Scientists Have Made a Huge Breakthrough In Cryogenics

March 30, 2017


Cryopreservation is the process of freezing organs and tissues at very low temperatures in order to preserve them. While it sounds simple in theory, only a handful of cells and tissues have survived this method. This is because while science has successfully developed ways to cool organs to the very low temperatures required for preservation, thawing them out has proven far more difficult. As the specimen thaws, it forms ice crystals, which can damage the tissue and render organs unusable.

Right now, the process is only a viable option for small samples, such as sperm or embryos. Previous efforts using slow warming techniques have proven to be effective on samples of that size, but haven’t worked for larger tissue samples, like whole human organs. The inability to safely thaw the tissue has also precluded the theoretical concept of cryogenically preserving entire human bodies, with the intention of reanimating them later. The concept has roots in cryogenic technology, but is actually referred to as “cryonics”, and the scientific community generally considers it to be more science fiction than science fact — at least for the time being.

A recent study has made a significant breakthrough which may well begin closing that gap even more. Using a new technique, scientists were able to cryopreserve human and pig samples, then successfully rewarm it without causing any damage to the tissue.

As lead researcher John Bischof from the University of Minnesota notes:

This is the first time that anyone has been able to scale up to a larger biological system and demonstrate successful, fast, and uniform warming of hundreds of degrees Celsius per minute of preserved tissue without damaging the tissue.

By using nanoparticles to heat the tissues at an equal rate, scientists were able to prevent the formation of those destructive ice crystals. The researchers mixed silica-coated iron oxide nanoparticles in a solution and applied an external magnetic field to generate heat. The process was tested on several human and pig tissue samples, and it showed that nanowarming achieves the same speed of thawing as the use of traditional convection techniques.

Preserving Organs and Saving Lives

One theoretical application for this discovery would be, of course, bringing cryogenic life-extension techniques out of the realm of science fiction and into reality. But we’re not quite there yet.

A more practical application for the technique would be to safely preserve and store organs for extended periods, thus improving the logistical challenges behind organ transplantation.

According to statistics from the United Network for Organ Sharing, 22 people die every day in the US while waiting for organ transplants. Contrary to popular belief, this isn’t because there is a shortage of organs being donated — it’s because organs cannot be preserved for more than a few hours. So, while there are available organs ready to be transplanted, the time it takes to find a matching recipient and transport the organ safely to their location often exceeds the window of time in which the organ remains viable for transplant.

Over half of donated hearts and lungs are thrown out each year because they don’t make it to patients in time. They can only be kept on ice for four hours, and while some organs can last longer than others without a blood supply during transport, it’s still not a long enough in many cases.

“If only half of these discarded organs were transplanted, then it has been estimated that wait lists for these organs could be extinguished within two to three years,” Bischof adds. With the help of cryopreservation technology, we may be well on our way to keeping donated organs viable for longer — meaning they could be transported to patients who need them even if distance and time stands between them.

Ark of the immortals: The future-proof plan to freeze out death

December 18, 2016


Life at the edge of death Murray Ballard, from the book The Prospect of Immortality

“WE’RE taking people to the future!” says architect Stephen Valentine, as we drive through two gigantic gates into a massive plot of land in the middle of the sleepy, unassuming town that is Comfort, Texas. The scene from here is surreal. A lake with a newly restored wooden gazebo sits empty, waiting to be filled. A pregnant zebra strolls across a nearby field. And out in the distance some men in cowboy hats are starting to clear a huge area of shrub land. Soon the first few bricks will be laid here, marking the start of a scientific endeavour like no other.

After years of searching, Valentine chose this site as the unlikely home of the new Mecca of cryogenics. Called Timeship, the monolithic building will become the world’s largest structure devoted to cryopreservation, and will be home to thousands of people who are neither dead nor alive, frozen in time in the hope that one day technology will be able to bring them back to life. And last month, building work began.

computer image
Computer rendering of the Timeship project

Cryonics, the cooling of humans in the hope of reanimating them later, has a reputation as a vanity project for those who have more money than sense, but this “centre for immortality” is designed to be about much more than that. As well as bodies, it will store cells, tissues and organs, in a bid to drive forward the capabilities of cryogenics, the study of extremely low temperatures that has, in the last few years, made remarkable inroads in areas of science that affect us all; fertility therapy, organ transplantation and emergency medicine. What’s more, the cutting-edge facilities being built here should break through the limitations of current cryopreservation, making it more likely that tissues – and whole bodies – can be successfully defrosted in the future.

