Synthetic biology: a huge “Gutenberg moment”
21 January 2022 <15 minute read
Synthetic biology (“synbio”), making living organisms and compounds that are not currently found in nature, will have a huge impact on mankind, impacts that have never ever been seen before in human history. The only question is what will be achieved and by when (and by whom…) and with what impact?
Never before has mankind been able to design an organism from scratch, and make “made to order” organisms and materials, from de-extincting the woolly mammoth (by 2027.. see www.Colossal.com) to making new enzymes not found in nature that can catalyze chemical reactions many times faster than previously possible; making precision medicines that are much more effective at curing disease, and so on. It will allow many new products to be developed that before were previously not scientifically or economically possible. Technological advances are speeding everything up and allowing many new possibilities, both economic and technically feasible.
McKinsey in 2020 stated that “As much as 60 percent of the physical inputs to the global economy could, in principle, be produced biologically—about one-third of these inputs are biological materials (wood or animals bred for food) and the remaining two-thirds are nonbiological (plastics or fuels) but could potentially be produced or substituted using biology. (However, produced economically is another matter..).
For the above reasons I classify the booming use of this technology as a “Gutenberg moment”, where the event(s) cause a momentus change for mankind. Gutenberg invented and commercialised the printing press in 1454, allowing knowledge to become widespread and cheap to obtain, spurring massive development and progress of the human race.
Note that I use the definition of synthetic biology as “Engineering and synthesizing genetic sequences that are not currently found in nature, providing organisms or materials with new abilities or properties”, where there are a number of other definitions other people use.
This note reviews Synthetic Biology and addresses:
1) What is Synthetic Biology and what could it do ie why does it have so much potential?
2) What is the current state of capabilities? How does it work?
3) What are the stages of synbio?
4) What are the implications of this and what industries can synthetic biology affect? ie how much of a disruptor will it be and when? And how is it structured?
5) Who are the main players?
6) What big things can we expect and when?
7) What are some of the key headwinds, issues & risks?
8) Summary
1) What is Synthetic Biology and what could it do?
Organisms (and some materials) are made up of sequences of DNA, the ACGT combinations that make an organism and determine how it will grow and operate second to second. DNA molecules are made from four types of bases, or nucleotides, each identified by a letter: adenine (A), thymine (T), guanine (G) and cytosine (C). They are the basis of all DNA code, providing the instruction manual or blueprint for building every living thing on earth.
A human has 3.2 billion base pairs (pairing of two DNA chemicals, A with C and G with T) (nucleotides) and around 24,000 genes; a fruit fly has some 169 million base pairs and some 14,000 genes; single celled brewers yeast has some 12.1million base pairs and some 6,000 genes; (yeast shares some genes with humans..); e-coli bacteria -often used a base to grow new genetic sequences (rapid growth, low cost, high yield, easy scale-up, harmless lab strains) - has some 4.6m base pairs, 4,000 genes, and has over 4,000 protein encoding modules (eg used to make human insulin); a chicken has some 1 billion base pairs and 20,000 to 23,000 genes. The flu virus genome contains only 15,000 nucleotides. (The human genome is approximately 200,000 times longer). The Megavirus chilensis genome (the largest virus..) is 1.2m base pairs, with 1,120 protein encoding genes.
Synthetic biology combines chemical synthesis of DNA with growing knowledge of genomics to enable researchers to quickly manufacture catalogued DNA sequences and assemble them into new genomes.
McKinsey in 2020 stated that “A pipeline of about 400 use cases, almost all scientifically feasible today, is already visible. These applications alone could have direct economic impact of up to $4 trillion a year over the next ten to 20 years. More than half of this direct impact could be outside human health in domains such as agriculture and food, consumer products and services, and materials and energy production”.
And it could have a huge economic impact, a $2 trillion to $4trillion impact by the 2030s, as estimated by McKinsey:
Source: McKinsey, 2020
Succeeding at this- it is still very early days - allows a huge number of new products and services to be developed, where application of engineering principles of standardization and controlled circuits create biological solutions to problems in industry, agriculture, environment, and healthcare, with some subsectors detailed below:
Healthcare / Pharma
Using high-throughput processes for the engineering of mammalian cell genomes enables a wide range of industrial and pharmaceutical applications. As more work is done then genetic sequence libraries will become ever larger and further speed development of future medicines. A few areas for synbio can encompass:
· Drug design eg designing microbes that will seek and destroy tumours in the body before self-destructing; or an anti-malarial drug made from synthetic chemicals, artemisinin; (not a new treatment for malaria, but the ability to produce the substance in a lab is. Traditionally, the drug is isolated from a plant, Artemisia annua. But by moving production into the lab, scientists are liberated from the vicissitudes of the plant’s growth cycle). OR a less expensive anti-malarial drug that can be grown from modified yeast
· Cancer Immunotherapy: Genetically engineering T-cells receptors with cancer targeting receptors has shown tremendous promise for eradicating tumours in clinical trials. There can be development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumours.
