Too often, the word “innovation” is preceded by the word “disruptive.” Although we’ve all heard the cry, “Move fast and break things,” we might be better off if we moved at a steady pace and kept things more or less intact—or even enhanced their cohesiveness. For this GEN editor, the idea of favoring cohesion over disruption emerged during a recent conversation I had with two synthetic biology experts, Kristy Hawkins, PhD, and Zack McGahey. Hawkins is the co-founder and chief scientific officer and McGahey is the chief operations officer at Antheia, a synthetic biology company specializing in the production of active pharmaceutical ingredients (APIs) and key starting materials (KSMs).
Antheia, like other synthetic biology companies, could help promote cohesiveness in various ways. For example, Antheia could help mitigate risks in the manufacturing supply chain. A prominent risk, we recently learned, is the spread of pandemics. Other risks include geopolitical turmoil, extreme weather events, and cyberattacks.
Supply chain risks
“We’ve had many conversations with interested parties in the federal government about what our technology and our products can do for surety of drug supply,” McGahey said. “The targets that we work with are regularly in shortage. These are products that are largely sourced from abroad, mostly from India and China.
“I think the pandemic really opened up a lot of eyes for people about how our supply chains work, especially for pharmaceuticals. Consider the drugs on the World Health Organization’s essential medicines list—these are very important products to our country.”
According to the American Society of Health-System Pharmacists,1 data from the University of Utah Drug Information Service indicates that “at the end of the second quarter of 2023, there were 309 active, ongoing drug shortages—the highest number in nearly a decade and close to the all-time high of 320 shortages.”
To address such shortages, a recent Brookings Institution report suggested that governmental action would be required.2 “Realigning hospital and manufacturer incentives requires involvement of multiple government agencies, supported with new funding, and, in some cases, with new authorities,” the report concluded. “But without a serious, coordinated effort on multiple fronts, policymakers will fail to change the dynamics and the unacceptably high number of costly shortages will persist.”
A coordinated effort would seem to be in the works. In September 2022, the Biden administration issued an executive order known as the National Biotechnology and Biomanufacturing Initiative. Then, in May 2023, the administration followed up with a new report, “Bold Goals for U.S. Biotechnology and Biomanufacturing: Harnessing Research and Development to Further Societal Goals.” To support the report’s goals—which included advancing biotechnology and biomanufacturing, strengthening America’s bioeconomy and supply chain, and supporting American innovation—the Biden administration announced more than $2 billion in funding, including $1 billion in funding from the U.S. Defense Department.
But, McGahey noted, ambitious goals require follow-through: “As with most things government-related, the challenge often involves getting from ‘We’re interested in helping support this’ to ‘How do we actually do it?’ Years later, that money is now beginning to find its way to appropriations.”
“We’ve had very productive conversations with various departments in the federal government about how they can support infrastructure development,” he continued. “We’re still continuously working to support the government and provide industry insight into how to most effectively utilize funding and impact the broader economy in the best way possible, whether that’s in pharmaceuticals or in other product spaces that are valuable for supply chains, but we certainly have made a compelling argument about what Antheia can do.”
“In general, we’re going after plant natural products that can’t be synthesized chemically,” Hawkins added. According to Hawkins, Antheia’s technology and biomanufacturing provides a way to onshore supply chains that might otherwise involve the harvesting of plants from remote places around the globe, including places where production is threatened by climate change.
“At a recent conference, the Department of Defense was there, emphasizing its support of biomanufacturing as well for the production of many specialty chemicals, commodity chemicals, and specialty proteins,” Hawkins remarked. “In addition to agreements to provide funds for the purchase of materials, there will need to be a mechanism for distributing those funds to help bring down the cost of goods for manufacturing.”
Biomanufacturing solutions
To address supply chain security issues, as well as more general sustainability issues, synthetic biology promises to do for a range of product types what biotechnology, or rather biomanufacturing, has already done for biologics. In one of its signature triumphs, biomanufacturing began generating large quantities of human insulin from bioreactors containing genetically engineered microbes, instead of harvesting tiny quantities of insulin from animal pancreases.
Before biomanufacturing, about 50,000 animals were needed for the production of just 1 kg of insulin. The figure suggests how biomanufacturing, at scale, can improve sustainability. Notice, however, that the previous sentence specifies “at scale.” Biomanufacturing capacity is costly and in high demand, and most of it is devoted to the production of biologics because even small volumes of biologics can generate large revenues.
