Scientists have long dreamed of discovering the secret to transforming chemicals into life. This month, a team from the University of Minnesota announced a major step toward achieving that dream, as reported by Carl Zimmer and Marco Hernandez.

Creating simple cells

By mixing dozens of components, researchers have managed to create simple cells that feed, grow, reproduce, and compete with each other for food. Although these cells are not fully alive, they possess most of the traits of life.

Kate Adamala, a synthetic biologist at the university who led the research, said: "Life is not binary... That's why I hesitate to describe it as 'alive.' There is no clear dividing line, no matter how much we wish there were."

So far, scientists have not mastered the recipe for a cell capable of performing such a vast array of functions, said John Glass, a synthetic biologist at the J. Craig Venter Institute in San Diego, who was not involved in the study. He added: "It's amazing that they were able to combine all these elements." Rosanna Zhia, a computational biologist at the University of Missouri who did not participate in the project, said: "We will remember this moment."

A cell resembling a potato

Drew Endy, a synthetic biologist at Stanford University, said: "It's a manufactured cell, not a natural one. It's constructed, but it performs cellular functions." Adamala named her creation "SpudCell," after its potato-like shape. Instead of patenting it, she and Endy are working to organize a community of scientists focused on making SpudCell more lifelike and adapting it to new types of experiments. They and their colleagues have founded a nonprofit research organization that Endy estimates will spend hundreds of millions of dollars on this effort over the next decade. Hundreds of scientists are expected to join.

Adamala and her colleagues published a detailed 190-page report of their work online. The research is currently under review for publication in a scientific journal.

Synthetic cell engineering for research purposes

Scientists hope that synthetic cells will allow them to understand aspects of life that natural cells cannot reveal, including fundamental questions such as the number of genes needed for the simplest form of life.

Synthetic cells could one day be engineered to do things natural cells cannot, such as producing new types of drugs or extracting large amounts of carbon dioxide from the atmosphere. In theory, engineered SpudCells could produce a wide range of proteins that natural cells cannot, or even toxic chemicals, such as rocket fuel. Glass said: "Now we can think about conducting chemical experiments that we still cannot understand."

Probing the mystery of life

The mystery of life as we know it lies in its enigmatic, intertwined complexity. Our DNA contains tens of thousands of genes, plus millions of molecular switches that activate and deactivate these genes. Scientists still do not know the functions of many of these DNA segments. Often, a gene they think they understand turns out to perform other unexpected functions.

Since the 1990s, several labs have been studying small parts of this problem. Some have mastered ways to make hollow bubbles from oily molecules. Others found ways to package simple genetic molecules inside these bubbles.

But scientists have struggled to assemble these parts into more complex systems, let alone form what could be called a cell.

In recent years, Adamala tackled one of the fundamental challenges: cell division. A natural cell divides with the help of proteins that intertwine to form a ring anchored to its inner wall. The ring then tightens around itself, splitting the cell in two. Other proteins act as cranes, moving DNA and other molecules into the newly formed cells to provide the components necessary for life to continue.

From simulation to manufacturing

Initially, Adamala tried to build a simpler version of the natural system. But she later decided not to mimic real cells at all.

Biophysicists had discovered that when proteins attach to a membrane, they generate pressure that causes the membrane to curve. So Adamala and her team created bubbles capable of capturing floating proteins around them. When a bubble collects enough proteins, its surface begins to curve inward until it bursts into two halves.

Despite the simplicity of the idea, implementing it in the lab took a year of experimentation. Adamala said: "But once it works, it does the job."

*The "recipe" contained about a hundred types of proteins and simple molecules needed for biochemical reactions*

Building a complete synthetic cell

This success encouraged the team to attempt building a complete synthetic cell. The first step was to prepare a "broth," a mixture of molecules necessary for cell function. The final recipe contained about a hundred types of proteins and simple molecules needed for biochemical reactions, such as producing new proteins from genes.

The researchers also equipped their synthetic cell with genes borrowed from a virus and the common bacterium Escherichia coli. They selected 36 genes for essential functions, such as DNA replication. After mixing these components, the scientists added the basic components of membranes. These components spontaneously merged to form bubbles, each swallowing part of the mixture.

Many of these bubbles ended up encapsulating the right mix of genes, proteins, and other molecules, and began performing the chemical reactions that occur in real cells. As the new cells floated in flasks, Adamala and her colleagues added food. The cells absorbed small molecules through channels on their surfaces.

The scientists also placed small bubbles loaded with proteins and other molecules too large to pass through the channels. By colliding and fusing with one of these bubbles, the cell feeds on the nutrients inside them.

As the cells fed, they began to grow. Within a few hours, they became large enough to divide. Then the scientists added a special protein to the flasks, which attached to the cell surfaces and forced them to curve inward. Once the cells split into two, the new cells continued to grow.

Growing generations of synthetic cells

Thus, SpudCells grew, fed, and reproduced. It turned out that these cells have a primitive ability to evolve. Adamala and her colleagues created a mutant version that adhered more strongly to the nutrient-filled bubbles floating around them. To test it, they prepared a 50-50 mixture of original and mutant SpudCells.

The cells competed for food for five generations. In the end, the mutant cells outnumbered the original ones, indicating they outcompeted them for food.

Rosanna Zhia commented: "This is the achievement that will revolutionize the field." Scientists will be able to pit different synthetic cells against each other in competition, speeding up the development of more advanced cells.

A fundamental deficiency in the synthetic cell