Why inbreeding really isn’t as bad as you think it is

By Alasdair Wilkins for io9.com

Inbreeding is where cousins and other close relatives have children together. Most cultures have strong taboos against it, primarily because of the increased risk of birth defects. Here’s why that risk isn’t all it’s cracked up to be.

Of course, there can be some very serious consequences to inbreeding, particularly when it’s sustained over multiple generations. Genetic diversity is important, and inbreeding erodes that. There are some dramatic, tragic examples of the dangers of sustained inbreeding. We’ll get to all that in due course.

But the fact is that two cousins with no prior history of inbreeding in the family don’t have a much greater risk of birth defects in their children than an unrelated couple, and in fact slightly more distant relatives actually appear to produce healthier offspring than the general population. So let’s put the taboos to one side and examine what the consequences of inbreeding really are.

A Problem Of Overlapping Genes

While the dangers of inbreeding are generally overstated, they certainly do exist, and can get quite extreme over multiple generations. At its root, the problem is all about recessive genes. While most of the genes that we carry are either beneficial or neutral in character – otherwise, we wouldn’t survive – we all have a handful of genes that have the potential to have a serious negative impact on our health. These are known as autosomal recessive disorders, and they include cystic fibrosis, sickle cell anemia, Tay-Sachs disease, albinism, and a variety of other conditions.

These recessive genes, however, generally remain inactive because they are the recessive form of the gene. This means that of our parents, only one carried that gene in the first place and passed it onto us. The other half of the pair came from the other parent, and it was the dominant, harmless form of the gene. The recessive form, or allele, cannot be expressed in the presence of the dominant gene, and so we end up just being a carrier of these potentially harmful genetic conditions rather than a sufferer.

We’re all carriers of these potentially harmful genes, but the recessive alleles are so rare that it’s unlikely a random reproductive partner will also carry it, and there’s always 50-50 chance that we won’t even pass on our various dangerous recessive genes. With inbreeding, however, we’re talking about family members who already share an unusual percentage of their genes. Cousins, for instance, have a relationship coefficient of about 12.5%, meaning on average an eighth of their genes are identical by descent.

So let’s look at a simple hypothetical and consider the case of two cousins who carry the same dangerous recessive gene – say, the one linked to cystic fibrosis – who marry and have four children. Since both parents carry one benign, dominant allele and one dangerous, recessive allele, there are three possible outcomes. Of the four kids, we would expect one to inherit both dominant alleles, meaning she is no longer a carrier. Two of the children would inherit one dominant and one recessive allele, meaning they are still carriers. And one child would inherit both recessive alleles, meaning he would suffer from cystic fibrosis. In a single generation of inbreeding, the risk of cystic fibrosis has hypothetically jumped from 0.1% in the general US population to a whopping 25% for the children of this particular inbreeding couple.
The Real Risks Of Inbreeding

That’s an alarming figure, of course, and for many that sort of increased risk is likely to confirm all the taboos about the dangers of inbreeding. And yes, it would be silly to pretend such risks don’t exist. But still, while we all carry the genes for such potentially deadly conditions, not all autosomal recessive disorders are so easily activated, with many requiring multiple generations of inbreeding before becoming a serious problem. There does tend to be a gradual decrease in reproductive fitness and general health – children of inbreeding tend to have more trouble having kids and are slightly sicklier, and that gets worse over time – but those don’t preclude such children from living rich, full lives.

Let’s take a look at some actual figures to see what the real risks are. Perhaps the best example is the work of Professor Alan Bittles, an adjunct professor at the Centre for Comparative Genomics at Australia’s Murdoch University, who has worked on the subject for over three decades and in 2008 conducted a review of forty-eight studies from eleven countries on the rate of birth defects in the children of first cousins.

He found that increased risks do exist, but not nearly to the extent that we might imagine. While there’s about a 2% risk of birth defects in the general population, first-cousin children have about a 4% chance. Of course, you can phrase that in any number of ways, depending on how you want to spin it. On the one hand, that means that there’s double the risk of birth defects in the children of first cousins. On the other hand, 96% of such children are born completely healthy, which is still the vast majority.

What’s more, Professor Bittles found that only 1.2% suffered increased infant mortalityrates. Generally speaking, these are marginal increases we’re talking about, hardly the sort of guaranteed horrific outcomes that are often associated with inbreeding. But all that shows is that inbreeding isn’t as bad as we often think – a statement worth making to be sure, but probably not totally earth-shattering. To that end…

Why A Little Inbreeding Can Be Good For You

Yes, let’s go there. Here, we need to look beyond first cousins to more distant relations, specifically third cousins, people who share a common set of great-great-grandparents. Their relationship coefficient isn’t huge – just 1/128. But that still means about 200 of their 23,000 protein-coding genes are identical by descent, a level of relationship easily detected by geneticists.

