Humanity: Good News, Bad News

[Thought]

People want a purebred dog, so breeders breed them without any thought as to what recessive alleles they may carry. As such their lifespan is drastically shortened.

You forgot to qualify the statement. It took a while, but with the advent of genetic testing, there are some responsible breeders who are specifically trying to breed out genetic defects. Indeed, for breeds that are supposed to have docked tails and clipped ears, some breeders are trying to breed those traits into them. Better to be born with a short tail than to have it cut off (course, better if neither, but you can't have everything all the time).

[chrono eric]

You forgot to qualify the statement. It took a while, but with the advent of genetic testing, there are some responsible breeders who are specifically trying to breed out genetic defects. Indeed, for breeds that are supposed to have docked tails and clipped ears, some breeders are trying to breed those traits into them. Better to be born with a short tail than to have it cut off (course, better if neither, but you can't have everything all the time).

Yes, but these breeders are few and far between, and you seem to give more weight to the abilities of genetic tests than they deserve. For example, while it is possible to test for major congenital defects within breeds that have a genetic cause, it is impossible to test for them all. And even if you could test for them all, it wouldn't matter - because continued linebreeding eventually always results in novel and unpredicted congenital defects. For example, at some point a random mutation occurs in a gene that controls the cell cycle. This pup becomes a carrier, unbeknownst to the breeder. Linebreeding that pup produces a high likelihood of a homozygous carrier for that gene in his offspring. Now that pup becomes predisposed to certain types of cancer. But once again the breeder doesn't know that, because this is not observed until after the pup reaches sexual maturity and has a bunch of pups on his own, and so on and so forth.

My point is that inbreeding inevitably perpetuates maladaptive genotypes regardless of the precautions that responsible breeders take. Although, I will agree, that the breeders that order genetic tests for their pups are leagues ahead of the breeders that do not, and they deserve praise for doing so.

[Thought]

And even if you could test for them all, it wouldn't matter - because continued linebreeding eventually always results in novel and unpredicted congenital defects.

Actually, no, especially at no greater a degree than such defects enter the species naturally.

Inbreeding and linebreeding are staples of biomedical science; it is absolutely necessary for all the mice in an experiment to be genetically similar (except insofar as the variable that is being tested). Indeed, they've been so handled as two brothers might as well be clones for all the genetic varience between then. You'll still get freak mutations, but incredibly rarely.

Inbreeding and linebreeding do not themselves create new genetic disorders, they just help rare genetic disorders come to the surface when they would have overwise been unnoticable, potentially indefinately.

A bit off topic, but relevant insofar as breeding and genes go.

[chrono eric]

I didn't mean to imply that the inbreeding and linebreeding caused the mutations, and I thought the rest of my post made it abundantly clear that I was talking about a random point mutation entering the breeding population. Here, I'll take the liberty of quoting myself:

For example, at some point a random mutation occurs in a gene that controls the cell cycle. This pup becomes a carrier, unbeknownst to the breeder.

Summed up with:

My point is that inbreeding inevitably perpetuates maladaptive genotypes regardless of the precautions that responsible breeders take.

Which is exactly what you said here:

Inbreeding and linebreeding do not themselves create new genetic disorders, they just help rare genetic disorders come to the surface when they would have overwise been unnoticable, potentially indefinately.

Perhaps you should read my post in it's entirety before responding to it, as what I meant by this:

And even if you could test for them all, it wouldn't matter - because continued linebreeding eventually always results in novel and unpredicted congenital defects.

...was exactly what I meant to say. I didn't say that continued inbreeding and linebreeding causes random point mutations to occur, I said that it "eventually always results in novel and unpredicted congenital defects". By "congenital defect" I was obviously referring to the phenotypic expression of that defect. A congenital defect is usually caused by a homozygous recessive genotype, and as such they would be much more rare if these pups were outcrossed to the general breeding population rather than being continually linebred. The inbreeding always perpetuates novel congenital defects at a frequency much higher than the general population, which is exactly what I said and what I meant to say.

[Thought]

Yes, I did misunderstand what you were claiming, though that was in part because your real point was so dubious that I even though I had considered it, discarded it quite quickly.

You are so horrendously overestimating the rate at which noteworthy genetic variance enters a species that I assumed you must have been trying to say that inbreeding caused the mutation (a much more plausible, if ill informed, position).

That is why I brought up biomedical science.

