In a first, scientists keep cells alive in the brains of dead pigs | Science News for Students

In a first, scientists keep cells alive in the brains of dead pigs

This technique might one day lead to better brain therapies for living people
May 24, 2019 — 6:45 am EST
a domestic pig on a farm

In a feat that has shaken up neuroscience, scientists used an artificial fluid to keep cells alive in the brains of pigs that had been slaughtered for pork.

ChristiLaLiberte/ E+/Getty Images

Scientists have kept cells alive in the brains of dead pigs. This first-of-its-kind feat was done with a sophisticated system of artificial fluid. The pigs had died four hours earlier at a slaughterhouse.

“This is a huge breakthrough,” says Nita Farahany. An ethicist and legal scholar at Duke University in Durham, N.C., Farahany wasn’t involved in the research. “It fundamentally challenges existing beliefs in neuroscience,” she says. The research hints that in some cases, the loss of brain function doesn’t have to be permanent. The findings appeared April 17 in Nature.

In the study, the brains showed no signs of consciousness. For that, they’d need more widespread activity. But individual nerve cells were still firing. “There’s this gray zone between dead animals and living animals,” says Farahany. She coauthored another piece in Nature offered as a commentary on the new study.

The goal was never to create true zombies. Instead, the results may one day lead to better treatments for brain damage. Strokes and other types of injuries can harm brain tissue by starving it of oxygen. The study also raises major ethical questions about research on brains that are neither alive nor yet completely dead.

How to make an undead brain

“No animals died for this study,” the authors of the new work write in their paper. They did the experiments on pigs that had been killed in a food processing plant. These animals were destined to become pork.

An artificial fluid flows through this pig brain after death. It kept the cells oxygenated and fed.
Z. Vrselja et al/Nature 2019

After death, the heads of some 300 pigs were put on ice. They they were sent to a lab at Yale University in New Haven, Conn. There, researchers cut out the brains.

Four hours after the animals had died, researchers put 32 of these brains in an artificial system called BrainEx. It includes a fluid designed to stay at the animal’s body temperature and replace its blood. The fluid moves through the blood vessels, carrying oxygen, sugar and other ingredients needed to keep the brain cells fed.

During six hours in the BrainEx system, these dead brains showed signs of activity. Oxygen and sugar went into the brain tissue, and carbon dioxide came out. That suggested some cells in the brains were still alive. Some of the nerve cells in the hippocampus and prefrontal cortex looked healthy under a microscope. These are key brain areas for complex thinking. And studies on brain slices showed that individual nerve cells could still fire off signals. In contrast, brains that weren’t in the BrainEx system broke down over those six hours.

The results suggest that brains are much tougher than once thought. The same thing might even be true of human brains. “That’s the punchline,” says study coauthor Nenad Sestan. He’s a neuroscientist at Yale University. The technique offers a new way to study animal brains in labs, Sestan says. Those experiments might help researchers learn how to treat human brain damage caused by strokes or other injuries.  

an image of pig brain cells
Ten hours after death, cells in a pig brain have deteriorated (left). But a new system called BrainEx kept cells healthy. In the image on the right, nerve cells are green, and support cells called astrocytes are red.
Stefano G. Daniele, Zvonimir Vrselja/Sestan Lab/Yale School Of Medicine

Ethical puzzles

The study also is notable for what researchers did not see. Electrodes placed on the surface of the brains’ didn’t find coordinated, widespread activity. That sort of activity can indicate some level of awareness. If the scientists had observed such signals, they would have stopped the experiment immediately, says Stephen Latham. He’s a bioethicist at Yale and one of the study’s authors. “It would pose this unique problem of creating some kind of experience or awareness in an organ that’s completely isolated from any living being,” he explains.

In the BrainEx system, the fluid included a compound that blocks brain cell activity. Researchers suspected that too much nerve-cell action would be harmful to the brains. (They removed the blocker when they sliced up the brains to study them more closely — and that’s when they saw activity in the cells.) The scientists don’t know whether removing that blocking compound altogether would have let more complex patterns of brain activity develop. Or maybe such signals would show up after the brains spent more time in the fluid.

The method isn’t close to being ready to use with human brains, the scientists say. Still, this new research raises the possibility that similar approaches might one day restore some function to tissue starved of oxygen in human brains.

Rules for experiments involving living people are strict, Christine Grady said in an April 16 news briefing. She’s a bioethicist at the National Institutes of Health in Bethesda, Md.

