Human Brain Cells

Pigs With Human Brain Cells and Biological Chips: How Lab-Grown Hybrid Life Forms Are Bamboozling Scientific Ethics

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two-cell embryo mitosis under a microscope in 3D

In September, scientists at the Guangzhou Institutes of Biomedicine and Health announced they had successfully grown “humanized” kidneys inside pig embryos.

The scientists genetically altered the embryos to remove their ability to grow a kidney, then injected them with human stem cells. The embryos were then implanted into a sow and allowed to develop for up to 28 days.

The resulting embryos were made up mostly of pig cells (although some human cells were found throughout their bodies, including in the brain). However, the embryonic kidneys were largely human.

This breakthrough suggests it may soon be possible to generate human organs inside part-human “chimeric” animals. Such animals could be used for medical research or to grow organs for transplant, which could save many human lives.

But the research is ethically fraught. We might want to do things to these creatures we would never do to a human, like kill them for body parts. The problem is, these chimeric pigs aren’t just pigs—they are also partly human.

If a human–pig chimera were brought to term, should we treat it like a pig, like a human, or like something else altogether?

Maybe this question seems too easy. But what about the idea of creating monkeys with humanized brains?

Chimeras Are Only One Challenge Among Many

Other areas of stem cell science raise similarly difficult questions.

In June, scientists created “synthetic embryos”—lab-grown embryo models that closely resemble normal human embryos. Despite the similarities, they fell outside the scope of legal definitions of a human embryo in the United Kingdom (where the study took place).

Like human–pig chimeras, synthetic embryos straddle two distinct categories: in this case, stem cell model and human embryo. It is not obvious how they should be treated.

In the past decade, we have also seen the development of increasingly sophisticated human cerebral organoids (or “lab-grown mini-brains”).

Unlike synthetic embryos, cerebral organoids don’t mimic the development of a whole person. But they do mimic the development of the part that stores our memories, thinks our thoughts, and makes conscious experience possible.

A microscope image shows a grid of squares covered with an irregular growth of strand-like neurons.
A network of neural cells grown on an array of electrodes to produce a ‘biological computer chip’. 

Most scientists think current “mini-brains” are not conscious, but the field is developing rapidly. It is not far-fetched to think a cerebral organoid will one day “wake up.”

Complicating the picture even further are entities that combine human neurons with technology—like DishBrain, a biological computer chip made by Cortical Labs in Melbourne.

How should we treat these in vitro brains? Like any other human tissue culture, or like a human person? Or perhaps something in between, like a research animal?

A New Moral Framework

It might be tempting to think we should settle these questions by slotting these entities into one category or another: human or animal, embryo or model, human person or mere human tissue.

This approach would be a mistake. The confusion sparked by chimeras, embryo models, and in vitro brains shows these underlying categories no longer make sense.

We are creating entities that are neither one thing nor the other. We cannot solve the problem by pretending otherwise.

We would also need good reasons to classify an entity one way or another.

Should we count the proportion of human cells to determine whether a chimera counts as an animal or a human? Or should it matter where the cells are located? What matters more, brain or buttocks? And how can we work this out?

Moral Status

Philosophers would say these are questions about “moral status,” and they have spent decades deliberating on what kinds of creatures we have moral duties to, and how strong these duties are. Their work can help us here.

For example, utilitarian philosophers see moral status as a matter of whether a creature has any interests (in which case it has moral status), and how strong those interests are (stronger interests matter more than weaker ones).

On this view, so long as an embryo model or brain organoid lacks consciousness, it will lack moral status. But if it develops interests, we need to take these into account.

Similarly, if a chimeric animal develops new cognitive abilities, we need to reconsider our treatment of it. If a neurological chimera comes to care about its life as much as a typical human does, then we should hesitate to kill it just as much as we would hesitate to kill a human.

This is just the beginning of a bigger discussion. There are other accounts of moral status, and other ways of applying them to the entities stem cell scientists are creating.

But thinking about moral status sets us down the right path. It fixes our minds on what is ethically significant, and can begin a conversation we badly need to have.

Real AI Will Need Biology: Computers Powered by Human Brain Cells

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Summary: The human brain continues to massively outperform AI technology in a range of tasks, a new study reports. Researchers outline their plans for biocomputers and organoid intelligence systems as future improvements for artificial intelligence technology.

Source: Cortical Labs

The time has come to create a new kind of computer, say researchers from John Hopkins University together with Dr Brett Kagan, chief scientist at Cortical Labs in Melbourne, who recently led development of the DishBrain project, in which human cells in a petri dish learnt to play Pong.

In an article published today in Frontiers in Science, the team outlines how biological computers could surpass today’s electronic computers for certain applications while using a small fraction of the electricity required by today’s computers and server farms.

