Playing God? British researchers want to artificially create human DNA

Our genetic material is what we inherit directly from our parents. It is passed on through fertilization, via egg and sperm. And every cell of the newly born child contains a combination of genetic information from both parents. This determines what we look like, how our body functions, which diseases we are prone to, and much more.

Now researchers want to artificially create human DNA for the first time. "A team of British scientists is developing a technology to create the first synthetic human chromosome," states the website of the Wellcome Trust , a major charitable foundation dedicated to promoting science and improving human health worldwide. It has just provided the equivalent of approximately 11.7 million euros to the British Synthetic Human Genome Project (SynHG) to advance its research.

The large-scale project is initially planned for five years. Its goal is to synthetically create a complete human chromosome in the laboratory for the first time, following many intermediate steps. Researchers from the universities of Cambridge, Kent, Manchester, Oxford, and Imperial College London are involved. The project is led by molecular biologist Jason Chin , a professor at Cambridge, who is heading a "world-leading institute for technical biology" currently being established, which will bring together more than 300 leading researchers from around the world. The facility is called the Generative Biology Institute (GBI).

New therapies, climate-resistant plants and novel materials

"Biology naturally fulfills an impressive variety of functions. Used correctly, it holds the key to solving some of our greatest challenges. However, we are not yet able to reliably engineer biology," the institute states in its self-description. To achieve this, they must face a major challenge. "We must be able to write in the natural language of biology and understand which DNA sequences generate biological systems with the desired functions."

The researchers are enthusiastically envisioning their goal of unlocking the potential of biology "for good." This includes, for example, "the development of new therapeutic molecules and cells to treat diseases." Furthermore, they aim to create "climate-resilient crops" that simultaneously fix nitrogen and are less susceptible to diseases and pests. This should promote global food security and make agriculture more sustainable.

"In the field of climate change and clean energy, it will be possible to manipulate biological processes to capture greenhouse gases and produce fuels," the statement continues. Completely new types of materials could also be developed. "By creating the necessary tools and methods to synthesize a human genome, we will answer questions about our health and disease that we cannot even anticipate today, transforming our understanding of life and well-being," said Michael Dunn, Director of Discovery Research at the Wellcome Trust.

Synthetic production of human DNA raises ethical questions

While many researchers share this vision, others urge caution. By directly generating genetic material in the laboratory, humans are putting themselves in a position to truly "play God" by interfering with the basic building blocks of life.

It is already possible to modify sections of DNA using novel molecular biological technologies – such as the CRISPR-CAS "gene scissors." However, the synthetic creation of a human genome is not only highly challenging. It also raises "multifaceted ethical questions and also entails risks that must be considered and weighed against the benefits," says oncologist Eva Winkler , head of the Translational Medical Ethics Section at Heidelberg University and deputy chair of the German Ethics Council.

What exactly is the challenge? Every cell of an organism contains the complete set of genetic information, i.e. the entire genome. In humans, it consists of up to 25,000 genes. These form the blueprints, so to speak, for the production of various proteins, the tools and building blocks of the body. The genes themselves are stored in the cell nucleus in the form of deoxyribonucleic acid (DNA). DNA consists of a long row of four different building blocks with the bases adenine (A), thymine (T), guanine (G), and cytosine (C). These are arranged in pairs in different orders on the DNA double helix, whose structure resembles a spirally twisted rope ladder.

These individual rope ladders are packed in different packages, the chromosomes . There, they are coiled around specific proteins. Humans have 46 chromosomes, arranged in 23 pairs. One of these pairs, for example, determines sex: two X chromosomes in females and one X and one Y chromosome in males. These are named after the shape of the chromosomes.

Technical hurdles for more complex genetic syntheses

Two years ago, British researchers published methods that enabled them to produce complete genomes of the bacterium E. coli with novel properties, as reported by the Science Media Center (SMC) in a presentation on the topic. "The production of artificial DNA is nothing entirely new—it has been possible in bacteria for some time," says Malte Spielmann, Director of the Institute of Human Genetics at the University Hospital Schleswig-Holstein. For the first time, researchers are now attempting to produce large portions of human DNA synthetically.

