Is it possible to create life in a laboratory? The most recent advances in synthetic biology have made it possible to develop artificial cells with some of the functions typical of living organisms, rekindling the debate over the boundaries between the natural and the designed. This article analyzes the true scientific scope of these achievements, their potential applications, and the important bioethical questions they raise about the nature of life and human responsibility.
A few years ago, in my book Exploring Genes. From the Big-Bang to the New Biology,1 I reflected on the phenomenon of “life”. Given the difficulty in defining this fundamental concept in biology, I proposed that, as physicists have done with the concept of “energy”, the best approach is to describe its properties—in other words, to identify what characterizes life and what distinguishes it from inanimate objects. However, wondering about something as general as life means specifying what one wants to know, since the definition of life includes philosophical, metaphysical, biological, and theological aspects, which are not always complementary. In science, anything that lacks matter cannot be approached experimentally. Thus, rather than asking “What is life?”, biology seeks to answer the question “How does life work?”
The Belgian physician and biologist Christian de Duve (1917-2013), winner of the 1974 Nobel Prize in Medicine for his contributions to our understanding of the structure and functional organization of cells, said that “Life is what is common to all living beings”, highlighting the role of nucleic acids, which sit at the top of the information hierarchy that makes life possible.2 Additionally, the great British evolutionist John Maynard-Smith (1920-2004) stated that “The entities are alive if they have the properties necessary to evolve by Natural Selection. In other words, if they can multiply, if they possess a mechanism to insure the continuity of character and if they can vary”.3
Knowledge of the properties of living organisms and their material components was established during the first half of the 20th century, and has driven “genetic engineering” since the 1970s. This constitutes an important chapter in so-called “Synthetic Biology”, defined by the United Kingdom’s Royal Academy of Engineering as “a field that aims to design and engineer biologically based parts, novel devices and new systems, as well as redesigning existing natural biological systems”.
In short, it involves modifying living organisms for various purposes, ranging from simple curiosity to better understand their properties to their exploitation for practical applications. Within this field, there are approaches that go beyond the modification of genes or components of existing organisms. One such application involves designing new biological systems using a “bottom-up” approach, including the production of artificial cells by combining their constituent molecular elements from scratch to create systems that do not exist in nature.
The creation of synthetic cells
The aim of synthetic biology is to synthesize, rewrite, or recode genes, genomes, and even—more rhetorically than realistically—new cells and species. One of the main driving forces behind the Human Genome Project, the late Craig Venter (1946-2026), proposed the idea of determining the content of a “minimal genome”, i.e., the minimum information needed to sustain life in a single-celled organism, which would necessarily be the simplest and least demanding in terms of adaptation. The artificial synthesis of this genome would contain a set of genes that would collectively meet all the requirements for the maintenance and reproduction of the cell containing it in a particular environment. In 1999, in an article in Science, Venter stated “What is life? I don’t think there are that many biologists trying to answer that one… We’re… working on a reductionist view of trying to take the smallest genome that we have… and see if we can’t understand how those… [genes] work together to create life”.4 This marked the beginning of efforts to synthesize a biological entity in the laboratory.
In mid-2010, the media sensationally reported that Venter’s team had obtained a “self-replicating synthetic bacterial cell” in their laboratory, emphatically hailing it as the creation of “synthetic life”.5 In reality, it was neither the synthesis of a living cell nor a living organism in the laboratory; rather, it involved introducing a synthetic genome that modeled the genome of the bacterium Mycoplasma mycoides into an existing cell of a related species, Mycoplasma capricolum, whose natural genome had previously been removed. Although it was a technological feat, it did not constitute the creation of life in the laboratory, as Venter himself pointedly said, but rather consisted of copying and recreating something that already existed in nature, which is in itself a remarkable scientific achievement.
