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Are rats with human brain cells still just rats?

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Are rats with human brain cells still just rats?


It’s a tricky one. The scientists behind the work argue that there’s nothing really human about these rats. Throughout the study, the team examined the rats to see if those with human cells were any smarter, or experienced more suffering, than rats that didn’t receive organoid transplants. They found no sign of human traits or behaviors.

But the whole point of implanting human cells is to get some insight into what happens in the human brain. So there’s a trade-off here. Essentially, the animals need to represent what happens in humans without becoming too human themselves. And if the rats don’t show any human behaviors, can they really tell us that much about human disease?

“The question is: What percentage of animal cells would be needed in the brain to reduce animal behavior and see a different type of behavior?” asks Jeantine Lunshof, a philosopher and ethicist at the Wyss Institute for Biologically Inspired Engineering at Harvard University.

This raises another question. What would it take for us to accept that an animal is no longer a typical member of its own species? Many of the discussions on this topic focus on moral status. Most people would agree that humans have a greater moral status than other animals—and that it is not acceptable to treat people the same way we treat animals, whether for research or in other contexts.

It can be difficult to pinpoint exactly what it is about us that makes us special, but the consensus is that it has something to do with our brains, which are larger and more complex than those of other animals. It is our brains that allow us to think, feel, dream, rationalize, form social bonds, plan our futures, and, more generally, experience consciousness and self-awareness. Could rodents with human brain cells have these same experiences?

It’s an important question for bioethicists like Julian Koplin at Monash University in Victoria, Australia. “If we’re talking about humanizing the brains of non-human animals … by introducing human brain organoids and allowing them to integrate into the animal brain,” he says, “I think we do need to start thinking about whether this could have any follow-on effect for the moral status of the research animal.”

In the current study, the answer appears to be no. But that doesn’t mean we won’t see “humanized” or “enhanced” rats in future, according to Koplin and other bioethicists who specialize in this field.

We need to tread carefully.

In this study, scientists put human brain organoids into a region of the rats’ brains that helps them sense their environment. But there’s no reason they couldn’t put the same organoids into regions that play a role in cognition or consciousness—which might make cognitive enhancement more likely.

Then there’s the question of how much of the rat’s brain is made up of human cells. Transplanting bigger organoids might mean that the rat is technically “more human” at the cellular level—but that’s not what’s important. What matters is how, if at all, its mental state changes.

The mental changes aren’t just about how “human” the rats’ mental states become, either. “You might have an animal that thinks in a very different way to we do, but is acutely susceptible to suffering, or is really intelligent in ways that are not familiar to us as humans,” says Koplin.

So far, we’ve focused on rats. But what would happen if the organoids were put into baby monkeys instead? Non-human primates have brains that look and work much more like ours, so they’d be better models for studying human disease. But “it does raise the possibility that you will create a humanized primate,” says Julian Savulescu, a bioethicist at the National University of Singapore.

Savulescu is also concerned about cloning. The cells that make up organoids contain a person’s DNA. What would happen if a large chunk of a monkey’s brain were made up of cells with an individual’s genetic code?

“If you were to introduce an advanced organoid into a developing primate, you may well essentially create a clone of an existing person,” he says. “Not only would it be humanized—it would be a clone of somebody that’s already in existence.” This would be the very bottom of an ethical slippery slope, says Savulescu.

There are a lot of questions here, and few definitive answers. No one really knows how to measure moral status, or the point at which animals with human cells become special—or even some kind of new animal.

But it provides plenty of food for thought. To read more, check out these articles from Tech Review’s archive:
 
In this piece from 2016, Antonio Regalado describes researchers’ attempts to grow human organs in pigs and sheep. The aim here is to create new organs for people who need transplants.

A Spanish stem-cell biologist told a reporter that the pope had given his blessing to this kind of research. But the Vatican later disputed the claim and called it “absolutely unfounded.”

A few years later, that same biologist went on to create embryos that are part human and part monkey, as reported by El País. Antonio explained why the research was so controversial.

