AI + Synthetic Biology: The Most Transformative Technology in Human History | Ben Lamm (Colossal)

Ben Lamm's insight is that the hardest problems in biology are not in a specific disease but in reconstructing and engineering entire organisms. De-extinction demands understanding how genetic changes manifest in whole-animal traits, which many biomedical fields ignore. Colossal intentionally chose this path to develop a comprehensive platform incorporating computational biology, cellular engineering, gene editing, cloning, and eventually artificial wombs. This contrasts with the typical biotech approach of targeting a single therapeutic. By tackling de-extinction, they built a system that could then quickly spin out companies like Breaking for plastic degradation, demonstrating the power of a platform. He advises that this 'start with the hardest thing' strategy, powered by AI, yields superior capabilities and multiple revenue streams, making the company undervalued at $10B.

Colossal's spin-out Breaking originally thought they had a single enzyme from a microbe discovered at the Wyss Institute. Deeper analysis showed a consortium of microbes cooperating. This was better because they could edit each microbe to produce different enzyme variants tailored to various plastics. The plastic crisis affects oceans, food, and human health (microplastics in brain, reproductive tissue). Current solutions often just shred plastic into microplastics, worsening the problem. Breaking's approach chemically breaks plastic, and they aim to develop a supplement to degrade microplastics in the gut before absorption. This protocol emphasizes the importance of looking beyond single-strain solutions and leveraging ecosystem complexity.

Ben emphasizes that Colossal doesn't always lead with AI even though AI is fundamental. Without AI, they couldn't achieve the hundreds of multiplex edits or 5x DNA synthesis delivery. The product and systems approach contrasts with traditional academic or biotech point solutions, which are siloed and slower. By treating synthetic biology as an engineering discipline with a robust platform, they've achieved rates of progress that outpace the field. This model is applicable beyond de-extinction: they've spun out companies for plastics, artificial wombs, vaccines, etc. The platform effect means each new breakthrough improves all spin-outs through shared editing efficiencies and data.

The invasive species problem is massive—$5.4 trillion globally—and current methods like poison and trapping are environmentally damaging and cause immense animal suffering. Ben gives the example of the screwworm, which is moving into Texas and threatening cattle. Traditional vaccines face regulatory hurdles and public resistance due to anti-GMO sentiment. Gene drives offer a precise alternative: they only affect the target species and reduce populations without direct killing. Colossal's proprietary tech includes roll-back capabilities to increase safety, which could ease regulatory and public fears. They are working with governments. He also notes that earlier mosquito gene drive trials were halted due to food web concerns, but invasive species are not integral to ecosystems, making them ideal targets. This approach could be applied to cane toads, carp, cats, etc., in Australia and New Zealand, where millions of animals are culled inhumanely.

Ben explains that to succeed with artificial wombs for mammals, they had to innovate in embryo culture. They built a device that keeps embryos healthier longer. They discovered that the standard morphological grading used in IVF—where embryos are graded at day 3 or 5 based on cell symmetry and fragmentation—misses the healthiest embryos. In animal models, embryos that looked bad early turned out to be the best if given more time. This insight came from non-model species research. He draws from his personal IVF journey, where he felt the process was archaic and emotionally fraught. Although Colossal's direct work is on non-human species, the same principles apply to humans. They are considering spinning out an IVF improvement company based on this technology. This protocol challenges the status quo in fertility clinics and could increase success rates.

Ben recounts having to educate the Australian government that Tasmanian tigers, even if 100% genetically identical to original, are technically GMOs, and their anti-GMO stance would prevent rewilding. He argues that GMOs have saved millions of lives (e.g., insulin, crops) and that the fear is akin to early resistance to seat belts. He suggests using this analogy to depersonalize the fear. This is a marketing/education protocol derived from their real-world experience with governments. He also analogizes current invasive species control (poison) to archaic cancer treatments, urging a shift to modern genetic approaches.