As weird as it might sound, third cousin marriages actually might produce healthier offspring than the general population, at least if Iceland is anything to go by. In 2008, researchers at the deCODE Genetics company in Reykjavik conducted a study of all Icelandic couples born between 1800 and 1965, a cohort that included some 160,811 couples. The results were, to put it mildly, unexpected:

Researchers were shocked to find that for women born between 1800 and 1824, marriages between third cousins produced an average of 4.04 children and 9.17 grandchildren, while marriages between eighth cousins or more distantly related couples had averages of only 3.34 children and 7.31 grandchildren. For women born between 1925 and 1949, with mates related at the degree of third cousins, the average number of children and grandchildren were 3.27 and 6.64, compared with 2.45 and 4.86 for those with mates who were eighth cousins, or more distantly related.

Lead author Dr. Kari Stefanson called these “counterintuitive, almost dislikable results”, and yet after isolating for possible socioeconomic factors – a particularly easy task in Iceland, which is one of the most homogeneous countries on the planet – he and his team were left to conclude that there is some biological basis for this apparent increase in reproductive fitness.

So Where Does This Biological Benefit Come From?

That’s a very good question, and one to which nobody really knows the answer. Interviewed by ABC News, Dr. Bruce Buehler, the director of HBM Genetics at the University of Nebraska Medical Center, tried to explain these surprising results. He frankly admitted that the explanation eluded him:

“At least genetically, this information doesn’t suggest that second or third cousins would be at any higher risk for passing down unfavorable traits. [I] can’t think of any genetic explanation for why the third or fourth cousins would have more babies. Maybe what we’re seeing here is biologic attraction. If you really look alike, feel alike and think alike, then maybe you have sex more often and have more babies. We do know that there are pheromones which cause attraction, and I wouldn’t be surprised if related people have higher sexual desire for one another.”

For his part, Dr. Stefansson suggested what we might call a Goldilocks Zone for inbreeding. That term, which we usually see applied to exoplanets, refers to the idea that planets need to neither too far away from nor too close to their star in order to be able to support life. In much the same way, third cousins might actually have just the right amount of genetic overlap, neither too similar nor too dissimilar, and so they enjoy a reproductive advantage. However, the underlying genetics of that explanation remain unknown.

Ultimately, Stefansson concluded that maybe our taboos against consanguinity, or the marriage of related people, haven’t just overestimated existing risks – they’ve actually covered up potential benefits:

“The take-home message is that …we, as a society of [the] 21st century, have basically ruled against the marriages of closely related couples, because we do not look at it as desirable that closely related people have children. But in spite of the fact that bringing together two alleles of a recessive trait may be bad, there is clearly some biological wisdom in the union of relatively closely related people.”

The Tragic Case of Charles II

Lest you think I’m simply here to extol the undiscovered benefits of inbreeding, let’s look at the the sad story of Charles II, the last King of Spain from the House of Habsburg, who lived from 1661 to 1700 and reigned from 1665 onwards. Through a series of cleverly organized dynastic marriages two centuries previous, the House of Habsburg had acquired massive land holdings that included the Holy Roman Empire (now Germany), the Low Countries (The Netherlands, Belgium, and Luxembourg) and, most importantly, Spain, complete with its massive overseas empire.

The branch of the family that inherited the Spanish throne was loathe to share power with outsiders, and so they hit upon the same solution that countless other monarchies did – if you don’t want to share power, then keep it within the family. Cousins married cousins, uncles married nieces, and second cousins married second cousins. From 1550 onward, not a single outsider married into the Spanish royal line. The result of all this was Charles II, quite possibly the most inbred person in history.

Charles’s ancestry was so ridiculously intertwined that he actually had a higher relationship coefficient than the child of two siblings, and 95.3% of his genes could be traced back to just five ancestors. While the previous kings had escaped their already considerable inbreeding relatively unscathed, Charles suffered from massive mental, physical, and emotional disabilities, earning him the nickname El Hechizado, “The Hexed.” In their examination of the role that inbreeding played in the fall of the House of Habsburg, three Spanish researchers offer this summary of his various maladies:

According to contemporary writings, he was often described as “big headed” and “weak breast-fed baby”. He was unable to speak until the age of 4, and could not walk until the age of 8. He was short, weak and quite lean and thin. He was described as a person showing very little interest on his surroundings (abulic personality). He first marries at 18 and later at 29, leaving no descendency. His first wife talks of his premature ejaculation, while his second spouse complaints about his impotency. He suffers from sporadic hematuria and intestinal problems (frequent diarrhea and vomits). He looked like an old person when he was only 30 years old, suffering from edemas on his feet, legs, abdomen and face. During the last years of his life he barely can stand up, and suffers from hallucinations and convulsive episodes. His health worsens until his premature death when he was 39, after an episode of fever, abdominal pain, hard breathing and comma [sic].

Charles II also displayed an extreme version of what’s known as the Habsburg jaw, a pronounced underbite that had grown progressively more acute over successive royal generations. Charles’s great-great-grandfather, Charles I, already had a severe enough underbite that he couldn’t chew properly, and as a result suffered lifelong indigestion. By Charles II’s time, he was completely unable to chew, his tongue was so large that he could barely speak intelligibly, and he drooled constantly.