· Newly created and designed human cells: You can buy human cells that can be programmed any way you like. For example a company active in this field is www.bit.bio where you can call up and order brain cells, muscle cells etc and then a biotech or pharma company can test out the reaction of their own new product or proposed new drug on real human cells to see if their proposed new drug or product is safe or possibly efficacious, therefore significantly reducing the costs of trials in humans and significantly increasing the likelihood of success of the drugs. The cells are made from IPSC- Induced pluripotent stem cells, which can be made by taking say a humans fat cells, and applying chemical factors to them to revert them to stem cells (IPSCs) and then reprogramming them to become the new cells that you want, eg brain or muscle cells. With bit.bio’s brain stem cell line, a functional neural network is available from their IPSCs within 17 days.
· Vaccines: when antibodies are produced in response to a virus, Synbio firms can rapidly collect these antibodies and synthesize the genes associated with these antibodies and create thousands of variations to develop the most precise therapeutic molecules
· Drug Tests: eg create synthetic urine to pass drug tests…! Welcome to Synthetic Biology - Synthetic Urine, Detox Drinks & News (synbioproject.org)
· Replacement Organs: Making replacement organs such as livers, kidneys, hearts etc (many die each year from lack of transplants availability)- solving tissue and organ rejection, and artificial wombs, will go on to help improve and extend life and healthspan for all humans, and could also be used in making new animals without the presence of the mother- important for de-extinction. Research is being done in space (microgravity) to see if organs can be built more effectively due to lack of gravity (eliminating the need for scaffolding to build some organs)
Source: McKinsey, 2020
Industrial Biotech & Life Sciences
Synthetic biology will offer the opportunity to produce a vast array of products from starch, and other sources
Enzyme discovery & production: making new enzymes: enzymes are used in applications from cheesemaking to pharmaceuticals to stonewashed jeans- making enzymes better to speed or improve production processes
·
Biofuels; Bio-based specialty products; Bulk chemicals
Flavours & fragrances- making fine chemicals: Eg Yeast engineered to produce rose oil as an eco-friendly and sustainable substitute for real roses that perfumers use to make luxury scents
New cosmetics: Amyris is producing new cosmetics, eg Biossance Official Website - Award Winning Clean Skincare Vitamin C Rose oil for skin hydration. Amyris also developed its version of squalane — a synthetic form of shark-derived squalene. In 2016, it launched Biossance based on the squalane ingredient story, which mimics the skin’s natural oils with emollient and anti-aging properties. Cut to 2021: Biossance is on track to earn up to $160 million in sales this year. Squalane makes up 20% of Amyris’ total revenue, Melo said. Amyris now sells squalane to companies like Shiseido, L’Oréal Group and AmorePacific. The ingredient is found in brands like JLO Beauty, The Ordinary and Peter Thomas Roth.
Where fermentation is already used in bioindustrial applications, organism engineering can improve efficiency and sustainability of existing strains.
Advanced Materials / Materials Science
Source: McKinsey, 2020
Environment / Environmental remediation:
· Biofuels eg eg expand the sugar content of biomass crops to increase their density and decrease the cost of biofuels produced from them
· Biosensors for pollution:
· Bioremediation – eg building organisms to consume toxic chemicals in water or soil or air that would not otherwise decompose, from oil and plastic cleanup to carbon sequestration
· Waste treatment: New bacteria to more efficiently process waste.
Food & Beverage & Consumer Products
Bio-based specialty foods: eg Rice modified to produce beta-carotene, a nutrient usually associated with carrots, that prevents vitamin A deficiency. Vitamin A deficiency causes blindness in 250,000 - 500,000 children every year and greatly increases a child's risk of death from infectious diseases. OR Vanilla made from yeast- it is less expensive than pure vanilla made from vanilla beans, and tastes better than artificial vanilla. Vanilla and rose oil, which are currently extracted from nature, but which can be manufactured by reengineering the metabolism of microorganisms instead. The important thing is we can use biological engineering, instead of the chemical manipulation of oil and coal feedstocks.
