Strange and complex behavior of frog cell blobs

A xenobot “parent,” shaped like a hungry Pac-Man (shown in red false color), created an “offspring” xenobot (green sphere) by gathering loose frog cells in its opening.

Tiny “living machines” made of frog cells can make copies of themselves. This newly discovered renewal mechanism may help create self-renewing biological machines.

According to Kirstin Petersen, an electrical and computer engineer at Cornell University who studies groups of robots, “this is an extremely exciting breakthrough.” She says self-replicating robots are a big step toward human-free systems.

Researchers described the behavior of xenobots earlier this year (SN: 3/31/21). Small clumps of skin stem cells from frog embryos knitted themselves into small spheres and started moving. Cilia, or cellular extensions, powered the xenobots around their lab dishes.

The findings are published in the Proceedings of the National Academy of Sciences on Dec. 7. The xenobots can gather loose frog cells into spheres, which then form xenobots.
The researchers call this type of movement-induced reproduction kinematic self-replication. The study's coauthor, Douglas Blackiston of Tufts University in Medford, Massachusetts, and Harvard University, says this is typical. For example, sexual reproduction requires parental sperm and egg cells. Sometimes cells split or budded off from a parent.

“This is unique,” Blackiston says. These xenobots “find loose parts in the environment and cobble them together.” This second generation of xenobots can move like their parents, Blackiston says.
The researchers discovered that spheroid xenobots could only produce one more generation before dying out. The original xenobots' shape was predicted by an artificial intelligence program, allowing for four generations of replication.

A C shape, like an openmouthed Pac-Man, was predicted to be a more efficient progenitor. When improved xenobots were let loose in a dish, they began scooping up loose cells into their gaping “mouths,” forming more sphere-shaped bots (see image below). As many as 50 cells clumped together in the opening of a parent to form a mobile offspring. A xenobot is made up of 4,000–6,000 frog cells.

Petersen likes the Xenobots' small size. “The fact that they were able to do this at such a small scale just makes it even better,” she says. Miniature xenobots could sculpt tissues for implantation or deliver therapeutics inside the body.

Beyond the xenobots' potential jobs, the research advances an important science, says study coauthor and Tufts developmental biologist Michael Levin. The science of anticipating and controlling the outcomes of complex systems, he says.

“No one could have predicted this,” Levin says. “They regularly surprise us.” Researchers can use xenobots to test the unexpected. “This is about advancing the science of being less surprised,” Levin says.

Quenched lava may have aided in the formation of long RNA strands required by primitive life.

It took a long time for life to emerge. Microbes were present 3.7 billion years ago, just a few hundred million years after the 4.5-billion-year-old Earth had cooled enough to sustain biochemistry, according to fossils, and many scientists believe RNA was the genetic material for these first species. RNA, while not as complicated as DNA, would be difficult to forge into the lengthy strands required to transmit genetic information, raising the question of how it may have originated spontaneously.

Researchers may now have a solution. They demonstrate how basaltic glasses assist individual RNA letters, also known as nucleoside triphosphates, join into strands up to 200 letters long in lab studies. The glasses are formed when lava is quenched in air or water, or when melted rock generated by asteroid strikes cools rapidly, and they would have been plentiful in the early Earth's fire and brimstone.

The outcome has caused a schism among top origin-of-life scholars. "This appears to be a great story that finally explains how nucleoside triphosphates react with each other to create RNA strands," says Thomas Carell, a scientist at Munich's Ludwig Maximilians University. However, Harvard University's Jack Szostak, an RNA expert, says he won't believe the results until the study team thoroughly describes the RNA strands.

Researchers interested in the origins of life like the idea of a primordial "RNA universe" since the molecule can perform two different functions that are essential for life. It's made up of four chemical letters, just like DNA, and can carry genetic information. RNA, like proteins, can catalyze chemical reactions that are necessary for life.

However, RNA can cause headaches. No one has yet discovered a set of plausible primordial conditions that would cause hundreds of RNA letters—each of which is a complicated molecule—to join together into strands long enough to support the intricate chemistry required to kick-start evolution.