In this recent piece, Hannah Thomasy explores eight technologies that are helping us understand the mysteries of the human brain and how we form memories.

And you can read more about how our brains make our minds in this piece from Lisa Feldman Barrett, which was featured in last year’s Mind issue.

From around the web

Could an algorithm help people who choose to end their own lives? The founder of this nonprofit thinks so. (MIT Technology Review)

Monkeypox cases have been declining for a couple of months now. But there are several ways things could play out from here. (Nature)

Covid boosters have been approved for children as young as five in the US. (Reuters)

Long covid is an enduring problem. Almost half of those who get sick with covid still haven’t fully recovered months later. (New York Times)

Watch this game of Pong. And then realize that it is being played by brain cells in a dish. (Neuron)

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The hunter-gatherer groups at the heart of a microbiome gold rush

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The hunter-gatherer groups at the heart of a microbiome gold rush


The first step to finding out is to catalogue what microbes we might have lost. To get as close to ancient microbiomes as possible, microbiologists have begun studying multiple Indigenous groups. Two have received the most attention: the Yanomami of the Amazon rainforest and the Hadza, in northern Tanzania. 

Researchers have made some startling discoveries already. A study by Sonnenburg and his colleagues, published in July, found that the gut microbiomes of the Hadza appear to include bugs that aren’t seen elsewhere—around 20% of the microbe genomes identified had not been recorded in a global catalogue of over 200,000 such genomes. The researchers found 8.4 million protein families in the guts of the 167 Hadza people they studied. Over half of them had not previously been identified in the human gut.

Plenty of other studies published in the last decade or so have helped build a picture of how the diets and lifestyles of hunter-gatherer societies influence the microbiome, and scientists have speculated on what this means for those living in more industrialized societies. But these revelations have come at a price.

A changing way of life

The Hadza people hunt wild animals and forage for fruit and honey. “We still live the ancient way of life, with arrows and old knives,” says Mangola, who works with the Olanakwe Community Fund to support education and economic projects for the Hadza. Hunters seek out food in the bush, which might include baboons, vervet monkeys, guinea fowl, kudu, porcupines, or dik-dik. Gatherers collect fruits, vegetables, and honey.

Mangola, who has met with multiple scientists over the years and participated in many research projects, has witnessed firsthand the impact of such research on his community. Much of it has been positive. But not all researchers act thoughtfully and ethically, he says, and some have exploited or harmed the community.

One enduring problem, says Mangola, is that scientists have tended to come and study the Hadza without properly explaining their research or their results. They arrive from Europe or the US, accompanied by guides, and collect feces, blood, hair, and other biological samples. Often, the people giving up these samples don’t know what they will be used for, says Mangola. Scientists get their results and publish them without returning to share them. “You tell the world [what you’ve discovered]—why can’t you come back to Tanzania to tell the Hadza?” asks Mangola. “It would bring meaning and excitement to the community,” he says.

Some scientists have talked about the Hadza as if they were living fossils, says Alyssa Crittenden, a nutritional anthropologist and biologist at the University of Nevada in Las Vegas, who has been studying and working with the Hadza for the last two decades.

The Hadza have been described as being “locked in time,” she adds, but characterizations like that don’t reflect reality. She has made many trips to Tanzania and seen for herself how life has changed. Tourists flock to the region. Roads have been built. Charities have helped the Hadza secure land rights. Mangola went abroad for his education: he has a law degree and a master’s from the Indigenous Peoples Law and Policy program at the University of Arizona.

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The Download: a microbiome gold rush, and Eric Schmidt’s election misinformation plan

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The Download: a microbiome gold rush, and Eric Schmidt’s election misinformation plan


Over the last couple of decades, scientists have come to realize just how important the microbes that crawl all over us are to our health. But some believe our microbiomes are in crisis—casualties of an increasingly sanitized way of life. Disturbances in the collections of microbes we host have been associated with a whole host of diseases, ranging from arthritis to Alzheimer’s.

