An artist's rendering of an Ice Age mammoth —Leonello Calvetti—Science Photo Library
If you’ve been excitedly awaiting the return of the woolly mammoth, you’ll have to be patient a little longer. It was in 2021 that the newly established, Dallas-based company Colossal Biosciences announced plans to use modern gene-editing technology and DNA harvested from mammoth remains to manufacture a mammoth embryo, implant it in the womb of an elephant surrogate, and bring the great, gentle, six-ton beast—which vanished from the planet more than 4,000 years ago—back into the modern world. The target date for a pregnancy was 2027; the target date for the birth was 2028.
No more. In a recent conversation with TIME, Colossal CEO and co-founder Ben Lamm concedes that those goal posts have moved more than a little. “We are thinking it will be in the early 2030s,” he says. “We don’t have a hard date. Not 2036, but not 2030 either.”
In just the past year, Colossal has learned vastly more about both the mammoth and the elephant genomes than has ever been known before, not only improving the odds that the mammoth can be brought back to life, or de-extincted, but also unpacking basic genetic science that could one day have knock-on effects for humans—including potentially increasing resistance to cancer.
Bringing back the dire wolf
Colossal proved its de-extinction chops in the spring of 2025, when it announced that it had brought the extinct dire wolf back to life, editing the genome of the closely related gray wolf to replicate the features of its vanished cousin—including a white coat, larger size, more powerful shoulders, wider head, larger teeth and jaws, more-muscular legs, and characteristic vocalizations, especially howling and whining.
To work that genetic magic, Colossal scientists collected dire wolf DNA from an ear bone and a tooth unearthed in two ancient samples, sequenced the genome, and compared it to that of the gray wolf. They then harvested cells from a living gray wolf and made 20 edits on 14 genes using the CRISPR-Cas9 gene-editing tool, which produced the critical dire wolf characteristics. Finally, they extracted the nucleus of the edited cell, inserted it into a domestic dog ovum whose own nucleus had been removed, and implanted the resulting embryo into the womb of a domestic hound. Nine weeks later, the dire wolves were born.
Why woolly mammoths are so hard to de-extinct
To do something similar with the woolly mammoth, Colossal discovered that the work would be a heavier genetic lift than their research teams had originally expected. The initial estimate was that it would take edits to about 60 genes to turn an elephant nucleus into a mammoth nucleus that could then be used to create a mammoth embryo. Now that number is about 150—and rising.
Among the genes and regulatory switches that have been discovered are ones that shrink the mammoth ear to about one-tenth the size of an elephant’s ear. In the hot climates in which Asian and African elephants live, large, heavily vascularized ears serve as heat dumps, cooling the blood and the body as a whole. That would not do for the mammoth, which made its home during the Ice Age and needed to husband all the heat it could. Mammoth tails are shorter than those of elephants too— for the same heat-retention reason—and Colossal scientists have found the gene that expresses that as well.
The genetics of the mammoth’s characteristic heavy coat have also been unpacked. Nearly all hairy mammals—humans included—have oil-secreting glands known as sebaceous glands in the skin. The oil keeps individual hairs supple and prevents them from drying and breaking. Elephants, which have a very sparse covering of bristly hair across their bodies, were thought to be an exception to this rule. That made the job of engineering a mammoth from an elephant more difficult, since mammoths surely had sebaceous glands to sustain their extravagant coat. But Colossal researchers conducted dissection and close examination of samples of elephant skin and found that that earlier received wisdom was wrong—the skin does contain small, rudimentary sebaceous-like structures. The trick now is to isolate the genes that code for the glands and edit them to create the fully developed version the mammoth will need.
The researchers also analyzed the makeup of elephant hair and determined that 90% of every strand is composed of nine different proteins. They then tracked down which genes code for that protein production and govern hair developmental patterns, which typically include periods of growth, rest, and regrowth. Tests of these genes are underway, sometimes with the assistance of other animals.
In March 2025, Colossal revealed that it had created a small brood of 38 woolly mice, engineered with mammoth coding for shaggy hair written into their genome. The mice have thrived and bred, passing on their long, coarse hair to their pups. That was a good start, but mice aren’t mammoths, and to study how effective the genetic editing is, researchers will need to work with a larger mammal. Colossal promises that a woolly pig is coming, though the company does not say when it will be revealed.
