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Trouble at Santa Cruz Biotechnology

The commercial antibody market is already a mess, although that’s not a new development, but it’s gotten messier. Santa Cruz Biotech, one of the big suppliers, is getting out of a big part of the business. Actually, “being forced out of the business through their own actions” is probably a better description. The company has been hit with a $3.5 million dollar fine over its treatment of its goats and rabbits, and has to give up its license under the Animal Welfare Act. That means they can continue with mice, rats, and chickens, but the rabbit and goat antibody production is now shut down.

The USDA had found evidence of mistreatment at the company’s facilities in California, and (in a bizarre development) also found an entire goat facility that the company had not been reporting. The current settlement includes the “neither admits nor denies” language about the company’s culpability, but you don’t give up a big piece of your business and agree to the largest animal-welfare fine in USDA history if you think you have a good case. You also don’t suddenly cause 4,000 animals to vanish right before an inspection, which is what apparently happened a few months ago

Using animals in biopharma research is still unavoidable (go find another way to make antibodies, for example). It’s true that monoclonal antibodies are produced in cell culture, but that process still begins by injecting a mouse. Meanwhile, polyclonal antibodies, of the sort that Santa Cruz was producing, use animals directly for production. You inject a mouse, or a rabbit, or a goat (or what have you) with your antigen of choice, let their immune system reaction to it, and draw blood to harvest the resulting antibodies. Animal care and use committees come in because all of these steps can be run humanely, or not so humanely. In addition to basic standards for keeping lab animals, there are regulations about how strongly you can challenge their immune systems, how often you can draw blood (and how much), and so on, and Santa Cruz appears to have been accused of violations up and down the list.

As human beings, we have a responsibility to treat our research animals as befits a species that can understand the consequences of its own actions. Losing Santa Cruz Biotechnology’s rabbit and goat production is going to disrupt the work of a number of research labs around the world, and not in that hot, happenin’ Silicon Valley sense of the word. But it still sounds like a fair trade. There’s enough pain and suffering in this world already – creating more of it just because you can’t be bothered is not an acceptable way for human beings to act, not towards animals and not towards other humans.

 

49 comments on “Trouble at Santa Cruz Biotechnology”

  1. Steve says:

    I appreciate the defense of these traditional techniques but, regardless of compliance with the law, some initiative from the industry might lead to better and more humane methods. I hope at least a few in industry are interested in making alternatives a high priority.

  2. bhip says:

    And to add insult to (apparently real) injury, a reasonable percentage the ab that they sell to to unwitting scientists (who really should be more…witting?) are crap.

    1. Another Grad Student says:

      After getting burned by Santa Cruz a couple of times I haven’t bought an anti-body from them in three years. The anti-body market is a total mess, the only company that seems to be in the 21st century is Abcam, who at least have real reviews and actual data on their website (something that should be a minimal requirement these days)

      1. Da Vinci says:

        They are mostly crap, but there is some real gold in there. I’ll never use another doublecortin antibody than theirs. Which is goat, so means I’ll have to stock up……

    2. johnnyboy says:

      I’m surprised Santa Crap actually kept animals. I thought they just hired some minions to spit into tubes and ship them out.

      1. Mai says:

        I thought they have only one goat for different antibodies… It is really a big surprise that they actually build a hidden farm for this single goat.

    3. MR says:

      Our lab has a love hate relationship with them; we refer to them as Santa Crap. However, there are a handful of antibodies we use regularly that are quite good, so having to now find replacements for them will not be fun…

  3. Technology to generate monoclonal antibodies from clone libraries by phage, bacterial or yeast display have been around for about 3 decades, and can completely avoid immunizing an animal — but they’ve never really caught on, probably because it is hard to find a good one.

    Apatamers (RNA or DNA which can recognize specific targets) are the other great hope for specific affinity reagents on demand without any animals involved, but also always seem stuck being the technology of tomorrow.