Some might not be completely gone, though. Scientists believe many might still be hiding inside the intestines of people who don’t live in the polluted, processed environment that most of the rest of us share. They’ve been studying the feces of people like the Yanomami, an Indigenous group in the Amazon, who appear to still have some of the microbes that other people have lost. 

But there is a major catch: we don’t know whether those in hunter-gatherer societies really do have “healthier” microbiomes—and if they do, whether the benefits could be shared with others. At the same time, members of the communities being studied are concerned about the risk of what’s called biopiracy—taking natural resources from poorer countries for the benefit of wealthier ones. Read the full story.

—Jessica Hamzelou

Eric Schmidt has a 6-point plan for fighting election misinformation

—by Eric Schmidt, formerly the CEO of Google, and current cofounder of philanthropic initiative Schmidt Futures

The coming year will be one of seismic political shifts. Over 4 billion people will head to the polls in countries including the United States, Taiwan, India, and Indonesia, making 2024 the biggest election year in history.

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Navigating a shifting customer-engagement landscape with generative AI

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Navigating a shifting customer-engagement landscape with generative AI


A strategic imperative

Generative AI’s ability to harness customer data in a highly sophisticated manner means enterprises are accelerating plans to invest in and leverage the technology’s capabilities. In a study titled “The Future of Enterprise Data & AI,” Corinium Intelligence and WNS Triange surveyed 100 global C-suite leaders and decision-makers specializing in AI, analytics, and data. Seventy-six percent of the respondents said that their organizations are already using or planning to use generative AI.

According to McKinsey, while generative AI will affect most business functions, “four of them will likely account for 75% of the total annual value it can deliver.” Among these are marketing and sales and customer operations. Yet, despite the technology’s benefits, many leaders are unsure about the right approach to take and mindful of the risks associated with large investments.

Mapping out a generative AI pathway

One of the first challenges organizations need to overcome is senior leadership alignment. “You need the necessary strategy; you need the ability to have the necessary buy-in of people,” says Ayer. “You need to make sure that you’ve got the right use case and business case for each one of them.” In other words, a clearly defined roadmap and precise business objectives are as crucial as understanding whether a process is amenable to the use of generative AI.

The implementation of a generative AI strategy can take time. According to Ayer, business leaders should maintain a realistic perspective on the duration required for formulating a strategy, conduct necessary training across various teams and functions, and identify the areas of value addition. And for any generative AI deployment to work seamlessly, the right data ecosystems must be in place.

Ayer cites WNS Triange’s collaboration with an insurer to create a claims process by leveraging generative AI. Thanks to the new technology, the insurer can immediately assess the severity of a vehicle’s damage from an accident and make a claims recommendation based on the unstructured data provided by the client. “Because this can be immediately assessed by a surveyor and they can reach a recommendation quickly, this instantly improves the insurer’s ability to satisfy their policyholders and reduce the claims processing time,” Ayer explains.

All that, however, would not be possible without data on past claims history, repair costs, transaction data, and other necessary data sets to extract clear value from generative AI analysis. “Be very clear about data sufficiency. Don’t jump into a program where eventually you realize you don’t have the necessary data,” Ayer says.

The benefits of third-party experience

Enterprises are increasingly aware that they must embrace generative AI, but knowing where to begin is another thing. “You start off wanting to make sure you don’t repeat mistakes other people have made,” says Ayer. An external provider can help organizations avoid those mistakes and leverage best practices and frameworks for testing and defining explainability and benchmarks for return on investment (ROI).

Using pre-built solutions by external partners can expedite time to market and increase a generative AI program’s value. These solutions can harness pre-built industry-specific generative AI platforms to accelerate deployment. “Generative AI programs can be extremely complicated,” Ayer points out. “There are a lot of infrastructure requirements, touch points with customers, and internal regulations. Organizations will also have to consider using pre-built solutions to accelerate speed to value. Third-party service providers bring the expertise of having an integrated approach to all these elements.”

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