I promise, this will be my last semen post for a while.

I’ve talked about allergy to semen.
I’ve talked about allergens in semen.
And I’ve talked about autoimmunity to semen.

All of these are problems, leading to discomfort or infertility. But what if those problems could be leveraged for our benefit?
i-124bd5cd88cf3b85607cdd350df44eda-Sperm_Anton_van_Leeuwenhoek_Rabbit_dog-thumb-500x380-72031.jpg

[Source: These drawings were made by Antonie von Leeuwenhoek - the first man to view sperm cells under a microscope]


Using the immune system as a contraceptive is not a new idea. In 1899, Karl Landsteiner
and Elie Metchnikoff (both of whom would later win Nobel Prizes) independently demonstrated that injection of sperm into animals could produce an antibody response, and others later demonstrated that this could lead to infertility. The first study in humans was in 1929, and a patent for a “spermatoxic” vaccine was filed in 1937.

Since then, there have been a number of advances in the using the immune system to intentionally induce infertility. But you may be asking yourself, “Why bother?” After all, hormonal birth control is safe and highly effective. But there are a number of problems associated with hormonal birth control that could be addressed by a vaccine. And I’m not even talking about side effects:

An estimated 80 million women have unintended/unwanted pregnancies worldwide annually, and 45 million of these end in abortion. In the United States, each year, half of all pregnancies are unintended, which results in over 1 million elective abortions. In over half of these unintended pregnancies, the women were using some type of contraceptive.

Another major problem is access. In the developing world, where one might argue family planning is most needed, medical services are not always readily available. Since hormonal birth control requires consistant use, and access to a daily pill or monthly shot just won’t cut it.

This calls for a better method of contraception that is acceptable, effective, and available both in the developed and developing nations. It should be non-steroidal, non-barrier, non-surgical, intercourse independent, and reversible. Contraceptive vaccines (CV) have been proposed as valuable alternatives that can fulfill most, if not all, of the properties of an ideal contraceptive. Because of their high target specificity, long-term action, low cost, and without any side-effect, the development of CV is indeed an advancement in the field of contraception. As the developed and most of the developing nations have an infrastructure for mass immunization, constructing vaccines for contraception is an exciting proposition.

There are several approaches to a contraceptive vaccine*, all involving different targets. Some target certain hormones, which would prevent the production or development of sperm/eggs. However, as many of these hormones are required for non-reproductive processes, these vaccines can have unwanted side effects. As an example, a protein called GnRH triggers the release of other hormones necessary for the development of sperm and eggs, and can be effectively targeted by a vaccine. However, loss of these hormones also leads to impotence, and so is essentially off the table for human use (though it is currently being used as a non-surgical way to sterilize pets and feral animals).

Another target of vaccines is HcG, which is expressed on fertilized embryos. The selectivity of this protein is its strength – since there are no targets except those associated with pregnancy, the side effects should be minimal. However, scientists have had trouble achieving an effective immune response against this protein**. Plus, it leaves the burden of birth control on women (since an immune response against an embryo wouldn’t mean much in a man).

By contrast, a vaccine against sperm could solve many of these problems; it could be effective in both men and women (blocking production in men or stopping fertilization in women). And the inheritant immunogenicity of sperm that I’ve mentioned earlier means that it shouldn’t be hard to generate an effective immune response. Indeed, several groups are currently working on making this a reality.

The main drawback of this approach that I see is lack of intentional reversibility. So far, in all of the human trials dating back to 1929, the effect of the vaccine was not permanent – antibody titers against the sperm waned over time, and fertility returned – but turning the immune system off should the patient want to have a baby is not controllable. In principal, it should be possible to target only the B-cells making anti-sperm antibodies for destruction, but until such a process is validated, this method will not be a tenable option for anyone that may want to get pregnant at a later time.

In any case, it seems we’re stuck with hormonal and barrier methods for now, but I think this is a great example of leveraging the power of the immune system in ways nature never intended.

——————–

*It should be noted here that in many parts of the developing world, anti-vaccineconspiracy theories, which postulate that polio vaccination campaigns are really a secret plot to sterilize the population, have taken root. Should and actual contraceptive vaccine campaign ever occur in the developing world, folks had better make damn sure the intentions are out in the open.

**Since the date of the review that I’m reading, there have been some advances on this front, but still no effective vaccine in humans.

