Scientists claim to have built a cell from scratch for the first time

Scientists claim to have built, for the first time from scratch, a cell capable of feeding, growing and replicating like a natural cell. This revolutionary discovery in synthetic biology could usher in an era of custom-made organisms that function like living machines.

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Kate Adamala, a synthetic biologist and professor at the University of Minnesota, and her team built the cell piece by piece from non-living chemical components. The creation is a limited and fragile prototype, but it could help scientists better understand the origins of life and potentially be programmed to help mitigate some of the world's biggest biological problems. The cell is not specific - it is neither plant nor animal - but more closely resembles a simple bacterium.

"I know the cell's full list of ingredients, I know exactly which chemicals, which molecules and in what concentrations," she said. "It's fully defined, which means we can genetically modify it."

For decades, scientists have been bioengineering natural cells to solve human problems. A famous example is the insertion of human insulin genes into bacterial cells of the bacterium E. coli to produce insulin and treat diabetes. Scientists argue that synthetic cells represent the next frontier; they have the potential to lead to the development of new cancer treatments and new ways of capturing carbon or producing chemicals.

Cells are the fundamental building blocks of life, but they are far from simple. The human body has 37 trillion cells, more than the number of stars in the sky, and scientists still don't know how each type of cell works or what exactly they contain.

The synthetic cell that Adamala and his colleagues built was not "lab-created life" but a "real milestone on the way to answering this question," said Yuval Elani, associate professor of biochemical technologies at Imperial College London, who was not involved in the study.

"Building a cell from scratch means you are no longer bound by the limitations and evolutionary legacy of natural biology. It opens up the possibility of designing systems and programming them to do things that living cells may not do easily, or may not do at all," said Elani.

"In my opinion, this is a real advance in the long-standing effort to ask whether chemistry can be organized so convincingly that we can begin to call it life."

The field of synthetic biology is distinct from stem cell research, in which scientists reprogram and manipulate existing cells derived from biological resources.

'An incredibly weak organism'
Adamala named her creation "SpudCell", partly as a joke, as she did not want it to bear her own name. It's also a pun on Sputnik, the Russian satellite that ushered in the space age in the 1950s.

"We hope that we are truly ushering in the true era of the bioeconomy, enabling technologies that will allow people to manipulate biology," she said.

On Wednesday, Adamala and his colleagues made public the scientific paper detailing how SpudCell works, although the research has not yet been published in a peer-reviewed scientific journal. Adamala said the article will be submitted for publication this week. Along with two other scientists, Drew Endy and Jan Jedryszek, and biotechnology entrepreneur Chris Raggio, Adamala founded a public interest institution called Biotic, which hopes to expand the capabilities of the synthetic cell, making it available to other researchers.

Composed of 150 to 200 molecules, SpudCell feeds, grows and replicates for around five generations, according to Adamala. It is much less complex than a biological cell, which contains millions, if not billions, of molecules.

Adamala described SpudCell as "an incredibly fragile organism that, at the moment, does basically nothing other than feed itself and occasionally generate a daughter cell." Each generation needs to be fed and takes about 12 hours to replicate at a temperature of 30 degrees Celsius (86 degrees Fahrenheit). In comparison, E. coli divides every 30 minutes.

The genome of a synthetic cell is much smaller than that of a natural cell, with 90,000 base pairs. (The E. coli genome is 4.6 million base pairs.) Although it can replicate like a natural cell, the synthetic cell uses a different mechanism. A natural cell uses a cytoskeleton, a structure that SpudCell does not have. The synthetic cell, on the other hand, produces proteins that clump together on the membrane, forcing it to divide.

SpudCell is also unable to produce its own ribosomes, essential components of a natural cell that synthesize proteins. Instead, it uses ribosomes from E. coli bacteria, supplied through food.

"It's just the beginning," said Adamala. "It's a foundation we hope to build on, and that's significant because now we can have a reasonable idea of how to build on top of it."

