1. Pace of Biotechnology Development
February 2018
Presented by: Rocco Casagrande, Ph.D.
Research conducted by:
Froggi Jackson, Ph.D. and Louise Sumner
Work funded by DHS S&T, under Scott White, Ph.D.

2. Goals of the Study Assess developments in biotechnology to estimate:
The time between when a new trait is discovered/understood in a microorganism until that trait can be manipulated beyond what is seen in nature
These data inform us as to when an adversary could imbue a pathogen with traits that make it more usable in a weapon than the most dangerous natural strains
The time over which a cutting edge technique in biotechnology can be accessed by individuals of modest skill
These data inform us about the time when a powerful technique could be usable by an adversary with little technical training

3. Manipulation of traits
Describe a timeline for those modifications that affect traits of a microorganism relevant to weaponization
Understanding the genetics underlying the biology of the modifiable parameter
Reproduction of the modification
Manipulation of the modification
Creating a modification not seen in nature (i.e. more pathogenic than wild type)
Understand
Reproduce
Manipulate
Not Seen in Nature 1

4. Duration (Yrs) Required to Reach a “Beyond Natural” Phenotype
At 2020 = 2.3 y 1

5. Biotechnology Development Timelines Approach
For technologies/techniques, use a case-study approach to describe timelines for:
Spread throughout the field
Spread to additional organisms
Equipment development
Kit-ification/fee-for-service development
Reduction in required cost and skill

6. Case Studies Cell-free protein synthesis (CFPS)
Clustered regularly interspaced short palindromic repeats (CRISPR) genome editing
DNA/RNA extraction/purification
DNA microarray
DNA sequencing
Genetic circuits
Green fluorescent protein (GFP)
In situ hybridization
Polymerase chain reaction (PCR)
Mammalian cell culture
Molecular cloning (including restriction enzymes)
Oligonucleotide synthesis
Phage display
Protein extraction/purification
Recombinant protein expression
RNA interference (RNAi)
Site-directed mutagenesis
Solid-phase peptide synthesis (SPPS)
Targeting Induced Local Lesions in Genomes (TILLING)
Transcription activator-like effector nuclease (TALEN) genome editing
Yeast 2-hybrid system
Zinc-finger nuclease (ZFN) genome editing

7. Example Case Study of Biotechnology Development Timeline: PCR
Resource Thresholds
Event
Year
Technical Resources (Education/Skill)
Financial Resources
Enabling discoveries
-14 to -9
N/A
First discovery
0 (1985)
High
Ultra High
Essential equipment development
Essential technical advancement (Taq)
Reproduced in other labs 1
Essential equipment / materials commercially available 2
Medium
Improved price / accessibility of equipment 3
Low
Reproduction outside academic laboratory (commercial service) 4
Commercial kit available 5
Taught at undergraduate level 6
Essential technical advancements (Pfu; qPCR)
6 to 7
Improved equipment commercially available (qPCR) 11
Taught at high school level 12
Further developments; improved price / accessibility of equipment
18 to 25

8. Post-1973 Analysis
Inclusion of biotechnologies developed before the advent of molecular biology (1973) skewed the analysis since there was really no improvement in the speed of their development during the decades preceding 1973
Pre-1973: Time to medium skill
Pre-1973: Time to low skill

9. Medium/Low Skill vs Initiation Year
Time to medium skill vs initiation year
(2.3y in 2020) (R2=0.17)
Time to low skill vs initiation year
(3.5y in 2020) (R2=0.38) 1

10. Fee for Service vs Initiation Year
Time to fee for service vs initiation year (0.9y at 2020) (R2=0.77) 1

11. Medium/Low Finance vs Initiation Year
Time to medium finance vs initiation year
(2.2y in 2020) (R2=0.17)
Time to low finance vs initiation year
(3.6y in 2020) (R2=0.30) 1

12. Comparing future years-to-develop predictions
Metric
2020
2025
Medium skill
2.3
2.1
Low skill
3.5
3.0
Medium finance
2.2
2.0
Low finance
3.6
3.1
Fee-for-service
0.9
0.6 1

13. Conclusions Conclusions:
The time between the scientific understanding of a trait is established and the ability to manipulate it beyond what is seen in nature is already short, and getting shorter.
We can expect that once complex traits are understood in the most dangerous pathogens, scientists will describe the ability to create even more dangerous strains in less than five years
The time that a powerful biotechnology technique, discovered by experts, gets into the hands of those with more modest skill sets is already short, and getting shorter.
The pace at which biotechnology outsourcing is developing is accelerating the fastest
We can expect that a powerful new technique will be taught in college courses in less than five years 1