Scientists create simple synthetic cell

https://www.nist.gov/news-events/news/2021/03/scientists-create-simple-synthetic-cell-grows-and-divides-normally

by sdht0 • 5 years ago

345 138 5 years ago

nist.gov

fiftyfifty• 5 years ago

So can we say science has finally achieved a biological “Hello World”?

tgv• 5 years ago

More like a quine, isn't it? Pretty impressive.

TimTheTinker• 5 years ago

Not exactly. These lines of cells weren't created from scratch. From the article:

Scientists at JCVI constructed the first cell with a synthetic genome in 2010. They didn’t build that cell completely from scratch. Instead, they started with cells from a very simple type of bacteria called a mycoplasma. They destroyed the DNA in those cells and replaced it with DNA that was designed on a computer and synthesized in a lab. This was the first organism in the history of life on Earth to have an entirely synthetic genome. They called it JCVI-syn1.0.

maverick744• 5 years ago

Exactly what i was writing!!! :)

Now, i guess that - like last time - we're going to have news everywhere claiming that scientists "created life" (again).

LOL

thereisnospork• 5 years ago

I'm curious if they are going to 'ship of Theseus' it. First replace the dna, done, then the lipid membrane, then feed it C13 labelled amino acids to prove that the entirety of the cell proteom is from their synthetic genes.

Not quite creating life but definitely hijacking it.

dnautics4• 5 years ago

"Hello World" isn't exactly created from scratch either. You're using libc in most cases.

maverick744• 5 years ago

No, because like in JCVI-syn1.0

"They didn’t build that cell completely from scratch. Instead, they started with cells from a very simple type of bacteria called a mycoplasma. They destroyed the DNA in those cells and replaced it with DNA that was designed on a computer and synthesized in a lab. This was the first organism in the history of life on Earth to have an entirely synthetic genome."

In another words, like in the previous attempt (in which i was equally amazed - at first - only to then became disappointed latter) THEY DID NOT CREATE LIFE!!!

They picked up an already living organism and "reprogrammed it".

Its like having a computer. They are learning to program, and remove all the unnecessary parts but they still don't have a clue on to build the hardware.

The problem, it seems, is in transforming bare lifeless quimicals into something "alive".

Creating life, it seems, is still something reserved only to God Himself! (and i suspect it's going to be like that for a loooong time, if we ever manage to accomplish it anyway)

camjohnson269• 5 years ago

Intelligent Design as a theory for life’s origins has received a lot of unfair criticism because people think it’s code for “young earth creationism”. It’s not though, it’s an observation that random natural processes are too slow at generating information to be responsible for life on earth.

It’s the same deductive logic you would use if you found an artifact in the middle of the desert. Yes natural forces could have carved an image from the rock, but the more detailed the image the less likely it arose naturally.

The fact that even now, no one has any idea of how to create the basic forms of life shows the astonishing amount of information that exists in even a simple cell. It’s time to reconsider intelligent design, even if the designer is an alien species or a programmer of a simulation. There’s too much information to spontaneously generate, and we have never seen life come from non life.

The theory has been essentially banished from academia for political, not scientific, reasons, but Michael Behe and Stephen Meyer’s books, specifically Darwin’s Doubt and Signature of the Cell, lay out the case in detail.

lupire• 5 years ago

What would that mean?

yread• 5 years ago

More like proof of concept of a buffer overflow vulnerability. It's smart but we have no idea what do all these transistors do

swiley• 5 years ago

Perhaps "Hello world copy and pasted from StackOverflow."

kazinator• 5 years ago

Yes ... using a copy and paste of seven existing functions, knowing what two of them do. Oh, and bootstrapped using a copy of an existing execution environment.

mrguyorama2• 5 years ago

So basically the React tutorial app?

svachalek• 5 years ago

It's a 480 line (gene) Hello World. For this to be the minimum viable cell, when we don't even know what so many of the genes do, would be surprising to me. It would mean pre-cellular life somehow gathered these genes or equivalents without the benefits a cell provides. Not saying it's impossible, but it would be pretty interesting.

f6v2• 5 years ago

Of the seven genes added to this organism for normal cell division, scientists know what only two of them do.

