Science
Opinion: How bringing back the woolly mammoth could save species that still walk the Earth
As more species are pushed to the brink of extinction, conservationists are responding to our biodiversity crisis in new and sometimes controversial ways. One such novel approach could be described as the mammoth in the room: “de-extinction” technology that has the potential to protect and restore species on the brink of extinction and, more provocatively, those that disappeared from the planet long ago.
We can avoid such innovation and the controversy that comes with it. But the reality is that many milestone moments in conservation have been contentious.
Take the California condor, whose population was down to 22 known individuals in 1982. At the time, taking all the animals out of the wild for a captive breeding program sparked outrage among conservation professionals and in local communities. Today, however, thanks to those efforts and subsequent reintroductions of the birds into the wild, their population exceeds 500. Now captive breeding programs are regularly used to maintain and restore a variety of threatened species.
Or consider conservationists’ difficult decision in 1995 to relocate eight female mountain lions from Texas to infuse new genes into the population of Florida panthers, a subspecies of the puma. Only about 30 Florida panthers were left at the time, and inbreeding had rendered them susceptible to disease and other health problems. Although this genetic rescue effort was highly controversial at the time, it was also very successful, decreasing the effects of inbreeding and allowing the population to steadily grow. Today about 200 adult panthers live in southwest Florida, and the intervention is regarded as a model.
The use of assisted reproductive technology such as artificial insemination and in vitro fertilization to bolster dwindling species has been a more recent subject of debate within the conservation community. But since these tools were introduced, they have become standard among zoos’ “insurance” populations of threatened species and in captive breeding programs aimed at reintroducing species into the wild.
Our organizations, the biotechnology company Colossal Biosciences and the conservation group Re:wild, recently announced a partnership to use de-extinction technology to protect and restore species on the brink of extinction. It is a powerful collaboration between an organization with extensive experience in wildlife and ecosystem conservation and a company that is using gene editing and genetic engineering technology to make extinction a thing of the past.
Both Re:wild and Colossal want to save species that are going extinct now. But at the heart of Colossal’s mission is a belief that the science to restore and recover species on the brink can be accelerated by moonshot projects such as reviving the mammoth or the dodo. This focus on de-extinction, or bringing back extinct species, is understandably a subject of vigorous debate.
So it’s no wonder that our partnership caught some in the conservation community by surprise. Even internally, it took lots of thoughtful and nuanced discussion — involving often passionate and sometimes seemingly insurmountable differences — to align around shared goals.
In the end, even though Re:wild has reservations about whether the woolly mammoth and other extinct species should be returned to Earth, the organization will advise on the feasibility of such reintroductions because of the projects’ potential to generate technology that could save hundreds of critically endangered species. We will work together to study the advantages, disadvantages and feasibility of each reintroduction, working with local interests and a cross-section of the conservation community. With the world’s sixth great extinction event upon us, we need every available tool to prevent extinctions and accelerate species restoration.
The conservation community has recovered species from the brink of extinction — some of which were down to a few individuals — but every one of those recoveries has been hard-fought. We will be able to restore critically endangered species much more quickly by combining Colossal’s technology with proven approaches such as conservation breeding programs, translocations of endangered species populations, assisted reproductive technology, biobanking of threatened species’ tissues and cells, and genetic rescue.
We are already seeing the benefits of Colossal’s technology for threatened species. The tools and techniques developed for every effort to bring a species back from extinction will also benefit closely related species that still live.
The woolly mammoth project, for instance, has sequenced the genomes of both the Asian elephant and the African elephant; has developed induced pluripotent stem cells with the ability to differentiate into other types of elephant cells; and is accelerating a cure for the deadly elephant herpes virus. Many extant marsupials will likewise benefit from the technology Colossal is developing to bring back the thylacine, an extinct carnivorous marsupial also known as the Tasmanian tiger or Tasmanian wolf. That includes the development of artificial pouches and synthetic milk, which will enable expanded conservation breeding programs and reintroduction efforts.
We’re also using or planning to use this technology to protect and restore northern white rhinos, Sumatran rhinos, pink pigeons, Tasmanian devils, northern quolls (a small carnivorous marsupial) and many other species.
