January 1, 1970 (Vol. , No. )
Zachary N. N. Russ Bioengineering graduate student UC Berkeley
Thanksgiving again! It’s a time for celebrating the year’s bountiful returns. From the supermarket that stocks ingredients and even prepared dishes, to sophisticated ovens and online recipe searches, preparing Thanksgiving dinner has never been easier. But when it comes to preparing the concomitant feast on time and intact, the cook should share some credit.
Though the budgets, tools, and goals are vastly different, biotechnologists have many of the same elements to be thankful for.
When an ingredient has gone missing, a quick run to the grocery store can usually resolve the situation; when a recipe proves too daunting, there’s usually a canned or fresh surrogate available at the grocery store as well; often, you leave with more ingredients than you came in to buy.
As Carl Sagan emphasized, you don’t really start from scratch—and neither does biotechnology. The simplest protocols and most sophisticated treatments all rely on repurposed biological parts. Sometimes those elements have remained in use virtually unchanged. Some examples are Taq or Pfu for PCR; T4 DNA ligase and restriction enzymes for gene assembly; beta-galactosidase for gene reporting and treatment of lactose intolerance; and firefly luciferase for luminescent readout. Recombinant chymosin has seen widespread use in cheese-making since FDA approval 20 years ago.
With a little more engineering, enhanced fluorescent proteins found their way from jellyfish and coral into organisms the world over. Light-sensitive ion channels and pumps from all three domains of life formed the foundation for optogenetics. Viruses were turned into vectors for therapeutic genes, rather than harmful ones.
When the function isn’t known to exist in nature, using natural components as raw materials is a good start—zinc finger nucleases, made from joining DNA-binding zinc fingers to a restriction enzyme, have entered clinical trials for treatment of HIV by knocking out CCR5.
If a particular functionality is desired, odds are you can save a lot of time by looking for natural parts as a starting point: Bacteria living in nylon factory wastewater developed the ability to digest these unnatural chemicals within 40 years.
With its bountiful supply of different forms and functions, life is like a supermarket full of ingredients—a dimly lit supermarket with everything labeled in a foreign language.
Fortunately, the scene has been improving. The combination of widespread sequencing, software tools for genomics and proteomics, and scientific literature search has made finding and using sequences much, much more convenient. Useful components and advice on how to use them can be found using only an internet connection (and perhaps library access to scientific journals).
Finding potential ingredients is easier with software; so is using those ingredients. Calculators exist to predict transcription (and to some extent, translation) levels of a given sequence within a cell, to predict hairpins and melting temperatures. Protocols for genetic engineering are improving alongside the kits to implement them—there are even kits for preparing zinc finger proteins and virus vectors. Lab equipment itself has improved, from micropipets to automated systems for high-throughput screening.
Each year brings more techniques, more kits, and better information. So, celebrate! A field where “starting from scratch” lets you rest on an ever-greater body of knowledge with a better selection of ingredients, tools, and recipes every year is a good field to be in—even if you can’t snack on your experiments.