Elani stated that the synthetic cell does not exactly imitate a natural cell - but that is not necessarily a flaw. "Some of these life-like behaviors are achieved by mechanisms quite different from those used in biology," he said in an email. "This is important, because synthetic biology is not always about imitation. Sometimes it allows us to do things differently and take shortcuts."

Other scientists not involved in the research described the work as an exciting advance. SpudCell sits on the border between a "cluster of chemicals and a cell that evolved naturally in nature," said Elizabeth Strychalski, group leader in the National Cell Engineering Group at the U.S. National Institute of Standards and Technology. She called the research "important and impressive", saying it would be "extremely useful".

Tom Ellis, professor of synthetic genomic engineering at Imperial College London, described the cell as "probably the biggest advance in recent times in the field of synthetic cells."

"Creating a synthetic cell helps us understand the exact minimum requirements for life and how life could have arisen from chemistry - it's a fascinating thing to try to understand," Ellis said in an email.

Chenli Liu, a distinguished professor at the Shenzhen Institutes of Advanced Technology and founding director of the China State Laboratory of Quantitative Synthetic Biology, said that synthetic cell research is an exciting and rapidly evolving field, but that it is not possible to make a meaningful assessment of the work before its publication in a peer-reviewed scientific journal.

Is it life?
One of the main achievements of the work, according to the researchers, was to demonstrate that synthetic cells are subject to the forces of natural selection, the process by which certain characteristics become more or less common. When they introduced a genetic change that increased the production of a growth protein, the cells that contained it grew and divided more quickly. However, because this change was introduced into the system rather than arising as a spontaneous genetic mutation, SpudCell cannot be said to have "evolved."

SpudCell also cannot be considered life, said Endy, an associate professor of bioengineering at Stanford University. Endy was not involved in Adamala's research, but is a co-founder of Biotic.

"We don't fully understand life - far from it. We don't have an omnipotent ability to manipulate matter to create things. I would say Kate built a cell. I don't think it created life," Endy said, noting that while physicists still don't fully understand the mysteries of gravity, engineers can still build bridges.

In its current form, he said, SpudCell poses no biosecurity risk and could not, for example, be used to manufacture a biological weapon. "It can only divide if you give it everything it needs, including ribosomes. It has no ability to reproduce outside of this context," he added.

"However, does this promise a future where more people can build cells? Yes. Are there potential security concerns related to this? Yes. Do we need to manage them well? Yes," he said.

Adamala and Endy noted that because SpudCell can be built from the ground up, it will be possible to engineer safeguards and safety mechanisms into the cell's genome that would prevent it from posing safety risks if released into the environment. Furthermore, they said, there are much easier ways for bad actors to create a pathogenic organism.

Scientists have also warned about the potential creation of mirror bacteria - synthetic organisms in which the molecular structure found in nature is reversed. The molecules in a mirror cell would be replaced with identical versions, which could expose humans, animals and plants to the risk of contamination by dangerous pathogens.

Through Biotic, which will license the core technology, Endy and Adamala said they hope SpudCell will become a shared global standard for synthetic cell biology, functioning as an open source operating system like Linux.

Laurie Zoloth, professor of religion and ethics at the University of Chicago, said the creation of Biotic could help address some of the ethical questions that arise when new technologies are introduced: Who benefits from it? Who decides its use? Who sets the guidelines?

"We'll have to see how this holds up in its initial, idealized form," Zoloth said. "I hope so."

Ellis, from Imperial College London, said a standard, shareable, open-source framework would help scientists build on each other's work more quickly. "However, I'm not sure the work presented in this paper is something everyone in the world wants to pursue," he said.

"A synthetic cell is a common goal for many teams around the world, but how they approach this challenge and how they define success is very different."

Adamala said the goal is to keep SpudCell's core technology open to anyone who wants to work on it, adding that academics or non-profit organizations will be able to use it for free, while there will be licensing fees for commercial use.

"Right now, SpudCell can't produce anything useful, it's not efficient enough," she said. "What excites me is that we are bringing the international community together to accelerate development and make it useful."

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Source: CNN