Biochemical, Reagents Kits Offer Scientists Good Return On Investment

Investment Author:Holly Ahern If you were to ask several life scientists to name a particular biochemical product that they simply could not do without, you'd probably get a myriad of answers that would mirror the research interests of the group you questioned. A molecular evolutionist trying to differentiate two closely related species of monkeys by restriction fragment-length polymorphism (RFLP) analysis might cite restriction enzymes, which can cut DNA into pieces of varying length. A cell biologist growing cells in culture would probably consider culture media and biological buffers crucial to his or her experiments. Gene mappers searching through the millions of bases in the human genome are likely to name products for sequencing, such as acrylamide for gels or electrophoresis buffer. Although individual answers might differ, all would probably agree that their science could not progress without biochemicals, from those as basic as buffers to others as complex as DNA. HOT SELLER: Pierce's Slide-A-Lyzer 10K Dialysis Kit, 0.5-3ml capacity, is the most widely used in its product line. "Biochemicals are the backbone of the research laboratory," notes Michael Lapointe, a biophysicist in the department of physics at Arizona State University. "Without buffers and other chemical solutions, research in most laboratories would grind to a halt." There is a broad spectrum of biochemical products available to researchers in nearly every discipline of science. While many are supplied in their simplest chemical form, an increasing number of these products are delivered to researchers ready-made. Electrophoresis buffer, for example, a mainstay in molecular and cell biology laboratories, can be prepared by carefully weighing out chemicals such as tris (hydroxymethyl) aminomethane (Tris), sodium dodecyl sulfate (SDS), and glycine, dissolving them in purified water, then adding acid or base to achieve the desired pH for electrophoresis. Or, electrophoresis buffer can be purchased already in liquid form from any one of a number of biochemical suppliers, guaranteed to have the correct concentration of ions and the perfect pH. Companies such as Research Organics of Cleveland and Pittsburgh-based Fisher Scientific sell the standard chemicals that go into the biologicals and chemical reagents frequently found lining the shelves in life science laboratories. However, rather than making the solutions themselves, a growing number of researchers are opting to purchase the premade versions of their basic biochemicals, which also can be purchased from biochemical suppliers like Research Organics and Fisher. "Buying chemical products that are already made saves an enormous amount of time," explains Elliott Dawson, a molecular biologist and president of BioVentures Inc. in Murfreesboro, Tenn., a company that specializes in kits for molecular biology applications. "Before such products were widely available, preparing research biochemicals and reagents was a labor-intensive and time-consuming task." Restriction enzymes are an example. Fi rst isolated in 1970 from bacteria such as E. coli, which produce these biochemicals naturally (T.J. Kelly, Jr., H.O. Smith, Journal of Molecular Biology, 51:393-409, 1970), restriction enzymes cut DNA at very specific nucleotide sequences. During the early years of the molecular biology revolution that many say began with this significant discovery, researchers who wanted to apply these highly selective molecular scissors to their scientific problem had to first spend weeks isolating the enzyme from huge batches of bacterial cells growing in culture. Budding molecular biologists found that they needed to become expert microbiologists, enzymologists, and protein chemists before they could even begin to consider the molecular aspects of their research. "In the early days, if you needed a particular restriction enzyme, you started with the literature and followed the procedures of other researchers who had already isolated the enzyme," recalls Dawson. "Now, you can select an enzyme from a menu with over 200 choices and have it delivered to your lab the next day." This comprehensive selection of restriction enzymes and other specialized biochemicals, such as cytokines and custom peptides, is offered to molecular and cell biologists by several companies, including Quality Controlled Biochemicals, located in Hopkinton, Mass.; New England Biolabs Inc. of Beverly, Mass.; and Indianapolis-based Boehringer Mannheim Corp. Worthington Biochemical Corp., a chemical supplier in Freehold, N.J., manufactures several different types of enzymes, including trypsin and papain for tissue dissociations, in addition to the standard fare of restriction enzymes. The list of restriction enzyme suppliers has expanded significantly since the 1970s, when a small array of enzymes first became commercially available. As the research interests of investigators in many areas of science~as varied as ecology and neurobiology~became more molecular in nature, companies that originally focused on other areas, such as immunochemistry (including Pierce Chemical Co. of Rockford, Ill.)