This gives you an appreciation of how little we know. I work in bioinformatics, and every one in the field will tell you that there's been an explosion in the number of datasets. However, try finding recent data on your condition of interest! The number of experiments grows incredibly fast, but we're not there yet to build a comprehensive model even of a simple organism.

koeng3• 5 years ago

https://vizbi.org/Posters/Images/2021/vB26.png

They're working towards it :)

choeger• 5 years ago

I wonder if this is going to be incredibly useful or totally over the top for research. Imagine a development like the BioNTech vaccine. With an atomic-resolution cell simulator, you could verify your mRNA code, including the delivery into the cell itself and watch it perform.

But would that be like watching my CPU decode and fetch instructions, interesting but completely useless for most practical applications, or like a debugger introspecting a running process, an incredible useful tool?

dnautics4• 5 years ago

so fyi I worked in that lab, we called many of them MUFs ("membrane proteins of unknown functions")... We kind of suspect that all they do is maintain membrane integrity and isotonicity just by being present. One easy way for a cell to do to increase the yield of a stuff is to have literally more genes.

So there are a lot of interesting things to do (which I don't know if they did), like instead of having those last five genes in there, copying one of those five genes five times...

azernik• 5 years ago

One easy way for a cell to do to increase the yield of a stuff is to have literally more genes.

Wat

How does this work? Do they encourage expression of the genes that actually make stuff?

pishpash• 5 years ago

Maybe it's rather better to ruthlessly focus resources on a few things rather than know a little but not enough about everything.

sliken• 5 years ago

So grey goo version 0.01?

stcredzero2• 5 years ago

We are grey goo version 0.0.1!!! That is, life on Earth. Life has already become a solar powered self replicator that caused a global catastrophe, burying the whole Earth in a toxic gas.

mrguyorama2• 5 years ago

I always get angry about the conservative idea that "It's hubris to think humanity is so powerful that we could possibly change the whole environment!" (occasionally sprinkled with "only god is that powerful")

Guess what? Such simple creatures as an early bacteria did it even harder over 2 billion years ago, making the earth nearly inhabitable by anything that came before it.

lgats• 5 years ago

https://en.wikipedia.org/wiki/Gray_goo

relax88• 5 years ago

Eh, this biological grey goo is likely so crappy at surviving that it would get snuffed out or out competed by any random culture from the bottom of your shoe.

I'd be more concerned about viral gain of function research and the weaponization of synthetic biology in general.

koeng3• 5 years ago

JCVI-Syn3A has been around for a while. Here is the genome sequence from 2018 - https://www.ncbi.nlm.nih.gov/nuccore/1241355755

Back at FreeGenes we synthesized all of the genes from this organism with codon optimization for Escherichia coli (https://stanford.freegenes.org/collections/gene-sets/product...), the workhorse of synthetic biology. If you combine the right transcriptional and translational elements, you should be able to build a fully modular genome from this gene set! We also did a couple other organisms in pursuit of this modular genome. As a nice bonus, you can also easily do in-vitro cell-free experiments since the codon tables are nice (and I've heard from Kate Adamala's group that JCVI-Syn3 has pretty bad cell free, though that was a couple years ago)

It's important to note that JCVI-Syn3A has a LOT of problems when it comes to its practical use. There just isn't enough energy being put into making an understandable and practical modular/minimal genome.

mercurywells• 5 years ago

What is "pretty bad cell free"?

koeng3• 5 years ago

If you burst open the cells and extract all the goop inside, you can use that goop to express proteins. For certain organisms, like E.coli, this works quite well, and you can get a significant amount of protein. For others, like JCVI-Syn3, the goop sucks at expressing protein. So it’s a “pretty bad cell free” [expression platform]

tmabraham2• 5 years ago

While this top-down approach (removing unnecessary parts of an organism and keeping the essential parts) is really impressive, I personally find the bottom-up approach more interesting: building an "artificial cell" by adding all the transcription and translation machinery into a lipid vesicle, allowing for this "artificial cell" to produce proteins to do various tasks. For example, people have developed "artificial /synthetic cells" that communicate with each other [1] and even bacteria [2]. There has also been some recent study on dividing cell-sized lipid vesicles with membrane proteins [3]. I know there were some comments about science has achieving a biological “Hello World”, and I think this sort of work is what is going to get us there.