Digging deeper into the genome of the mammoth, Colossal scientists have extracted bits of its regulatory DNA and inserted them into living elephant skin cells and watched as regulators turned the behavior of the genes up or down—critical work if you want to design other genes to order.
“It’s a little weird and Frankensteiny,” says Lamm, “but we’ve done that.”
Potential implications for humans
Colossal researchers are also exploring one of the elephant’s more remarkable features: its resistance to cancer. As a large-bodied mammal, elephants ought to be highly susceptible to the disease, especially considering that an elephant's body contains 100 times more cells than a human’s, creating more opportunities for cancer to occur. But cancer accounts for less than 5% of elephant deaths, compared to 16% for humans.
That was a longstanding mystery until recently. Both human and elephant cells are now known to carry a tumor-suppressor gene labeled TP53. When DNA in a cell is damaged—by cancer or other means—the gene codes for the release of the p53 protein, which either halts the damaged cell’s growth cycle to allow for repair, or, if the DNA is too corrupted, kills the cell. Humans carry two copies of the TP53 gene, while elephants carry 20—making for much greater cancer resistance. Additionally, elephants but not humans carry what is known as an LIF6 gene, which also produces a p53 protein, one that specifically targets the mitochondria—an energy-producing organelle located in the cellular cytoplasm—of damaged calls, killing them before they can divide and spread.
Other researchers are already exploring if p53 proteins can be manipulated in humans to increase cancer resistance. Colossal is casting a wider net. On August 20, it announced the launch of a new company, Astromech, which uses AI and deep learning to analyze the genomic data of any species, trace its evolutionary history, and forecast its future, anticipating its adaptation to changing environment, its disease susceptibility, and the possibility of so-called genetic bottlenecks—or lack of genetic diversity—that occur when an endangered population of animals grows too small. Colossal scientists are using Astromech to study elephants’ cancer resistance in depth—which could have broader uses and implications.
“Colossal is not conducting research on humans, but its work with mammoth, elephant, and other genomic datasets could yield insights relevant to human cancer research,” says a company spokesperson. “Understanding mechanisms such as elephants’ TP53-related cancer resistance is exactly the kind of problems Astromech is trying to understand, leveraging the mammoth, elephants and other datasets.”
For now, the goal of turning all of this scientific benchwork into a walking, breathing, breeding mammoth goes on—even if at a slower pace than originally predicted. “I hate to say this, because I don’t want to call the mammoth a product,” says Lamm, “but it will be a better product because of our deeper analysis of what truly made a mammoth a mammoth.”
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In January 2025, Linda-Gail Bekker stood inside a vaccine manufacturing plant and allowed herself to believe that the first HIV vaccine candidate conceived through African science and led by Africans might finally become a reality.
Key takeaways
HIV has stubbornly resisted prevention via a vaccine. But in mRNA, scientists think they have finally found a technology to develop one.
mRNA, which was used for the successful Covid vaccines, is a way to agilely iterate and develop new candidate vaccines quickly.
Funding for HIV research has been yanked away by the Trump administration, and mRNA vaccines have faced political scrutiny, all threatening this breakthrough.
No virus has proved more evasive. Hundreds of HIV vaccines have entered testing; none has succeeded at providing durable protection against infection. And the need remains vast: In 2025, roughly 1.2 million new HIV infections were reported; anti-retroviral treatments have turned it into more of a survivable disease, but more than half a million people died from AIDS-related causes the same year. There is still no known cure.
So researchers like Bekker, an infectious disease specialist at the University of Cape Town, have more hope now, in part because there is finally a clearer idea of what an effective vaccine needs to do. It must coax the immune system into producing a particular type of protective antibody, a rare class of defender, capable of recognizing and disabling HIV despite the virus’s extraordinary diversity and rapid ability to mutate.
No one yet knows how to reliably do that. But mRNA is uniquely suited to the task of finding out, vaccinologists say. Thanks to the platform’s speed and flexibility, researchers can iterate rapidly through the otherwise laborious process of designing, testing, and refining the series of vaccine components needed to guide the body toward making those essential antibodies.
At the start of last year, Bekker and her colleagues were ready to put that strategy to the test. The clinical trial for their new mRNA-based HIV vaccine was just on the verge of enrolling its first participants. But the project depended on the same backing that had sustained HIV vaccine research for decades: US government funding. Washington had long supplied roughly 90 percent of the world’s investment in the field. Then President Donald Trump returned to office.