Line- and inbreeding are so incredibly stable, producing so few unexpected genetic variants, that mice have undergone such treatment so that they may be used for scientific purposes. They are so stable that you can be quite assured that a scientist using a particular strain of mice in Florida will have the same mice - genetically speaking -- as a scientist in Cambodia using the same strain.

Now if the occurrence of potentially harmful genetic mutations in inbred stock is so low as to be scientifically negligible, why should the average individual worry about it? Why should a responsible breeder worry?

Indeed, mice reproduce and reach maturity at a much faster rate than dogs. As such, the problems of inbreeding and genetic mutation would be more of a concern for scientists than breeders.

While it sounds like you probably already know this, it is worthwhile to be sure.

Most genetic mutations that occur are utterly harmless. The same protein can be produced from a variety of sequences, so a different sequence that produces the same protein has no effect. Some mutations occur in junk DNA. Some mutations merely add or subtract a few copies of a gene. In another generation, those will be added back or taken away. Some mutations are even shut off through epigenetics and can't be passed on to children anywho.

Of the remaining portion, the next most significant group of genetic mutations are irrelevant. They occur to polygenetic traits. To use your example, the pup in question might be 0.01% more likely to contract a particular form of cancer. Course, mutations can go both ways. It might also be 0.01% less likely to contract that particular form of cancer. Even assuming every single dog in the species eventually carried that mutation, the end effect would be unperceivable. With enough other mutations, over an ecologically significant time scale, those mutations might play a role, but not on the human-scale of time. In other words, on average the dog breed might live 5 seconds less than it otherwise would have.

The next most significant portion of genetic mutations that occur are so harmful that the being can't survive. Something actually important got mutated. The code to start a critical protein was messed up, perhaps. Those creatures are never born and thus never pass those genes on.

Then of course there are monogentic mutations that the animal can survive. A gene gets switched off and the dog suffers hyperphagia, for example.

To sum-up, you are making a big deal about something that is as harmful to a dog as the solar radiation it receives when taken for a walk (actually, significantly less harmful, but I'm being generous).

[chrono eric]

Thought, do you happen to have a formal biology education by chance? You and I seem to be much more informed about biology and genetics than the average Compendiumite. I went to school for biochem, and worked in a genetics lab for a couple years doing research on recombination genetics. If you perhaps are into something similar, I would love to have some discussions with you via PM.

You are so horrendously overestimating the rate at which noteworthy genetic variance enters a species that I assumed you must have been trying to say that inbreeding caused the mutation (a much more plausible, if ill informed, position).

I said nothing about the rate at which a mutation enters a species, only that it is perpetuated via inbreeding. And I respectfully disagree with you on a fundamental point - the rate of spontaneous mutation and the maladaptive effect it has on pups is not negligible.

That is why I brought up biomedical science.

Line- and inbreeding are so incredibly stable, producing so few unexpected genetic variants, that mice have undergone such treatment so that they may be used for scientific purposes. They are so stable that you can be quite assured that a scientist using a particular strain of mice in Florida will have the same mice - genetically speaking -- as a scientist in Cambodia using the same strain.

You are overlooking a very important point of creating linebred mice for genetics studies. Yes, the line and inbreeding are incredibly stable - in the genes of interest. The probability that a mutation will arise within the gene that is being studied by the mice is astronomical, but the probability of a mutation arising in any other genes is not. Linebred laboratory mice do indeed suffer from frequent congenital defects and a shortened lifespan, it's just that they aren't considered relevant for the purpose of studying a single gene.

Now if the occurrence of potentially harmful genetic mutations in inbred stock is so low as to be scientifically negligible, why should the average individual worry about it? Why should a responsible breeder worry?

See above, the occurrence of genetic mutations in inbred stock is only low with regards to a particular gene.

Indeed, mice reproduce and reach maturity at a much faster rate than dogs. As such, the problems of inbreeding and genetic mutation would be more of a concern for scientists than breeders.

The rate of spontaneous mutation within a mice population is indeed higher than that rate within a breeding dog population, but you are missing the point - eventually maladaptive phenotypes are perpetuated via inbreeding. Every single purebred breed of dog on the planet suffers disproportionately from recessive genetic disorders which are not common within mutts. Some of them have even been named after their respective breeds, such as "Cocker Spaniel Syndrome". The point is not the frequency at which the mutations occur and are perpetuated but that they are perpetuated in the first place. This is the point on which we seem to fundamentally disagree. If the practice of inbreeding to produce purebred dogs did not occur, there would be limited perpetuation. I consider this to be a more ideal situation, you seem to not consider it to be.