Comments

  1. #1 WINGS Guatemala
    January 18, 2012

    Very interesting, well-written post! In a country like Guatemala with high pregnancy rates(and unfortunately high mortality rates that follow), we can never have enough ways to try and reduce these pregnancies. The question is now, how well would the population in developing countries respond to a treatment as radical as this? I will tweet this!

  2. #2 Marry Me, Mindy
    January 18, 2012

    To put it bluntly, you aren’t talking about birth control, you are talking about an approach to sterilization. You note that immunities wanes, but without a mechanism for deliberate reversal, this is dead in the water. Perhaps you could expound on the potential for that? Are there approaches for selectively eliminating other types of antibodies?

  3. #3 James
    January 18, 2012

    Tunable immunity seems possible with some sci-fi combination of control circuits from synthetic biology and cellular therapy with one’s own modified B-cells.

    But, this requires long lasting immunity in the first place. Can you comment on what limits the life time of the B-cells?

  4. #4 Kevin
    January 18, 2012

    @ WINGS – Thanks!

    @ Mindy – You’re right, and I think this is why people aren’t lining up around the block to get this sort of treatment, despite the fact that the idea has been around for almost 100 years. I have some ideas for possible solutions – for example, you could attach the antigen you use in the immunization to a cytotoxic (cell killing) chemical, which would selectively destroy B-cells that can see that antigen. However, this is introducing what is essentially chemotherapy to a contraceptive method, which I think most doctors and patients would be reluctant to do – for many, the risks outweigh the benefits over hormonal birth control (including things like cost).

    In my reading, I didn’t actually find any examples of intentional reversal ideas – most papers just cite the fact that these approaches tend to be temporary, but I agree that this is a major hurdle.

  5. #5 Kevin
    January 18, 2012

    @ James – Memory B-cells can last a lifetime and continue to be poised for rapid production of antibodies. However, we still don’t know exactly how to maximize this response (which would be ideal for vaccines against infectious diseases), or to limit this response to only last a short time (which would be necessary for a contraceptive vaccine as MMMindy pointed out). Hopefully, the work of labs like mine studying innate immunity will help us better understand how to prime the immune system for a long term (or short term response), but right now it seems to be mostly trial and error.

  6. #6 John
    January 18, 2012

    Can the waning antibody action produce an insult that doesn’t kill the sperm but leaves genetic damage?

  7. #7 Kevin
    January 18, 2012

    @ John – Interesting question. I don’t think that genetic damage would be much of a concern – there’s no mechanism of antibody action that would cause genetic damage but leave a viable spermatozoon. The proposed hypothesis for the action of anti-sperm antibodies (ASA) is either binding to the tail and damaging motility or binding to the head and preventing fusion with the egg. Presumably, they would also make it easier for resident phagocytes to gobble them up, but none of these actions would cause DNA damage and leave the cell intact.

  8. #8 Diane
    January 19, 2012

    Just a point of clarification that we aren’t limited to the choice between hormonal vs barrier methods. The copper IUD is a long-lasting (12+ years per device), fully reversible, non-hormonal form of birth control that is used widely around the world.

    I’m not saying we shouldn’t keep looking for more and better options (IUDs don’t work for all women, and obviously they do nothing for men) but just wanted to remind you of this method.

  9. #9 IW
    January 19, 2012

    “I promise, this will be my last semen post for a while.”

    Now you’ve, er, sown the seed, you’re just going to lie back and think of England?

  10. #10 Tom Fitzsimmons
    January 19, 2012

    Hasn’t the immune response to sperm in men who have had vasectomies led to an increase in early onset dementia? The theory being that this immune reaction to the sperm also causes the immune system to attack neuronal cells? I know it is something of a controversy but it sure seems unlikely that given the genetic material that the immune system is reacting to there wouldn’t be unintended consequences.

  11. #11 Kevin
    January 19, 2012

    @ Diane – In the papers I was reading, an IUD was considered a barrier method. I probably could have been clearer though, since most people probably would think first of condoms.

    @ IW – … no comment.

    @ Tom – I’m not aware of that literature. It’s not inconceivable that there are some antigens on sperm that are also present in the brain. But a vasectomy would expose the immune system to all potential antigens, while a vaccine would be targeted at a particular antigen – presumably one only present on sperm.

  12. #12 Kylyssa Shay
    January 19, 2012

    I think that if our culture were slightly different this method of birth control would have been aggressively pursued a long time ago.