Or Codexis: efficiently produce better tasting, clean-label sweeteners, for Tate & Lyle
Agriculture & Agrochemicals
Biomanufacturing, using cells to create desired compounds.
· Sustainable farming: Better bacteria to optimise plant growth and health with less negative side effects on the environment
· Soil additives: eg At MIT, researchers are working to build a process that will allow plants to fix nitrogen. If successful, farmers will no longer require fertilizer for their crops;
· Disease-resistant plants:
Source: McKinsey, 2020
And the potential impact on existing meat production systems:
Source: McKinsey, 2020
The question remains if cell cultured meat ie “alternative protein” can be scaled efficiently enough to be cost competitive and profitable. And the product is still “processed” so may have additives that are unhealthy for humans. However the animal cruelty currently in the food system will be prevented. Some alt protein experts believe that cell cultured meat will never be cost competitive, others believe it will happen in the 2020s. The cost of re-agents, (eg growth media/ substances) and the ability to build much bigger bioreactors than those currently available are key things that have to happens.
Digital Data Storage
DNA is itself a four-letter code (ACGT) for passing along information about an organism.
Today many terabytes of data is stored using the basics of computers, in binary sequences on a computer disc drive. A magnetic drive may still be reliable for data retrieval for 10 or 20 years, where heat, vibration, humidity, and magnetic field can further reduce the storage devices useful life.. SSDs are suggested to be replaced every 10 years or so or sooner, and optical drives (up to 100gb per disc, can last over 100 years but are very slow for data writing and retrieval). Perhaps [40%] of data is selected for long term storage, meaning massive amounts of data that is not retrieved and read very often.
DNA can archive a staggering amount of information in an almost inconceivably small volume. Consider this: humanity will generate an estimated 33 zettabytes of data by 2025—that’s 3.3 followed by 22 zeroes. DNA storage can squeeze all that information into a ping-pong ball, with room to spare. The 74 million million bytes of information in the Library of Congress could be crammed into a DNA archive the size of a poppy seed—6,000 times over. Split the seed in half, and you could store all of Facebook’s data.[Source: Scientific American, May 2021].
DNA can be very stable, so it is being investigated to be used for data archiving.
The process of DNA data storage combines DNA synthesis, DNA sequencing and an encoding and decoding algorithm to pack information into DNA more durably and at higher density than is possible in conventional media. That could be up to 17 exabytes per gram. DNA doesn't require maintenance, and files stored in DNA are easily copied for negligible cost. DNA properly encapsulated with a salt remains stable for decades at room temperature and should last much longer in the controlled environs of a data center.
So DNA as a storage media can store huge amounts more in much smaller sizes than current hard drives, is very stable, does not require maintenance. However it currently has very high cost and very slow read and write times.
By synthesizing DNA molecules—making them from scratch—researchers have found they can specify, or write, long strings of the letters A, C, G and T and then read those sequences back. The process is analogous to how a computer stores binary information. From there, it was a short conceptual step to encoding a binary computer file into a molecule.
The method has been proven to work, but reading and writing the DNA-encoded files currently takes a long time. Appending a single base to DNA takes about one second. Writing an archive file at this rate could take decades, but research is developing faster methods, including massively parallel operations that write to many molecules at once.
Unfortunately, compared to traditional digital systems, the error rates while writing to molecular storage with DNA synthesis are very high. These errors arise from a different source than they do in the digital world, making them trickier to correct. On a digital hard disk, binary errors occur when a zero flips to a one, or vice versa. With DNA, the problems come from insertion and deletion errors. For instance, you might be writing A-C-G-T, but sometimes you try to write A, and nothing appears, so the sequence of letters shifts to the left, or it types AAA.
All the world’s data—all your digital photos and tweets; all the records of the global financial sector; all those satellite images of cropland, troop movements and glacial melting; all the simulations underlying so much of modern science; and so much more—have to go somewhere. The “cloud” isn’t a cloud at all. It is digital data centers in huge warehouses consuming vast amounts of electricity to store (and keep cool) trillions of millions of bytes. Costing billions of dollars to build, power and run, these data centers may struggle to remain viable as the need for data storage continues to grow exponentially.