Within hours of his inauguration, Trump signed an executive order freezing foreign aid. The $45 million contract from the US Agency for International Development (USAID) that was supposed to fund clinical trials like Bekker’s disappeared, as did a web of other funds, many routed through the National Institutes of Health (NIH), that had helped fuel the field’s progress for years.
The timing could hardly be more cruel. After 40-odd years of chasing a shape-shifting foe, scientists believe they now know what kind of immune response an HIV vaccine must generate — and have in mRNA a powerful new tool for pursuing it. But just as many researchers have finally glimpsed a path to victory, the United States and much of the funding has pulled away from the fight.
Pushing the envelope
From the outset, the target for preventing HIV was clear. Within a year of identifying the virus as the cause of AIDS in 1983, researchers had zeroed in on its envelope protein as the most promising point of attack for a vaccine.
Protruding from the virus’s surface in knobby clusters, the envelope protein acts like a molecular grappling hook, latching onto immune cells before pulling the virus itself inside. Without this feature, HIV cannot infect a cell.
Much as the coronavirus spike protein would later become the basis for Covid vaccines, this protein on the surface of HIV seemed an obvious bullseye. But identifying the target didn’t mean researchers could hit it. Most of what the immune system sees of the envelope protein is actually just a decoy. The parts that stick out and draw the strongest immune response are also its most changeable, differing from one strain to the next and mutating freely whenever antibodies close in, leaving the body to waste its firepower on a target that keeps slipping away.
Candidate vaccines kept making the same mistake. They would elicit plenty of antibodies, but not the kind that could keep up with the virus. Time and again, promising candidate vaccines generated excitement in the laboratory, only to come up empty when it mattered most in large-scale clinical testing.
The field’s fortunes started to change in the late 2000s when researchers began studying the small fraction of people living with HIV who developed antibodies capable of recognizing the virus’s concealed, conserved features. Though these hard-won antibodies came too late to protect their makers, they gave scientists a molecular blueprint for the defenses a vaccine would need to build.
As the field came to learn, these “broadly neutralizing antibodies” do not appear overnight but rather after years of battle with the virus.
The challenge, then, was to design a vaccine that would not just trigger an immune response but guide a person’s immune system through the same evolutionary journey. This would require a succession of vaccine components to prompt a carefully choreographed process within the body, rather than the single, fixed target that suffices for shots against measles or hepatitis B.
It was a strategy rooted in rational design but dependent on trial and error. Progress would come through a steady stream of small proof-of-concept studies, each informing the next generation of vaccine candidates. Ordinarily, it would take at least a year — often longer — to manufacture and prepare each vaccine iteration before it could be tested in people.
But then the Covid pandemic rocketed mRNA into the spotlight.
The mRNA advantage
mRNA technology upends the old recipe of vaccine development. Conventional shots work by showing the immune system a mugshot of the enemy: a killed or weakened germ, or one of its proteins, grown batch by batch in vats of cells or eggs. An mRNA vaccine takes a different route. Rather than supplying the mugshot, it supplies the instructions to draw one: a short, lab-printed strip of messenger RNA, the molecule cells normally use to ferry genetic directions from DNA to their protein-making machinery.
Inject the right sequence, and it will program the body’s own cells to become tiny factories, producing the target protein and presenting it to the immune system as if it were the real intruder. Because it is all just code, refining a design means editing text, not rebuilding a factory — the work of days, not months.
“We’ve been able to design vaccines in real time,” said University of Pennsylvania Perelman School of Medicine assistant professor Ted Kreider, who is a specialist in infectious diseases.
To HIV researchers, the appeal was obvious. HIV’s greatest weapon was its ability to shift and adapt. Now, at last, a vaccine could, too.
The timing was ideal. Just as researchers were beginning to map the path to an effective vaccine, mRNA offered a way to move down that path at speed. With vaccine designs no longer bottlenecked by design and manufacturing, what once might have taken decades of stepwise vaccine development could, thanks to mRNA, be compressed into years.
Across a growing number of clinical trials, researchers are now testing different vaccine components, different sequences, and different delivery platforms, searching for the combination that most effectively nudges the immune system toward a truly HIV-thwarting response.