Timeship is the brainchild of Bill Faloon and Saul Kent, two entrepreneurs and prominent proponents of life extension research. Their vision was to create a building that would house research laboratories, DNA from near-extinct species, the world’s largest human organ biobank, and 50,000 cryogenically frozen bodies. Kent called it “all part of a plan to conquer ageing and death”.

In 1997, Kent asked Valentine, an architect based in New York, whether he could design a building that was stable enough to operate continuously for 100 years with minimal human input. It needed to withstand earthquakes, to be protected from natural disasters and acts of violence, and to survive without the main power supply for months on end. It was a list of demands that no building in the world currently satisfies.

Valentine spent months drawing up proposals for the building, together with advice from engineers who had previously worked for NASA and security experts from around the world. “We had to address everything from pandemics and cyberattacks to snipers and global warming,” says Fred Waterman, a risk mitigation expert on the Timeship team. The designs were approved by Kent but immediately put on ice. He believed the technology that would make the building worthwhile was not yet advanced enough to warrant its construction.

At body temperature, cells need a constant supply of oxygen. Without it they start to die and tissues decay. At low temperatures, cells need less oxygen because the chemical activity of metabolism slows down. At very low temperatures, metabolism stops altogether. The problem faced when trying to preserve human tissue by freezing it is that water in the tissue forms ice and causes damage. The trick is to replace the water with cryoprotectants, essentially antifreeze, which prevent ice from forming. This works well for small, uncomplicated structures like sperm and eggs. But when you try to scale it up to larger organs, damage still occurs.

But in 2000, Greg Fahy, a cryobiologist at 21st Century Medicine in Fontana, California, made a breakthrough with a technique called vitrification. It involves adding cryoprotectants then rapidly cooling an organ to prevent any freezing; instead the tissue turns into a glass-like state. Fahy later showed that you could vitrify a whole rabbit kidney that functioned well after thawing and transplantation. This was the breakthrough Kent and Faloon had been waiting for.

Cold comfort farm

The pair gave Valentine a multimillion-dollar budget and told him to find land on which to build Timeship. Valentine spent five years scouring the US, believing it to be the country most likely to remain politically stable for the next 100 years. He homed in on four states that fitted his exacting criteria. And after evaluating more than 200 sites in Texas alone, Valentine ended up in Comfort. Here he discovered the Bildarth Estate, which came with acres of land, a 1670-square-metre mansion and even a few zebras.

“There’s an urgent need to be able to store whole organs for longer”

Since then, Valentine, together with a team of specialists, has fine-tuned the project. Timeship’s architectural plans make it look like something between a fortress and a spaceship. The central building is a low-lying square with a single entrance. This sits inside a circular wall surrounded by concentric concrete rings. Inside are what Valentine calls “neighbourhoods”, collections of thermos-like dewars that will store the cryopreserved DNA, organs and bodies (see “Cool design”).

Parts of the project are somewhat theatrical – backup liquid nitrogen storage tanks are covered overhead by a glass-floored plaza on which you can walk surrounded by a fine mist of clouds – others are purely functional, like the three wind turbines that will provide year-round back-up energy.

The question is, do we need Timeship? Such an extravagant endeavour might not be vital, but it looks as if something similar will be necessary sooner or later. In fact, the strongest argument for such a facility, and the technological developments it promises, might have nothing to do with the desire to be frozen for the future.

We already have small biobanks for storing bones from human donors, as well as tendons, ligaments and stem cells. But with rapid advances in regenerative medicine, there is a growing need for large-scale facilities in which we can store more cryogenically frozen biological material.

Stem cells, for instance, are increasingly cryopreserved after being extracted and grown outside the body for use in regenerative therapies. “Beyond the age of 50, it’s harder to isolate stem cells for regenerative medicine,” says Mark Lowdell at University College London. “If I were in my 30s, I would certainly be cryopreserving some bone marrow for future tissue to fix my tennis injuries.” Lowdell will soon do the first transplant of a tissue-engineered larynx created from a donor larynx that has been seeded with cryopreserved stem cells to reduce the risk of rejection.

Then there’s the problem of organ shortage. In the US, almost 31,000 transplants were carried out in 2015, but at least six times as many people are on the waiting list – each day 12 people die before they can get a kidney. To make matters worse, many organs go to waste because their shelf life is too short to find a well-matched patient. Nearly 500 kidneys went unused in the US last year because the recipient couldn’t get the organ in time.