So the economic feasibility of using DNA sequences to store huge amount of archive data will been dependent on massively improved read/ write capability for DNA sequences, and the development of cost effective processes. So as of 2021, this still seems many years off. But the need is there.
Genomic development…
Some consider Genome Editing to be the same thing as synthetic biology, as often one can design an edit to a genome to change an organism and insert it in to an existing genome. Or one can simply use Crispr and cut out or add in a sequence.
One has been cross breeding animals and plants for centuries trying to create an organism that is closely to what one wants, and then we had genetic engineering- GMO- genetically modified organisms, where some genes were changed to produce a desired new organism eg a stalk of corn that was resistant to drought or certain pests or pesticides eg Glyphosate etc, to increase crop yields, or cross breeding dogs to produce a more desired breed; making new fruits eg new apple varieties. Or the chickens that you eat, have been “selectively breed” to optimise the amount of chicken meat you get for the lowest possible cost.
But now we can start with a blank sheet of paper and design from scratch.
2) What is the current state of capabilities? How does it work?
Many things can be done. Virtually anything with a genome can be made. George Church, a famous Harvard Geneticist, has obtained the woolly Mammoth genome- which went extinct about 3,700 years ago, and is looking to re-create it. (Said to be for climate change and de-extinction reasons).(See www.colossal.com)
Scientists have access to ever more genetic information and more powerful genetic engineering capabilities than ever before.
But as of 2020, very few small molecules in medicine are manufactured using a synthetic biology process; it remains very difficult to engineer microbes to carry out processes not intended by nature. From an evolutionary perspective, the performance of microbes is “good enough” . Microbes evolved to address the specific needs and challenges of their natural environments not those of industrial fermenters and bioreactors.
Making a new organism..?
You can actually order a biochemistry kit over the internet for under $2,000 with all the components needed to make your own organism from scratch (or rather insert a genomic sequence in to an organism).
When it comes to risk from synthetic biology applications, one source of concern is the community of DIY biologists and biohackers using bioengineering technologies outside of certified laboratories.
The popularity of DIY biology may lead to “someone getting hurt.” Due to the wide availability of cheap custom-made DNA, it is in theory easy even for lone individuals to produce pathogenic agents. “I can order gene fragments for any biological toxin and if I want, I can create the strain in my basement”.
As benchtop DNA synthesizers drop in cost, individuals could make their own DNA, circumventing any quality controls.
However there are many skills needed, to make a number of organisms, such as a bio-reactor.
Making new foods:
“Fake meat” can generally be made from plant proteins, or “cultured meat” which is essentially growing a biopsy of an animal eg a cow or pig or chicken, and then creating just the meat desired using arrange of re-agents, nutrients and growth factors. Perhaps the meat of up to 75 cows can be made from one pinhead of a biopsy from a cow, with a huge saving in water and stopping animal cruelty which is endemic in the factory farms of today, and stopping the unhealthy practices damaging human health- such as overuse of antibiotics and hormones. Or one can design a completely new food, with an optimal nutrition, taste and texture profile for each consumer.
Dual Uses & Ethics:
Synthetic biology is like iron: You can make sewing needles and you can make spears; or with nuclear knowledge you can make nuclear power or nuclear bombs and so on. Of course, with synbio there could be also dual use.
Synthetic biologists are also working hard to minimize potential adverse effects. For example, Silver’s lab is working to create genetic self-destruct traits, termed “auto-delete,” as a way to ensure that genetically modified organisms don’t escape into the environment.
On the engineering side, SynBio uses principles and ideas from biotechnology, biophysics, computer science, nanotechnology, bioinformatics, machine learning, artificial intelligence, and in silico analysis and testing
Synthetic biology focuses on creating technologies for designing and building biological organisms. A multidisciplinary effort, it calls biologists, engineers, software developers, and others to collaborate on finding ways to understand how genetic parts work together, and then to combine them to produce useful applications.
As a fairly new field developed over recent years it has been driven by the enormous improvements in our ability to synthesize and sequence DNA.
The first replicating organisms genetic code created “from scratch” was made by the world renowned geneticist, Craig Venter, who was first to sequence the human genome, in 2008. Whilst it was a simple organism, a 375 gene bacteria,(582,000 base pairs) Micoplasma genitalium, (a bacterium that can cause urinary and genital tract infections in humans).it was a living organism, that then could replicate. The entire genome was synthesized in vitro, and exchanged with the original, natural one – so it was like an organ transplant – so not yet made entirely from scratch.