The Craig Venter Institute, which initially focused its work on minimal genetic information, has provided the tools to alter, reconstruct, investigate, and identify essential genes. The “minimal genome” based on Mycoplasma, designated as strain JCVI-syn1.0, contained a combination of 901 genes. These were then progressively eliminated, ultimately obtaining strain JCVI-syn3.0 with only 473 genes. This is a synthetic genome smaller than that of any free-living organism. Although the function of many of the essential genes contained in these synthetic strains was unknown, the synthetic genome fulfilled all the essential functions required by the cells into which it had been inserted, allowing them to grow and divide in the artificial culture media. The artificial mycoplasma strains JCVI-syn1.0 and JCVI-syn3.0 would lay the foundations for understanding essential processes widely conserved across cellular life, and have served to guide new, useful approaches in creating synthetic cells.7
These studies are driven by multiple interests. Essentially, they aim to create artificial genomes with a specific function to obtain synthetic organisms capable of producing proteins of industrial or pharmacological interest that can be readily cultured in bioreactors. Numerous commercially available drugs such as insulin, interferon, erythropoietin, clotting factors, growth factor, etc. are now produced efficiently and cost-effectively in genetically modified bacteria using transgenic techniques. Nevertheless, the idea of creating synthetic cells goes even further, aiming to produce cells with a designer genome that allow researchers to test the ability to mimic nature, expand knowledge, and incorporate new functions with practical applications. This bottom-up approach of synthetic biology is fundamentally different from the top-down approach of transgenesis, in which the goal is to modify the cells of existing organisms by adding or removing elements such as genes or other cellular components.
Since these initial experiments were conducted, several attempts have been made to produce designer cells from scratch, with properties similar to those of natural cells. To that end, synthetic biologists are attempting to combine synthetic genomes with biochemical knowledge about cellular function and the various materials of which cells are composed. The numerous strategies and materials developed in recent decades have allowed investigators to design synthetic organelles to enrich the essential functions and behaviors of their artificial cells. Researchers have focused their attention primarily on genetic information, compartmentalization, energy supply, DNA replication, and cell division. Some notable examples are synthetic cells that can generate ATP from light energy, sustain metabolic activity through enzymatic networks, replicate genes and—perhaps the most difficult of all—undergo cell growth and division.7
The latest breakthrough: SpudCell
On July 2, various news and scientific dissemination outlets announced the production of a new form of synthetic cell, which its developers have named “SpudCell”. This is a type of artificial cell developed from scratch by synthetic biologist Kate Adamala and her research team at the University of Minnesota. To achieve this, they combined inert chemicals and encapsulated a minimal genome split across seven plasmids inside a fatty acid membrane (lipid bilayer).
The DNA genome of this cell-like system contains only 90,000 base pairs, corresponding to just 36 genes, which essentially means that it lacks sufficient information to be comparable to that of any natural living cell. Remember that a simple bacterium like Escherichia coli has about 4.6 million base pairs and around 4,400 genes, and that the human genome contains around 3.1 billion base pairs and around 21,000 genes.
Unlike previous attempts, SpudCell does not start with the replacement of natural cell components. Rather, it is built from scratch, piece by piece, combining non-living chemical compounds with structural and functional elements to produce a synthetic entity similar to a cell and capable of growing, reproducing, and transmitting its genetic material over a few generations.
SpudCell is able to replicate its DNA, grow, and divide. To grow, molecular tags have been provided on its surface that can absorb small vesicles loaded with nutrients and other elements needed to sustain cellular activity. It lacks a cytoskeleton, so cell division is achieved by adding a tag called FLAG, which interacts with an external protein, causing the cell to constrict. This does not guarantee the complete distribution of the replicates of the seven plasmids that make up the genome.
SpudCell is not able to develop the full set of molecular functions of natural cells, and cannot synthesize ribosomes, which are the cytoplasmic organelles on which protein synthesis takes place. Because of this, it does not synthesize either structural proteins or the enzymes required for its metabolism, which must be provided externally. Therefore, it can undergo division for only 5-10 generations.
The limitations of protein synthesis and the lack of an efficient mechanism for maintaining copies of the genome in the daughter cells, as well as dependence on the addition of many external components, mean that, in reality, it is a product far removed from a true natural cell. The researchers who have produced these artificial cells are working on a new version that overcomes these constraints.
The initial manuscript of this work was not accepted in the journal Cell, and has not been peer-reviewed. The researchers submitted it for dissemination on the Biotic pre-publication platform and it was announced as news in Science and the New York Times.