Not everyone agrees that a headline-grabbing de-extinction of the woolly mammoth would be beneficial to our planet. But it’s hard to dismiss the project’s capacity to create tools and technologies that can prevent countless species from going extinct in the first place.
Our partnership is also allowing us to tap into new sources of conservation funding that would not be available without the interest that de-extinction generates. Even though it will always be cheaper and easier to save a species from extinction than to bring it back, we still need more resources to combat the biodiversity crisis.
Conservation is not easy, and the extinction crisis has no single solution. With an estimated 12% of bird species, 26% of mammals, 31% of sharks and rays, 36% of reef-building corals and 41% of amphibians at risk, we need to consider every tool we have to secure the future of our planet and all the life on it. We look forward to the day de-extinction technology is commonly used to restore endangered species and we’re considering the next conservation moonshot.
Matt James is Colossal’s chief animal officer. Barney Long is Re:wild’s senior director of conservation strategies.
Science
An industrial chemical is showing up in fentanyl in the U.S., troubling scientists
An industrial chemical used in plastic products has been cropping up in illegal drugs from California to Maine, a sudden and puzzling shift in the drug supply that has alarmed health researchers.
Its name is bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate, commonly abbreviated as BTMPS. The chemical is used in plastic for protection against ultraviolet rays, as well as for other commercial uses.
In an analysis released Monday, researchers from UCLA, the National Institute of Standards and Technology (NIST) and other academic institutions and harm reduction groups collected and tested more than 170 samples of drugs that had been sold as fentanyl in Los Angeles and Philadelphia this summer. They found roughly a quarter of the drugs contained BTMPS.
Researchers called it the most sudden change in the U.S. illegal drug supply in recent history, based on chemical prevalence. They found that BTMPS sometimes dramatically exceeded the amount of fentanyl in drug samples and, in some cases, had made up more than a third of the drug sample.
It was also a growing presence in fentanyl over the summer: In June, none of the L.A. fentanyl samples tested by the team contained BTMPS, the analysis found. By August, it was detected in 41% of them.
“This is effectively unprecedented,” said Morgan Godvin, one of the authors of the study and project director for Drug Checking Los Angeles, a UCLA project that works in partnership with the L.A. County Department of Public Health to analyze illicit drugs.
“We have no idea just how many people have been exposed,” Godvin said, but if the high prevalence among drug samples tested so far is any indication, “that translates to tens of thousands of fentanyl users being exposed to BTEMPS, sometimes at very high volume.”
The findings were publicly released as a preprint — research that has not been peer reviewed — on the website of Drug Checking Los Angeles and have been submitted to medRxiv, a website where scientists share preliminary findings.
BTMPS has been studied in rats for its potential to reduce withdrawal symptoms from morphine and affect nicotine use, but it can be toxic and even deadly to rodents at sufficient doses, and health researchers say there is an urgent need for more studies on its effects on the human body.
The PubChem database lists a number of possible hazards associated with BTMPS, including skin irritation and eye damage. Godvin was alarmed by animal studies indicating dangers from inhaling BTMPS — such as tremors and shortness of breath — because smoking is now common in L.A. among people who use fentanyl.
People who use drugs have said that BTMPS can smell like bug spray or plastic and have reported blurred vision, nausea and coughing after ingesting it. One told researchers that “it smelled so bad I could barely smoke it.” The UCLA and NIST researchers warned that “with such a sudden and sustained prevalence in the drug supply, users are at risk of repeated, ongoing exposures, which may compound health effects.”
A 35-year-old man in Los Angeles said that in recent months, he had noticed a rubbery or synthetic taste in the fentanyl he used. “I was asking my friend that I buy from, ‘What the hell is this?’” said the man, who requested anonymity to speak about his drug use.
When he took samples that were supposed to be fentanyl to Drug Checking Los Angeles to analyze, he learned that some contained the strange chemical. The 35-year-old said he now tries to avoid BTMPS, but “a lot of people are just trying to get anything to keep from being sick” from opioid withdrawal.
Whatever clandestine labs are doing, he said, “we’re the guinea pigs.”
L.A. and Philadelphia are far from the only places where the chemical has popped up: The team also detected BTMPS in trace amounts of drugs left behind on drug paraphernalia from other locations, including Delaware, Maryland and Nevada.