They’re starting by making small clusters of 50,000 brain cells grown from stem cells and known as organoids. That’s about a third the size of a fruit fly brain. They’re aiming for 10 million neurons which would be about the number of neurons in a tortoise brain. By comparison, the average human brain has more than 80 billion neurons.

The article highlights how the human brain continues to massively outperform machines for particular tasks. Humans, for example, can learn to distinguish two types of objects (such as a dog and a cat) using just a few samples, while AI algorithms need many thousands. And while AI beat the world champion in Go in 2016, it was trained on data from 160,000 games – the equivalent of playing for five hours each day, for more than 175 years.

Brains are also more energy efficient. Our brains are thought to be able to store the equivalent of more than a million times the capacity of an average home computer (2.5 petabytes), using the equivalent of just a few watts of power. US data farms, by contrast, use more than 15,000 megawatts a year, much of it generated by dozens of coal-fired power stations.

In the paper, the authors outline their plan for “organoid intelligence”, or OI, with the brain organoids grown in cell-culture. Although brain organoids aren’t “mini brains”, they share key aspects of brain function and structure. Organoids would need to be dramatically expanded from around 50,000 cells currently.

“For OI, we would need to increase this number to 10 million,” says senior author Prof Thomas Hartung of Johns Hopkins University in Baltimore.

Brett and his colleagues at Cortical Labs have already demonstrated that biocomputers based on human brain cells are possible. A recent paper in Neuron showed that a flat culture of brain cells could learn to play the video game Pong.

“We have shown we can interact with living biological neurons in such a way that compels them to modify their activity, leading to something that resembles intelligence,” says Kagan of the relatively simple Pong-playing DishBrain.

“Working with the team of amazing people assembled by Professor Hartung and colleagues for this Organoid Intelligence collaboration, Cortical Labs is now trying to replicate that work with brain organoids.”

“I would say that replicating [Cortical Labs’] experiment with organoids already fulfils the basic definition of OI,” says Thomas.

This shows a brain
The article highlights how the human brain continues to massively outperform machines for particular tasks.

“From here on, it’s just a matter of building the community, the tools, and the technologies to realise OI’s full potential,” he said.

“This new field of biocomputing promises unprecedented advances in computing speed, processing power, data efficiency, and storage capabilities – all with lower energy needs,” Brett says. “The particularly exciting aspect of this collaboration is the open and collaborative spirit in which it was formed. Bringing these different experts together is not only vital to optimise for success but provides a critical touch point for industry collaboration.”

https://www.youtube.com/embed/Dgihhl2SR20?feature=oembedCredit: Frontiers

And the technology could also enable scientists to better study personalised brain organoids developed from skin or small blood samples of patients suffering from neural disorders, such as Alzheimer’s disease, and run tests to investigate how genetic factors, medicines, and toxins influence these conditions.

Note: TH is named invent

or on a patent by Johns Hopkins University on the production of brain organoids, which is licensed to AxoSim, New Orleans, LA, United States, and receives royalty shares.

TH and LS consult AxoSim. JS is named as inventor on a patent by the University of Luxembourg on the production of midbrain organoids, which is licensed to OrganoTherapeutics SARL, Esch-sur-Alzette, Luxembourg. JS is also co-founder and shareholder of OrganoTherapeutics SARL.

AM is a co-founder and has equity interest in TISMOO, a company dedicated to genetic analysis and human brain organogenesis, focusing on therapeutic applications customized for autism spectrum disorders and other neurological disorders with genetic origins.

The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. BK is an inventor on patents for technology related to this paper along with being employed at and holding shares in Cortical Labs Pty Ltd, Melbourne, Australia.

No specific funding or other incentives were provided for involvement in this publication.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Human brain cells implanted in rats prompt excitement — and concern

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Rat–human hybrid brains offer new ways to study human neurological disorders, but also raise ethical questions

Micrograph of a human brain organoid in a rat brain
Researchers have transplanted a human brain organoid (bright green) into the brain of a newborn rat pup, creating a hybrid brain in which the neurons interface.Credit: Stanford University

Miniature human-brain-like structures transplanted into rats can send signals and respond to environmental cues picked up by the rats’ whiskers, according to a study1. This demonstration that neurons grown from human stem cells can interface with nerve cells in live rodents could lead to a way to test therapies for human brain disorders.Hybrid brains: the ethics of transplanting human neurons into animals

Scientists would like to use brain organoids — tiny brain-like structures grown from human stem cells — to study neurodegenerative and neuropsychiatric disorders that humans develop. But the organoids mimic human brains only so far. They don’t develop blood vessels and so can’t receive nutrients, meaning that they don’t thrive for long. And they don’t get the stimulation they need to grow fully: in a human infant’s brain, neurons’ growth and how they develop connections with other neurons are based in part on input from the senses.