., cell biology (Gibco BRL, now Life Technologies Inc. of Gaithersburg, Md.), and basic biochemicals and organic compounds (Fisher Scientific and Sigma Chemical Co. of St. Louis) expanded their product lines to include restriction enzymes and other molecular biology products. Sigma, for example, now supplies restriction enzymes, molecular weight markers for DNA and proteins, and nucleic acids to its customers along with the company~s broad line of chemical products. "Pierce Chemical Co. started as a protein chemistry company, then moved into immunology while maintaining the original product lines," says Mark Reichardt, technical assistance specialist for molecular biology at Pierce. "More recently, Pierce has expanded into the areas of molecular biology and signal transduction." Signal transduction is the latest field of research to attract the attention of scientists interested in studying cellular events as they occur at the molecular level. The increase in the number of molecular biology products available from companies such as Pierce has given molecular biologists a new outlook on their scientific endeavors. "Twenty years ago, we routinely purified our own restriction enzymes, recrystallized acrylamide for gels, and redistilled and equilibrated the phenol we used in organic extractions," recalls Richard Cunningham, a biochemist at the center for biochemistry and biophysics at the State University of New York, Albany. Today, a wide selection of restriction enzymes, polymerases, and ligases are commercially available; phenol comes pre-equilibrated and ready to use; and gels for electrophoresis can be purchased already poured. "Most of the things we had to make ourselves [in the past] can [now] be obtained in ready-made form. Having this vast array of premade products allows you to focus all of your attention on the scientific aspects of a particular problem, without spending excessive time on technical considerations," Cunningham concludes. The major advantages of purchasing products that come already prepared -- such as restriction enzymes, gels, and buffers --are that it enables investigators to save time and money. "Originally, making resins for affinity chromatography required starting with a basic matrix material, such as Sephadex [produced by Pharmacia Inc. in Piscataway, N.J.], chemically attaching a protein or an antibody, and then packing the matrix into a column," explains BioVentures' Dawson. "Then you could start purifying your protein of interest." It takes considerably less time to purchase a separation medium that is already activated and packed into a column, time that could be spent generating data for publications. "Making buffers and other reagents is essentially an uncomplicated process, but it takes time, and a scientist's time is expensive," says Pierce Chemical's Reichardt. Although premade reagents may cost more than the basic chemicals that go into the reagents, the amount of time that researchers save makes purchasing these products cost-effective. "You do pay a bit of a premium for prepared reagents, but an actual cost accounting indicates that it is cheaper to buy these products already made than it is to develop them yourself because of the amount of time involved," reasons Dawson. KIT AT WORK: Pierce Chemical Co.'s Slide-A-Lyzer 10K dialysis cassettes shown in a beaker of dialysis buffer. Whereas once chromatography reagents were available from only a limited number of companies that concentrate on products for biological separations~such as Pharmacia and Bio-Rad Laboratories in Hercules, Calif.~within the last decade products for small-scale chromatographic separations of biological substances like DNA, RNA, and proteins have flooded the market. Reagents and kits for the rapid and simple (in some cases, one-step) isolation of nucleic acids from all kinds of sources~including cells as well as dried blood~can be obtained from a great number of companies (H. Ahern, The Scientist, May 15, 1995, page 17). Among them are Life Technologies (GlassMAX DNA isolation systems) and Pierce Chemicals (XTreme purification kits), as well as Schleicher and Schuell of Keene, N.H. (Elu-Quick kit), and Gaithersburg, Md.