Fictional portrayals of artificial life always seem to wonder at creating something ‘alive’ – and worry about the ethical dilemmas such creation sparks. In Philip K. Dick’s seminal sci-fi novel Do Androids Dream of Electric Sheep, a focus on humanoid androids (with muscles and bones, almost indistinguishable from humans) shows how powerful unnatural life can be. The book also muses over whether these creations count as life itself – and therefore whether they should be treated with the same sanctity. Elsewhere, in Never Let Me Go, Nobel Prizewinning novelist Kazuo Ishiguro considers the purpose of human-derived clones and whether they should be allowed to live, and even love, as their ‘real’ counterparts. In I, Robot, meanwhile, Isaac Asimov grappled with the dangers of creating machines similar to humans, forcing his readers to ask: should we be making synthetic life at all?
When it comes to research around synthetic cells, the ‘should we be doing this?’ discussion is certainly part of the scientific discourse. That’s not least when research into both fundamentals of synthetic cells – and how they might ultimately be used beyond their usual function – is so dynamic. But since the furore surrounding Dolly the Sheep in the 1990s, there have been fears that experimenting with artificial life, and especially synthetic cells, could result in material ripe for bioterrorism. Ethically, meanwhile, some believe that cellular creation violates the sanctity of nature, commoditises life and ultimately amounts to playing God.
Dr Petra Schwille, director at the Max Planck Institute of Biochemistry and steering committee member at SynCellEU, gives short shrift to such discussion – especially in her area of nonapplicative, fundamental research. When it comes to bottom-up biology – or creating a cell in a lab – she says “we’re not talking about human life or anything that is even close, in terms of being self-conscious”, instead describing her creations as a minimal living unit that would be much, much simpler than even the simplest bacterium. As Schwille adds, no such cell could compete with species that have already evolved on Earth. Ergo: the risks are simply not there.
Artificial work
Indeed, ethical quandaries don’t appear to be preventing research into understanding these cells – or how they might be used medically. Since Thomas Ming Swi Chang was credited with creating the first artificial cell, in 1957, the field has bubbled with innovation. From sustainable synthetic cell systems that feed off carbon dioxide; to how magnetic field stimulation might help synthetic cells deliver therapeutics in biological tissue; to how synthetic stem cells might battle conditions like arthritis – this is clearly a sector on the move. And in a turn that feels almost fictional, at least for the meantime, an article in Synthetic Biology details how synthetic cells may allow for so-called ‘designer’ therapeutics, tailored to the genetic make-up of an individual patient and which can target tumorous cells while ignoring healthy biological material.
From within Schwille’s SynCellEU network, meanwhile, there are claims that synthetic cells could have a future in patient-tailored treatments for cancer, even as they could help target drugs more accurately and fight antimicrobial resistance. Elsewhere, scientists are exploring how synthetic cells might be controlled to respond to their environment, critical in the length of treatment delivery and specificity, and how their use might result in less wasteful manufacturing processes. It sounds, in short, like pioneering stuff – and the markets have certainly taken notice. The value of synthetic biology companies is expected to hit a cumulative capitalisation of over $37bn by 2027, almost quadrupling in size from $9.5bn in 2021.
“With this discovery, we can think of engineering fabrics or tissues that can be sensitive to changes in their environment and behave in dynamic ways.”
Ronit Freeman, University of North Carolina
Sector insiders may have noticed recent headlines around research from the University of North Carolina at Chapel Hill, led by Ronit Freeman, which centres on claims that it has created synthetic cells that look and act like cells from the body. “With this discovery,” Freeman told Science Daily, “we can think of engineering fabrics or tissues that can be sensitive to changes in their environment and behave in dynamic ways,” adding that these materials could ultimately surpass pure biology. No less important, Freeman also argued that there is potential for these cells to operate in environments unsuitable to human life, and that they might even be able to modify themselves to serve multiple functions. In what is described as a first-ever breakthrough, this is done via a new programmable peptide-DNA technology that directs peptides – the building blocks of proteins – to form a so-called cytoskeleton. When added to water, meanwhile, this cell-structuring mechanism forms an effective synthetic cell.
473
The number of genes that scientists created in 2016, as a single-celled synthetic organism that was the simplest living cell ever known.
National Institute of Standards and Technology, US
A hard cell
All the same, Schwille is unsure how quickly this breakthrough might be used in actual medical treatment. Given her research into the smallest unit of life, she understands how difficult it is to know and control which external environmental factors ultimately impact artificial cells. That’s critical if a synthetic cell were to be used for delivering drugs into a patient when responding to a specific trigger. “We need to see what’s actually going on in such a cell system before it can be put into patients,” she stresses. “You have to know what is happening under controlled conditions and we could say this research is a step further away from synthetic cells which have been created before.” No less crucial, Schwille notes that needing water to exist could prove challenging. So far, these artificial cells can’t survive without it.
$37bn
The amount the synthetic biology (inclusive of synthetic cells) market is expected to grow to by 2027.
Markets and Markets
At the same time, Schwille highlights how difficult it can be to control or wholly understand the mechanics of a synthetic cell. Her own research, which looks at the fundamentals of life itself, involves artificially building cells or parts of cells (vesicles, cytoskeletons, membranes) and looking at how they interact with inputs to divide and create new life. “It can be a headache to work with reconstituted proteins,” she admits, referencing one way of synthetically recreating a cytoskeleton. “And it is difficult to measure in a controlled setting the features of the biological molecules [we create].” Of course, these are problems researchers who are interested in creating synthetic cells for applicative use will also face.
5,000
The amount, in expert years, that researchers in 2017 estimated it would take, to engineer a living cell configured from entirely artificial components.
National Library of Medicine
The German scientist is not the only expert wary of getting ahead of themselves. For instance, a recent article from the Max Planck Institute of Molecular Cell Biology and Genetics concludes that, when it comes to artificial cells being able to sense where they are in living tissue, hurdles remain. That’s crucial to be able to then deliver medicine or complete other tasks. “With [only] a handful of studies,” the article concluded, “it is difficult to explore the practical application of artificial cells fully.” Even if that milestone was reached, meanwhile, regulatory hurdles would also need to be surmounted. As it stands, US regulations for synthetic drug delivery systems do not yet exist – and the authorities would want guarantees over clinical trials and manufacturing safety. There may even be issues around how a synthetic cell would be classified. With regulations often created in a cautious manner, and on a caseby- case basis, moreover, EU guidelines on usage are some way off too. That’s even before getting onto the ethical dilemmas, notably around playing God or worries about not being able to control a synthetic cell.
This isn’t to say that regulators are inactive. Over 50 countries have a bioeconomic strategy – inclusive of synthetic biology, including cells – as a way to drive innovation. That’s hardly surprising given bold claims on how cells could soon transform various corners of medical life. Though she’s doubtful of how soon the University of Carolina research might be put into action in a medical use, indeed, Schwille is mindful of just how dynamic synthetic cell research already is. “Even if we’re a far way from practical use in regenerative medicine,” she says, “there are so many applications being explored for synthetic cells right now.” For that to happen, though, it just might require stakeholders, from researchers to policymakers, to find a suitable and safe way forward together – moving synthetic life, and cells, from the world of sci-fi and into the real world of medical use.
