Scientists say they have built a cell from scratch for the first time

SpudCell resembles a natural cell but is not identical to cells found in nature. (Orion Venero/Adamala Lab via CNN Newsource)

Scientists say they have built a cell from scratch for the first time that can feed, grow and replicate like a natural cell. This breakthrough in synthetic biology could usher in an era of made-to-order organisms that function like living machines.

Kate Adamala, a synthetic biologist and professor at the University of Minnesota, and her team constructed 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 could potentially be programmed to help mitigate some of the world’s biggest biological problems. The cell is non-specific — neither plant nor animal — but most closely resembles a simple bacterium.

“I know the full ingredient list of the cell, I know exactly what chemicals, what molecules at what concentrations,” she said. “It is fully defined, which means we can engineer it.”

Scientists have for decades bioengineered natural cells to solve human problems. A famous example is how human insulin genes can be inserted into E. coli bacterial cells to manufacture insulin and treat diabetes. Scientists argue synthetic cells are the next frontier; they could potentially lead to the development of new cancer treatments and novel ways to capture carbon or manufacture 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 every different cell type works or what exactly they contain.

The synthetic cell that Adamala and her colleagues built was not “life created in the lab” but a “genuine milestone on the road to toward that question,” said Yuval Elani, an associate professor in biochemical technologies at Imperial College London, who was not involved in the work.

“Building a cell from scratch means you are no longer tied to the constraints and evolutionary baggage 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,” Elani said.

“To my mind, this is a real advance in the long-running effort to ask whether chemistry can be organized so convincingly that we begin to call it life.”

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

‘An incredibly wimpy organism’

Adamala named her creation “SpudCell,” partly as a joke because she didn’t want it named after herself. It’s also a play on Sputnik, the Russian satellite that launched the space age in the 1950s

“We’re hoping we’re really starting the true age of bioeconomy, enabling technology that will let people engineer biology,” she said.

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

Made up of 150 to 200 molecules, SpudCell feeds, grows and replicates for about five generations, according to Adamala. It is far less complex than a biological cell that holds millions, if not billions, of molecules.

Adamala described SpudCell as “an incredibly wimpy organism that right now basically does nothing other than to eat and occasionally make a daughter cell.” Each generation requires feeding and takes roughly 12 hours to replicate at a temperature of 30 C. By comparison, E. coli divides every 30 minutes.

The synthetic cell’s genome is far smaller than that of a natural cell, with 90,000 base pairs. (E. coli’s genome has 4.6 million base pairs.) While it can replicate like a natural cell, the synthetic cell deploys a different mechanism. A natural cell uses a cytoskeleton, a structural framework that SpudCell lacks. The synthetic cell, by contrast, produces proteins, which crowd at the membrane, forcing it to split.

SpudCell is also unable to make its own ribosomes, key parts of a natural cell that make proteins. Instead, it uses E. coli ribosomes that are supplied through feeding.

“It’s just the beginning,” Adamala said. “It’s a chassis that we’re hoping to build on, and that’s significant, because now we actually can have some reasonable idea of how to build on it.”

Elani said the synthetic cell doesn’t exactly mimic a natural cell — but that isn’t necessarily a flaw. “Some of these life-like behaviours are achieved by mechanisms quite unlike those used in biology,” he said via email. “This matters, because synthetic biology is not always about imitation. Sometimes it allows us to do things differently, and to take shortcuts.”

Other scientists not involved in the research described the work as an exciting advancement. SpudCell straddles the line between a “pile of chemicals and a naturally evolved cell in nature,” said Elizabeth Strychalski, a group leader at the US National Institute of Standards and Technology’s National Cellular Engineering Group. She called the research “important and impressive,” saying it would be “tremendously useful.”

Tom Ellis, a professor of synthetic genome engineering at Imperial College London, described the cell as “probably the biggest breakthrough in recent times in the synthetic cell field.”

“Making a synthetic cell helps us understand the exact minimum requirements for life and how life might have emerged from chemistry — that’s a cool thing to try to understand,” Ellis said via email.

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

Is it life?

A key achievement of their work, the researchers said, was showing that the synthetic cells are subject to the forces of selection, the process by which certain traits become more or less common. When they introduced a genetic change that increased production of a growth protein, cells carrying it grew and divided faster. However, because this change was introduced to the system rather than arising as a spontaneous genetic mutation, SpudCell can’t be said to “evolve.”

Nor can SpudCell really 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 totally understand life — far from it. We don’t have an all-powerful ability to manipulate matter to make stuff. I would say Kate has constructed a cell. I don’t think she’s created life,” Endy said, noting that while physicists still don’t fully understand the mysteries of gravity, engineers can nonetheless build bridges.

In its current form, he said, SpudCell does not pose any biosafety risks and could not, for example, be used to manufacture a biological weapon. “It can only divide if you feed everything, including ribosomes. It has zero capacity to reproduce itself outside that context,” he added.

“However, does it promise a future where more people will be able to build cells? Yes. Are there potential safety and security concerns around the doing of that? Yes. Do we have to well manage them? Yes,” he said.

Adamala and Endy noted that because SpudCell can be built from the bottom up, it will be possible to engineer safeguards and fail-safes in the cell’s genome that would prevent the cell from posing safety risks if released into an environment. Plus, they said, there are far easier ways for bad actors to make 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 mirror-image versions that could put humans, animals and plants at risk of exposure to dangerous pathogens.

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

Laurie Zoloth, a professor of religion and ethics at the University of Chicago, said establishing Biotic may help address some of the ethical issues when new technology is introduced: Who does it benefit? Who decides its use? Who sets guardrails in place?

“We will have to see how it endures in its first, idealistic form,” Zoloth said. “I hope it does.”

Imperial College London’s Ellis said a standard, shareable and open-source framework would help scientists build upon one another’s work more quickly. “However, I’m not sure that the work in this paper is something everyone else in the world will want to fall in line behind,“ he said.

“A synthetic cell is a common goal for many teams around the world, but how they are tackling it and how they define success is very different.”

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

“Right now, SpudCell cannot make anything useful, it’s not efficient enough,” she said “What I’m excited about is we’re gathering the international community to actually speed-run the development for it to become useful.”