What does SynBio offer?
SynBio is a diverse branch of science encompassing various technologies, from genetic and metabolic engineering to machine learning, big data techniques and biotech manufacturing. In personal care, it’s increasingly used as a tool for producing cosmetic ingredients, including functional active ingredients, bio-surfactants, colourants, flavours, and fragrances. This includes the production of secondary plant and animal metabolites through processes such as fermentation and cell culture, as well as the creation of alternative versions of ingredients with superior characteristics. SynBio can also be used to produce alternative packaging materials. But the possibilities don’t end there. Some areas of SynBio have the potential to unlock new developments in sensing and diagnostics, which could pave the way for more sophisticated personalisation strategies.
Of the many exciting and versatile SynBio tools available, some have become synonymous with innovation. A recent film published by The Economist, Could cosmetics get a makeover?4, claims that following centuries of natural resource exploitation, genetic engineering with gene editing could help the industry meet demands for sustainably sourced products in a cost-effective way. This is an interesting long-term prospect, but it would be unrealistic to expect a single tool to resolve all the industry’s challenges in one swoop. It makes more sense to look at gene editing within the broader context of synthetic biology to identify benefits that might be harnessed for the sector.
Technical developments
Recent years have seen accelerated developments in the tools that are fundamental to synthetic biology: DNA synthesis and sequencing, genetic engineering (with gene editing, especially CRISPR), ‘omics technologies, data analytics, and machine learning have become more powerful and cost-effective. This allows for faster and more sophisticated metabolic engineering which has forced a shift in the biotech market.
Gene sequencing and genomics offer ways to understand biological pathways that may be used or modified. Closely linked to this is the field of genetic engineering which encompasses gene editing techniques, including CRISPR.
So, what does gene editing offer? Primarily, it allows for more subtle, versatile, and efficient genetic modifications. Unlike conventional genetic engineering (which requires the introduction of DNA from other species), gene editing allows modifications such as additions, removals, or cuts to be made at specific locations in the genome. What’s more, because gene editing does not introduce foreign DNA, organisms modified in this way do not have to be labelled as genetically modified (GMO) in some jurisdictions. This can be advantageous when it comes to gaining consumer acceptance for the products they are used in. It’s also worth noting that provisions in Directive 2001/18/EC on the deliberate release into the environment of GMOs do not apply to the cosmetic ingredients produced by GMOs.
Of the available gene editing techniques, CRISPR-Cas9 is considered the easiest, simplest, cheapest, and most efficient. Some genomics experts believe it will revolutionise how the personal care industry sources ingredients. In fact, CRISPR-Cas9 is already being used to modify terpenoid synthesis pathways in microbes to bring about overproduction of squalene.3 Several biotech companies have also used advances in CRISPR to successfully generate a microbial palm oil alternative using various strains of yeast. Meanwhile, Swiss biotech Evolva employs the technique to develop nature-based flavours, fragrances, and other cosmetics ingredients.3
In a similar vein, biotech firm Amyris has used genetic engineering to transfer biosynthesis to a different host organism to produce squalene. The ingredient is now used in its award-winning Biossance skincare range.
Machine learning and big data techniques are key enablers of the above approaches.
Applying machine learning algorithms to DNA library databases facilitates the rapid discovery and enhancement of new enzymes for targeting DNA that occurs naturally in microorganisms. Alongside this, data analytics can support cost-effective largescale production by identifying optimal parameters for microorganismal growth. This is particularly powerful if combined with technologies such as microreactors, which enable developers to test high numbers of different conditions in parallel.
In the medical space, big data has already been used to identify more than 10,000 CRISPR systems, and this may allow the targeting of new sections of DNA that are inaccessible to Cas9 and other similar enzymes. Advancements like this are likely to transfer to personal care in the coming years, which could facilitate convergence in areas where cosmetics and consumer healthcare currently run in parallel, such as the development of products for skin-related medical conditions including acne and eczema.
Finally, the development of platform recombinant expression systems of mammalian, plant, fungal (including yeast), microalgae, and bacterial origin allows for rapid scale-up of a range of biological ingredients. This reduces the complexity and capital cost of biotech production, aiding the creation of alternative biological ingredients.
“Applying machine learning algorithms to DNA library databases facilitates the rapid discovery and enhancement of new enzymes for targeting DNA that occurs naturally in microorganisms”
Key drivers, benefits and barriers
Obtaining key ingredients through SynBio techniques may offer better security and flexibility in production as well as improving consistency by reducing batch-to-batch variation. For example, Evolva emphasises ‘availability’ and ‘quality’ as core supply chain benefits for its fermentation-produced ingredient Nootkatone.5 Enhancing consistency and constancy may have a beneficial impact on products’ safety assessments too.