Basaltic glasses may have played a role, according to Stephen Mojzsis, a geologist at the University of Colorado, Boulder. They're high in metals like magnesium and iron, which help to trigger a variety of chemical reactions. "Basaltic glass was omnipresent on Earth at the time," he adds.

He provided the Foundation for Applied Molecular Evolution samples of five different basalt glasses. Each sample was ground into a fine powder, sanitized, and combined with a solution of nucleoside triphosphates by molecular biologist Elisa Biondi and her colleagues. The RNA letters were unable to link up without the presence of glass powder. However, when the molecules were mixed with the glass particles, they formed long strands of hundreds of letters, according to the researchers, who published their findings in Astrobiology this week. There was no need for heat or light. Biondi explains, "All we had to do was wait." After only a day, little RNA strands produced, yet the strands continued to grow for months. Jan Paek, a molecular biologist at Firebird Biomolecular Sciences, says, "The beauty of this approach is its simplicity." "Mix the components together, wait a few days, and look for RNA."

Nonetheless, the findings pose a slew of problems. One of the questions is how nucleoside triphosphates came to be in the first place. Recent study by Biondi's colleague Steven Benner suggests that the same basaltic glasses may have aided in the creation and stabilization of individual RNA letters.

The form of the lengthy RNA strands, according to Szostak, is a significant challenge. Enzymes in modern cells ensure that most RNAs form long linear chains. RNA letters, on the other hand, can bind in complicated branching sequences. Szostak wants the researchers to reveal what kind of RNA was produced by the basaltic glasses. "It irritates me that the authors made an intriguing initial finding but then chose to follow the hype rather than the research," Szostak says.

Biondi acknowledges that her team's experiment almost probably results in some RNA branching. She does acknowledge, however, that some branched RNAs are seen in species today, and that analogous structures may have existed before the origin of life. Other studies carried out by the study also confirmed the presence of lengthy strands with connections, indicating that they are most likely linear. "It's a healthy argument," says Dieter Braun, a Ludwig Maximilian University origin-of-life chemist. "It will set off the next series of tests."

Let's take a look back at the internet's history and see where we're going — and why.

Tim Berners Lee had a problem. He was at CERN, the world's largest particle physics factory, at the time. The institute's stated goal was to study the simplest particles with the most sophisticated scientific instruments. The institute completed the LEP Tunnel in 1988, a 27 kilometer ring. This was Europe's largest civil engineering project (to study smaller particles — electrons).

The problem Tim Berners Lee found was information loss, not particle physics. CERN employed a thousand people in 1989. Due to team size and complexity, people often struggled to recall past project information. While these obstacles could be overcome, high turnover was nearly impossible. Berners Lee addressed the issue in a proposal titled ‘Information Management'.

He had an idea. Create an information management system that allowed users to access data in a decentralized manner using a new technology called ‘hypertext'.
To quote Berners Lee, his proposal was “vague but exciting...”. The paper eventually evolved into the internet we know today. Here are three popular W3C standards used by billions of people today:

(credit: CERN)

HTML (Hypertext Markup)

A web formatting language.

URI (Unique Resource Identifier)

Each web resource has its own “address”. Known as ‘a URL'.

HTTP (Hypertext Transfer Protocol)

Retrieves linked resources from across the web.

These technologies underpin all computer work. They were the seeds of our quest to reorganize information, a task as fruitful as particle physics.

Tim Berners-Lee would probably think the three decades from 1989 to 2018 were eventful. He'd be amazed by the billions, the inspiring, the novel. Unlocking innovation at CERN through ‘Information Management'.
The fictional character would probably need a drink, walk, and a few deep breaths to fully grasp the internet's impact. He'd be surprised to see a few big names in the mix.

Then he'd say, "Something's wrong here."

We should review the web's history before going there. Was it a success after Berners Lee made it public? Web1 and Web2: What is it about what we are doing now that so many believe we need a new one, web3?

Per Outlier Ventures' Jamie Burke:

Let's explore.