The same protein can be produced from a variety of sequences, so a different sequence that produces the same protein has no effect.

You have this backwards. Different proteins can be produced by the same sequence due to alternate splicing of the introns in messenger RNA. Often a single point mutation will completely eradicate the function of a protein, many times it won't.

Some mutations occur in junk DNA.

Most mutations occur in junk DNA. But it is besides the point. The fact that some mutations occur within genes and are maladaptive is what we are talking about. You don't see the mutations that don't present phenotypically, but that doesn't mean they don't occur.

Then of course there are monogentic mutations that the animal can survive. A gene gets switched off and the dog suffers hyperphagia, for example.

To sum-up, you are making a big deal about something that is as harmful to a dog as the solar radiation it receives when taken for a walk (actually, significantly less harmful, but I'm being generous).

Once again, you are confusing the frequency of spontaneous mutations with the relative harm caused by those mutations. You are comparing two unlike things here - namely, the frequency of spontaneous mutations caused by replication errors and the frequency of spontaneous mutations caused by UV radiation. The frequency with UV radiation is proportionately higher, yes. But to a dog that is already born with a congenital defect as a direct result of inbreeding, it is the defect which is more harmful.

The point is not the frequency at which these mutations occur and are perpetuated by inbreeding, but that they are perpetuated in the first place. A point which you do not seem to be getting for some reason. As I pointed out, every purebred dog has an increased frequency of suffering from breed-specific diseases. The perpetuation of novel mutations is in fact insignificant during a single reproductive cycle, but it has been shown that even within the span of several decades new recessive disorders can be introduced into linebred dogs. As long as inbreeding continues as a practice, unhealthy dogs will continue to be born disproportionately and for no reason.

And you seem to be overlooking the larger harm of inbreeding, in that it perpetuates harmful genotypes that already exist and that will continue to exist as long as the practice continues. You are erroneously equating inbreeding with being a harmless practice. It is not.

Be back later I need to get some fooooooooooood from the OG.

[KebreI]

Hmm, let's see - because the breeders are condemning countless innocent animals to a life of suffering and death because of an aesthetic quality that can easily be changed? All it would take to eliminate the practice is to not allow any boxers with any white fur to breed. Problem solved.

An analogous example is the number of purepred dogs that have an enormous predisposition to certain types of cancer because of inbreeding practices. People want a purebred dog, so breeders breed them without any thought as to what recessive alleles they may carry. As such their lifespan is drastically shortened.

Are you saying that is a moral practice? Or that the lives of animals are not worth caring about because they are unimportant compared to us big, powerful, cosmically important human beings?

Man that sounds pretty bad, but the thing I am trying to say is I really don't care. This is a huge disaster, this isn't personally interesting. I don't want to be one of those ass' on the internet but something really don't concern me and this is one of them.

[chrono eric]

Which is fine, of course - you don't have to care. There are plenty of things that I don't give a shit about. If any one of us could care about everything that needed attention then we would have no time on our hands. But because I am going to be a veterinarian, this is a subject which I have a vested interest in.

There was this shithole breeder that used to bring pups into the clinic that I worked at. We reported her to the SPCA several times not because of her breeding practices (they can't really do anything about that) but because of the living conditions of the animals. Regardless though, she was never shut down, and continued to bring on average between 3-5 pups born a month with some genetic defect or another. One was a hermaphrodite, which was interesting. Another was lacking an essential liver enzyme and died a month after he was adopted by this young lady. She seemed oblivious to the reason why this was happening to her animals. We asked if she kept breeding records and planned which animals would breed, and she said no. When asked if she removed from the breeding population the parents or siblings of these animals that were being born this way, she seemed surprised and said "of course not, that would cost me money". Bitch.

It's people like that that need to be shut down immediately.

[V_Translanka]

Khan (Ricardo Montalbán) is dead. Long live Khan!

http://latimesblogs.latimes.com/herocomplex/2009/01/ricardo-montalb.html

But seriously, that's sad...How are they going to make Spy Kids 4 NOW?!? >_>

[HyperNerd]

NOOOOOOOO!!!!!
KHAAAAAAAAAN!!!!
WHYYYYYYYY!!!!!!!