But those rules are less strict after death, Grady said. “Once a human dies and their tissue is in a laboratory, there are many fewer restrictions on what can be done.” New abilities to preserve dead tissue will make people think about “whether or not there need to be new rules about how we deal with those tissues,” she says — whether they come from a pig or a person.

Power Words

(more about Power Words)

blood vessel     A tubular structure that carries blood through the tissues and organs.

carbon dioxide (or CO2)    A colorless, odorless gas produced by all animals when the oxygen they inhale reacts with the carbon-rich foods that they’ve eaten. Carbon dioxide also is released when organic matter burns (including fossil fuels like oil or gas). Carbon dioxide acts as a greenhouse gas, trapping heat in Earth’s atmosphere. Plants convert carbon dioxide into oxygen during photosynthesis, the process they use to make their own food.

cell     The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall.

commentary     (in science) An opinion piece, often written to accompany — and add perspective to — a paper by others, which describes new research findings.

compound     (often used as a synonym for chemical) A compound is a substance formed when two or more chemical elements unite (bond) in fixed proportions. For example, water is a compound made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H2O.

electrode     A device that conducts electricity and is used to make contact with non-metal part of an electrical circuit, or that contacts something through which an electrical signal moves. (in electronics) Part of a semiconductor device (such as a transistor) that either releases or collects electrons or holes, or that can control their movement.

ethics     (adj. ethical) A code of conduct for how people interact with others and their environment. To be ethical, people should treat others fairly, avoid cheating or dishonesty in any form and avoid taking or using more than their fair share of resources (which means, to avoid greed). Ethical behavior also would not put others at risk without alerting people to the dangers beforehand and having them choose to accept the potential risks. Experts who work in this field are known as ethicists.

hippocampus     (pl. hippocampi) A seahorse-shaped region of the brain. It is thought to be the center of emotion, memory and the involuntary nervous system.

microscope     An instrument used to view objects, like bacteria, or the single cells of plants or animals, that are too small to be visible to the unaided eye.

National Institutes of Health (or NIH)    This is the largest biomedical research organization in the world. A part of the U.S. government, it consists of 21 separate institutes — such as the National Cancer Institute and the National Human Genome Research Institute — and six additional centers. Most are located on a 300 acre facility in Bethesda, Md., a campus containing 75 buildings. The institutes employ nearly 6,000 scientists and provide research funding to more than 300,000 additional researchers working at more than 2,500 other institutions around the world.

nerve     A long, delicate fiber that transmits signals across the body of an animal. An animal’s backbone contains many nerves, some of which control the movement of its legs or fins, and some of which convey sensations such as hot, cold or pain.

neuroscience     The field of science that deals with the structure or function of the brain and other parts of the nervous system. Researchers in this field are known as neuroscientists.

organ     (in biology) Various parts of an organism that perform one or more particular functions. For instance, an ovary is an organ that makes eggs, the brain is an organ that makes sense of nerve signals and a plant’s roots are organs that take in nutrients and moisture.

oxygen     A gas that makes up about 21 percent of Earth's atmosphere. All animals and many microorganisms need oxygen to fuel their growth (and metabolism).

prefrontal cortex     A region containing some of the brain’s gray matter. Located behind the forehead, it plays a role in making decisions and other complex mental activities, in emotions and in behaviors.

slaughterhouse     A facility where animals are killed in order to produce meat.

sophisticated     A term for something that is advanced, complex and/or elegant.

stroke     (in biology and medicine) A condition where blood stops flowing to part of the brain or leaks in the brain.

tissue     Made of cells, it is any of the distinct types of materials that make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues.

unique     Something that is unlike anything else; the only one of its kind.

Citation

Journal: Z. Vrselja et al. Restoration of brain circulation and cellular functions hours post-mortemNature. Vol. 568, April 18, 2019, p. 336. doi: 10.1038/s41586-019-1099-1.

Journal: N.A. Farahany, H.T. Greely and C.M. Giattino. Part-revived pig brains raise ethical quandariesNature. Vol. 568, April 18, 2019, p. 299. doi: 10.1038/d41586-019-01168-9.

Journal: S. Youngner and I. Hyun. Pig brain study could fuel debates around deathNature. Vol. 568, April 18, 2019, p. 302. doi: 10.1038/d41586-019-01169-8.