"Until now, it was only possible to synthesize short sections of a few hundred base pairs. New methods now allow the production of sections with hundreds of thousands of base pairs," says Spielmann. He refers to the bases A, T, G, and C arranged on the DNA double helix – the genetic building blocks. For the first time, it will be possible to synthetically produce larger portions of chromosomes – possibly even entire artificial chromosomes. However, the process is technically extremely demanding and usually takes place in a cell culture, often using yeast cells.

Furthermore, complex processes occur within cells that are difficult to replicate in the laboratory. According to the SMC, "human cells with significantly larger genomes, abundant jump segments in the genome, and unique structures such as telomeres and centromeres with highly repetitive DNA sequences on the chromosomes" have so far presented insurmountable technical hurdles for more complex genome synthesis.

Numerous risks of misuse of new technologies

At the same time, there is fear of the consequences of the research. "Obvious concerns – similar to the debate surrounding cloning – include designer humans, synthetic humans, and organs as 'spare parts stores,' the commercialization or patenting of the genome, and possible military applications," summarizes medical ethicist Eva Winkler.

Nils Hoppe, Professor of Ethics and Law in Life Sciences at the University of Hanover, also points to the "numerous risks of misuse" of the new technologies being developed. "This could lead to the creation of novel biological warfare agents or attempts to produce certain physical characteristics 'to order.' That would run counter to fundamental social principles."

However, the perception of ethical boundaries—what "one may and may not do"—often differs in laboratories than in the general public. This is also demonstrated by the debate surrounding so-called gain-of-function research on pathogens in connection with the question of whether or not the coronavirus SARS-CoV-2 originated in a Chinese laboratory. Another example: In 2019, Chinese researchers were sentenced to prison terms for using the "gene scissors" CRISPR-CAS to modify the genome during artificial insemination. The method was first used on human embryos, which were ultimately born.

An artificial human is supposedly not to be created

The taboo-breaking aspect of this approach was that the researchers were interfering with the germ line (egg cells, sperm). This means that the genetically modified twins Lulu and Nana, who were born, will pass the changes on to their offspring. Although the researchers had "well-intentioned" (they wanted to protect the children from infection by their HIV-infected father), such genetic interventions can have unforeseen consequences. Critics said the technology was still too uncertain to be used irreversibly.

There are calls for global regulation of such research. Declarations of intent to respect ethical boundaries are not enough, especially since the potential creation of artificial DNA opens up truly fantastic prospects. "From a scientific perspective, this is a highly exciting and timely project," says Malte Spielmann, a specialist in human genetics. He emphasizes that this is basic research. "The stated goal is not to create an artificial human."

Spielmann finds it exciting that this project opens up new possibilities for "analyzing and understanding the functioning of our genetic information." It is a "well-conceived project, both in terms of content and ethics," that will enable groundbreaking scientific discoveries while simultaneously being "supported in a socially responsible manner." For example, the University of Kent is running a special social science program within the project. "In this combination, it is a very welcome and important step for future genome research," says Spielmann.

What becomes of the biological legacy of one’s own DNA?

Other researchers emphasize the need for regulation more strongly. "Here, it seems important that risks are not only managed technically, but also socially accountable," says medical ethicist Eva Winkler. "This includes transparent procedures from the outset, social participation, the need for ethical reflection, clear boundaries for possible applications, openness to normative dissent, and ultimately, democratically legitimized and ethically justified responsibility toward new forms of biological design."

The creation of a human genome in the lab—albeit still a distant prospect—would raise fundamental ethical questions, says Eva Winkler. "Until now, the rule was: Your DNA is your biological heritage. But synthetic DNA is generated in the lab—that is, designed, not inherited. Are companies allowed to patent synthetically created sequences, even if they resemble natural ones?" Completely artificially created babies would have no biological parents. "This changes our understanding of biological kinship, parenthood, and reproduction."

And what if we were to create artificial twins of ourselves – as potential spare parts stores? Would they have the same rights as biologically created individuals? These are just a few questions from a barely imaginable, but entirely possible, future.