Posted By: Gretchen Reynolds via WP March 7, 2025

A synthetically engineered virus containing targeted genes that can change the DNA of every cell in your body? Scientists can then control the genes from outside the body? Welcome to cellular reprogramming. Human trials could start by the end of 2025.

Here is how external control works

The mechanism that allows scientists to control genes from outside an organism, such as turning them on and off, typically involves advanced genetic engineering techniques, particularly those using optogenetics or CRISPR-Cas systems with external control elements.

Optogenetics involves using light to control cells within living tissue, typically neurons, that have been genetically modified to express light-sensitive ion channels. By shining light on these cells, researchers can activate or silence them. This method is primarily used in neuroscience but can be adapted for other applications.

CRISPR-Cas systems, especially CRISPR-Cas9, are powerful tools for editing genes. To control these systems externally, researchers often use inducible promoters or other regulatory elements that respond to external signals.

Recent advancements include using magnetic fields to control gene expression. This involves incorporating magnetically sensitive proteins into the genetic system, allowing for activation or deactivation via external magnetic fields.

Frequencies in the terahertz (5G, 6G) range can alter gene expression but it cannot be precisely controlled and mostly causes DNA degradation. However, the coming 6G will be used extensively in Internet of Bodies (I0B) and Body Area Networks (BAN). ⁃ Patrick Wood, Editor.

For those hoping to cure death, and they are legion, a 2016 experiment at the Salk Institute for Biological Studies in San Diego has become liminal — the moment that changed everything. The experiment involved mice born to live fast and die young, bred with a rodent version of progeria, a condition that causes premature aging. Left alone, the animals grow gray and frail and then die about seven months later, compared to a lifespan of about two years for typical lab mice.

But the Salk scientists had a plan to change the aging animals’ fate. They injected them with a virus carrying four genes that can reshape DNA and, in effect, make every cell in the rodents’ bodies young again. The scientists could even control the genes from outside the mice, turning them on and off to manage the safety and potency of the genetic changes.

The experiment worked: The animals lived 30 percent longer afterward, a marked improvement, if not quite a normal mouse lifespan.

And, with that, the longevity gold rush entered a new era. Tech titans and venture capitalists started throwing billions of dollars at labs exploring the technique, called cellular reprogramming. Experiments began on other mice, as well as worms and monkeys.

Cellular reprogramming is now hailed by its supporters as the most promising scientific approach to improving human healthspans and lifespans. Proponents claim it has the potential to reshape how — and whether — we grow old. And later this year, a biotech company called Life Biosciences expects to file an application with the Food and Drug Administration to get approval for the first human trial of a version of the technique, according to Sharon Rosenzweig-Lipson, the company’s chief scientific officer.

But there have been serious side effects during some of the animal experiments, including gruesome tumors and even deaths. Some researchers worry that science is moving too fast, and basic questions about cellular reprogramming’s safety and effects for people and society still need to be addressed. What are the long-term health consequences? Who will benefit most: wealthy donors or anyone who’s aging or chronically ill? How much will it cost? And how far are humans willing to go for the possibility of more life?

“Honestly,” said Lucy Xu, a postdoctoral research fellow at Harvard Medical School who’s studied reprogramming in mice, “those questions keep me awake at night.”

Reversing aging in our cells

If you’ve never heard of cellular reprogramming, you’re hardly alone. A relatively new field, it began with the jaw-dropping 2006 revelation that just four genes could return even the oldest, most decrepit cell to a state resembling youth.

Those genes and their effects were discovered by the Japanese scientist, Shinya Yamanaka, who won the Nobel Prize in 2012 for his work and had the genes named after him. They became known as Yamanaka factors.

When introduced into a cell, the Yamanaka factors rapidly strip it of the outer layer of its DNA, known as the epigenome.

Our epigenome is the key to cellular reprogramming and also, frankly, life itself. If you’ve ever wondered how the cells in your heart know to be heart cells and not skin, bowel or some other cells, you can thank your epigenome. It’s what gives every cell its identity.

Our DNA starts out alike in almost every cell. But almost immediately, tiny clumps of molecules known as methyl groups start attaching themselves like mollusks to the outside of various genes, with different configurations in different cells. Depending on the number and patterns of these molecules, the genes beneath will be able to receive biochemical signals telling them to turn on, or they won’t.