Industrial-scale synthetic biology presents a different economic challenge. Compared with biologics, many products are less valuable per unit volume and would have to displace products that are already available from established (and often subsidized) sectors such as the agribusiness sector and the chemical industry.
The report was less clear about the definition of precision fermentation, perhaps because the term is fairly new and means different things to different people. According to Hawkins, precision fermentation implies a high degree of control over media composition and conditions such as feed rate, pH, and temperature.
Precision fermentation usually involves organisms that result from advanced strain engineering. “With traditional fermentation, you’re largely taking advantage of what microorganisms naturally like to do. Yeast cells, for example, love to make ethanol,” Hawkins observed. “With precision fermentation, you’re working with genetically modified organisms to make a target, a small molecule or a protein, with high specificity. These organisms have been engineered to divert them from doing what they naturally like to do.”
The organisms Hawkins described sound a lot like the organisms that are the mainstays of biotechnology. However, she also suggested that they can be more elaborately engineered. For example, organisms can reflect the installation of multistep metabolic pathways. “We have some heavily engineered strains,” she noted. “These include some of the most complex and heavily engineered pathways that have been scaled to date for the production of small molecules.”
Good fits
Rather than emulate the technology world’s enthusiastic disruptors, synthetic biology companies may try to fit in. That is, rather than upend established markets or obviate established businesses, they may focus on delivering value not only for their own investors and customers, but also for their partners and the broader economy. They may even reinvigorate established market segments.
These possibilities were entertained by McGahey, who said, “The large-scale fermentations and the types of plants that we would design and build and/or operate with partners don’t require a ton of manpower, but they do require a lot of raw materials. They also involve energy costs and other things that are associated with just the building and infrastructure.
“That’s something that the United States has in abundance. We have relatively stable energy costs, and the other thing we have an abundance of is corn in the Midwest, which supports the largest component of our bill of materials.
“There’s an opportunity to boost to the agricultural society here in the United States and to reinvigorate a region of the country that has lost a lot of manufacturing, especially after the bioethanol bust. There are unused facilities in the Midwest that could be refurbished and refitted—all the substrates are there: the energy, the waste management, the feedstock, and they are there in abundance.”
McGahey also suggested that synthetic biology may fit into the broader economy where needed. “Synthetic biology is at a pivotal moment where we’re starting to realize, ‘Hey, we can really make everything.’ But that doesn’t necessarily mean that everything needs to be made with synthetic biology. There are certain applications, certain fields, certain programs where we will succeed. And there are other areas where traditional chemical manufacturing might still be the best methodology. Over the next decade, I think we’ll see a funneling of that core expertise and technology that’s been in development into all the right winning categories.”
In the meantime, Antheia is looking at industry partnerships to secure manufacturing capacity. For example, the company recently announced that it had expanded its partnership with the Olon Group. An Olon Group division, Olon Biotech, has more than 50 years of experience providing fermentation manufacturing services and is a globally licensed API manufacturer.
“Olon has over 5 million liters of fermentation capacity between their multiple sites in Italy,” McGahey pointed out. “They’re very used to dealing with our types of processes. Our first lots are being made and scheduled to be delivered to our first customers toward the end of this year.
“We’re in discussions with various entities here inside the United States because we truly believe that future of this technology should be here in the United States. Ultimately, Antheia’s product portfolio is large enough and diverse enough that it’s going to require us having sites on multiple continents.”
References
- American Society of Health-System Pharmacists. Severity and Impact of Current Drug Shortages. June/July 2023. https://www.ashp.org/-/media/assets/drug-shortages/docs/ASHP-2023-Drug-Shortages-Survey-Report.pdf
- Wosińska M, Frank RG. Federal policies to address persistent generic drug shortages. The Brookings Institution. June 21, 2023. https://www.brookings.edu/articles/federal-policies-to-address-persistent-generic-drug-shortages/
- Bobier J-F, Cerisy T, Coulin AD. Breaking the Cost Barrier in Biomanufacturing. Ind. Biotechnol. 2024; 20(3): 99–136. DOI: 10.1089/ind.2024.58943.jfb.