A paper published last month in Nature offered one such path forward, showing in monkeys that a painstaking sequence of eight shots could coax the immune system into producing potent antibodies capable of neutralizing a broad range of HIV strains. But even the study’s authors see a catch. “It’s still too many [shots] to be practical in humans,” said Dennis Burton, a professor of immunology and microbiology at Scripps Research who worked on the project.
Whether mRNA ultimately becomes the vaccine itself — or simply the tool that helps researchers discover it — remains an open question.
The fundamental challenge for now, after all, is vaccine design, notes Mark Feinberg, president and CEO of IAVI, a nonprofit research organization focused on developing vaccines against HIV. And for that task, he says, “the most obvious advantage of mRNA is simply the speed of getting an idea from the laboratory to the clinic.”
But if the technology reaches the finish line, researchers say it could offer other advantages as well. Because the protein is made inside the body’s own cells rather than in a lab, it folds and displays itself much as it would on the real virus, giving the immune system a more faithful target to train against. That way, when the real virus arrives, the body already knows its true face.
It also gives vaccine designers an unusual number of knobs to turn, notes Kristie Bloom, an mRNA vaccine researcher and molecular biologist at the University of Witwatersrand in South Africa. By altering the vaccine’s formulation, dose, or genetic design, researchers can shape not just the magnitude of the immune response but also its balance: favoring antibody-producing B cells, virus-killing T cells, or some mix of the two.
With mRNA, “there’s quite a bit of flexibility,” she said.
Not so fast
For all the putative upsides, however, mRNA does carry some baggage. There are concerns about public acceptance given the intense backlash and misinformation campaigns that followed the rollout of Covid-19 vaccines. And though those shots ultimately proved remarkably safe, with very low rates of serious side effects, a peculiar skin problem has emerged in early-stage trials of mRNA vaccine candidates for HIV specifically.
In two separate trials reported last year, around one in 12 participants who received mRNA-based HIV vaccines manufactured by Moderna developed chronic urticaria, a form of persistent hives that in some cases endured for years. The vaccines encoded different portions of HIV’s envelope protein, yet both produced the same unexpected side effect.
The fact that the reactions appeared across distinct vaccine designs — but never before in Moderna’s other mRNA vaccine programs — has fueled suspicion that something about HIV’s envelope protein itself may be involved. Even so, no clear explanation has emerged.
“We’ve ruled a bunch of things out,” said William Schief, a professor at Scripps Research’s department of immunology and microbiology who doubles as vice president for protein design at Moderna, “but there’s no smoking gun.”
Schief is continuing to investigate the source of the immune reactions. But not wanting an unresolved safety signal to bring the program to a halt, he and his collaborators have pressed ahead with lower-dose versions of the vaccine, betting that the hives will fade while the desired immune response remains intact.
That strategy is now being evaluated in an IAVI-backed trial led by Bekker in South Africa. Known as IAVI G004, it has yielded encouraging early results. (Unlike the African-developed vaccine whose launch was derailed by the USAID funding freeze, this study is testing a different mRNA vaccine candidate, manufactured by Moderna.)
At the lowest dose tested, just one-tenth of the amount used in the original studies, the hives that had troubled earlier trials never materialized, Bekker said. Her team has since moved on to a somewhat higher dose, seeking the sweet spot between safety and immune potency.
All of these discoveries and challenges along the way have helped map a path forward. “We know what we need to do,” said Barton Haynes, director of the Human Vaccine Institute at the Duke University School of Medicine. The task for them now is to move through the necessary iterations as quickly as the science — and the funding and political landscape — allow.
“A black hole”
When Bekker and her team learned about the sudden funding cut that would halt their African-designed, USAID-funded vaccine study in January 2025, they were already in Tanzania to prepare its launch. They immediately had to stop work on the project, which had been years in the making. “It was like falling into a black hole of depression,” she said.
And the setbacks kept coming. With prominent vaccine critic Robert F. Kennedy Jr. overseeing US health policy, the federal government moved to undermine both vaccine science broadly and mRNA technology in particular.
The NIH, in addition to terminating dozens of smaller HIV-related grants, began winding down its flagship Consortia for HIV/AIDS Vaccine Development (CHAVD) program, which has long served as a cornerstone of global HIV vaccine research, while other federal agencies curtailed support for mRNA vaccine projects across multiple disease areas.