[attachment deleted by admin]

[placidchap]

bad news:
not anything "new" but just an excuse to say that those cunt israelis are still at it
http://news.bbc.co.uk/2/hi/middle_east/7829912.stm

good news, maybe.
http://www.cnn.com/2009/WORLD/europe/01/14/flying.car/index.html
the Epoch won't be far off now!

[Shadow D. Darkman]

How are they going to make Spy Kids 4 NOW?!? >_>

Maybe have Grandfather Cortez die of old age between Game Over and SK4?

[Thought]

Thought, do you happen to have a formal biology education by chance? You and I seem to be much more informed about biology and genetics than the average Compendiumite. I went to school for biochem, and worked in a genetics lab for a couple years doing research on recombination genetics. If you perhaps are into something similar, I would love to have some discussions with you via PM.

Nope. However, I am married to a geneticist who is currently working with mouse models (that might change to a cheaper model in the future; NIH funding isn't so hot right now).

Anyways, a lot of what we seem to be doing at this point is going back on forth on something that probably doesn't really matter. It appears we both have a good understanding of inbreeding, linebreeding, genetics, etc, and that we are just considering different factors to have different significances, and in turn that is affecting our end perspectives. For example:

Yes, the line and inbreeding are incredibly stable - in the genes of interest. The probability that a mutation will arise within the gene that is being studied by the mice is astronomical, but the probability of a mutation arising in any other genes is not. Linebred laboratory mice do indeed suffer from frequent congenital defects and a shortened lifespan, it's just that they aren't considered relevant for the purpose of studying a single gene.

A mutation, yes. A significant mutation, that is the question. As noted, the majority of mutations aren't going to have an detectable effect on a human-scale of time. Also, given how genes interact, one does have to pay attention to the genes other than the one being studied. For example, say one is studying the FAT gene (I'm terribly amused that there is a gene called FAT... its somewhere upstream of MC4R). That is a monogenetic form of obesity in mice (there is a similar gene in humans, but right now I can't remember its name). A mutation in other genes that effect a mouse's weight could potentially totally skew the experiment. That wouldn't just include genes that control fat storage and metabolism; that could include genes related to exercise, related to eating, related to social interaction, etc.

So here I think we are largely agreeing that certain things happen in certain ways to certain results; the pathology, for lack of a better word. However, we are disagreeing on the significance. I'm not sure any amount of arguing is going to change how we perceive that significance... actually, I think I lost the significance of the argument about significance towards the end of my last post. Why is this an issue again?

This is the point on which we seem to fundamentally disagree. If the practice of inbreeding to produce purebred dogs did not occur, there would be limited perpetuation. I consider this to be a more ideal situation, you seem to not consider it to be.

Ah, yes, thank you for already answering my question. I both agree and disagree to an extent.

Irresponsible inbreeding certainly should be curtailed. For example, some friends of mine own a purebred Rottweiler; when they were looking to purchase him they found a breeder who was selecting for head size. That was it. That was a bit of a WTF moment; head-size? Really? That is what someone cares about? That person shouldn't have been allowed to own dogs, much less breed them. Needless to say, they did not buy from that person.

Actually, that is why I am so annoyed with Obama; he's looking to buy a dog from irresponsible breeders, in my opinion (as no responsible breeder would call "labradoodles" a breed).

Where I think we diverge is in that I believe responsible breeding, while perhaps not ideal in general, is still good in specific (and hence, in turn, our argument over genetic significance; you seem to be claiming that the genetic harms of in- and linebreeding outweigh the potential benefits of purebreed dogs, whereas I am essentially claiming that though those genetic harms exist, they exist in such low numbers as to be insignificant to the end goal).

To offer an example of "not ideal in general," the topic of tail docking I noted earlier. As the practice is falling out of favor in many countries and legislation is being passed against it, breeders have turned to attempting to produce dogs with naturally docked tails. While leaving dogs as is might be best, a dog born with a nub is better than a dog born with a tail that is then docked. Insofar as demand for such dogs continues, we'll never get what is best. Therefore line-and-inbreeding are desirable practices so that we can at least have the "better" when what is "best" is unobtainable.