    Many people want to be sterilized but either can’t afford it or are not allowed to be sterilized. A vaccine would eventually be extremely inexpensive and would not require a doctor to administer it.

    I’ve known numerous women who wanted to get sterilized and had to really struggle either to afford it or to convince a doctor to do it, including those women who already had multiple children. The women I’m referring to live in America. Presumably women’s freedom to choose not to have children or not to have more children is even less in developing countries. The biggest problems with a sterilization vaccine, even a temporary one, are political and ideological rather than biological.

    If the politics and ideology could be removed from the issue an effective vaccine producing permanent or near permanent sterility could likely be produced in short order. A cheap, safe, and effective method of causing permanent or near permanent sterility would be a wonderful thing for those who want it. I’m betting many women living in poverty around the world would be eager to not be forced to die in childbirth.

    And isn’t ormeloxifene a non-hormonal, non-steroidal form of birth control?

  13. #13 Evgenia
    January 20, 2012

    Are you sure you are talking about “Karl Landsteiner and Elie Metchnikoff”?

    I think Nobel Prize for the theory of immunity in 1908 was shared between Paul Ehrlich and ILYA METCHNIKOV

    Karl Landsteiner got his prize for blood groups discovery.

  14. #14 kevin
    January 20, 2012

    @ evgenia – Yes. Elie and Ilya Metchnikov are the same person. Landsteiner did indeed get his Nobel for blood groups (i didn’t mean to imply they got the Nobel at the same time), but all those early guys had their hands in a lot of different topics.

  15. #15 b.
    January 20, 2012

    “But there are a number of problems associated with hormonal birth control”

    How about hormonal pollution – estrogen et.al. of the environment (and, ultimately, ourselves)? The more widespread the use of the pill, the more this is going to become a lasting problem.

  16. #16 Tom Fitzsimmons
    January 23, 2012

    Regarding vasectomies and early onset dementia and PPA(primary progressive aphasia)
    I can find no further research published beyond the original 2007 study from Northwestern. Here’s an article on that.

    [I edited this comment to embed the hyperlink - KB]

  17. #17 Kevin
    January 23, 2012

    @ b. – That’s definitely one of the problems – I didn’t want to go into the problems too much (I had some stuff written, but it seemed to drag the rest of the post down).

    @ Tom – Thanks for the link. I took a look at the original study, and it’s still fairly preliminary, but definitely intriguing. The anti-sperm antibody link is pretty tenuous though, it will be interesting to see if they follow up and can actually causally link the immune response with the dementia. In any case, as I said above, that’s a much more generalized response than would occur with a vaccination, so I doubt the risk would be very high.

  18. #18 Tom Fitzsimmons
    January 23, 2012

    @kylyssa-“A cheap, safe, and effective method of causing permanent or near permanent sterility would be a wonderful thing for those who want it. I’m betting many women living in poverty around the world would be eager to not be forced to die in childbirth.”
    Permanent sterility? I wouldn’t bet on it. I think you are imposing your logics on a population that would find your reasoning faulty. There is power in children to help in the present and to take care of you in your old age. This gets poo pooed a bit since we think our society has the role of old age care but that belief is wearing thin and seems to be more sheer and translucent every year.

  19. #19 Milli
    January 24, 2012

    “An estimated 80 million women have unintended/unwanted pregnancies worldwide annually, and 45 million of these end in abortion. In the United States, each year, half of all pregnancies are unintended, which results in over 1 million elective abortions. In over half of these unintended pregnancies, the women were using some type of contraceptive.”

    These are horiffic figures. Especially the over 50% of these unintended pregnancies, the women were using some type of contraceptive

  20. #20 Kevin
    January 24, 2012

    @ Tom – Plenty of people opt for vasectomies or tubal ligation, which does cause permanent sterility. In the developing world, surgery of this sort is more dangerous and more difficult to access, but if you could just get a shot that had the same consequences, there would likely be people that were interested. Your point about the value of children in the developing world is well taken, but there are still people trying to take advantage of family planning services and are having problems with it, so some solution is needed.

    @ Milli – I just want to clarify: Condoms and hormonal birth control are more than 99% effective when used properly. But I agree with you.

  21. #21 mazibo
    Adelaide
    January 9, 2013

    Regarding possible brain damage caused by antibodies, therewas a study done on monkeys that confirmedthe effect of sperm antibodies on brain. I find it a little odd that vertually no research followed.

  22. #22 mazibo
    January 9, 2013

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