Sam Lee is a biotech veteran currently working in R&D program management at BioNTech. He set up the IndieBio incubator in New York and previously served as Head of Innovation at Dr. Reddy's Laboratories. His career spans management consulting, pharma research direction, and his first job at DuPont packaging. He holds a PhD in chemistry from the University of Toronto.
In this episode, we cover the history and fundamentals of synthetic biology and biomanufacturing—from the early days of bio-based polyester to the latest developments in cell-free systems and cultured meat.
Episode Chapters
| Timestamp | Topic |
|---|---|
| 0:00 | Intro & Sam's Background |
| 4:13 | History of Synthetic Biology |
| 7:16 | What drove the first forays into Synthetic Biology, bio-based polyester |
| 10:42 | Sugar vs Oil as a feedstock |
| 13:59 | Unit Economics of Biofuel & building block chemicals |
| 18:24 | Plastics & the End of Globalization |
| 22:04 | Examples of Biomanufacturing Businesses |
| 25:09 | Biomanufacturing Version 1.0, 1.1 and 2.0 |
| 27:45 | Human Milk Oligosaccharides |
| 30:51 | How does Synbio R&D work? |
| 37:59 | Cell-free Systems |
| 45:42 | Where is Synbio going, cultured meat |
| 48:21 | Final Thoughts |
Slides from Sam Lee with the Podcast
Sam's Background
Sam Lee's career trajectory is a fascinating journey through multiple corners of the biotech and pharmaceutical world. Starting at DuPont in packaging, he moved through management consulting and pharma research before landing at the intersection of innovation and biology. His experience setting up IndieBio in New York gave him a front-row seat to the emerging synthetic biology startup ecosystem, and his current role at BioNTech places him at one of the most influential biotech companies in the world.
History of Synthetic Biology
Synthetic biology as a field has its roots in the early attempts to engineer biological systems to produce useful materials. The first major commercial forays were driven by the desire to create bio-based alternatives to petroleum-derived products, particularly bio-based polyester.
The field has evolved through several distinct phases, each driven by different economic and technological forces.
Sugar vs Oil: The Feedstock Question
One of the fundamental economic questions in biomanufacturing is the choice of feedstock. Traditional chemical manufacturing relies on oil, while biomanufacturing typically uses sugar as a carbon source for microbial fermentation. The relative economics of sugar versus oil have a profound impact on the viability of biomanufacturing businesses.
Unit Economics of Biofuel and Building Block Chemicals
The economics of biofuels have been challenging. Producing fuel through biological processes must compete with the extraordinarily efficient and scaled petroleum industry. However, building block chemicals—higher-value molecules used as intermediates in manufacturing—represent a more promising target for biomanufacturing.
Plastics and the End of Globalization
The intersection of plastics manufacturing, supply chain disruption, and the potential deglobalization of industry creates interesting opportunities for biomanufacturing. Local, bio-based production of plastics and materials could become increasingly attractive as global supply chains face new pressures.
Biomanufacturing: Version 1.0, 1.1, and 2.0
Sam describes the evolution of biomanufacturing in three phases:
- Version 1.0: Early attempts at biofuels and commodity chemicals—many of which struggled with economics
- Version 1.1: Pivot to higher-value specialty chemicals and ingredients with better unit economics
- Version 2.0: Advanced applications including cell-free systems, cultured meat, and programmable biology
Human Milk Oligosaccharides
One of the fascinating examples of successful biomanufacturing is the production of human milk oligosaccharides (HMOs). These complex sugars, naturally found in breast milk, play critical roles in infant nutrition and immune development. Producing them through microbial fermentation has made them available as infant formula ingredients at scale.
How Does Synbio R&D Work?
Synthetic biology R&D follows the Design-Build-Test-Learn (DBTL) cycle:
- Design: Use computational tools to design genetic constructs
- Build: Synthesize and assemble DNA, transform into host organisms
- Test: Characterize the engineered organisms for desired traits
- Learn: Analyze results and feed insights back into the next design cycle
Advances in DNA synthesis, high-throughput screening, and machine learning are accelerating each step of this cycle.
Cell-Free Systems
Cell-free systems represent a paradigm shift in biomanufacturing. Instead of engineering living cells to produce target molecules, cell-free approaches use extracted cellular machinery—enzymes, ribosomes, and other components—in a test tube. This offers several advantages:
- No need to keep cells alive or deal with cellular metabolism
- Greater control over reaction conditions
- Ability to produce toxic molecules that would kill living cells
- Faster prototyping and iteration
Where Is Synbio Going? Cultured Meat and Beyond
Looking to the future, Sam discusses several frontier applications of synthetic biology, with cultured meat being one of the most visible. Growing meat from animal cells in bioreactors, rather than raising and slaughtering animals, could transform food production. However, significant challenges remain around cost, scale, and consumer acceptance.
Final Thoughts
Synthetic biology is at an inflection point. The convergence of cheaper DNA synthesis, better computational tools, and growing market demand for sustainable alternatives is creating unprecedented opportunities. While challenges remain—particularly around scale-up economics and regulatory frameworks—the potential for synbio to reshape manufacturing, food production, and medicine is enormous.
About Bio2040
There are so many challenges in drug discovery. We are a group of entrepreneurs and scientists who want to improve things.
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