As of last week, a University of North Carolina program that tests drug samples from across the country had also found BTMPS in more than 200 samples from a dozen states stretching from the West Coast to Maine. UNC senior scientist Nabarun Dasgupta said the chemical began showing up in drug samples that it tested this summer, most often mingled with fentanyl, both in powder form and in fake pills.
Alex Krotulski, a director at the nonprofit Center for Forensic Science Research and Education in Pennsylvania, said the amount of BTMPS found in drug samples it has tested varies dramatically — sometimes making up a small amount, sometimes amounting to the “primary component” in the sample.
Unlike other adulterants added to fentanyl for their psychoactive effects, “it’s not like it’s something that you go out and you use a bunch of to get high,” Krotulski said. The UCLA and NIST team found that people who use drugs rated samples high in BTMPS as “bunk” — low in quality — and broadly saw it as “highly undesirable.”
Yet another oddity is that BTMPS has not followed a familiar path for new drugs in the U.S. Instead of showing up in one area and spreading to others, “this one has hit all at once across the U.S. within a two-week period,” said Tara Stamos-Buesig, founder and chief executive of the Harm Reduction Coalition of San Diego.
Stamos-Buesig, whose group helps analyze the contents of illegal drugs in San Diego to inform and protect people, said that “I’ve told people for a while — we can’t hyper-focus on fentanyl” as if it were the only threat.
“There’s a lot of other stuff coming on board,” Stamos-Buesig said.
The UCLA and NIST analysis suggested one possible scenario: Illegal drug manufacturers might be adding BTMPS to fentanyl precursors or to the final product “at a high level in the supply chain,” possibly to stabilize them from degrading from light or heat exposure as illicit drugs are made, stored and transported, they wrote.
UCLA assistant professor Chelsea Shover added that the team had found BTMPS for sale on online platforms like Amazon and Alibaba with similar wording to what Chinese chemical companies had used in the past to market to fentanyl producers, with sellers touting their “experience getting through Mexican customs.”
“This is clearly implying that this is to be used to make illicit drugs,” Shover said. “It’s stuff you wouldn’t expect to see if it was just selling an industrial chemical in a standard way.”
As it stands, there is no test strip that can quickly detect BTMPS as there is for fentanyl. Nor is the chemical routinely tested for by doctors or medical examiners, which means that if someone has been harmed by BTMPS they took accidentally, “clinicians would have no way of knowing,” the UCLA and NIST team wrote.
The UNC Street Drug Analysis Lab likewise said that much remains unknown at this point, including whether BTMPS poses an overdose risk, although the lab cautions that “EVERY substance at some volume will be toxic.”
Dasgupta said the detection of BTMPS represents the first example of the burgeoning network of drug checking programs working together to find a substance “before any health authorities or any law enforcement did.” Godvin said that “just a few years ago, we wouldn’t have even known about this” and urged Angelenos to get drugs analyzed through Drug Checking Los Angeles if they are able.
In a drug supply already riddled with threats like fentanyl and the animal tranquilizer xylazine, “this gives us a whole other thing to worry about,” Godvin said.
Science
How AI can help researchers make esophageal cancer less deadly
Approximately 600 times a day, the esophagus ferries whatever is in your mouth down to your stomach. It’s usually a one-way route, but sometimes acid escapes the stomach and travels back up. That can damage the cells lining the esophagus, prompting them to grow back with genetic mistakes.
About 22,370 times a year in the United States, those mistakes culminate in cancer.
Esophageal cancer can be cured if it’s discovered and treated before it burrows in deep or spreads to other organs. But that’s rarely the case.
“The way this usually goes is a patient has had reflux symptoms for many years, they’ve taken Tums or something, and then all of a sudden they have difficulty swallowing so they come to the ER,” said Dr. Allon Kahn, a gastroenterologist and associate professor of medicine at the Mayo Clinic in Arizona. That’s when doctors discover a tumor that has grown into the walls of the esophagus, and likely beyond.
“At that point,” Kahn said, “it’s incurable.”
