2, New England Biolabs, Inc., Ipswich, MA, USA
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An innovation is one of those things that society looks at and says, if we make this part of the way we live and work, it will change the way we live and work.
—Dean Kamen
One of my primary objects is to form the tools so the tools themselves shall fashion the work and give to every part its just proportion.
—Eli Whitney
It's what you learn after you know it all that counts.
—Harry S. Truman
Since their initial development nearly 20 years ago, molecular biology kits have evolved from simple protocols and reagents for cloning of DNA to the more recent complex reagent sets that enable whole genomic sequencing. Initially met with resistance by some who felt that using them deprived researchers of the basic knowledge of how to create reagents, molecular biology kits have taken on an important role in the biological sciences. In this article we describe kit development, why kits have succeeded in molecular biology, and how they have paved the way for the more recent widespread use of core facilities.
Walk into any molecular biology laboratory and you will likely see shelves, refrigerators, and freezers filled not only with stand-alone reagents and biochemicals, but also with boxes and containers from reagent and instrumentation companies that include detailed instructions, helpful hints, and, most importantly, protocols for use (and for avoiding misuse!).
For BioTechniques’ 25th Anniversary we present a brief review of a phenomenon that appears to be unique to biology and that, for want of a better name, we call “kits.” When we first joined the BioTechniques Editorial Board (in the 1980s), kits were not common. What triggered this (r)evolution, and has it helped advance the field?
What Is a Kit?In its simplest form, a kit consists of more than one component and a set of instructions. How do we define a kit in the molecular biology universe? We would propose that a kit be operationally defined as comprising: (i) a set of one or more reagents having variable input materials; (ii) instructions that guide the individual researcher to perform the same reaction on the input materials; (iii) transformation of the input materials; and (iv) the obtaining of identical end-results each time the input material is the same. Characteristics of a good kit include ease of use, clear instructions, a good troubleshooting guide, a rapid protocol, and, of course, reliability and reproducibility. A kit may be very complicated (for example, a complete genome sequencing kit), or as simple as a DNA ligation kit containing a few reagents and controls.
A kit for site-directed mutagenesis would be an obvious example of a complex kit. Less evidently, a buffer sold with a restriction enzyme could also be considered a kit, if it includes a set of instructions for using it. In the early days of molecular biology, many restriction enzymes were originally sold without their associated buffers. Researchers made their own buffers, a different solution for each enzyme (universal buffer and low-, medium-, and high-salt buffers are more recent inventions) (1). And if the researchers used good laboratory procedures, they needed to first test the buffers, enzymes, and DNA for proper digestion. Today, standardized buffers supplied with enzymes—and prepackaged reagent kits generally—have eliminated the need for users to control quality.
Early DaysToday's kit manufacturers were not among the advertisers in BioTechniques’ early years. In fact, most of the ads in the journal's first two volumes offered medical and cell-fusion equipment, separations media, and specific chemicals. In 1983, several companies had put together kits—for M13 cloning (New England Biolabs, Bethesda Research Laboratories), exonuclease deletion (Stratagene Cloning Systems), and riboprobes (Promega)—but they promoted them mainly in their catalogs. Two years later, Promega advertisements in BioTechniques offered a system for making riboprobes using the company's pGem vectors. (Another trend: after 1985, equipment advertisements were increasingly oriented to molecular biology—centrifuges, microscopes, DNA synthesizers, power supplies, etc.—which likely reflected this journal's growing influence among biology lab researchers.)
In the early days, manufacturers often avoided using the word “kit.” Instead, we wrote and talked about “systems” for performing or developing certain applications. Today, by contrast, any recent issue of this journal carries many advertisements promoting the latest streamlined methods for performing complicated molecular biology protocols. Many are now even labeled kits.
Initial Opposition to KitsTwenty-five years ago, academics actually debated whether kits represented the beginning of the decline of graduate education. Mentors felt that graduate students lost something when they performed experiments using store-bought kits instead of assembling their own materials and reagents. The teachers feared that students would lose the deeper understanding of the enzymology and basic nature of the work when they simply followed the directions on the package insert.
There were also economic concerns: was it worth purchasing kits when the reagents could be made in-house? Modern researchers’ devotion to today's kits suggests that they consider consistent reagents and tested protocols a good buy. Many of us who have spent at least part of our careers producing kits know that what we are really selling is quality control, reliability, and reproducibility. If a kit is well developed, users should be confident that, if they follow the directions, they will obtain the desired results. Because of these elements—quality control of the reagents, matching of components, labeling, and the provision of detailed manuals— kits routinely cost more than the individual components together. Early kit-users may not have understood how time- and labor-intensive these steps are. But in this case the added cost does indeed represent added value. In the early days, a reaction from a kit could cost anywhere from several dollars (for a simple restriction enzyme digestion) to tens of dollars (for a ligation or lambda-packaging reaction). Nowadays, researchers can purchase a next-generation DNA sequencing kit that may cost several thousands of dollars for a single use.