    1. PUI Prof says:

      “…technology of tomorrow” and “hard to find a good one”

      So although you state it isn’t necessary to immunize animals… You really have to immunize animals to get good quality antibodies. Not to sound like I am defending SC, because most of the Ab I bought from them were crap that didn’t work.

      1. Dougie says:

        the only problem is aptamers don’t seem to work by western blot…Phage display and other protein display technologies can produce crappy antibodies as well because once you get the binding by ScFv you typically have to insert back into full length antibody and then all the typical problems happen, aggregation, loss of affinity..etc….

  4. SP says:

    Scientists at some large companies were already banned from ordering from them because their poor animal practices were already well known. On the plus side research at those companies will be minimally affected by this.

  5. Anon says:

    What’s wong with using phage display Ab libraries? I really don’t see the need for animals in either Ab selection nor production these days, besides laziness or a small cost saving.

  6. Mark Thorson says:

    I was wondering why this work is done in California rather than someplace like China. Allegedly, they are moving some of the business to China.

    https://www.glassdoor.com/Reviews/Santa-Cruz-Biotechnology-Reviews-E39955.htm

    Some other interesting comments, too.

    1. DCRogers says:

      Mr Thorson, you read my mind.

      I was immediately surprised that this “market failure” hadn’t already been solved by an appropriate amount of offshoring wrapped in layers of opaque shell companies. Heck, forget goats; strip away the need for pesky animal or human rights monitoring, and there’s lots of prisons and work camps where “volunteers” could be used to make fully-human antibodies.

      1. Anon2 says:

        Aside from being morally repugnant, there is also the little issue of “self-restriction” i.e. it would be hard to make Ab against human proteins in a human.

    2. Ano says:

      Chinese people are cheaper than American goats, while their human rights are not as stringent as US animal rights.

      1. Mark Thorson says:

        It’s win-win!

      2. one of the ex-Merck chemists says:

        here comes the point that I have to say…..Fuck you. man,

  7. eugene says:

    I’ve bought some chemicals from Santa Cruz and haven’t really had issues with those. They were the much cheaper price often, and actually pure. But I suppose it’s not so hard to make a substituted pyridine or whatnot without killing anything. I’ll probably still be buying from them if the opportunity comes up, as when I do it’s often a considerable cost savings and I’m guessing this division has nothing to do with their antibody outfit.

    1. exSCBT says:

      Their chemicals are ok because they don’t actually make them, they source them from other companies and repackage them.

  8. PeptoidChemist says:

    Glad to see I’m not the only one whose thought was “wait, people still order Abs from SCBT?”

    Although having said that I get that this means more macroeconomically to everyone else, one less supplier, yada yada. But I feel bad for you if you were relying on their products for your research.

  9. weezl says:

    I’m hardly surprised that SCBT had some shenanigans going on; they are the antibody supplier that I repeatedly warn people away from. Other than an antibody for c-fos, I don’t know of any of their antibodies doing what it says on the tin.

    True story: one of my professors ordered an antibody from SCBT and it didn’t work. He called their help line, which had tips like “It worked fine for us, according to the datasheet.” He had a hunch and had a friend run the vial through MS; SCBT had sent him a vial of buffer. He called SCBT back, asked for a refund, and so they sent him another vial…of buffer.

    1. Michel says:

      Oh, seems they are in the homeopathy business now?
      No go.

    2. exSCBT says:

      Former employees have admitted to photoshopping their WB data. Don’t trust their QC data at all!

  10. Chrispy says:

    It is amazing that SCBT is even in business. Their antibodies have always been terrible. Those of you who don’t find the Glassdoor reviews depressing enough should check out the SCBT subreddit. It is really amazing how a company with poor products and poor management can continue to to shamble on, year after year.

  11. Christophe Verlinde says:

    Derek, I laud your taking a stand with “As human beings, we have a responsibility to treat our research animals as befits a species that can understand the consequences of its own actions. ” I would add that people who decide that animal welfare is not worth considering are probably also exploitative in their interactions with other people.

  12. watcher says:

    What we received from them in the past was of poor quality, so stopped using them despite the better price. Surprised they have been able to stay in business.