In theory, SynBio methods also offer unlimited potential to produce ingredients with limited availability, such as those derived from endangered species. The Manool used to make woody, amber notes in the fragrance industry is one example. It’s traditionally sourced from endangered Manoao pine trees in New Zealand, but Amyris’ fermentation-based process offers a sustainable, reliable, and consistent supply.6
With consumers demanding high-quality, ethical, and sustainable personal care products, it would be easy for manufacturers to pin their hopes on this rise of SynBio techniques. However, major technical challenges still need to be addressed, especially in relation to versatility and scalability. It can also be difficult to fully integrate and streamline individual processes into automated SynBio workflows.
Achieving commercial-scale production that is cost-compatible with consumer products is widely seen as a major difficulty. Overall production costs remain high and can outweigh any marketing benefits. Hurdles include low yield of ingredients and ingredient expression variability as well as long production times and limited production capacity. The supply chain infrastructure is also immature, which exacerbates issues with costs as manufacturers pay market rates for materials.
These issues are not insurmountable, but they do require attention and investment in supporting technologies. A report published by Imperial College London’s bioengineering department, Frontier Manufacturing: Scaling up synthetic biology7, highlights several critical success factors. These include the need for new biologically based sensors that monitor production processes to enable real-time quality control. There’s also a need for robust production cells that can tolerate high levels of compounds. In the meantime, the report suggests that intermediate production methods combining biological and chemical catalysts will be required.
A unison of academia and industry
SynBio’s technical challenges are occupying attention at a global level, with extensive work underway in academic and commercial settings. A Kobe University team has developed the machinery to synthesise long chains of DNA for insertion into cells to bulk-edit genes. This precise tool is claimed to reduce the time taken for synthesis by half, as well as significantly cut the costs8. And professors at Boston University’s College of Engineering worked on the development of next-generation software tools to streamline the design of synthetic biological systems, from concept to assembly.9
Academia-industry partnerships have also been very fruitful. Imperial College London completed a multi-phase project in partnership with GlaxoSmithKline, Shell Global Solutions, Lonza Biologics and Dr Reddy’s Laboratories. It involved strategies for designing and optimising bio-based unit operations, the development of hybrid process systems, as well as platforms for artificial membrane compartmentalisation and cell extracts for manufacturing scale-up. Outputs include the production of novel therapies and synthesis of commodity chemicals for renewable feedstocks.7 Clearly, cross-sector learning and multi-disciplinary collaboration are to play a fundamental role in the development of SynBio solutions for largescale use in personal care applications.
Notable commercial examples more closely related to personal care include Locus Performance Ingredients’ patented modular fermentation platform for bio-surfactant ingredients with a near-zero carbon footprint. These ingredients could be customised to replace palm oil and petrochemical based ingredients.10 C16 Biosciences is also looking at ways to brew alternatives to palm oil, raising $20million in 2020 to support R&D and scale-up.11 CB Therapeutics captured the interest of investors in 2019, securing $7.6million to scale-up biosynthesis research and production which encompasses animal-free ingredients for the cosmetics market.12
Significant milestones include Biotensidon’s 2017 breakthrough in the mass-production of biosurfactants. It became the first company to achieve economically feasible production of rhamnolipids – widely held as a ‘green’ surfactant – on an industrial scale.13 Chemicals company Stepan has also filed several patents surrounding methods to increase the yield of biosurfactants via fermentation.
The commercial landscape
While large multinationals including Johnson & Johnson are exploring SynBio developments, most market activity is seen in smaller, specialised companies at present.
As mentioned above, Amyris has launched products containing ingredients and fragrances produced via SynBio techniques. Its Biossance range, positioned to consumers as ‘clean and sustainable’ has become a top-seller at Sephora stores in the US,2 and its bioengineered squalene is sold to other manufacturers, including The Ordinary and Terasana Clinical.
Geltor also supplies its HumaColl21 ingredient to skincare companies, positioning it as the first bio-designed vegan human collagen for skincare.14 Additional personal care categories benefiting from SynBio include haircare, sun care and colour cosmetics. Bolt Threads has developed b-silk, a biobased, biodegradable and vegan polypeptide inspired by the strength and elasticity of spider silk.15 And several consumer-facing hair and scalp products from Sederma use ingredients derived from SynBio techniques. Its innovative Silverfree product which supports progressive restoration of original hair colour is based on a biomimetic peptide, and the active ingredient of Apiscalp is derived from celery seeds via supercritical carbon dioxide extraction.16
There is much evidence of investment, corporate partnership and collaboration between large businesses and smaller, specialised firms. These include Unilever’s $120m investment in alternative palm oil production17, a partnership between Givaudan and Biosyntia18, and P&G’s collaborative training partnership with the Biotechnology and Biological Sciences Research Council19.