[1] https://www.nature.com/nchem/journal/v9/n5/abs/nchem.2644.ht...

[2] https://pubs.acs.org/doi/abs/10.1021/acsami.8b10029

[3] https://www.nature.com/articles/s41467-020-14696-0

callesgg3• 5 years ago

What do you mean? Like creating every protin without a ribosome? Why would you need to go to that lengths of artfical? Seams to like you have to start from the top up in one way or another. Starting from the complete bottom just seams over the top.

faeyanpiraat2• 5 years ago

If you can figure out how to go bottom up, it will result in new innovations in microscopic manufacturing methods.

hutzlibu2• 5 years ago

Starting from the bottom means, you really did understand it all, once completed ..

tmabraham2• 5 years ago

Starting from the complete bottom just seams over the top. Is it really?

"What I cannot create, I do not understand." - Richard Feynman

And to clarify, currently the ribosomes are provided as part of the cell-free transcription/translation system. Additionally, amino acids, tRNA (plus tRNA synthetase), RNA polymerase, and a primitive energy source (ATP with some extra energy in creatine phosphate) are all provided.

Here are the components of the most common cell-free transcription/translation systems (PURE): https://www.nature.com/articles/nprot.2015.082/tables/1

laurent92• 5 years ago

Yes. Starting from the bottom, we might in the process discover that 90%-99% of cell components are cruft/inefficient, and discover how to make cells 10 or 100 times smaller. Imagine being able to inject neurons in the brain that are 100 times smaller.

cambalache• 5 years ago

Meh, if you are not doing the atoms yourself from leptons and quarks then I am not interested.

pmiller23• 5 years ago

Of course, there's a relevant xkcd: https://xkcd.com/378/

ctdonath• 5 years ago

Man: “I shall create life from dirt, to show I am equal with you.”

God: “Get your own dirt.”

sizzle• 5 years ago

Couldn't messing around with these artificial cells expose us to the risk of creating some second order mutations in humans from accidentally introducing these cells to our microbiome from the lab akin to the COVID-19 escaping a 'gain of function' virus lab theory?

pmiller23• 5 years ago

It would be extremely unlikely that such an artificial cell could colonize humans in any way, and even more unlikely that such a cell would be pathogenic.

anigbrowl• 5 years ago

Here's hoping

restalis4• 5 years ago

Maybe that's the beauty of it. Maybe now's exactly the propitious time to play fast and lose with these things. The world today is more prepared than it has ever been - the overall impact may not even register as an independent event and be taken only as another wrinkle to current pandemic.

...but for the record, the above is not an advice. Here's the mandatory and responsible advice: kids, have fun (with science), but wear the things to keep it safe!

jchrisa• 5 years ago

If you can create something living by a combination of non living parts, I think that would be an interesting first. All of the life we know of, presumably has living ancestors. Hence the notion of a "spark" of life that is passed on like the flame of a torch. If we can create life from raw parts and supply the spark ourselves, it increases the relevance of science. Suddenly the idea of sending seeds of ecosystems in the form of printers and data would become viable.

throwaway889900• 5 years ago

We didn't create life from nothing, but we can certainly get close. https://en.wikipedia.org/wiki/Miller%E2%80%93Urey_experiment

kens3• 5 years ago

The approach of removing unnecessary parts from a genome to find the minimum brings to mind Muntzing. In the 1940s, Earl Muntz was a TV seller who reduced manufacturing costs by cutting out unnecessary components. He walked around the lab with diagonal cutters and snipped out components until the TV stopped working. He'd put the last component back and have a new lower-cost design. The TVs only worked in high-signal areas, but were much cheaper than the competition and sold a ton.

https://www.electronicdesign.com/technologies/boards/article...

at_a_remove• 5 years ago

Once you have mastered the top-down ("is this really the minimum? Or is it a local minimum?") approach, then you could attempt to bottom-up with an end product very firmly in mind. This way, you could skip aiming for parts that you might have thought required which were in reality redundant, or secure the existence of a piece you had once thought superfluous.