In 2017, another group of scientists partially synthesized the genome of Saccharomyces cerevisiae, the yeast that is used to make bread and brew wine and beer.
Since that time many more advances have been made with substantial companies now springing up to manufacture many things not currently found in nature, with a whole range of new applications, across the field of pharmaceuticals, food, energy, which will ultimately drive down the costs of many things in these industries.
Synthetic Biology is growing extremely fast, enabled by the explosion of new technologies and scientific breakthroughs, permitting more and more to be done, ever faster and ever cheaper.
3) What are the stages of synbio?
A number of synbio companies have the following components as set out below. However there are many CROs- contract manufacturing Organisations that can make your requested DNA sequences, such as groups like IDT : Integrated DNA Technologies ǀ IDT (idtdna.com)
Or alternatively you can simply order subsections / parts of what you want to assemble, with many making parts to order.
Go to their websites, request the sequences you want, and those sequences will arrive days or weeks later. The cost can be as low as 5 cents a base pair.
The components of a fully integrated Synbio organisation are as follows:
1) A Bio- FOUNDRY: see gingko bioworks video on their foundry: Ginkgo's Platform: A Foundry Tour (Ginkgo Bioworks Investor Day 2021) - YouTube
So the process is designing the new genomic sequence, possibly inserting it in to cells, and seeing how they perform, then redoing the sequence, so a continuous iterative of Design, Build, Test, learn, Repeat, until the required cells with the new genetic sequence is achieved.
Design Center:
As mentioned above, the process is designing the new genomic sequence, designed by yoru biotech experts or more and more by AI systems, possibly inserting it in to cells, and seeing how they perform, then redoing the sequence to get better performance, so a continuous iterative of Design, Build, Test, Learn, Repeat, until the required cells (or compounds) with the new genetic sequence is achieved.
Synthesis Operation:
When you have designed your required DNA sequence, you need it manufactured, where there are many gene synthesis companies that will manufacture it for you. The cost and time it takes depends on how long the gene sequence is e.g. 8kb, and how complex it is. The cost can therefore vary from $0.06 cents a base pair, to over 23 business days for a sequence over 8kb. This production will obviously reduce over time as better and better processes are established.
Many gene synthesis services are provided by Contract Research Organizations (CROs), of which there are thousands.
Example gene synthesis companies:
UK:
USA:
Gene synthesis & DNA synthesis – Guaranteed Delivery Time | GenScript (GenScript currently has more than 3000 employees globally and an annual revenue of $250M)
Assembly:
The components need to be “stuck together”.
Devices:
Evonetix of Cambridge UK is advanced on its work on producing a desktop synthesizer. There remain numerous problems in the synthesis of longer DNA. Current techniques are typically provided as a service, are slow, cannot synthesise all sequences and often incorporate random errors, requiring cloning time-consuming further analysis and sequencing to ensure acceptable quality. In addition, synthesis of error-free DNA becomes increasingly difficult as the length increases, creating challenges for its use in synthetic biology where the ability to access high-fidelity DNA at scale is an important requirement.
End Application:
Once the organism or compound is “operational” then it needs to be applied to the end use.
4) What are the implications of this?
As stated my McKinsey, up to 60% of the worlds products can be made biologically. Even if perhaps half or one third of this can be done with economic or other advantages then this implies a huge change in the worlds manufacturing processes. Or off course, there is the possibility of harm, addressed below.
5) Who are the main players, and where will a lot of money be made?
Much work is going on in Universities, with global co-operation. Igem, an annual gathering of synbio students with competitions, helps bring scientists together from all over the world.
Much money is flowing in to the space:
Leading companies such as Gingko Bioworks & Twist Bioscience, with a sampling of other firms also listed, are detailed below..
Source: CBI
Gingo Bioworks: (Boston, Listed; NYSE: DNA, Market Cap: Jan 2022, $7.5bn) The Organism Company - Ginkgo Bioworks c. 600 employees, specialises in producing bacteria with industrial applications. It is an analytics company that designs micro-organisms for customers in a range of industries. States it is like an app store- a platform for companies to develop applications for end uses, where gingko gets a slice of the end revenue. They get equity or royalty revenue.
A short seller, Scorpion Capital, did an “expose” of their practices in 2021, and claimed that much of their revenues were “fabricated” or “round tripping”. Their shares have more than halved over the past year.