This process, called methylation, is probably the most important part of our epigenome. Methylation continues throughout our lives and reflects those lives, for better and worse. Smoking strongly influences methylation patterns. So does exercise, although in almost the opposite fashion. Ditto for stress, nutrition, parenting, illness, air pollution and many other choices and conditions.

Through methylation, our epigenome functions, in effect, as our bodies’ diary, with the tiny molecular doodles on our DNA recording what we’ve been doing with ourselves.

But nothing affects methylation as much as aging. The patterns of methylation during infancy are distinctly different than during childhood, adulthood and old age. Many longevity researchers believe these changes in methylation don’t just record our aging process, they drive it, meaning our evolving epigenome may be responsible for aging itself.

Rapidly growing monster tumors

In petri dishes, cellular reprogramming works just as expected. Add the Yamanaka factors to skin cells from a wrinkled centenarian — as scientists have done — and many of the cells will shed their methyl marks and turn back into newborn cells, or what scientists call pluripotent stem cells.

With no cellular memory of having been skin, these cells can become almost any type of cell, with the right coaxing. Pluripotent stem cells from donated human cells are routinely used today for tissue engineering and other medical and research purposes.

But the process isn’t efficient or benign. In a dish containing millions of elderly cells, many will become youthful stem cells after exposure to Yamanaka factors. But many others won’t, for reasons that remain mysterious. Some resist the process. Some die. And some, almost invariably, transform into huge, rapidly dividing growths known as teratomas or monster tumors. These develop when a stem cell doesn’t know what to become and turns into the wrong kind of cell. With a teratoma, teeth cells can wind up growing in a pelvis or bone cells in an eyeball. Although rarely malignant, teratomas often swell to massive sizes.

Researchers can eliminate teratomas in petri dishes easily enough. But in living creatures, the growths create real-life horror films. When Spanish researchers activated Yamanaka factors in healthy mice for an early cellular reprogramming experiment, many of the animals died within weeks, sprouting teratomas and other cancerous tumors all over their bodies.

“You’ll always have teratomas” during cellular reprogramming, said Paul Knoepfler, a professor at the University of California at Davis, who studies epigenetics, stem cells and cancer. “It’s part of the process. It’s actually how you can tell reprogramming is working.”

So, to realize the promise of reprogramming in people, researchers realized they would need to find a better, safer way to turn back cellular time.

For those hoping to cure death, and they are legion, a 2016 experiment at the Salk Institute for Biological Studies in San Diego has become liminal — the moment that changed everything. The experiment involved mice born to live fast and die young, bred with a rodent version of progeria, a condition that causes premature aging. Left alone, the animals grow gray and frail and then die about seven months later, compared to a lifespan of about two years for typical lab mice.

But the Salk scientists had a plan to change the aging animals’ fate. They injected them with a virus carrying four genes that can reshape DNA and, in effect, make every cell in the rodents’ bodies young again. The scientists could even control the genes from outside the mice, turning them on and off to manage the safety and potency of the genetic changes.

The experiment worked: The animals lived 30 percent longer afterward, a marked improvement, if not quite a normal mouse lifespan.

And, with that, the longevity gold rush entered a new era. Tech titans and venture capitalists started throwing billions of dollars at labs exploring the technique, called cellular reprogramming. Experiments began on other mice, as well as worms and monkeys.

Cellular reprogramming is now hailed by its supporters as the most promising scientific approach to improving human healthspans and lifespans. Proponents claim it has the potential to reshape how — and whether — we grow old. And later this year, a biotech company called Life Biosciences expects to file an application with the Food and Drug Administration to get approval for the first human trial of a version of the technique, according to Sharon Rosenzweig-Lipson, the company’s chief scientific officer.

But there have been serious side effects during some of the animal experiments, including gruesome tumors and even deaths. Some researchers worry the science is moving too fast, and basic questions about cellular reprogramming’s safety and effects for people and society still need to be addressed. What are the long-term health consequences? Who will benefit most: wealthy donors or anyone who’s aging or chronically ill? How much will it cost? And how far are humans willing to go for the possibility of more life?

“Honestly,” said Lucy Xu, a postdoctoral research fellow at Harvard Medical School who’s studied reprogramming in mice, “those questions keep me awake at night.”