After you had bottom-upped a few times, one might even try to figure out a necessary order for the steps and possibly gain some more insight into evolution that way.

restalis4• 5 years ago

As all engineering, it boils down to requirements. Mycoplasmata, from which JCVI-syn3A has been developed, is reported to "survive without oxygen", which means that it's not necessarily a "pure" anaerobic organism. We must assume that there has to be an existing mechanism that protects this bacteria from highly reactive oxygen. If the design requirements don't include surviving the natural environment, then that is one of probably many more areas to trim genetic "fat" from. However, I don't know much about their work on synthetic bacteria nor the environment used for it, so it's possible that the aforementioned mechanism to be already removed from its genes.

Freestyler_3• 5 years ago

Could they make cells that can regulate, if there is abundance of X = do something? I mean that would end a lot of problems. Starting with diabetes.

mschuster91• 5 years ago

For that to end diabetes, you'd need to keep the cells in the body... which has two difficulties: first, the cells need to be protected from the immune system destroying them and second, the cells need to find a place in the body to live... and then you have to find a way to keep their numbers regulated.

gulli1010• 5 years ago

Are we creating new organisms that can kill us?

jebeng• 5 years ago

We already do that ourselves naturally as an organism, as does the environment around us.

A simple synthetic cell is so far off from the myriad of potentially deadly cellular organisms(or even deadly malformed protein chains) that already exist and evolve right this instant that it's not worth a second thought in the context of "organisms that can kill us" for now.

lujim• 5 years ago

Ahh boy that title. Clicking on the link to probably realize that this is totally harmless and my initial reaction is due to how much I've been stuck inside for a year.

dang• 5 years ago

I've truncated the title to try to make it less baity. If anyone wants to suggest a better—i.e. more accurate and neutral—title, preferably using representative language from the article, we can change it again.

ChuckMcM3• 5 years ago

This is an interesting result. Basically cellular biologists debugging cells the same way folks who don't understand how a program works debug it, by chopping parts off until it fails and then adding back bits one by one until it works again :-).

At some point, not today and perhaps not in the next 20 years, humans will understand exactly how cells and DNA "work" from first principles to final behavior. At that point, humans will either cease to age and never suffer from disease (Venter would have liked that), or humanity will be wiped out by a malicious organism that is designed by a deranged practitioner.

Yet another technology produced Lady or the Tiger challenge.

darkteflon• 5 years ago

I had to look this up:

https://en.m.wikipedia.org/wiki/The_Lady,_or_the_Tiger%3F

okl• 5 years ago

There's a fun Smullyan book with that title.

novaRom• 5 years ago

We already understand exactly how cells and DNA "work", the problem is methabolic networks are very large and hard to simulate with sufficient certainty.

dooopy• 5 years ago

Lol what are you talking about

andrewflnr• 5 years ago

That's rather the point. Those metabolic networks are not meaningfully separable from "how cells and DNA work".

koheripbal• 5 years ago

...and they also vary across groups of humans. We are not all the same.

Each of us is a n=1 genetic experiment.

IncRnd• 5 years ago

We already understand exactly how cells and DNA "work"

I must have read your comment differently than you intended, since understanding exactly how cells and DNA work implies that the first cell v1.0 would have divided as intended and that it would not have taken 5 years of painstaking research for v2.0.

From the article, "Of the seven genes added to this organism for normal cell division, scientists know what only two of them do."

monkeycantype• 5 years ago

we understand the translation of DNA bases to amino acids, and we once though that was going to be enough to understand inheritance, but we're still unpicking additional mechanisms that regulate gene expression and post translation modification. There's heaps more turtles down there.

WalterBright• 5 years ago

Knowing how something works is not at all the same thing as knowing enough to make significant improvements. It's just a first step.

ChuckMcM3• 5 years ago

True, but knowing how something works enables you to walk the path to learn how to make improvements. It allows you to make reasoned changes vs random changes.

misterkrabs• 5 years ago

There's also epigenetics to consider, like methylation and acetylation, which adds a whole extra layer of complexity. :/

forgotmypw17• 5 years ago

I think it's really difficult not to underestimate the complexity, although software engineers have a unique perspective.

