Puzzle of life? How the creation of artificial cells will transform our lives


“It was the pre-Christmas period, and I was about six years old. I came home from school and my mother confessed to me that the Christ Child” (who according to German tradition brings the presents on Christmas Eve) “didn’t exist. My world fell apart right there and then!” Kerstin Göpfrich began her lecture in the Mercedes-Benz Museum with this biographical anecdote, with which she took the audience along on a fascinating journey to synthetic biology. “Somewhat later, I realized that there are perhaps other questions that are just as magical as that of the Christ Child’s existence or non-existence. One such question is: What is life? And: Can life be created artificially?”

Kerstin Göpfrich pursues these questions in her scientific work. She has been a professor at Heidelberg University’s Center for Molecular Biology since November 2022 and heads a research group at the Max Planck Institute for Medical Research in Heidelberg. In 2022, she was awarded the European Research Council’s prestigious Starting Grant for her research into the evolution of artificial cells. She is also actively involved in science communication in the traditional print media, radio and television, as well as the social media.

At the beginning of her lecture, Göpfrich explained two methods used in synthetic biology to produce artificial cells. In the so-called top-down approach, a living or natural cell can be modified by means of methods such as genetic manipulation in order to produce cells with the desired properties. She pointed out the work of the American biochemist Craig Venter, for example, which is esteemed for its application of this approach. “With the top-down approach, an artificial cell is still created from a natural cell through cell division,” says Göpfrich. The bottom-up approach, on the other hand, sets out to assemble individual molecules in such a way that artificial cells with the characteristics of life are configured from scratch. “This type of artificial cell doesn’t yet exist,” she emphasized. “But life must have emerged from matter at some point. With the ‘Big Bang of life,’ molecules must have come together at some time in such a way as to create a cell with the ability to self-replicate and evolve. We are now trying to artificially recreate precisely this type of cell in the laboratory.” The objective is therefore the bottom-up construction of a living model system with the ability to self-replicate and evolve using the research group’s own molecular machinery.

Göpfrich’s research focuses on the construction of an artificial cell with its own molecular hardware, in order to produce a functional cellular model system: “We don’t proceed like an archaeologist, who tries to piece together the existing parts of a jigsaw puzzle – we’re looking for tools and materials that we can use to focus on the functional aspect, to recreate something de novo that has the same function as life as we know it.”

Microfluidics serves here as a tool for creating minute channels on chips, with about the thickness of a human hair. Cell envelopes can be sent through these small channels in a solution, Göpfrich continued, and components can be introduced into these artificial cell compartments to emulate a kind of cell cycle. 3D printing is used as a further tool to solve the “ship in a bottle” problem encountered in synthetic biology: “Once we have a cellular envelope – the so-called lipid vesicle – it is then very difficult to position components within it spatially and temporally. But light can in fact penetrate the envelope of the compartment into its interior,” said Göpfrich, explaining her approach of printing within artificial cellular vesicles using laser light. This is not just about structure, but also function. For example, small channels can be printed that enable the exchange of information and substances between vesicles and their environment.

With regard to the materials used to construct an artificial cell, Göpfrich pointed to proteins, which enable the machinery and dynamics of a natural cell, but have a major problem: “Unfortunately, proteins cannot reproduce. If you were to construct an artificial cell based on proteins, it wouldn’t be able to self-replicate. But life means reproduction.” Nature solves this problem by means of information transfer, which starts out with DNA (deoxyribonucleic acid) as a store of genetic information, translates this into RNA (ribonucleic acid) and in turn translates the RNA into proteins. “We call this the ‘central dogma of molecular biology.’ No form of life on our planet known to us can duplicate proteins: They need this flow – from information to function,” Göpfrich emphasized.

Another way of constructing life from scratch would be to search for simpler molecules with the inherent ability to copy themselves: “Yes, these exist: DNA and RNA.” The scientific field that uses these molecules as building materials is DNA/RNA nanotechnology. Göpfrich made it clear, however, that “this is not about genetics: We don’t really care about the genetic information contained in this DNA; it’s all about the art of building in the nanoworld.” To assemble complex structures such as an artificial cytoskeleton from DNA, we use a technique known as DNA origami, in which DNA molecules can be folded in any desired way to create various shapes.

The use of these technologies and the division of DNA-filled vesicles have now been mastered, Göpfrich continued. “But what is still needed for life is the coupling of cell division and information: This is what would make evolution possible. We need to genetically encode our DNA structures – the functional hardware.” RNA origami is also used here in addition to DNA origami. These structures can be encoded in DNA, and the functions can then be carried out with RNA origami. If we can succeed in encoding the division of vesicles in DNA, it will be possible to harness evolutionary processes in order to improve the artificial cells. “And that brings us closer to our goal,” which Göpfrich described in conclusion as “the bottom-up construction of a living model system with the ability to self-replicate and evolve using our own molecular machinery, which we would emulate with DNA and RNA origami.”

But what is the point of constructing a cell? The focus here is on exploiting the phenomenal medical opportunities offered. However, it is important to discuss the risks this entails together with ethicists, philosophers, and the public at large in order to come up with regulations, such as those for genetically modified organisms, that would protect us against the uncontrolled spread of these artificial cells. “Actually, our artificial cells – which don’t even exist yet – are so fragile that they would probably lose out in a competition with natural cells – which can be much faster, as they are based on proteins,” Göpfrich assumed. Finally, she ventured a look into the future: “I wouldn’t be doing this kind of research if I didn’t believe that – at least during the course of my career, which is yet to begin – science will succeed in producing life or an artificial cell.”

Dialog in the Museum
November 23, 2023
Mercedes-Benz Museum
70372 Stuttgart

Prof. Dr. Kerstin Göpfrich
Center for Molecular Biology at Heidelberg University and the Max Planck Institute for Medical Research