  13. Seattle Biotech says:

    To Anon. In regard to phage display-derived antibodies, they are only as good as the libraries they were derived from and they will never undergo “Somatic hypermutation” (look it up, standard Immunology). Only real B cells will utilize somatic hypermutation to create a higher affinity antibody. I have worked with both and still prefer the common lab mouse. Sometimes mother nature knows best…

    1. Anon says:

      Somatic hypermutation increases diversity in the variable loop regions, but isn’t that exactly what you can do in any case with synthetic DNA-encoded Abs libraies? So still, there seems to be little or no advantage other than cost and convenience at the unnecessary expense of an animal.

  14. Chemist says:

    Ha ha, they get away with this because a lot of biologists are pseudoscientists, take a look at how many believe that solulink’s hydrazones are stable covalent linkages suitable for conjugation.

  15. gippgig says:

    I wonder how long it will be before it’s easier to synthesize the genes, insert them in an expression vector, and make your own antibodies than buy them from a commercial supplier?
    I also wonder how far we are from being able to get the mammalian antibody-generating system to function in insects or even yeast.

    1. Ed says:

      I think this already happens – I think I remember Medarex working on such a technology with Biolex using duckweed or similar.

    2. It already happens at the company I work at! Check out Absolute Antibody (absoluteantibody.com)…we are sequencing all the classic antibody producing cell lines and produce antibody in a recombinant system without even using any animal serum. I can’t claim that animal welfare is the primary reason for this, as it was actually about the products being cleaner, but it’s a nice by-product…and I think we’re quite happy with that!

  16. Chrispy says:

    Regarding antibody generation: phage has sadly not worked out nearly to the hyped-up promises in the beginning. Herceptin is the only big ticket phage-derived antibody in the clinic, and it is plagued with a propensity to aggregate and immunogenicity. (We’ll see how Benlysta does.) Probably the big reason phage has not worked so well for antibodies is that the libraries do a sloppy job of matching the heavy and light chains. Phage works a lot better for tuning up an antibody that was already generated in a biological setting. Phage also works a lot better for binders that don’t suffer from having two chains, like Kunitz domains (e.g. Kalbitor). Finally, the ability to make fast polyclonals — inoculate and boost a couple of rabbits, harvest a few weeks later — is a powerful tool for early research, particularly if those polyclonals are cleaned up by binding to a column of the immunogen. All display platforms (phage, ribosome) have the misfolded-sticky-protein-as-false-positive issue, but in vivo systems have a lot of checks to get rid of sticky proteins like this. I can remember when, 20 years or so ago, people were claiming that phage would solve everything, and that we wouldn’t need animals anymore. It was a little like the biologists’ version of combichem.

  17. Don't Ask Don't Tell says:

    Proposed name for secret goat facility: Goatanamo Bay

    1. steve says:

      That joke was baaaaa d

      1. Hayden says:

        Now you’re just milking it.

        1. blaboo says:

          Ordered a compound from them over a month ago. Last week it was supposed to arrive, but didn’t, and our purchasing manager contacted them — they said it would be here yesterday. Yesterday rolled around and still nothing, he called all day today with no answer, finally got a hold of them and they said they forgoat to send it.

  18. anon says:

    Oh, how I am not surprised. Also, I don’t think the fine is nearly large enough to be an effective deterrent/punishment. Strong quantity who cares about quality, extract dollars from the research grant system vibe from the management.

    Lot-to-lot variation with polyclonals is such a problem they’ve been looking to move to monoclonals for a long time anyways (Hope ethical oversight for that division is tighter as a consequence of this…)

    There may be a benefit to the science community through the reduction of the opportunity for less thorough researchers recognize non-specific signal as indicating their actual protein of interest, and for everyone to stop wasting their time and money trying nonfunctional “antibodies.” I won’t even touch their licensed monoclonals!

  19. Richard Blaine says:

    There’s a horse farm near my home that includes the word “immunogenics” on their identifying sign. I presume that they are doing a similar process, but with 600 kg equines instead of little rabbits or goats. Does anyone know if this is actually a thing?