Have you ever maintained an application of vintage? You have some idea of how complex an application can get after a decade or two... Now, imagine an application which is X years old, where X is our age going back to the first ancestors...

mensetmanusman4• 5 years ago

Maybe computer ‘will’, but not humans. We have had thousands of years to try to come up with a definition of life and free will, and we haven’t even managed that :)

https://www.quantamagazine.org/what-is-life-its-vast-diversi...

ChuckMcM3• 5 years ago

It is important not to mix philosophical questions with pragmatic ones. We don't have a solid definition of what "life" is, but as this group demonstrated creating something that is unequivocally "alive" by our extant definitions.

Much like the COVID-19 vaccines are the first widely distributed "product" of our understanding of messenger RNA, I would expect the first widely available products that come from our understanding of building and operating single cell organisms to be things like water purification, drug production, Etc.

For example, an organism that secretes vanilla extract would be a multi-billion dollar product. And "all"[1] it would have to do is mimic what the vanilla Orchid does when growing seeds.

[1] This is a deep and wide void of knowledge about how it does what it does, not trying to gloss that over, just making the case for single cell organisms as useful products.

Traubenfuchs• 5 years ago

Stunning and beautiful: We are on our way to truly intelligently designed life.

ncmncm5• 5 years ago

"Truly intelligently designed life" would need to be designed by somebody truly intelligent. But all we got is us. So, that will always be beyond us.

Giorgi• 5 years ago

So at some point we can just print humans (or better organism) making organic life obsolete.

jonplackett2• 5 years ago

How much data is contained in the 500 genes of this cell?

I'm kinda curious the minimum number of bytes it takes to make a living cell.

QuantumG• 5 years ago

543,379 base pairs = 1,086,758 bits = 135,845 bytes.

https://www.ncbi.nlm.nih.gov/assembly/GCA_001708325.2/

johnwyles• 5 years ago

You don't need the other half of a base pair in your calculation

Jeud• 5 years ago

Interesting development. We already use cellular machinery to make some drugs like human insulin made with genetically modified bacteria. I think an application for this type of development might be nano construction of advanced materials that are hard to manufacture in quantity, like an engineered bacteria to build sheets of the materials as long as it has a supply of graphite and minimal nutrition.

rishabhd• 5 years ago

Stupid question from someone who has zero idea about this field :

What are the chances they unknowingly create a new virus/ bacteria for which no known defenses are present. How is this probability mitigated during design process and what protocols are followed for ensuring this doesn't happen. I did read about bio safety levels, but I feel they themselves could be bypassed.

restalis4• 5 years ago

Just think about the mass of all microscopic organisms outside the labs that suffer mutations all the time. Worrying about innocuous bacteria turning into something bad on accident within comparatively very limited environment of a laboratory doesn't make much sense. Think also of the many free floating bacteria cells in our environment that die due to various factors, whose bodies then have to break apart. Compared to what may happen in a lab, I imagine that those pieces of dead cells floating around freely may pose a greater risk of falling and fitting somehow within living host cells altering their function. (That's one of the mutation vectors, BTW, be it constructive or destructive.) The only scenario that makes sense to seriously worry about when a lab works with/on a virus or bacteria is if the material they started with carries inherently a high risk, or (worse) if they focus on weaponizing it (but that would not be "unknowingly" as you mention).

restalis4• 5 years ago

I imagine that from engineering POV, having self-replicating cells that will also do the useful work won't be optimal. This self-contained single-cell system was the only one that could work in the wild initially, but after a while even in natural systems like our bodies we have cells (like those red ones from our blood) that are produced by specialized tissues (red bone marrow), are designed with a specific function and with a simplified structure (like to be small, without cell nucleus), and disposed by other specific tissues (in the liver). If I had to design a system (and a business) it would involve printing specialized (non-replicating) work cells and some control/disposal mechanisms. The research focus on simplest living and self-replicating cells looks interesting but not that much oriented on any practical purposes.

Scientists create simple synthetic cell

Related Stories