And to offer an example of "good in specific," sometimes people do buy/adopt dogs for a specific trait. Like a geneticist studying a single gene, having a reliable model is necessary. Do you work on a farm and need help herding animals? A purebred herding dog is far far FAR more likely to be what you are looking for than a dog at the local animal shelter. Or perhaps you have rodents as pets as well and need a dog that is more trustworthy around them; you definitely do not want a rat terrier or a dog with rat terrier instincts. Adopting from an animal shelter is a risk that, if you love your other pets, you should be reluctant to take; you have the full range of dog behaviors to worry about, rather than a selected portion.

This isn't to say that a mutt couldn't be just as good or better at herding than a herding purebred, or just as likely to be fine with rodents as certain purebreds. We are getting back into the significance issue again; purebreds stack the odds in your favor of getting the traits you want (or of not getting the traits you do not want). If someone wants a dog with a stipulation, purebreds (and thus in turn, linebreeding) are the way to go. If someone has the freedom, however, to just have a dog, then a mutt is the way to go.

Yes, all purebreds already have genetic problems. Which is why attempting to breed those known problems out is desirable; in and linebreeding can get rid of the known mutations that are harmful. I think we are both agreed on that point, yes? So that is why de novo mutations are relevant (as those are the ones that a breeder wouldn't recognize, wouldn't test for, and could therefore come to be a new genetic disorder of the breed).

With mutts there is no such luxury; there are too many. Many of them still carry the same defects as purebreds, but it is much harder to find out and impossible to eradicate. Eventually, somewhere along the line, you'll get a mutt with the exact same genetic defects as a purebred might have just because both of its parents were carriers but did not themselves have the phenotype. The difference between a mutt and a purebred is that the specific phenotype will be expressed less often in mutts. So Mutts will be healthier in the short term (that is, in the next 100, 200 , etc years). On average they'll have significantly fewer cases of, say, hip dysplasia than many purebreds like Corgis or Labs. However, over time, responsible linebreeding could actually eradicate the known genes that cause the disease, so that eventually corgis and labs may actually have a lower rate of hip dysplasia than mutts.

However, to qualify all of the above, this would certainly not be the first time I’ve overestimated what is actually possible of applied science.

[chrono eric]

Nope. However, I am married to a geneticist who is currently working with mouse models (that might change to a cheaper model in the future; NIH funding isn't so hot right now).

I imagine from your FAT example that she is studying obesity in rats then? Yes, I had to stop doing some of the research because the NIH cut the funding. The research they cut was for the study of genes involved in nitrogen fixation in Medicago truncatula, a model legume. The ultimate goal of all research in that area would obviously be to genetically modify non-legume plants that are staple foods for much of the world's population, so that they could grow in nitrogen poor soil, thus alleviating many hunger issues. Apparently this research was no longer that important to the NIH. Who'd have thought they would have been concerned with people's health anyways?

Anyways, a lot of what we seem to be doing at this point is going back on forth on something that probably doesn't really matter.

I agree, which is what I said in the last post. Here are some points that I think you are underestimating the significance of:

Irresponsible inbreeding certainly should be curtailed. For example, some friends of mine own a purebred Rottweiler; when they were looking to purchase him they found a breeder who was selecting for head size. That was it. That was a bit of a WTF moment; head-size? Really? That is what someone cares about? That person shouldn't have been allowed to own dogs, much less breed them. Needless to say, they did not buy from that person.

Here you say something but then contradict yourself below. You seem to realize that selecting for a single trait is bad news, but the reason that you seem to think it is bad news is because the breeder is ignoring the presence of certain other maladaptive traits that have entered her breeding population, thus allowing them to perpetuate. This is true. But I submit for argument another reason why this is a bad practice, which I meant to explain before but we got side-tracked bickering about the significance of mutation rate.

Whenever a breeder selects for a single trait that produces a single desirable phenotype, there is an inherent danger that you have overlooked. This danger lies in the fact that many genes do not control a single trait, especially genes involved in developmental traits. Many genes are turned off in some cell types, on in others. Many genes perform one function during one stage of embryonic development, and another function later on. Which leads me to my next point:

To offer an example of "not ideal in general," the topic of tail docking I noted earlier. As the practice is falling out of favor in many countries and legislation is being passed against it, breeders have turned to attempting to produce dogs with naturally docked tails. While leaving dogs as is might be best, a dog born with a nub is better than a dog born with a tail that is then docked. Insofar as demand for such dogs continues, we'll never get what is best. Therefore line-and-inbreeding are desirable practices so that we can at least have the "better" when what is "best" is unobtainable.