Ben Lamm explains that when he met George Church, Church instantly said he'd work on mammoth de-extinction with unlimited capital. Lamm initially planned to fund it as a side project but quickly realized the potential to build an end-to-end pipeline. They reasoned that starting with de-extinction—solving some of biology's hardest problems—would create a system model for everything from disease-resistant plants to plastic-degrading microbes. The platform integrates computational biology, cellular engineering, genetic engineering, cloning, somatic cell nuclear transfer, and eventually artificial wombs. By solving genotype-to-phenotype and comparative genomics for extinct species, they built capabilities that can be applied broadly. This contrasts with the typical single-point solution approach in biotech. The result is a parent company that spins out multiple ventures, each attacking a global challenge. This 'platform' thesis allowed Colossal to reach a $10 billion valuation in four years.

Ben describes how they initially thought they had discovered a single enzyme from a microbe at the Wyss Institute, but further analysis revealed a consortium of microbes collaborating to break chemical bonds. This set of microbes and their enzymes can be edited to target different plastic types. They applied directed evolution and their gene editing pipeline to increase both the spectrum of plastics that can be degraded and the rate of degradation per surface area. The plastic crisis is not just an environmental problem; microplastics are found in human brains, reproductive tissues, and cross the blood-brain barrier. Breaking aims to tackle this by not making smaller plastics but by chemically destroying them. Ben envisions a future supplement that could break down microplastics in the gut before absorption, addressing the 5g of plastic estimated to be in the average brain. This spin-out exemplifies how Colossal's de-extinction platform yields solutions to global environmental health problems.

Ben contrasts the field's typical progress: most groups still do single-digit edits at 15% efficiency. Two to three years ago, Colossal did victory laps for a couple of edits at 40%. Now they routinely perform hundreds of edits at 90% efficiency, meaning almost all targeted cells are successfully edited. These edits are non-linear, spread across the entire genome, and precise enough that Ben would feel comfortable applying the technology to human healthcare (but they'd spin it out or license it). They also broke records on large DNA synthesis delivery, surpassing the previous largest delivery by 5x and expecting 20x by year-end. This rapid acceleration is attributed to their AI-driven product and systems model approach to synthetic biology, which differs from one-off point solutions common in biomedical research. The progress suggests that genome engineering is on an exponential curve, opening possibilities for de-extinction and beyond.

Ben shares that while working on mammalian artificial wombs (unsuccessful yet), they needed to innovate in keeping embryos viable longer. They built a hydrogel and microfluidics device that mimics in vivo conditions. In both model and non-model species, they found that embryos that appear morphologically poor at day 2 or 3 can become the healthiest if cultured longer. This insight could transform IVF, where parents currently make decisions based on a snapshot and poor imaging. Ben's personal IVF experience with his wife highlighted the emotional and archaic nature of the process, driving his passion to improve it. Although Colossal is not currently working with human embryos, the technology is transferable and they are considering a spin-out or license. The device not only improves embryo health but also enables a more accurate grading system. This is a direct spin-off from their de-extinction work on artificial wombs.

Ben explains that the invasive species problem costs $5.4 trillion globally (hard to quantify but immense). In the US alone, over $500 billion is spent annually dealing with them, mostly through poisons and lethal control, which is inhumane. The screwworm is a current threat moving into Texas, decimating cattle. Traditional methods require vaccinating animals (which meets USDA and anti-GMO hurdles) or poisoning. Gene drives offer a solution: release genetically modified insects (like screwworm) that bias offspring sex ratios so that over generations the population becomes all male and collapses. Colossal's version includes roll-back safety to reverse the drive if needed, and they focus strictly on invasive species to avoid food web disruption. They work with governments. The technology evolved from earlier mosquito gene drive controversies, but by targeting invasive species, it sidesteps the ecological concern. This approach could end the need for mass culling of cats, possums, etc., in Australia and New Zealand, addressing an animal welfare crisis.

Ben describes realizing early on that there was no 'GCP of species'—a global reference genome database for animals. To do de-extinction, they had to build reference genomes themselves, which they then saw as a public good. They conceived a bio vault that combines sample storage with genome sequencing and educational exhibits, placed in a high-traffic area rather than hidden. The UAE committed hundreds of millions of dollars to the first bio vault, focusing on the region's unique and threatened fauna. This serves multiple purposes: preserving genetic diversity, generating data for global science, and engaging the public and students. The deal included a living lab for continued research. This model can be replicated with other countries, turning species preservation into a subsidized, educational endeavor that also benefits Colossal's platform. It's a nine-figure initiative for both Colossal and the UAE.