SpudCell is the closest approximation to synthetic biology’s goal of creating artificial cells. However, based on what has been done so far, these artificial cells cannot be described as living organisms, since their reproductive independence is not guaranteed, nor do they have the capacity for evolution, both of which are specific properties of life. Nevertheless, this work serves as a proof of concept for improving our understanding of numerous functional and structural aspects of natural cells.
Bioethical aspects
Synthetic biology shifts between the pursuit of innovations with no clearly defined objectives, driven by the mere fact of seeing the effects of the creation of something that does not exist in nature, to practical applications, which, when properly used, benefit health, agriculture, livestock and industry and, where appropriate, that contribute to furthering knowledge. Therefore, any ethical assessment of the attempt to create artificial life must be based on respect for nature, the conservation of the environment and natural resources, and the dignity of human life.
In accordance with the precautionary principle and the principles of responsibility and justice—which must consider all practices in synthetic biology—there are three special aspects that must be taken into account in relation to the creation of artificial cells.
First, consideration should be given to what drives this type of initiative. Isn’t creating life in the laboratory a form of playing God? Creating artificial cells is like creating life from non-living inorganic matter. From a religious perspective, this role corresponds to God, but now, owing to their technological and intellectual abilities, humans may believe that they are elevating themselves to a superior or even limitless condition. However, at most, this makes man an imitator of something that remains a mystery. Progress has been made in understanding what life is, but the fundamental question of why life exists remains unanswered.
Second, there is the reductionism that stems from the idea of materializing the natural world. Do we really have all the necessary elements to synthesize a living organism? Removing, adding on, or joining pieces—typical of the DIY approach of synthetic biology—may make us think that cells and living organisms are like artifacts that function by simply assembling their components. The consequence of this approach is the loss of the distinction between living organisms and machines, which causes a weakening of the moral status that differentiates them, including humans, who would be considered a mere aggregate of molecules, cells, tissues, and organs. From this perspective, life is reduced to matter. This is the world of Richard Dawkins, Peter Singer, and other materialist geneticists and biologists. The reality, however, is very different and, in Biology at least, 2 + 2 do not always equal 4. There is something that transcends us, something that distinguishes the living from the non-living and that reaches levels that cannot be addressed in material terms, with an evident qualitative leap in humans. Moral status is not inherent to life itself, but to the characteristics possessed by living beings, which in man reaches its highest level through self-awareness and rationality, the basis of human dignity and of the consideration of humans as ends in themselves.
Third, it is worth asking about its applications: why do we want an artificial cell if we already have very efficient modifications that can be made in natural cells? Although the synthesis of artificial cells may have interesting applications in health and pharmacology, using these creations as factories to produce molecules of interest, as in other synthetic biology fields, it also raises concerns about the safety of these advances, their potential risks to the environment and to man, and ethical aspects related to the ends pursued. There is always the threat of dual use, for good or evil, including the potential application to create biological weapons for war or terrorist purposes, certainly more dangerous than nuclear weapons.
Important questions therefore arise about the need to create artificial cells that will never surpass natural ones. Looking ahead, we must be vigilant regarding the consequences of the potential uses that may be made of these technologies.
Nicolás Jouve
Professor Emeritus of Genetics at the University of Alcalá
Member of the Bioethics Observatory of the Catholic University of Valencia
References
[1] Jouve, N. Explorando los genes. Del big-bang a la nueva Biología. Ediciones Encuentro, Madrid, 2008. Cap. 7.
[2] de Duve Ch. La vida en evolución. Crítica, Barcelona, 2004, p. 25.
[3] Maynard Smith, J. “Time in the evolutionary process”, in Studium Generale 23 (1970): 266-272.
[4] Hutchison CA, Peterson SN, Gill SR, Venter JC. et al. Global transposon mutagenesis and a minimal Mycoplasma genome. Science. 1999 286(5447): 2165-2169.
[5] Gigson DG, Venter JC. et al. Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome. Scienceexpress: 20 May 2010 / Page 1 / 10.1126/science.119071
[6] Pelletier JF, Sun L, Strychalski EA. et al. Genetic requirements for cell division in a genomically minimal cell. Cell. 2021 184(9):2430-2440.