-based Oncor Inc. (NON-Organic DNA Extraction kit). If premade biochemicals and reagents offer scientists the opportunity to better manage their time, putting these products all together in kits takes the convenience one step further. Currently, a lab can purchase kits that contain all of the biochemicals needed to perform research applications from the molecular level right up to the level of the organism. "Today's research is accomplished with kits," declares SUNY's Cunningham. "More researchers are buying premade reagents and kits because they are convenient and they save time," Pierce's Reichardt points out. Rather than browsing through catalogs and buying individual chemicals from one or several suppliers, investigators can instead purchase a kit that supplies all of the necessary reagents for a particular research application and even provides them with detailed instructions to follow. Some scientists are concerned that graduate students and postdocs are becoming overly reliant on research techniques that come from a kit. "In general, graduate students today are more focused in just one area, like molecular biology," says Reichardt. "Rather than learning enough protein chemistry to purify restriction enzymes, they focus on how to use the enzyme to solve a scientific problem." Lapointe of Arizona State agrees: "Kits accelerate the research process, because I can get results quickly." "Perhaps graduate students don't develop the depth and experience of their predecessors," concedes Dawson, "but they can get results in less time. On the whole, however, it's enormously advantageous to have products such as these available. They give us more time to spend on our primary focus." What kinds of things can a researcher do with a kit? Molecular biologists, for example, can express proteins from cloned genes using kits such as Life Technologies' SFV Gene Expression System or Bac-to-Bac Baculovirus Expression System, or with Sigma~s FLAG expression system. Researchers who want to label DNA or RNA probes with radioisotopes or fluorescent tags can purchase the OligoLink Conjugation kit from Pierce Chemical to label oligonucleotides with the enzyme alkaline phosphatase, or a variety of products for labeling probes with radioisotopes from DuPont/New England Nuclear of Boston. For small-scale purifications of products, kits are in abundance. Pierce's Slide-A-Lyzer system, for example, can be used as a replacement for conventional dialysis approaches, which require nimble fingers and extreme patience to track down leaks in the tubes. Cell biologists can take advantage of NIM and FLYTE, two reagent systems marketed by Cardinal Reagents in Santa Fe, N.Mex., that, according to the company, contain everything necessary to isolate cells in one step from whole blood for cytotoxicity studies on pharmaceutical products. They also have the option of using kits such as the Whole Chromosome Painting Systems from Life Technologies to "paint" chromosomes with fluorescent dyes. In addition, they can cryopreserve mouse embryos with a kit from Sigma, or perform signal transduction research with products from Pierce and Biomol Research Laboratories Inc. of Plymouth Meeting, Pa. "There is enough variety on the market that there is flexibility in choosing kits that accommodate one~s budget, interests, and style of research," says BioVentures' Dawson. For investigators who are exceedingly short on time or lack the experience or expertise in a particular technical area, contracting out services -- such as synthesizing oligonucleotides or producing monoclonal antibodies -- may be an alternative to learning a whole new science. Molecular biologists, for example, may want to mass-produce an antibody to label the protein product of a mutated gene. Rather than learn the care and feeding of laboratory animals and the fine art of antibody production, the investigators may choose to contract with a laboratory such as the Berkeley Antibody Co. in Richmond, Calif., to do that work for them. Some tasks~such as constructing genomic libraries, designing primer sets for sequencing, or synthesizing nucleic acids or peptides~are so daunting that for many scientists it makes more sense to hire out. "In most cases, the customer knows exactly what they need. But because of the larger realm of their project [they] can~t perform some of the experiments, perhaps because of the lack the equipment or technical expertise," says Meg McCormick, marketing manager at National Biosciences Inc. (NBI) of Plymouth, Minn., a company specializing in custom DNA and RNA synthesis projects. NBI's molecular biologists complete research projects~including sequencing and library construction as well as baculovirus expression (for overexpression of cloned genes) and directed evolution~for their customers. The large selection of prepared biochemicals and kits for specific applications has certainly made life easier for countless researchers. Consequently, however, since these products in general are more expensive than buying basic biochemicals and taking the time to prepare them, the cost of basic research has increased as researchers increasingly turn to kits and ready-made products. "The cost of doing science tends to go up," acknowledges Dawson, "but the volume of data that is output has gone up commensurately. There's a good return on your investment by any standard." Holly Ahern is a science writer and an assistant professor of biology at Adirondack Community College in Queensbury, N.Y. (The Scientist, Vol:9, #15, pg 20, July 24, 1995) (Copyright, The Scientist, Inc.) garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A.

Biochemical, Reagents Kits Offer Scientists Good Return On Investment

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