This is why only about 20% of Americans with esophageal cancer are still alive five years after their diagnosis. To improve on that figure, doctors say they don’t necessarily need better medicines. What they need are better ways to find the cancer while it’s still in its earliest, highly treatable stages.
And to do that, they need a breakthrough in screening for the disease.
“The concept of screening is to find dangerous things before they do dangerous things,” said Dr. Daniel Boffa, chief of thoracic surgery at Yale.
It works for diseases like breast, lung and colon cancer. In those cases, there’s a clear progression of steps that leads to cancer — and only to cancer.
But that doesn’t seem to be the case with esophageal cancer.
“We don’t really know who to screen, how often to screen, and what is the thing that we can see that will tell us, ‘This person is going to develop a dangerous cancer,’” Boffa said.
He likened the situation to the difficulty of forecasting a tornado.
“Most tornadoes happen when conditions are favorable for a tornado,” he said. “But most of the time that conditions are favorable for a tornado, there’s not a tornado. And a lot of the time, tornadoes happen outside of those conditions.”
Another complicating factor is that cases of esophageal cancer are rare, accounting for about 1% of all cancers diagnosed in the U.S.
Picture the 100,000 college football fans packed into Michigan Stadium in Ann Arbor on a game day, said Dr. Joel Rubenstein, a research scientist based 3 miles away at the Lt. Col. Charles S. Kettles VA Medical Center and a gastroenterologist at the University of Michigan. Then picture yourself having to figure out which four of those fans will develop esophageal cancer this year.
Screening someone for esophageal cancer is not a trivial procedure.
The standard method involves inserting an endoscope — a flexible tube with a camera on one end — into a patient’s throat and threading it down to the stomach. The camera allows doctors to inspect the esophagus up close and check for abnormal cells that could become cancerous.
The tube also serves as a conduit for tools that can collect tissue samples, which can be sent to a pathology lab for diagnostic analysis. If a doctor sees a growth that looks like early-stage cancer, it can be removed on the spot.
It sounds straightforward, but patients must be sedated for the procedure, which means they lose a day of work. Endoscopy is also expensive, and there’s a shortage of doctors who can do it.
“We’re only catching 7% of cancers through endoscopy,” Kahn said. “We’ve got to find a way to increase that number.”
In the U.S., the most common form of the cancer begins at the base of the esophagus. The cells there aren’t built to withstand exposure to stomach acid, so in people with chronic acid reflux, they sometimes adapt by becoming more like intestinal tissue. That condition is called Barrett’s esophagus, and about 5% of U.S. adults have it.
“If that’s all that was, we’d say, ‘That’s great,’” Kahn said. “But unfortunately, when it makes that change in cell type, there are genetic changes that predispose a patient to cancer.”
About 0.3% of people with Barrett’s esophagus develop esophageal cancer each year, said Dr. Sachin Wani, a gastroenterologist and professor at the University of Colorado School of Medicine. And compared to people without Barrett’s, they are roughly nine times more likely to die of esophageal cancer.
That means screening for Barrett’s is tantamount to screening for esophageal cancer.
Doctors largely agree on a core group of risk factors, including chronic gastroesophageal reflux disease, smoking and carrying extra pounds in the abdomen. Other risk factors include being at least 50 years old, male, white and having a family history of either Barrett’s or esophageal cancer.
There is less agreement about how many risk factors a person must have to justify screening.
Based on recommendations from the American College of Gastroenterology, more than 31 million people are eligible for screening. Guidelines from the American Society for Gastrointestinal Endoscopy raise that figure to 52 million, and the American Gastroenterological Assn.’s advice expands it to 120 million, said Dr. Gary Falk, a gastroenterologist and professor of medicine emeritus at the University of Pennsylvania’s Perelman School of Medicine.
All of these recommendations leave room for improvement. Only 50% to 60% of people who meet screening requirements actually have Barrett’s, said Dr. Prasad Iyer, the chair of gastroenterology at the Mayo Clinic in Arizona.
“The screening criteria are not accurate enough,” he said.
Indeed, at least 90% of people who have risk factors for Barrett’s don’t actually have the condition, Iyer said. That includes the vast majority of people with acid reflux.
So doctors are turning to artificial intelligence to identify additional characteristics that can improve their ability to identify those most likely to have Barrett’s and esophageal cancer.