Source: Gingko Bioworks
Twist Biosciences: (San Francisco, Public, Market Cap: Jan 2022: >$3bn, TWST). Twist Bioscience | We lead innovation in DNA synthesis >400 employees. Revenues 2021 > $100m. Manufactures synthetic DNA and DNA products for customers in a wide range of industries.
Zymergan: (San Francisco/ Emeryville; Public; Market Cap: Jan 2022: $550m; ZY) Zymergen - We Make Tomorrow Their stock price is down over 80% over the last year. Their pitch was crafting products normally made of petrochemicals, from optical film for foldable smartphone screens to mosquito repellent. Unfortunately they could not scale the smartphone screen manufacturing causing the stock price implosion, compounded by the statement that they would have no material revenues for 2021 and 2022.
Codexis: (San Francisco / Redwood City, CA; Nasdaq, Market Cap: January 2022: $1.4bn; <$70m product revenue for 2021) Enabling the promise of synthetic biology | Codexis Enzyme engineering focus. 20 concurrent enzyme discovery projects. Used by Merck, GSK, Novartis, Pfizer. GRAS self-affirmed enzyme for Kalsec hop extract. Accelerating enzymes sales to T&L sweeteners. W Merck and Almelo establish generic sitagliptin positions. Enzyme for late-stage COVID-19 antiviral therapeutic candidate.
Novozyme: (Copenhagen, Denmark; Listed; Market Cap: January 2022: c$20bn ) > $2bn revenues in 2019. Novozymes | The world leader in biological solutions >6,000 employees. The company's focus is the research, development and production of industrial enzymes, microorganisms, and biopharmaceutical ingredients. Their enyzmes are used in many laundry detergents to enhance cleaning.
Arzeda: (Seattle, WA) (Private) Arzeda - About Arzeda Arzeda's uses computational protein design and state-of-the-art high-throughput screening, a change over what's possible with traditional protein engineering.
Amyris: (San Francisco; Public; AMRS; Market cap $1.4bn – Jan 2022) Amyris | Biotechnology Company Amyris serves the specialty and performance chemicals, flavours and fragrances, cosmetics ingredients, pharmaceuticals, and nutraceuticals markets. Amyris is producing new cosmetics, eg Biossance Official Website - Award Winning Clean Skincare Vitamin C Rose oil for skin hydration. Amyris also developed its version of squalane — a synthetic form of shark-derived squalene. In 2016, it launched Biossance based on the squalane ingredient story, which mimics the skin’s natural oils with emollient and anti-aging properties. Cut to 2021: Biossance is on track to earn up to $160 million in sales this year. Squalane makes up 20% of Amyris’ total revenue, Melo said. Amyris now sells squalane to companies like Shiseido, L’Oréal Group and AmorePacific. The ingredient is found in brands like JLO Beauty, The Ordinary and Peter Thomas Roth.
Aether Biomachines: (San Francisco; Private) Aether Bio — Build the next industrial revolution. Aether designs catalysts ie enyzmes that enable new chemistry (screening multiple enzymes against a large of panel of substrates)
Solugen: (Houston, Texas) (Private, $357m raised in 2021) Home - Solugen | Solugen Uses synthetic biology to take hydrocarbons out of the chemicals industry. The company makes chemicals from custom enzymes and renewable feedstock. It uses dextrose, a simple sugar, and in the future it aims to convert carbon into useful products like building materials and formaldehyde-free resins. Chemical companies have historically used petroleum, natural gas and phosphates to make their products, exacerbating air and water pollution. Solugen aims to replace many of these ingredients with chemicals using renewable resources like simple sugar. The Bioforge, as Solugen calls the facility, takes up just 20,000 square feet and produces 10,000 metric tons of chemicals a year.
