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."
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 scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five:
- Research on a "smart" bandage for wounds
- A breakthrough in fighting inflammation
- The pros and cons of a new drug for Alzheimer's
- Benefits of the Mediterranean diet - with a twist
- How to recycle a plastic that was un-recyclable
Sexually transmitted infections (STIs) are surging across the U.S. to 2.5 million cases in 2021 according to preliminary data from the CDC. A new prevention and treatment strategy now in clinical trials may provide a way to get a handle on them.
It's easy to overlook the soaring rates of gonorrhea, chlamydia, and syphilis because most of those infections have few or no symptoms and can be identified only through testing. But left untreated, they can lead to serious damage to nerves and tissue, resulting in infertility, blindness, and dementia. Infants developing in utero are particularly vulnerable.
Covid-19 played havoc with regular medical treatment and preventive care for many health problems, including STIs. After formal lockdowns ended, many people gradually became more socially engaged, with increases in sexual activity, and may have prioritized these activities over getting back in touch with their doctors.
A second blow to controlling STIs is that family planning clinics are closing left and right because of the Dobbs decision and legislation in many states that curtailed access to an abortion. Discussion has focused on abortion, but those same clinics also play a vital role in the diagnosis and treatment of STIs.
Routine public health is the neglected stepchild of medicine. It is called upon in times of crisis but as that crisis resolves, funding dries up. Labs have atrophied and personnel have been redirected to Covid, “so access to routine screening for STIs has been decimated,” says Jennifer Mahn, director of sexual and clinical health with the National Coalition of STD Directors.
A preview of what we likely are facing comes from Iowa. In 2017, the state legislature restricted funding to family health clinics in four counties, which closed their doors. A year later the statewide rate of gonorrhea skyrocketed from 83 to 153.7 cases per 100,000 people. “Iowa counties with clinic closures had a significantly larger increase,” according to a study published in JAMA. That scenario likely is playing out in countless other regions where access to sexual health care is shrinking; it will be many months before we have the data to know for sure.
A decades-old antibiotic finds a new purpose
Using drugs to protect against HIV, either as post exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP), has proven to be quite successful. Researchers wondered if the same approach might be applied to other STIs. They focused on doxycycline, or doxy for short. One of the most commonly prescribed antibiotics in the U.S., it’s a member of the tetracycline family that has been on the market since 1967. It is so safe that it’s used to treat acne.
Two small studies using doxy suggested that it could work to prevent STIs. A handful of clinical trials by different researchers and funding sources set out to generate the additional evidence needed to prove their hypothesis and change the standard of care.
Senior researcher Victor Omollo, with the Kenya Medical Research Institute, noted, “These are prevention interventions that women can control on their own without having to seek or get consent from another person,” as is the case with condom use.
The first with results is the DoxyPEP study, conducted at two sexual health clinics in San Francisco and Seattle. It drew from a mix of transgender women and men who have sex with men, who had at least one diagnosed STI over the last year. The researchers divided the participants into two groups: one with people who were already HIV-positive and engaged in care, while the other group consisted of people who were on PrEP to prevent infection with HIV. For the active part of the study, a subset of the participants received doxy, and the rest of the participants did not.
The researchers intentionally chose to do the study in a population at the highest risk of having STIs, who were very health oriented, and “who were getting screened every three months or so as part of their PrEP program or their HIV care program,” says Connie Celum, a senior researcher at the University of Washington on the study.
Each member of the active group was given a supply of doxy and asked to take two pills within 72 hours of having sex where a condom was not used. The study was supposed to run for two years but, in May, it stopped halfway through, when a safety monitoring board looked at the data and recommended that it would be unethical to continue depriving the control group of the drug’s benefits.
Celum presented these preliminary results from the DoxyPEP study in July at the International AIDS Conference in Montreal. “We saw about a 56 percent reduction in gonorrhea, about 80 percent reduction in chlamydia and syphilis, so very significant reductions, and this is on a per quarter basis,” she told a later webinar.
In Kenya, another study is following a group of cisgender women who are taking the same two-pill regimen to prevent HIV, and the data from this research should become available in 2023. Senior researcher Victor Omollo, with the Kenya Medical Research Institute, noted that “these are prevention interventions that women can control on their own without having to seek or get consent from another person,” as is the case with condom use, another effective prevention tool.
Antibiotic resistance is a potentially big concern. About 25 percent of gonorrhea strains circulating in the U.S. are resistant to the tetracycline class of drugs, including doxy; rates are higher elsewhere. But resistance often is a matter of degree and can be overcome with a larger or longer dose of the drug, or perhaps with a switch to another drug or a two-drug combination.
Research has shown that an established bacterial infection is more difficult to treat because it is part of a biofilm, which can leave only a small portion or perhaps none of the cell surface exposed to a drug. But a new infection, even one where the bacteria is resistant to a drug, might still be vulnerable to that drug if it's used before the bacterial biofilm can be established. Preliminary data suggests that may be the case with doxyPEP and drug resistant gonorrhea; some but not all new drug resistant infections might be thwarted if they’re treated early enough.
“There are some tradeoffs” to these interventions, Celum says, and people may disagree on the cost of increased resistance balanced against the benefits of treating the STIs and reducing their spread within the community.
Resistance does not seem to be an issue yet for chlamydia and syphilis even though doxy has been a recommended treatment for decades, but a remaining question is whether broader use of doxy will directly worsen antibiotic resistance in gonorrhea, or promote it in other STIs. And how will it affect the gut microbiome?
In addition, Celum notes that we need to understand whether doxy will generate mutations in other bacteria that might contribute to drug resistance for gonorrhea, chlamydia or syphilis. The studies underway aim to provide data to answer these questions.
“There are some tradeoffs” to these interventions, Celum says, and people may disagree on the cost of increased resistance balanced against the benefits of treating the STIs and reducing their spread within the community. That might affect doctors' willingness to prescribe the drug.
Turning research into action
The CDC makes policy recommendations for prevention services such as taking doxy, requiring some and leaving others optional. Celum says the CDC will be reviewing information from her trial at a meeting in December, but probably will wait until that study is published before making recommendations, likely in 2023. The San Francisco Department of Public Health issued its own guidance on October 20th and anecdotally, some doctors around the country are beginning to issue prescriptions for doxy to select patients.
About half of new STIs occur in young people ages 15 to 24, a group that is least likely to regularly see a doctor. And sexual health remains a great taboo for many people who don't want such information on their health record for prying parents, employers or neighbors to find out.
“People will go out of their way and travel extensive distances just to avoid that,” says Mahn, the National Coalition director. “People identify locations where they feel safe, where they feel welcome, where they don't feel judged,” Mahn explains, such as community and family planning clinics. They understand those issues and have fees that vary depending on a person’s ability to pay.
Given that these clinics already are understaffed and underfunded, they will be hard pressed to expand services covering the labor intensive testing and monitoring of a doxyPEP regimen. Sexual health clinics don't even have a separate line item in the federal budget for health. That is something the National Association of STI Directors is pushing for in D.C.
DoxyPEP isn't a panacea, and it isn't for everyone. “We really want to try to reach that population who is most likely going to have an STI in the next year,” says Celum, “Because that's where you are going to have the biggest impact.”