His inability to father an heir sparked the War of the Spanish Succession, in which half a million people fought over who should inherit his throne – a deadly outcome that might have been avoided had the Habsburgs not become so completely reliant on inbreeding to preserve control of their empire, which of course they ultimately lost anyway.

Inbreeding: Not Just For Royals

Charles II represents the extremest of examples, a sort of worse case scenario for inbreeding. And yet he – or at least a hypothetical person very much like him – remains a sort of benchmark for how people imagine the results of inbred relationships, when the most likely result of even first cousins inbreeding is a more or less healthy child. This taboo hasn’t always been so strong.

In fact, two of the top candidates for greatest scientist of all time married their cousins. Albert Einstein’s wife, whose maiden name was in fact Elsa Einstein, was a first cousin through Albert’s mother and a second cousin through his father. And, as we previously discussed, Charles Darwin married his first cousin Emma Wedgwood, and in fact their mutual grandparents, Sarah and Josiah Wedgwood, were themselves cousins. To be fair, after three of Darwin’s ten children died young, he and his son George conducted studies into whether the family’s long tradition of inbreeding had reduced his reproductive fitness. They ultimately decided this wasn’t the case, on the rather strange grounds that “the widely different habits of life of men and women in civilized nations, especially among the upper classes, would tend to counterbalance any evil from marriages between healthy and somewhat closely related persons.”

The list also includes luminaries like H.G. Wells, Igor Stravinsky, Edgar Allan Poe (though his marriage to his then 13-year-old cousin was supposedly never consummated, and more like a brother-sister relationship than anything else), film director David Lean, Morse code inventor Samuel Morse, Nazi-turned-NASA rocket scientist Wernher von Braun, and even noted criminals Jesse James and Carlo Gambino, not to mention a huge fraction of monarchs throughout history. And that’s just people who married their first cousins – the list gets even longer if we consider more distant relations.

Of Pedigree Collapse and Population Bottlenecks

The fact is that, at least until the greatly increased human mobility of the last couple of centuries, inbreeding was pretty much unavoidable. Most people lived in small communities where their ancestors had lived for generations, which meant finding someone in the local area who was completely unrelated to them was next to impossible. Sometimes, that’s created some pretty dramatic results – consider the Doma people of Zimbabwe, whose long isolation and extensive inbreeding has actually resulted in the widespread prevalence of ectrodactyly, in which their middle three toes are completely absent and the outer ones are turned inward.

In point of fact, we’re all technically inbred, if you go back far enough, because simple math demands that we have to be. Our number of ancestors grows exponentially with each generation, from two parents to four grandparents to eight great-grandparents, and so on. In less than a thousand years, you’ve accumulated tens of billions of ancestors, more than the amount of humans who have ever lived on this planet. This means you have to have a bunch of overlapping ancestors, even if they’re all buried so far back in your family tree than none of your later ancestors were aware they were marrying their distant cousins. This necessary duplication of ancestors is known as pedigree collapse, and Cecil Adams provides this example of how extensive it is:

Demographer Kenneth Wachtel estimates that the typical English child born in 1947 would have had around 60,000 theoretical ancestors at the time of the discovery of America. Of this number, 95 percent would have been different individuals and 5 percent duplicates. (Sounds like Invasion of the Body Snatchers, but you know what I mean.) Twenty generations back the kid would have 600,000 ancestors, one-third of which would be duplicates. At the time of the Black Death, he’d have had 3.5 million – 30 percent real, 70 percent duplicates. The maximum number of “real” ancestors occurs around 1200 AD – 2 million, some 80 percent of the population of England.

Admittedly, this sort of inbreeding is really more philosophical than genetic. Again, this is a matter of exponents. Of our 23,000 protein-coding gene base pairs, we get 11,500 from each of our parents, 5,750 from our grandparents, 2,875 from our great-grandparents, and so on. That repeated division means that by the fifteenth generation – which is only a few centuries ago – your average ancestor (assuming zero inbreeding) is contributing, on average, less than a single gene to your current genome. Go back a thousand years to the 30th generation, and the average genetic contribution is effectively zero.

While it isn’t really accurate to say that we’re all inbred, at least not in a genetic sense, it might actually be fair to say that we’re all the descendants of inbred people. Numerous theories have been put forward about a huge decrease in the human population tens of thousands of years ago – one particularly extreme version suggests the human population in sub-Saharan Africa remained under 2,000 for as much as 100,000 years, while more moderate hypotheses suggest a population bottleneck of about 15,000 that occurred about 70,000 years ago. Either population bottleneck would most likely necessitate fairly extensive inbreeding, and that’s backed up today by the relatively low level of genetic variation within humans.

So, what can we say about inbreeding, in the end? There’s no way of escaping the fact that it does increase the risk of birth defects, particularly over multiple generations, and it can have some fairly horrific consequences. That said, the risks of limited inbreeding do seem to be pretty massively overstated, and inbreeding by slightly more distant relatives like third cousins might actually confer a significant benefit. And, depending on just how low our population got in our deep prehistory, it’s entirely possible that without inbreeding, the human race would have long since gone extinct.


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