mess,” says Tamara Lea Spira, co-founder of PTF “It’s been very hard for people to access vaccines for children, particularly those under three.”
Seventeen states have passed laws that give pharmacists authority to vaccinate as young as six months. Under federal law, the minimum age in other states is three. Even in the states that allow vaccination of toddlers, each pharmacy chain varies. Some require prescriptions.
It takes time to make phone calls to confirm availability and book appointments online. “So it means that the parents who are getting their children vaccinated are those who are even more motivated and with the time and the resources to understand whether and how their kids can get vaccinated,” says Tiffany Green, an associate professor in population health sciences at the University of Wisconsin at Madison.
Green adds, “And then we have the contraction of vaccine availability in terms of sites…who is most likely to be affected? It's the usual suspects, children of color, disabled children, low-income children.”
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited. In Bibb County, Ala., vaccinations take place only on Wednesdays from 1:45 to 3:00 pm.
“People who are focused on putting food on the table or stressed about having enough money to pay rent aren't going to prioritize getting vaccinated that day,” says Julia Raifman, assistant professor of health law, policy and management at Boston University. She created the COVID-19 U.S. State Policy Database, which tracks state health and economic policies related to the pandemic.
Most states in the U.S. lack paid sick leave policies, and the average paid sick days with private employers is about one week. Green says, “I think COVID should have been a wake-up call that this is necessary.”
Maskless waiting rooms
For her son, Holmes spent hours making phone calls but could uncover no clear answers. No one could estimate an arrival date for the booster. “It disappoints me greatly that the process for locating COVID-19 vaccinations for young children requires so much legwork in terms of time and resources,” she says.
In January, she found a pharmacy 30 minutes away that could vaccinate Theo. With her son being too young to mask, she waited in the car with him as long as possible to avoid a busy, maskless waiting room.
Kids under two, such as Theo, are advised not to wear masks, which make it too hard for them to breathe. With masking policies a rarity these days, waiting rooms for vaccines present another barrier to access. Even in healthcare settings, current CDC guidance only requires masking during high transmission or when treating COVID positive patients directly.
“This is a group that is really left behind,” says Raifman. “They cannot wear masks themselves. They really depend on others around them wearing masks. There's not even one train car they can go on if their parents need to take public transportation… and not risk COVID transmission.”
Yet another challenge is presented for those who don’t speak English or Spanish. According to Translators without Borders, 65 million people in America speak a language other than English. Most state departments of health have a COVID-19 web page that redirects to the federal vaccines.gov in English, with an option to translate to Spanish only.
The main avenue for accessing information on vaccines relies on an internet connection, but 22 percent of rural Americans lack broadband access. “People who lack digital access, or don’t speak English…or know how to navigate or work with computers are unable to use that service and then don’t have access to the vaccines because they just don’t know how to get to them,” Jirmanus, an affiliate of the FXB Center for Health and Human Rights at Harvard and a member of The People’s CDC explains. She sees this issue frequently when working with immigrant communities in Massachusetts. “You really have to meet people where they’re at, and that means physically where they’re at.”
Equitable solutions
Grassroots and advocacy organizations like PTF have been filling a lot of the holes left by spotty federal policy. “In many ways this collective care has been as important as our gains to access the vaccine itself,” says Spira, the PTF co-founder.
PTF facilitates peer-to-peer networks of parents that offer support to each other. At least one parent in the group has crowdsourced information on locations that are providing vaccines for the very young and created a spreadsheet displaying vaccine locations. “It is incredible to me still that this vacuum of information and support exists, and it took a totally grassroots and volunteer effort of parents and physicians to try and respond to this need.” says Spira.
Kass, who is also affiliated with PTF, has been vaccinating any child who comes to his independent practice, regardless of whether they’re one of his patients or have insurance. “I think putting everything on retail pharmacies is not appropriate. By the time the kids' vaccines were released, all of our mass vaccination sites had been taken down.” A big way to help parents and pediatricians would be to allow mixing and matching. Any child who has had the full Pfizer series has had to forgo a bivalent booster.
“I think getting those first two or three doses into kids should still be a priority, and I don’t want to lose sight of all that,” states Renton, the researcher at Ariadne Labs. Through the vaccine equity planner, he has been trying to see if there are places where mobile clinics can go to improve access. Renton continues to work with local and state planners to aid in vaccine planning. “I think any way we can make that process a lot easier…will go a long way into building vaccine confidence and getting people vaccinated,” Renton says.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. Her husband had to drive four hours roundtrip to get the boosters for Charlee.
Michelle Baltes-Breitwisch
Other changes need to come from the CDC. Even though the CDC “has this historic reputation and a mission of valuing equity and promoting health,” Jirmanus says, “they’re really failing. The emphasis on personal responsibility is leaving a lot of people behind.” She believes another avenue for more equitable access is creating legislation for upgraded ventilation in indoor public spaces.
Given the gaps in state policies, federal leadership matters, Raifman says. With the FDA leaning toward a yearly COVID vaccine, an equity lens from the CDC will be even more critical. “We can have data driven approaches to using evidence based policies like mask policies, when and where they're most important,” she says. Raifman wants to see a sustainable system of vaccine delivery across the country complemented with a surge preparedness plan.
With the public health emergency ending and vaccines going to the private market sometime in 2023, it seems unlikely that vaccine access is going to improve. Now more than ever, ”We need to be able to extend to people the choice of not being infected with COVID,” Jirmanus says.
*Some names were changed for privacy reasons.
What causes aging? In a paper published last month, Dr. David Sinclair, Professor in the Department of Genetics at Harvard Medical School, reports that he and his co-authors have found the answer. Harnessing this knowledge, Dr. Sinclair was able to reverse this process, making mice younger, according to the study published in the journal Cell.
I talked with Dr. Sinclair about his new study for the latest episode of Making Sense of Science. Turning back the clock on mouse age through what’s called epigenetic reprogramming – and understanding why animals get older in the first place – are key steps toward finding therapies for healthier aging in humans. We also talked about questions that have been raised about the research.
Show links:
Dr. Sinclair's paper, published last month in Cell.
Recent pre-print paper - not yet peer reviewed - showing that mice treated with Yamanaka factors lived longer than the control group.
Dr. Sinclair's podcast.
Previous research on aging and DNA mutations.
Dr. Sinclair's book, Lifespan.
Harvard Medical School