January 14, 2010 – How is PZP made? Who makes PZP?

Yesterday I explained how PZP works. Today I will be discussing how and where PZP is made. However, I think it is also interesting to understand why PZP is made. That is, how did anyone figure that PZP could be used to manage wild horse populations?

In 1982, research was done to understand why a number of domestic mares were infertile. The researchers determined that there were mares whose own immune systems were developing antibodies that were working against the mares’ own eggs (Liu, I.K.M., and Shivers, C.A., 1982). An experiment was then conducted in which such an immune reaction could be induced in mares (Liu, I.K.M., and Shivers, C.A., 1982). In the late 1980’s, a group of domestic horses, along with horses from a wild horse sanctuary, were treated with PZP. The treatments resulted in successful contraception. The study also discussed how PZP could possibly be used as an alternative method of managing wild horse populations (Liu, I.K.M., Bernoco, M., and Feldman, M., 1989). With that, the first wild horses to receive PZP were a small group on Assateague Island. Among the findings of this study was evidence that PZP could be safely used to treat wild mares in a field setting (Kirkpatrick, J.F., Liu, I.K.M., and Turner, J.W., 1990).

It was thus determined that PZP was an acceptable alternative method of managing wild horse populations. There was a little challenge to this though: PZP cannot be synthesized. Making PZP is actually a difficult, labor intensive process. The objective of this process is to isolate pure zona pellucida from the eggs of pigs.

The process begins with the processing of pig ovaries. Why pig ovaries? In addition to the fact that a lot of research had been done on the zona pellucida of pigs, there are a couple of other reasons. For one, pigs have a large quantity of eggs in their ovaries. Second, there is a constant supply of pig ovaries available as a byproduct of the slaughter of pigs. These pigs aren’t slaughtered for their ovaries; they are slaughtered for their meat. If the ovaries weren’t used to make PZP, I have been told they would end up in restaurants or to be used in the development of pharmaceuticals. The batch of ovaries is first processed by being finely sliced by a specialized machine. The resulting substance is kept in a very controlled environment while it is continually processed and filtered over many days. Special care must be taken so that the zona pellucida is not damaged. With each step, the zona pellucida from the eggs becomes more and more isolated. The end result is pure zona pellucida from pigs; this is PZP. To give an idea of how involved this process is, consider this: It takes a very skilled scientist about a week to process 12 pounds of pig ovaries. This results in the production of 160-220 doses of PZP. (There are 100 micrograms of PZP in a standard dose.) It should also be noted that this PZP is subject to a very intensive quality-control process that is also quite time consuming.

The pure PZP obtained from the above process is in the one year vaccines that are used in many areas. Lately, it is common to hear discussion of “PZP-22.” This is the dose of PZP that is supposed to be effective for 22 months. Developing long-lasting contraceptives for wild horses has long been a goal due to practicality. PZP-22 is still PZP; it is just prepared a little differently than the one year vaccines. Instead of the pure PZP being prepared into a regular vaccine, PZP-22 describes PZP that has been incorporated into time-release pellets. These pellets are made through a secondary process that is also intensive; this process results in the loss of 10-50% of the pure PZP, depending on the process used. This is a reason why the pellets are more costly than the one-year dose.

As you can imagine, there aren’t many labs in the world that make PZP. A lab that is a leader in making PZP is actually only an hour and a half away from here in Billings, Montana. This is the Science and Conservation Center, which is associated with Zoo Montana. The Science and Conservation Center makes most of the PZP in the world today. I have been able to visit their lab to watch and learn about the process of making PZP, and I think it is amazing. Also, it is worth knowing that the pellets are made at the University of Iowa’s School of Pharmacy.

It may come as a surprise to some, but no one is really making any money off of PZP. In fact, people actually lose money making PZP; the Science and Conservation Center is a nonprofit organization that supplements its operating costs with grants and donations. Why is this? A major reason is that the process through which PZP was developed as an immunocontraceptive was funded with largely public money. The researchers involved with PZP do not believe that anyone should profit from work that resulted from tax-payer dollars. PZP is not commercially available; and the Science and Conservation Center provides PZP at the cost of production, which is about $24 per dose. It is also no surprise that it is hard to make money off of PZP due to the process through which it must be made.

Now that I have described who makes PZP and how they do it, it will next be useful to learn how one can get PZP to use. Tomorrow I will touch on the rules and regulations related to the distribution and use of PZP.

References

Liu, I.K.M., and Shivers, C.A., 1982, Antibodies to the zona pellucida in mares: Journal of Reproduction and Fertility, Supplement 32, p. 309-313

Shivers, C.A., and Liu, I.K.M., 1982, Inhibition of sperm binding to porcine zona ova by antibodies to equine zonae pellucidae: Journal of Reproduction and Fertility, Supplement 32, p. 313-318

Liu, I.K.M., Bernoco, M., and Feldman, M., 1989, Contraception in mares heteroimmunized with porcine zona pellucida: Journal of Reproduction and Fertility, v. 85, p. 183-189

Kirkpatrick, J.F., Liu, I.K.M., and Turner, J.W., 1990, Remotely delivered immunocontraception in feral horses: Wildlife Society Bulletin, v. 18, p. 326-330

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Published in: on January 14, 2010 at 6:54 pm  Comments (1)  

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One CommentLeave a comment

  1. Matt,
    This is fascinating stuff! I have learned so much from your blogs, and you are to be commended for your skill in translating science into terms that anyone can understand.
    I had never heard of PZP until my visit to the Pryors in September. The fact it is made in Billings, and you had a chance to tour the lab is an added bonus.
    Hopefully the use of this vaccine will help to control herd size in a less aggressive manner than is currently being done.
    I also agree with your earlier post, that alternatives must be considered and explored when deciding the best approach, in this case, what is best for the horses.
    We would all like to see the wild horses remain on the range, in freedom, but that is not being realistic, as time and politics have shown that, for many reasons, excess horses will continue to be removed.
    So if PZP can help, then great. It may not be perfect, but then the world isn’t perfect either.
    Keep doing what you are doing; it is much appreciated.
    Wendy D


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