    The horses look pretty healthy, and have a lot of room to run around in. I can’t say how well they are actually treated.

    1. Tom Womack says:

      Horses definitely were a thing – diphtheria antitoxin was famously produced in horses, and apparently botulin antitoxin and snake antivenins are still produced in horses.

  20. Jonny says:

    Phage display is definitely only as good as what you do with it. Often, it is a great tool to get the best of both worlds: super high quality monoclonals, quickly, derived from a very small number of hyperimmune animals.

    http://www.ncbi.nlm.nih.gov/pubmed/20978962
    http://www.ncbi.nlm.nih.gov/pubmed/20978977
    http://www.ncbi.nlm.nih.gov/pubmed/23148212

  21. Lord Kelvin says:

    This is ridiculous. We slaughter animals and eat them lol
    And then some draw up their skirts and clutch their pearls because of some nebulous “inhumane” treatment.
    This is totally arbitrary.
    Who gives a fig.

    1. zero says:

      Food animals are stunned and then killed while insensate (we hope/think). It’s over before they know it.
      Lab animals can be kept alive in agony for weeks.

      We allow pain and damage in research animals only when necessary and when the potential benefit is significant. I would hope as an intelligent species that we continue to choose compassion over expediency.

      Let’s continue to improve our treatment of all animals. That doesn’t mean banning beef or lab rats.

  22. ae says:

    Polyclonal antibodies such as those produced in goats and rabbits are often superior to monoclonal antibodies (usually produced in mice and in culture dishes) for applications such as immunoprecipitation. Basic biological laboratory research can not continue to advance without doing immunoprecipitations. Some of Santa Cruz’s antibodies for immunoprecipitation were superb and they were the only ones who had them. It will take our lab many months and lots of $$$ to test and find alternatives, if these even exist. This will be a big hit to many biology laboratories. I wish Santa Cruz would have adhered to the rules and treated the animals as they should have. The real price of this will be paid by the public, since research progress in some areas will inevitably be slowed, at least for a while, and the money to adjust the methods will also need to come from somewhere. This was being shortsighted from the company’s side, but also the government: the good of the public requires to understand the consequences and find a way to solve the problem without causing irreparable damage to society.

  23. Just to say that there are protein alternatives to antibodies that have been developed, including Darpins, Anticalins, Affibodies and our own Affimer binders (full disclosure- I work for Avacta Life Sciences). Companies commercialising these mostly use phage, mRNA or ribosome display, but because the proteins are much simpler there is less of the ‘sticky protein’ problem found with phage-displayed antibodies referred to in the comments here. As with aptamers, most of the focus has been on therapeutics rather than reagents, but I’m pleased to say that we are finding people willing to give Affimer binders a go- and that they are coming back for more. So, again in response to one of the comments, some of us in industry and addressing the problem- but it can be hard convincing scientists to try something new- as evidenced by the fact that so many of you have ‘taken the risk’ of buying from a company you’d heard poor things about! I’d also say that we are engaging with the 3Rs- and have indeed been featured by the UK’s National Centre for the 3Rs: https://www.nc3rs.org.uk/affimers-animal-free-alternatives-antibodies-0

  24. Carole Reed says:

    I am just a pet owner who began ordering cases of Lactated Ringers from SantaCruz to be used for rehydrating a pet cat who has chronic Renal Failure ( a common practice for home care for cat owners in-the know), because a few years ago the prices everywhere else doubled for LRS yet SCBT’s price had stayed quite reasonable. I recall even asking the phone rep one time I called about what kind of research was done by them- her answer- NONE!! Only some simple supplement testing on horses kept on premises. Boy do I feel stupid. This part of SCBT is apparently in Texas, so she sidestepped my question by answering in response to ONLY “their” part of the company. I feel deceived and absolutely disgusted that I have supported this company in ANY way. And to think I told many other people about their great prices on pet medical supplies. I am horrified now by their gross mistreatment of animals.

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