So there’s an urgent need to be able to store whole organs for longer. The issue is so important that the US government this month pledged to start funding research into this very area. We can already reversibly cryopreserve small bundles of cells – many thousands of babies have been born from vitrified human embryos. Doing the same with large organs, like kidneys or hearts, is harder, but not impossible. Over the past decade, for instance, several babies have been born from ovarian tissue that was removed before chemotherapy, cryopreserved and later replaced. Similarly, rabbit kidneys and rat limbs have been cryopreserved, thawed and placed in a new body. Fahy says his team is well on its way to the first human trial of a cryogenically frozen organ. “After decades of research, we’re now at a tipping point,” he says. Having improved both the vitrification technique and the cryoprotectant solution, they are moving to trials in pigs, and human trials could follow within five years, he says.

That might help prevent wastage, but we would still have a shortage of organs for transplant. Another solution is to grow them from scratch using our own stem cells, and keep them until we need them. So far, tiny 3D heart-like organs have been made from stem cells alone, as well as mini kidneys and livers, all with the ultimate aim of bioengineering replacement organs for transplantation.

Once organs can be produced like this, we will need a way of storing either the raw material or the organs themselves. “I’m not enthusiastic about the notion of freezing whole heads, but I can certainly imagine people needing to freeze cells, or ‘starter kits’ for the development of tissues, or even whole organs – and in the not-so-distant future,” says Arthur Caplan, a bioethicist at New York University Langone Medical Center.

Like Caplan, most scientists I spoke to said it was becoming more likely that we could bring individual cryopreserved organs back to life, but were less convinced by the idea of freezing whole bodies. So I decided to visit Alcor Life Extension Foundation, the world’s biggest cryonics facility, in Scottsville, Arizona, to find out what happens when a body is put on ice.

Alcor’s lobby has the feel of a doctor’s waiting room, except that lining the walls are portraits of men, women, children and the occasional dog. The people in the pictures are preserved there, some alongside their beloved pets.

Cool design

Aaron Drake, head of Alcor’s medical response team, says the company has more than 1000 clients signed up worldwide – 99 per cent are healthy, but 1 per cent have a terminal disease. Some of them want to freeze their whole body, others – known as “neuros” – opt for just the head.

Drake admits that the techniques his firm uses aren’t perfect, which is why they continue to research the process. Recently, Alcor scientists placed acoustical devices on the brains of neuros as they were lowered into liquid nitrogen, listening as the heads cooled to -196 °C. The colder they got, the more frequently the team heard acoustical anomalies, which they attribute to micro-fracturing of the tissue. “That’s damage happening,” says Drake. It’s difficult to say what effects this might have. “It’s not universal or consistent, but it’s something we know doesn’t happen at around -140 °C.”

The problem is, to store a person at -140 °C, you have to keep them warmer than nitrogen’s boiling point, which is incredibly hard to do – certainly much harder than placing a body in a giant thermos full of liquid nitrogen, letting it boil and occasionally topping it up.

But at Timeship, Valentine thinks he’s cracked the problem. After years of experimentation, he has designed a system called a Temperature Control Vessel (TCV), a dewar that houses cryogenically preserved bodies, heads or tissues. Inside the dewar are moving rods that can be dipped into a pool of liquid nitrogen whenever a sensor notes that the temperature has risen from -140 °C. This would provide a relatively autonomous way of maintaining the contents at an ideal temperature (see “Cool design”).

Each TCV can carry hundreds of samples of tissue and organs, or four bodies and five heads.They are designed to be stacked together in a tessellating pattern that forms the neighbourhoods within the main building.

This should reduce some of the damage to brain tissue that the Alcor team heard. But even with that technology, is there any hope of reanimating a brain?

There is some evidence to suggest that certain properties of the mind – memories, for instance – can survive cryopreservation. In 2015, researchers trained worms to recognise a smell, then froze them. On thawing, the worms retained the smell memories. And this year, Fahy’s team cryopreserved a rabbit brain in a near-perfect state. Although the group used a chemical fixative that is not yet used in human preservation, the thawed rabbit brain appeared “uniformly excellent” when examined using electron microscopy.

“These kinds of experiments show that it’s not such a massive leap of faith to think that we could preserve the human mind,” says Max More, president and CEO of Alcor. But not everyone is convinced. Even if you could preserve the delicate structures of the human brain, the cryoprotectants themselves are toxic. “No matter how smart scientists are in the future, you can’t change mush into a functional brain,” says Caplan, “and I just don’t think that what we’re able to do right now to preserve the brain is good enough to ever bring it back to life.”