- Whenever you select for a single trait only, especially a single physical trait that is ultimately active during development, you are risking not only selecting for it to produce the desired phenotype you want but you are also altering any other potential ways it is expressed. Thus, it is not as simple as just selecting for a single trait when you are attempting to modify the physical look of an animal. This is possibly one way that Cocker Spaniel Syndrome came about.

And since you decided to use the example of selecting for shorter tails, here is a paper that has discovered exactly what I am talking about in mice:

Seller MJ, Wallace ME. Tail short variable: Characterization of a new mouse mutant, and its possible analogy to certain human vascular disruption defects. Teratology. 1993 Oct;48(4):383-91.

And the abstract:

A new mouse mutant, tail short variable (Tsv) produces a reduction deformity of the tail, growth retardation, and, in adults, a mild anemia. Genetic and embryological studies show that on all genetic backgrounds there is variable viability of Tsv/Tsv and Tsv/+ and phenotypic overlap within these and with +/+. A modifier is located to a short segment of chromosome 7, which alters the tail length of Tsv/+ mice up to 15%. The modifier, Tsv, and a coat texture mutant come from the same wild Peru mouse. The tail deformity is associated with, and may be caused by, a vascular disruption of the caudal aorta starting on day 11 of gestation. Thus Tsv appears to be different from each of the thirty known mouse mutants involving the tail. It is suggested that Tsv could be a mouse model for human conditions involving transverse terminal limb defects such as Moebius and de Lange syndromes.

This is just one example of many you could envision. My point is that you cannot predict the physiological side effects of selecting for a trait that alters an animal during embryological development.

And there is a second danger to selecting for only one trait, and that is that you are also selecting for traits that are genetically linked to the one you are interested in. If a breeder, say, selects for head size in Rottweilers only and pays no heed to other maladaptive traits that are appearing, and if those traits happened to be linked to the trait of interest that is involved with head size, they can become perpetuated simply because she wanted to perpetuate the trait for head size. Which leads me to my final point:

However, to qualify all of the above, this would certainly not be the first time I’ve overestimated what is actually possible of applied science.

I don't think you have overestimated what is actually possible of applied science, but what is actually possible of people applying that science. Whenever you select for a single trait, or even many traits, you ultimately end up 1) perpetuating novel mutations, 2) perpetuating mutations that already exist, and 3) possibly introducing new and unintended pathological phenotypes due to genes that control multiple physical traits.

No amount of genetic testing will allow a breeder to predict everything, and even if it could - most wouldn't care. Although, I admit that my major beef lies with irresponsible breeders that don't have even the most basic education in Mendelian genetics. If more breeders used genetic testing to say, breed out hip dysplasia in labradors - I would be satisfied, because I'm not an idealist.

But the most major, major beef that I have is the original Boxer example that I posted - namely, the deliberate perpetuation of a pathology by breeders for aesthetic purposes. Should these dogs have to suffer from deafness, or be euthanized because no one wants them, all because we think colored Boxers with some white on them look prettier? No, of course not. And you don't need a genetic test to test whether or not the animal carries the recessive trait because it displays incomplete dominance. It would be incredibly easy to eradicate it from the population.

[Thought]

Wow, this thread died. Well, I've never let a little thing like death stop me before.

So, today's Good News/Bad News is the same news: Prop 8 Upheld by California Court

Why this is bad news should be fairly obvious: the result is that homosexuals are not allowed to marry partners of their choice in California.

Why this is good news should also be fairly obvious: even though the net outcome is undesirable, the process is commendable. The right to vote and the power of the vote were essentially held to be more important than anything else.

The court was in a no-win scenario. Rule one way, and the votes of every citizen would be belittled. Rule the other, and it would prevent all citizens from being effectively equal. Even though I'd prefer California to explicitly allow same-sex marriage, I believe the court made the right decision. If a minority forces an unwilling majority to give them rights, even if the minority deserves those rights, then the majority will constantly work to take back those rights. Indeed, that is what happened in California; the road to same-sex marriage just became longer there.

Instead of trying to force the issue exclusively political means, the political front should be merely the tip of a larger, social movement designed to change the minds of the majority. Political change has to be backed by social change or it will fail.

Of course, that doesn't mean that same-same marriage proponents should stop fighting the legal system, but they'll continue to fail until they can change the minds of the majority.