“The sustainability benefit is one of the prime attractions of SynBio. But innovators and users of these techniques can’t simply assume their solutions are ‘sustainable’.”
Sustainability under scrutiny
The sustainability benefit is one of the prime attractions of SynBio. But innovators and users of these techniques can’t simply assume their solutions are ‘sustainable’. Companies using this technology should expect product claims to receive heavy scrutiny from NGOs and advocacy groups. Similar can be expected from the investment community. Consumers too are increasingly aware of the whole lifecycle impact of products, and more likely to challenge sustainability claims.
Applications of SynBio techniques must be examined on a case-by-case basis, with direct and consequential impact on sustainability considered. For instance, techniques that involve microorganismal fermentation which uses media based on plant sugars may rely on resource-intensive agriculture. A solution that seems to have it all could simply result in a new set of problems.
With accusations of corporate greenwashing hitting the headlines in recent months, personal care brands need to ensure that environmental claims on their products abide by ‘truthful and non-misleading’ principles. A routine sweep of websites (encompassing a range of sectors, including cosmetics) conducted by the International Consumer Protection Enforcement Network found that 40% appear to be making misleading environmental claims20.
There are guardrails and principles that organisations can use to help pre-empt some of these issues and new standards of practice should be anticipated. Collaborative efforts between different disciplines and organisations will be pivotal. One such initiative involved Science Group and Chief Technology Officers from seven major corporations: Amcor Global Flexibles, Bayer Crop Science, Mars Incorporated, PepsiCo Inc, Solvay SA, Stepan Company and Proctor & Gamble. The product of their collaboration is the Net Zero Playbook21 which details key principles innovation teams can use to shape the way they think and work to help drive material gains in sustainability. It focuses on carbon reduction, but the principles it advocates resonate more widely.
Exciting prospects for personalisation
Future SynBio developments are likely to be closely aligned with advancements in personalisation, requiring increased use of bioinformatics. We can already assess an individual’s genetics, then recommend or provide a personalised skincare routine enhanced for functions that are impaired in that person, such as skin hydration, or anti-oxidative activities. The number of companies offering such services is growing rapidly in personal care as well as in the nutrition and fitness sectors. Companies tend to differentiate themselves via factors such as genetic coverage, premium ingredients or in-person clinic consultations.
Other desirable functions which can be achieved by SynBio, such as anti-inflammatory activity and alteration of metabolism (e.g., collagen metabolism), are out of the scope of the function of a cosmetic product according to the EU and UK regulations. Products with these functions are regulated as a medicine or a medical device.
As science accelerates its understanding of the impact of the genetics that varies between us all, bioinformatics techniques will aid the assessment of gene variants. This will allow us to make sense of the large and complex biological datasets that come from gene-based diagnostic tests. From a personal care perspective, it will provide valuable insights to enable better sequence conservation of skincare proteins, or identification and quantification of proteins in skin or hair. For instance, there are many ways to enhance skin protein quality but there are also many different sources; it is still unclear whether hydrolysed collagen from mammals, fish, caviar, or recombinant bacteria is best. Once this question is resolved, sustainability and quality factors will be improved by cloning the target gene into a production vector, probably yeast.
Combining genetic knowledge, SynBio, and largescale bioinformatics presents vast opportunities to reconfigure the personal care market toward full personalisation, offering each customer exactly what they need rather than a choice of standard formulations. In this scenario, the large-scale manufacture of separate ingredients remains similar, but for true personalisation, final formulation and mixing may be moved closer to point-of-sale with immediate customer benefit.
The short, medium, and long-term outlook
So, what does the future hold for SynBio in personal care?
In the short to medium term, we can expect a shift from the niche production of small-volume functional ingredients to greater support of the entire product. SynBio-led production of high-volume ingredients such as carriers, surfactants, and excipients would have a greater impact on overall product sustainability. Packaging is also likely to receive a SynBio overhaul. Also in the near future, sophisticated personalisation services like those outlined above will come to fruition at a premium price, offering tantalising commercial prospects.
Looking further ahead, learnings from activity in the medical space surrounding non-proteinogenic (unnatural) amino acids are likely to filter through to personal care. The sector’s SynBio work to date has largely focused on reproducing the amino acids that make up proteins in plants and animals. However, unnatural amino acids may reveal different ways to enhance product functionality or unlock entirely new physiological benefits.
While the major material benefits that SynBio can bring to personal care still lie some way in the future, there is much promising activity underway. For now, we can feel cautiously optimistic about the potential it brings to meet heightened consumer demand for clean, sustainable, and personalised products.