There are precedents for the idea that the human brain can be revived after being cooled, however. In 1986, two-and-a-half-year-old Michelle Funk fell into an icy creek where she was submerged for just over an hour. Despite showing no signs of life, doctors spent 2 hours warming her blood through a heart-lung machine. Eventually, she recovered fully. Her doctors figured that the sudden cooling of her brain must have slowed the organ’s need for oxygen, staving off brain damage.

“What we are doing is just an extension of emergency medicine – we are stretching time“

Funk’s recovery was so remarkable it spurred researchers to repeat the scenario experimentally in pigs and dogs – cryopreserving them for hours before bringing them back to life. The same procedure is now being tested in humans in a groundbreaking trial by surgeons at UPMC Presbyterian Hospital in Pittsburgh, Pennsylvania. There they are placing patients in suspended animation for a few hours, to buy time to fix injuries that would otherwise be lethal, such as gunshot wounds. The technique involves replacing the person’s blood with a cold saline solution and cooling the body. They will then try to fix the injuries and bring the patient back to life by slowly warming the body with blood.

That’s not so different from what goes on at Alcor, says More. “What we’re doing is trying to stretch the time in which the person is suspended. It’s just an extension of emergency medicine.” I ask More whether he really believes that his members will be brought back to life. “I don’t know if it will ever happen,” he says, “but we’re breaking no laws of physics here. Who is to say that in 100 years we won’t have the medical tools – some kind of nanotechnology perhaps – that can fix cells at an individual level and repair what’s necessary to revive someone in good health.”

This is the central argument in favour of cryonics – the possibility, no matter how slim, that it offers a chance of survival. “We think of cryonics as a scientific experiment,” says More. “People that are buried or cremated are our control group, and so far, everyone in the control group has died.”

Facing the future

It is an expensive experiment, however. Cryopreserving your body will set you back up to $220,000, payable on death – often via life insurance, with Alcor as the beneficiary.

“People often say that the money would be better spent on family or given to charity,” says Ole Moen, a philosopher and ethicist at the University of Oslo, Norway. “But what’s strange about this is that nobody complains when people spend money on expensive cancer treatments or long-term care – people drain the public healthcare budget trying to stay alive all the time,” he says. “So why complain when people want to spend their own money trying to live longer via cryonics?”

If you’re happy to fork out, there’s the big question of what kind of future you’d wake up to. “Even if you could get this technique up and running by some magical future science I believe you’d be a freak – you’d be so far out of it culturally, so lost, that you’d be at risk of being driven mad,” Caplan says.

With so many big unknowns, I leave Alcor and Timeship undecided on the utility of cryonics. What’s clear, though, is that the underlying research into cryopreservation is worthwhile. Whether it’s to help me have children, fix a future tennis injury or potentially even provide me with a new heart, I’d be first in line to freeze cells and tissues today that might help my future self live longer, and healthier.

On my way out of Alcor, I ask Drake whether he wants to be frozen, given that he has cryopreserved so many others. “Yes,” he says. “Not because I want to be immortal, I don’t think that’s possible. I just want to see if all this work was futile. I was the last person these people saw before they took their last breath. Will they see me again? Will they thank me? I don’t know if that will ever happen. But wouldn’t that be nice?”

What is death?

Death has been redefined several times over the past century. It was once considered the cessation of a heartbeat and breathing. Today it includes other scenarios, such as the cessation of brain activity. But even that’s not good enough for some.

“Death is a process, not a switch,” says Max More, president and CEO of the Alcor Life Extension Foundation in Scottsdale, Arizona. “If you go back 100 years and someone falls over in the street and stops breathing, doctors would say ‘this person is dead’. Today we can do CPR and defibrillation to restart their heart and they can be brought back to life. So when that doctor declared them dead, were they? With today’s standards, no they weren’t.” Instead, says More, what we’re really saying is “given today’s technology and the medicine I have available to me right now, there’s nothing more I can do for you”.

A definition that emerged in the 1990s in response to this problem is the information-theoretic definition of death. It states that a person is dead only when the structures that encode memory and personality are so disrupted that it is no longer possible in principle to restore them.

Therefore a person who is cryogenically frozen, with brain structures preserved in a state close to what they were before the pronouncement of clinical death, is not by this definition, actually dead. So if the people frozen at Alcor aren’t dead, what are they? “There’s no good word for what they are,” says More (see Interview “I want to put your death on ice so that you can live again“). “Some people say they are de-animated.”

This article appeared in print under the headline “The big freeze”

from Health – New Scientist