Web1: The Read-Only Web

Web1 was the digital age. We put our books, research, and lives ‘online'. The web made information retrieval easier than any filing cabinet ever. Massive amounts of data were stored online. Encyclopedias, medical records, and entire libraries were put away into floppy disks and hard drives.

In 2015, the web had around 305,500,000,000 pages of content (280 million copies of Atlas Shrugged).

Initially, one didn't expect to contribute much to this database. Web1 was an online version of the real world, but not yet a new way of using the invention.

That doesn't mean developers weren't building. The web was being advanced by great minds. Web2 was born as technology advanced.

Web2: Read-Write Web

Remember when you clicked something on a website and the whole page refreshed? Is it too early to call the mid-2000s ‘the good old days'?
Browsers improved gradually, then suddenly. AJAX calls augmented CGI scripts, and applications began sending data back and forth without disrupting the entire web page. One button to ‘digg' a post (see below). Web experiences blossomed.

In 2006, Digg was the most active ‘Web 2.0' site. (Photo: Ethereum Foundation Taylor Gerring)

Interaction was the focus of new applications. Posting, upvoting, hearting, pinning, tweeting, liking, commenting, and clapping became a lexicon of their own. It exploded in 2004. Easy ways to ‘write' on the internet grew, and continue to grow.

Facebook became a Web2 icon, where users created trillions of rows of data. Google and Amazon moved from Web1 to Web2 by better understanding users and building products and services that met their needs.

Business models based on Software-as-a-Service and then managing consumer data within them for a fee have exploded.

Web2 Emerging Issues

Unbelievably, an intriguing dilemma arose. When creating this read-write web, a non-trivial question skirted underneath the covers. Who owns it all?

A good plot line emerges. Many amazing, world-changing software products quietly lost users' data control.
For example: Facebook owns much of your social graph data. Even if you hate Facebook, you can't leave without giving up that data. There is no ‘export' or ‘exit'. The platform owns ownership.

While many companies can pull data on you, you cannot do so.

On the surface, this isn't an issue. These companies use my data better than I do! A complex group of stakeholders, each with their own goals. One is maximizing shareholder value for public companies. Tim Berners-Lee (and others) dislike the incentives created.

It's easy to see what the read-write web has allowed in retrospect. We've been given the keys to create content instead of just consume it. On Facebook and Twitter, anyone with a laptop and internet can participate. But the engagement isn't ours. Platforms own themselves.

Web3: The ‘Unmediated’ Read-Write Web

Tim Berners Lee proposed a decade ago that ‘linked data' could solve the internet's data problem.

The Web of Data also allows for new domain-specific applications. Unlike Web 2.0 mashups, Linked Data applications work with an unbound global data space. As new data sources appear on the Web, they can provide more complete answers.

At around the same time as linked data research began, Satoshi Nakamoto created Bitcoin. After ten years, it appears that Berners Lee's ideas ‘link' spiritually with cryptocurrencies.

What should Web 3 do?

Here are some quick predictions for the web's future.

Users' data:
Users own information and provide it to corporations, businesses, or services that will benefit them.

Defying censorship:

No government, company, or institution should control your access to information (1, 2, 3)

Connect users and platforms:

Create symbiotic rather than competitive relationships between users and platform creators.

Open networks:

“First, the cryptonetwork-participant contract is enforced in open source code. Their voices and exits are used to keep them in check.” Dixon, Chris (4)

Global interactivity:

Transacting value, information, or assets with anyone with internet access, anywhere, at low cost

Self-determination:

Giving you the ability to own, see, and understand your entire digital identity.

Not pull, push:

‘Push' your data to trusted sources instead of ‘pulling' it from others.

Where Does This Leave Us?

People believe web3 can help build a better, fairer system. This is not the same as equal pay or outcomes, but more equal opportunity.

It should be noted that some of these advantages have been discussed previously. Will the changes work? Will they make a difference? These unanswered questions are technical, economic, political, and philosophical. Unintended consequences are likely.

We hope Web3 is a more democratic web. And we think incentives help the user. If there’s one thing that’s on our side, it’s that open has always beaten closed, given a long enough timescale.

We are at the start.