At the same time, South Africa, the continent’s leading center for biomedical research, found itself in the Trump administration’s crosshairs over allegations of anti-white discrimination. New federal research grants were no longer permitted to support collaborations with South African scientists, severing ties that had underpinned years of international HIV research.
“That’s a perfect storm to prevent us from building on the most exciting science HIV vaccines have had in 45 years,” said Mitchell Warren, executive director of AVAC, a nonprofit dedicated to HIV prevention access and policy.
Yet for all the financial and political disruption, the scientific momentum hasn’t stopped. Philanthropic organizations and governments elsewhere have stepped up to help fill the funding gap, allowing key trials to move forward, although in scaled-down forms with more modest ambitions.
The Africa-led effort that Bekker had dreamed of was salvaged, with emergency backing from the South African Medical Research Council, albeit in diminished form and built, in the end, on the same protein-based technology that mRNA was meant to leapfrog.
The only mRNA-based HIV vaccine study that is actually underway in Africa is IAVI G004: a program designed by US scientists, not by locals, and funded largely by the Gates Foundation.
A longtime backer of HIV research, that foundation is estimated to invest around $70 million annually — with $64 million being invested in 2022, and $70 million in 2026 — across a global portfolio of HIV vaccine programs. That’s a substantial sum, though only a fraction of the hundreds of millions of dollars once provided by the NIH, USAID, and other federal agencies.
For now, some of that funding continues to flow. But even what remains is far from assured. The Trump administration’s proposed 2026 budget would slash the National Institute of Allergy and Infectious Diseases — the NIH institute that has long anchored HIV vaccine science — along with the Office of AIDS Research that coordinates HIV research across the entire NIH, leaving the field’s longer-term future in doubt.
“We’re not going to be able to fill the gap that’s been left by the US government,” said Nina Russell, director of TB& HIV research and development at the Gates Foundation. Still, she says, the foundation remains determined to keep the most promising vaccine programs moving forward: “We are super committed to it.”
All of these changes have left the research field daunted, but not hopeless. “It’s been a very disruptive time,” said Burton, who leads one of the CHAVD research hubs. But he remains convinced the field is on the right track. “The pieces of the puzzle are in place,” he said. “It’s obviously been a long, long journey, but you can begin to see the end.”
A higher bar
The funding crisis and political challenges are not the only forces reshaping HIV vaccine development.
For much of the HIV epidemic, which has killed over 40 million people worldwide, even a partially effective vaccine might have been enough to transform the course of HIV. Today, however, vaccine researchers are also competing against long-acting preventive drugs that can protect people for months at a time with just two injections.
These drugs are an enormous step forward for HIV protection, but they also raise the standard the vaccine field must meet, Warren said. “The bar for a licensed vaccine that is going to have a public health impact has gotten much higher,” he said.
But these prophylactic drugs, which began as daily pills and have evolved into long-acting injectables, are only as good as the systems that deliver them. Cost, stigma, and the need for regular clinic visits have limited access in many countries with the highest HIV burdens. A vaccine, by contrast, that provided years of protection after a handful of doses could overcome many of those barriers.
That is precisely why many scientists view the current retreat of the US government with such alarm. After decades of disappointments and billions of dollars in investment, the field finally believes it has a coherent strategy for building an effective HIV vaccine.The fear is that momentum could stall just as researchers have begun to see a path across the finish line. As a result, what once seemed like a scientific problem increasingly looks like a political one.
For Bekker, the current moment feels all too familiar. In the early 2000s, South Africa’s government embraced AIDS denialism, delaying the rollout of lifesaving treatments and forcing researchers and clinicians to battle both the virus and the state. A quarter-century later, she says, the political opponent has merely changed address to Washington, DC, threatening once again to undermine the fight against HIV and cost countless lives.
“When politics interferes in science,” Bekker said, “that is the death of scientific progress.”
Bekker still does not know whether the vaccine she watched being manufactured last year will ever reach the people it was designed to protect. She and her colleagues still hope to carry out the made-in-Africa mRNA vaccine trial they spent years designing — if they can find a way to pay for it. But Bekker remains convinced that the scientific strategy behind it is the right one, and that mRNA may yet do for HIV what it did for Covid-19, rapidly transforming decades of scientific groundwork into an effective shot.
She only hopes politics does not succeed where HIV itself has failed in slowing the field’s progress. “We should only be fighting the virus,” Bekker said. “But we’re fighting the administration and its policies, and that is a waste of our energy.”
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