To give brain organoids this stimulation and support, neuroscientist Sergiu Pasca at Stanford University in California and his colleagues grew the structures from human stem cells and then injected them into the brains of newborn rat pups, with the expectation that the human cells would grow along with the rats’ own cells. The team placed the organoids in a brain region called the somatosensory cortex, which receives signals from the rats’ whiskers and other sensory organs and then passes them along to other brain regions that interpret the signals.Can lab-grown brains become conscious?

Human brain cells mature much more slowly than rat cells, so the researchers had to wait for more than six months for the organoids to become fully integrated into the rat brains. But when they examined the animals’ brains at the end of that time, they saw that the integration had been so successful that it was almost like adding “another transistor to a circuit”, Pasca said at a 10 October press conference.

Paola Arlotta, a molecular biologist at Harvard University in Cambridge, Massachusetts, is excited about the results. “It’s an important step in allowing organoids to tell us more complex properties of the brain,” she says, although she thinks that the transplantation procedure is probably still too expensive and complex to become a standard research tool. The next step, Arlotta adds, will be to work out how individual human neurons — not just fully developed organoids — are integrated into the rat brain.

Behaviour trigger

In their report, published in Nature on 12 October1, the researchers describe how they genetically engineered the neurons in the organoids to fire when stimulated with light from a fibre-optic cable embedded in the rats’ brains. The team trained the rats to lick a spout to receive water while the light was switched on. Afterwards, when the researchers shone the light on the hybrid brains, the rats were prompted to lick the spout, meaning that the human cells had become integrated well enough to help drive the animals’ behaviour. Furthermore, when the researchers prodded the rats’ whiskers, they found that the human cells in the sensory cortex fired in response, suggesting that the cells were able to pick up sensory information.

Black and white image of a small human neuron grown next to a large neuron.
Human neurons created from stem cells and transplanted into a rat brain (right) grow more fully than those cultivated in a dish (left).Credit: Stanford University

To demonstrate the promise of their work for studying brain disorders, Pasca and his colleagues also created brain organoids from the stem cells of three people with a genetic condition called Timothy syndrome, which can cause symptoms similar to some seen in autism. The tiny structures looked the same as any other brain organoids grown in a dish, but when the researchers transplanted them into rats, they did not grow as large as others and their neurons didn’t fire in the same way.

Rusty Gage, a neuroscientist at the Salk Institute for Biological Studies in La Jolla, California, is glad to see these results. In 2018, he and a team of researchers found that transplanted human brain organoids could be integrated into the brains of adult mice2. Mice don’t live as long as rats, and Pasca and his colleagues hoped that because newborn rat pups’ brains are more plastic than those of adult animals, they would be better able to receive the new cells.

“We’ve got challenges out there for us,” Gage says. “But I do believe the transplantation procedure will be a valuable tool.”First monkey–human embryos reignite debate over hybrid animals

Some of the challenges are ethical. People are concerned that creating rodent–human hybrids could harm the animals, or create animals with human-like brains. Last year, a panel organized by the US National Academies of Sciences, Engineering, and Medicine released a report concluding that human brain organoids are still too primitive to become conscious, attain human-like intelligence or acquire other abilities that might require legal regulation. Pasca says that his team’s organoid transplants didn’t cause problems such as seizures or memory deficits in the rats, and didn’t seem to change the animals’ behaviour significantly.

But Arlotta, a member of the National Academies panel, says that problems could arise as science advances. “We can’t just discuss it once and let it be,” she says. She adds that concerns about human organoids need to be weighed against the needs of people with neurological and psychiatric disorders. Brain organoids and human–animal hybrid brains could reveal the mechanisms underlying these illnesses, and allow researchers to test therapies for conditions such as schizophrenia and bipolar disorder. “I think we have a responsibility as a society to do everything we can,” Arlotta says.

Source: Nature

Scientists Implant Mice With Human Brain Cells

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I have some mixed feelings about this, scientifically it’s very interesting, but it also raises some ethical concerns…

What would Stewart Little make of it? Mice have been created whose brains are half human. As a result, the animals are smarter than their siblings.

The idea is not to mimic fiction, but to advance our understanding of human brain diseases by studying them in whole mouse brains rather than in dishes.

The altered mice still have mouse neurons – the “thinking” cells that make up around half of all their brain cells. But practically all the glial cells in their brains, the ones that support the neurons, are human.

“It’s still a mouse brain, not a human brain,” says Steve Goldman of the University of Rochester Medical Center in New York. “But all the non-neuronal cells are human.”