[TECH] Bio-Techne: part 1
This is the first part of a two-part post. I wanted to better understand the tools behind drug research and diagnostics and writing up Bio-Techne seemed like a good way to do that. Bio-Techne sells lots of stuff, from recombinant proteins to instruments. But it isn’t an “everything store” like Thermo Fisher. Its products interlock in a way that facilitates understanding of one fat slice of the broader life sciences pie.
The story of Bio-Techne took root nearly 50 years ago, when an obscure Minneapolis-based company, Research and Diagnostics Systems, came to market with its first product, hematology controls…that is, blood samples, containing standard levels of hemoglobin, cells, and other components, that hospital labs run to make sure their blood analysis instruments are working as they should and producing accurate values. In the early ‘80s, R&D Systems identified in platelets the presence of “growth factors”, proteins that stimulate cell growth and differentiation, and began selling those proteins to drug researchers, setting the trajectory for all that was to come.
Coincident with the rise of recombinant DNA technology, Bio-Techne (as the company was rebranded decades later) began synthesizing other naturally occurring proteins, a process that involves isolating a gene that codes for the desired protein; delivering that gene, through a virus or some other vector, into host cells; multiplying those cells in a bioreactor under precise environmental conditions; and separating the targeted protein from the cells that produced it. The lab-made protein can then be deliberately introduced to cell cultures or lab animals to simulate disease states for the purpose of validating drug candidates. For instance, a cytokine (a naturally occurring protein that acts as a messenger between immune cells, coordinating immune reactions) like TNF-beta induces an inflammatory reaction symptomatic of rheumatoid arthritis. IL-6, another type of cytokine, promotes tumor growth by hindering the immune system’s ability to kill cancer cells. By seeing which receptors those proteins bind to and how that binding impacts cell behavior, researchers can evaluate the extent to which drug therapies alleviate mimicked disease states.
Lab-synthesized proteins also serve as key inputs to another instrument of drug research: antibodies. A disease-simulating recombinant protein is injected into a host animal, whose immune system deems the protein a foreign antigen and, in response, produces antibodies that bind to it. Blood is collected from the animal, serum is separated from the blood, and antibodies are extracted from the serum.
Those antibodies are then deployed into immunoassays, lab procedures that detect the presence and concentration of target proteins in a sample. Among the oldest and most common immunoassays, pioneered by Bio-Techne, is the ELISA (enzyme-linked immunosorbent assay). In an ELISA, a “capture antibody” binds to the target protein, isolating it from the surrounding mix of blood and serum, while a “detection antibody”, bound to a different site of the protein, links to a “reporter enzyme” whose interaction with a chemical substrate produces a signal, like a change in color or light, the strength of which corresponds to the amount of target protein in the sample. In a research context, you can think of antibodies as barcodes for proteins, a unique signature that allows researchers to, for instance, track whether a drug reduces the number of inflammatory proteins associated with arthritis or whether a drug is binding to its intended protein targets or whether tumor-attacking immune cells have been activated.
To make sensitive assays, you need good antibodies; and to get good antibodies, you need good proteins. As the only player that runs bioassays validating how well each of its proteins bind to receptors or stimulate cell activity, Bio-Techne claims to deliver unrivaled reagent quality. The premium it charges, which can sometimes run 2x-3x above the “same” protein supplied by a competing vendor, is generally accepted by pharma customers, who will pay extra for proteins and antibodies in the discovery phase if it means obtaining better signals on the therapeutic potential of a drug that will ultimately cost billions to develop and market (academic labs, who are funding constrained, are more price sensitive and willing to gamble a bit on lower quality products). Proteins, antibodies, and assays from R&D Systems (the widely recognized trade name through which Bio-Techne continues to take those consumables to market) have been cited in hundreds of thousands of peer-reviewed journal articles, an important source of validation for scientists1.
There is supposedly a lot of tacit knowledge behind protein design and production that makes it difficult to reliably replicate the lot-to-lot consistency for which Bio-Techne is renown, so it perhaps comes as little surprise that the industry for research-use-only (RUO) proteins has consolidated around a few players, namely Bio-Techne, Peprotech (now part of Thermo Fisher), and MilliporeSigma. Polyclonal antibodies, on the other hand, aren’t nearly as difficult to produce as recombinant proteins (monoclonal Abs, sourced from single cells, are an entirely different matter). Injecting the right proteins into some goats will yield an antibody starter pack. Low entry barriers have invited myriad players2, many of whom compete with a portfolio of just several hundred varieties. As such, the market for antibodies is fragmented across ~60-80 players. Abcam, the leader in antibodies, has ~10% market share. Bio-Techne claims just ~5%. The market is so fragmented, the universe of antibodies so vast, that Bio-Techne differentiates from smaller players not only by validating efficacy but by aggregating hundreds of thousands of antibodies across suppliers and making those antibodies easily discoverable online.