Evonetix: (Cambridge UK) (Private) Home - Evonetix Synthesis Platform | Our mission | The synthetic biology company is developing a desktop platform for scalable, high-fidelity and rapid gene synthesis, raised $30 million USD (£23 million GBP) in its 2020 Series B round, which was led by new investor Foresite Capital. Existing investors, Draper Esprit, DCVC (Data Collective), the Morningside group, Providence Investment Company, Cambridge Consultants Ltd, Rising Tide Fund, and Civilization Ventures, also all participated in the round. For more than three decades DNA has been synthesised by constructing individual strands through sequential chemical addition of bases and then combining them to create longer, double-stranded DNA. there remain numerous problems in the synthesis of longer DNA. Current techniques are typically provided as a service, are slow, cannot synthesise all sequences and often incorporate random errors, requiring cloning time-consuming further analysis and sequencing to ensure acceptable quality. In addition, synthesis of error-free DNA becomes increasingly difficult as the length increases, creating challenges for its use in synthetic biology where the ability to access high-fidelity DNA at scale is an important requirement. The Evonetix approach utilises a silicon chip, made by MEMS processing, that integrates physics with biology, and controls the synthesis of DNA at many thousands of independently controlled reaction sites or ‘pixels’ on the chip surface in a highly parallel fashion. The approach is compatible with both chemical and enzymatic DNA synthesis. Following synthesis, strands are assembled on-chip into double-stranded DNA in a process that identifies and removes errors, providing accuracy that is several orders of magnitude better than the conventional approach.
6) What big things can we expect and by when?
Bio innovation is occurring in 4 key areas:
With the potential timeline as follows:
Source: McKinsey, 2020
7) What are some of the key headwinds, issues & risks?
As mentioned above, like any big discovery that can have a lot of good for humanity, there is often a flipside, where it is a “dual use technology”. Nuclear energy provides cheap and clean power to millions of people and companies, yet a bomb can be made with it to kill millions. Some would argue that synthetic biology poses an existential risk, but so does nuclear power, artificial intelligence, or climate change brought on by a myriad of technological advances (cars, trucks, ships, coal or gas power stations, aircraft, computers consuming electricity etc). But the production of biofuels, food security and more effective medicines will have a huge number of beneficiaries.
Synthetic biology can fall within the same argument. Foods will be able to be made much cheaper and better, feeding possibly billions. New drugs can be made to save lives. Yet, a terrorist could design a biological weapon from it, to kill millions. Or even an incompetent lab / scientist could inadvertently release a pathogen- some believe that the Covid 19 virus escaped from a Chinese virology lab in Wuhan, and now over 5 million are dead and counting.
A possibly religious argument can be made, that man should not “interfere with nature”, and “play God”, but simply leave development of species to the randomness of nature and evolutionary forces of nature. But man has been “interfering with nature” for millennia, by selectively cross breeding animals and organisms, so one could argue that man is simply speeding things up and making them more efficient.
Many of these synbio companies will need a lot of funding to be able to progress the science through to a cost competitive end product. Huge amounts of funding have been available in the last decade, and prices had shot up in to the stratosphere, however as of January 2022 it appears that the funding cycle may be turning down with the increasing interest rates, which may result in certain synbio companies going bankrupt.
From the danger of biological terrorism angle, or accidental escape of pathogens (eg Wuhan and Covid-19?) biosecurity labs rankings are as below. There are 13 BSL-4 labs in the USA; 600 BSL-3 labs in the UK. In the UK these are referred to as Containment Level 3 and 4 (CL3 & CL4). Most work with dangerous pathogens is carried out in Government and Research Council laboratories. Of these around 150 are in research institutes and 150 at universities, although differentiating between research institutes and university laboratories is difficult. There are around 75 BSL-3 laboratories operated by private companies. Two universities have 84 BSL-3 laboratories between them; and one institute has 60 BSL-3 laboratories. However the more labs there are and the more and more advanced work being done, then the risks of an escape or terrorist incident is increasing, especially as the barriers to entry ie set up your own facility keeping dropping.
8) Summary
Synthetic Biology holds tremendous promise for the betterment of mankind, as outlined above, but with risks and some issues remaining to be resolved, if possible.
There has been a huge boom in funding for synbio companies but it is still early days and many have still to produce a very useful product that has widespread adoption with a high level of sales. This will come, but there will likely be many “bumps in the road” before then, perhaps some funding issues, and a number of companies will not make it, as in any booming new technology.
It is unclear what the 100 year outcome will be, either Utopia or dystopia, or somewhere in between? Will it be the movies like The Terminator, Blade Runner, Lucy or Elysium? I am more optimistic and think that there could be a utopia, with great benefits for all mankind.
References:
1. De-extinction Projects, Facts & Statistics | Colossal Recreating the woolly mammoth (targetting 2027)
3. igem.org (independent, non-profit organization dedicated to the advancement of synthetic biology, education and competition)
4. DNA as a digital information storage device: hope or hype? Panda. 2018
5. McKinsey Report, 2020: The Bio Revolution: Innovations transforming economies, societies, and our lives | McKinsey
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