Forging a Biosecure Future

1. Introduction

With the conclusion of the Human Genome Project at the turn of the 21st century, synthetic biology capabilities have been increasing at a blistering pace, but the rate of improvement in biological defense has been crawling along in comparison.

As biotech capabilities are democratized, it will become easier and easier to create potentially harmful pathogens. Air travel has made the world more interconnected than ever before, allowing infectious diseases to spread faster and further than ever before. As a result, future pandemics may become more frequent and harmful, whether through natural causes, lab leaks, or intentional development and release.

2. Proposal

Kaido Labs is a research group that aims to combat the critical absence of biodefense research. Kaido has two primary objectives: directly contribute to biodefense research, and train the next generation of biosecurity leaders.

We aim to explore both practical technologies and also novel, high-potential ideas.

To attract top talent, all research fellows will receive:

  1. Competitive funding (and seed funding for especially promising ideas)
  2. Mentorship and advising on research direction
  3. Access to a network of world-class biosecurity experts

In version 1.0, Kaido will rely on donations from philanthropic organizations and individuals. We’re exploring pathways for self-sustaining growth in the future. Possible revenue streams include licensing IP, research consulting, and seeding spin-out companies.

In line with our unerring commitment to biosecurity, all research fellows will go through training programs covering topics such as biosafety practices in the laboratory, ethical considerations of biosecurity, and biodefense policy and regulation.

3. Initial Research Directions

To start, Kaido will research three promising paths.

A. Genetic Firewalls

Genetic engineering techniques like codon and tRNA recoding provide immunity against viral infections by establishing a genetic firewall. The promise of a virus-resistant cell line has several useful applications, especially in agriculture and biomanufacturing.

However, there are several challenges facing codon swap. Firstly, plant synthetic biology is underdeveloped and difficult to implement. Furthermore, codon optimization often results in subtle tradeoffs in the post-translational phase and stability of resultant proteins. There is also the inevitable challenge which comes with scaling genome size and complexity.

Finally, it’s worth researching the other pillars of genetic firewalls: mirror DNA, prion resistance, transposon deletion, radiation resistance, etc.

B. Review of Genome Project Write

The Human Genome Project profoundly transformed the life sciences. Sequencing costs decreased 3-million-fold, from $3B to less than $1000.

In 2016, Genome Project-Write was started as a sequel to the original HGP, also known as HGP-Read, with the goal of decreasing the cost of genetic synthesis by 1000-fold. The original plan included a 10-year roadmap for ambitious pilot projects.

Despite the fanfare when it started, progress on GP-Write has been relatively quiet. How far have we come in these past years? What new techniques and technologies have emerged from this research? Where has the project overshot and undershot?

With respect to specific projects, how close are we to synthesizing the genomes of yeast, viruses, mice, Drosophila, and human cells? How much progress has been made on the ultrasafe cell lines and prototrophic proteins?

By answering these questions, we can present a clear view of the landscape of genomic synthesis.

C. Pathogen-Agnostic Sequencing

An important pillar of the grand biosecurity strategy involves establishing reliable pathogen detection sites across the world. Successful monitoring for pathogens and genetic fragments requires sensitive and high-throughput sequencing techniques, which can reliably detect pathogens without relying on specific molecular signatures.

Kaido will pursue two initial promising research directions: nanopore sequencing and MALDI-TOF mass spectrometry.

Nanopore sequencing is accurate, real-time, and capable of performing long-reads. Companies like Oxford Nanopore are improving the throughput of their devices (e.g. PromethION). Research would seek to improve upon error rate and multiplex throughput.

MALDI-TOF MS is used to analyze the proteomic profiles of microorganisms, generating a unique fingerprint that can be used for identification. MALDI-TOF is fast (results in minutes), high-throughput, broadly applicable (e.g. fungi, viruses, bacteria), and is more cost-effective than sequencing techniques such as PCR especially for large-scale screenings.

Advances in these techniques can contribute to the development of more effective tools for pathogen detection, identification, and monitoring, ultimately enhancing global biodefense capabilities.

4. Conclusion

The current state of biosecurity resembles the landscape of government defense contracts before Anduril and SpaceX came along—slow and lumbering, enormous cost structures. It is time for change.

By embracing a technology-centric innovation mindset, Kaido strives to ensure security and peace against the forces of nature.