“Everyone in medicine is looking at AI,” Falk said. “We think it’s going to revolutionize things.”
Iyer and his colleagues are developing an AI tool that scours the electronic medical records of Mayo Clinic patients to find those who should be screened for Barrett’s. The tool considers more than 7,500 distinct data points, including past medical procedures, lab test results, prescriptions and more. (Among the surprises: A patient’s triglycerides and electrolytes had predictive value.)
“This is probably something a human would not be able to do efficiently,” Iyer said.
In tests, the overall accuracy of both tools was 84%. While those are substantial improvements, the team would like to bump that up to 90% before they are rolled out in the clinic, Iyer said.
Rubenstein and his colleagues in Michigan created something similar, using machine learning techniques to analyze the health records of VA patients across the country. Their tool also performed better than the official guidelines of medical societies, with an accuracy of 77%. Now the team is working to refine its threshold for screening by adding cost-effectiveness to the mix.
Once in use, tools like these could lighten the load of overburdened primary care doctors, who aren’t necessarily up to date on the latest screening guidelines and refer fewer than half of their eligible patients for testing.
“It will flag a patient and say, ‘This patient should be screened,’ or, ‘This patient should not be screened,’” Iyer said. “That’s what the future really needs.”
Science
Just out of high school and blockading the door to JD Vance's office
When Camp Hess Kramer burned down in 2018, I cried. My family had gone to the summer camp for generations. My grandma won the “best camper” award in the same dining hall where I tried soda for the first time. Overnight, it was gone. The place I grew up, once ringing with songs and laughter, had mutated into a black abyss strewn with the wiry corpses of oak trees.
It was one of the worst fire seasons in California history. Entire towns and many lives were lost.
In 2020, when COVID hit, I was just about to finish middle school. Instead of playing Magic: The Gathering with my friends in the hallways, I stared into my computer screen consuming information about the climate crisis. Feelings of terror morphed into anger. Decades of warning signs had been ignored because big oil was buying out politicians. These disasters were preventable; Hess Kramer didn’t have to burn.
So, I signed up for every climate organization I could find online. My first meeting with the Sunrise Movement’s new Los Angeles youth hub was filled with the intimidating faces of high school seniors. I saw the gleam in their eyes as they talked about a future where everyone had a right to clean air, clean water, and good and meaningful jobs. They led protests and created spreadsheets and cold-called people — things I had no idea how to do.
I was 15 when Sunrise asked me to help lead the local portion of a campaign for a national Civilian Climate Corps. The idea was to push the federal government to create a program employing young people in good-paying jobs fighting the climate crisis.
Soon I was planning a sit-in at Sen. Dianne Feinstein’s Los Angeles office. It was 2021. We slept on the sidewalk for two nights until Feinstein agreed to support the program. Then we demanded a Zoom meeting with Sen. Alex Padilla to get his support too. Around the country for many years, our movement continued to push for a Civilian Climate Corps. In June, the first cohort of 9,000 young people were sworn in by the White House.
But fire season is here, and the places I love are still in danger and my future is still uncertain. We could be looking at four years with a presidential administration that is in the pocket of fossil fuel billionaires.
On July 29, eight of us blockaded the wooden door of JD Vance’s Senate office in Washington. Many more Sunrisers lined the marble hallways. Young people from all walks of life sang in unison: “I went up to JD Vance and I took back my humanity/ Ain’t nobody gonna walk all over me.”
In 2020, Vance, now a potential vice president, asserted that climate change was a threat. Yet after receiving nearly $300,000 from the fossil fuel industry during his 2022 Senate campaign, Vance seems to no longer believe this crisis is human-made.
Police began shoving their way through the crowd toward the door. Handcuffs dangled by their side. I wanted to run, but as the police gave their third warning, I remembered why I was here: An image of Camp Hess Kramer flashed through my head.
I was taken outside with my hands behind my back. I was told I was under arrest, alone in a sea of blue uniforms, but in the distance I heard 150 Sunrisers break out into another song. I could just make out the words. “Where you go, I will go, Simon. Where you go, I will go.”
Simon Aron is a freshman at Brown University, where he plans to continue his activism.
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