Dishing on biobots like xenobots & anthrobots vs. organoids

If you remember xenobots, mobile clusters of frog cells, now you might be interested to learn that some of the same team brings us human cell clusters called anthrobots.

Both frog and human cellular clusters are considered types of biobots or robots made of cells.

An image of a biobot from Anthrobots research. Source: Gizem Gumuskaya, Tufts University.

To me, anthrobots seem akin to human organoids or assembloids. Is there a difference? We’ll talk it through.

Why are these biobots being made? Hopefully, anthrobots will be able to do specific helpful jobs like repairing diseases or injuries in people. Yes, someday they might be let loose inside of people’s bodies to do repairs.

These biobots may also advance core knowledge of cell and tissue biology. For these reasons, this research has potential and is interesting.

Biobots vs. organoids

Unfortunately, in my view this stuff is also getting hyped though. There was also a tendency to anthropomorphize the xenobots.

Now some are characterizing anthrobots in over-the-top ways too.

Can we tease apart the media hype or overexuberance here from the interesting core science?

To try let’s start by taking a look at the new anthrobots paper in Advanced Science: Motile Living Biobots Self-Construct from Adult Human Somatic Progenitor Seed Cells.

How are anthrobots made?

Here’s the beginning of the methods:

“Each Anthrobot begins as a single cell, derived from the adult human lung, and self-constructs into a multicellular motile biobot after being cultured in extra cellular matrix for 2 weeks and transferred into a minimally viscous habitat.”

The authors go on, “Anthrobots are found to be capable of traversing, and inducing rapid repair of scratches in, cultured human neural cell sheets in vitro.”

That could be useful, but only if anthrobots and their behavior are 100% controllable. These bot actions would also have to be reproducible including in multiple distinct labs.  Has such replication of results happened with xenobots? A PubMed search for xenobots doesn’t find many labs working on them. Or at least mentioning them.

What about the reported repair function? Do the bots help with scratch repair by secreting growth factors? Is scratch repair relevant to human disease? Would simple conditioned media spark scratch repair in the same way?

Anthropomorphizing cells: xenobots vs. anthrobots

Many in the media can’t get enough of biobots. They aren’t always careful in their coverage. For example, a recent CNN article on anthrobots says these human cellular robots “explore” their environments. That seems to overstate things and humanize cellular clusters. Is “explore” really the right word?

By exploring, I guess it means that these cellular clusters can move around via cilia. Such movement might be responsive to environmental clues.

More generally, cells or clusters of motile cells within tissues can migrate in response to signals. For example, immune cells can move around to surveil tissues for signs of pathogens. Maybe that’s a kind of “exploring”?

By contrast, from this anthrobot study and earlier xenobot work, it seems to me like much of biobot movement is random and not controllable or programmed coherently as is seen with immune cells.

Just another fancier name for organoids?

In the end, how are these anthrobot clusters fundamentally any different from organoids or assembloids? Organoids usually start from groups of cells rather than one cell, so that’s a difference from the bots.

Perhaps the key difference between biobots and organoids/assembloids is mostly one of intent of the scientists who make them.

The primary goal with organoids/assembloids is to recapitulate specific organs or parts of tissues. The main intent with biobots is for them eventually to be made to do specific jobs. In that sense is it reasonable to call them bots instead of organoids?

What are the risks of xenobots and anthrobots?

It’s also worth pointing out that it is unclear whether anthrobots or xenobots can predictably do only one specific job.

They couldn’t be used as a cell therapy in people unless their behavior was highly controllable. Imagine billions of self-replicating biobots loose inside a person’s body doing thousands of different, unpredictable things. Not good. You could end up with tumors or tissue destruction, which are just two risks that come to mind.

Another risk could be that the bots would clog up small blood vessels.

What is the purpose of xenobots, anthrobots, and organoids?

Getting back to the bot-organoid comparisons, another point is that beyond just being like an organ, organoids can also perform certain jobs too.

Researchers have produced dozens of kinds of organoids, including some with cilia and just about any other cellular or tissue structure you can imagine. Some organoids can move.

We’ve seen organoids that make tears. That could be useful for dry eye treatments.

Some organoids make snake venom, which could advance research to help people with snake bites. There have been organoids with primitive eye-like structures. Organoid-produced cerebrospinal fluid could someday be used as a treatment.

Do bots or robots by definition have to move?

This also led me to a more general question as to whether something has to move to be defined as a robot.

In the past, I think most people would have said “yes”.

However, these days, it seems like a tougher question and some robots and bots clearly don’t move.

The language of science

Does how we name cellular structures matter? The language we use in science is quite important but we don’t want it to be overly constraining.

Perhaps researchers with more of an engineering background tend to think of (and name) cellular things as “robots” and those with more of a developmental or cell biology mindset are more inclined to think of cellular objects as akin to miniature organs.

It’s also notable that the authors here capitalize the word “Anthrobot.” Why? Are they over-endowing these cellular clusters with some identity?

In the end we should evaluate cellular constructions mostly on the rigorousness and reproducibility of the data, what the objects can do, how they can be controlled, and what they can teach us.

Would an organoid by any other name still be as sweet a lab creation?

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