Belgian Blues, the Schwarzeneggers of cows.

It’s been more than a decade since humans have cracked their own genetic code, but we’ve yet to wake up to a world of engineered lifeforms on the Island of Dr. Moreau. While we’re waiting for genetic science to mature maybe we should take a good long look at cows. Specifically, the Belgian Blue. This muscle bound meathead is a monument to the genetic power of selective breeding. A single genetic defect, a faulty myostatin gene, is responsible for its enormous bulk, and that defect was carefully passed on through the breed for more than a century before it was even known what was causing the cattle’s impressive ‘double muscling.’ Watch the introduction to life of the modern Belgian Blue in the video from National Geographic below. Before we dive into modifying the human gene pool, we better learn the lessons that working with the Belgian Blue has taught us: even the most primitive genetic tools are immensely powerful, they raise serious ethical concerns, and their results are so impressive as to almost guarantee their use. With genetic testing on the rise, and artificial insemination more prevalent, sex is primed to undergo a major renaissance in the years before it’s outdone by genetic engineering.

For those who have never seen a Belgian Blue in person, the experience is…dramatic. Imagine walking past a dozen or so regular bulls and being intimidated by their sheer size and strength. Then imagine passing a bull so heavily laden with muscle it makes all those scary bulls look like cupcakes. That’s the Belgian Blue, and despite the breeds docility, it never fails to impress onlookers as a very frightening animal.

In the clip above we hear about some of the amazing advantages associated with the Belgian Blue strain. They can have 40% or more additional edible muscle mass, most of which is lean meat! They gain weight well, and quickly, and produce high protein milk for their young. While they comprise a relatively small percentage of the international market, the meat itself is highly prized as its lean nature makes it healthier (and some say more tender and juicy as well). Unless you’ve specially requested it, I doubt most of you have tasted Belgian Blue, but if you are interested here’s a listing of where you can find it offered in the US and Canada.

What the breeder in the National Geographic video doesn’t have time to outline is the physical problems associated with uninhibited muscle growth. The Belgian Blue and the Piedmontese, another breed with myostatin problems, are viable farm strains of cattle. They can live, reproduce, give milk, and be consumed with no risk to humans. To themselves, however, these Conan-looking cows are less friendly. They experience a wide range of health risks associated with their muscle – calves can develop enlarged tongues and stiff legs which make it difficult, if not impossible, to feed, leading to early death. Many of the cattle develop cardio-respiratory ailments. In almost all modern herds, Caesarean sections are common due to complications in pregnancy, and in some cases C-section rates have climbed to nearly 90% of all births!

Caesarean scars are clear on this cow, and are common in most herds.

Both the impressive bulk and health issues of the Belgian Blue have been maintained through the relatively simple technology of line breeding. Essentially, a very few bulls are selected to be the fathers for calves in all of the females. By choosing those bulls which clearly demonstrate the myostatin defect phenotype, breeders can make more and more of the muscled cattle. Once semen is collected from bulls (as the video so graciously shows us – eww) it can be tested and then used to impregnate cows through artificial insemination. Anecdotally it is suggested that most of the world’s current Belgian Blue herds were derived from just three bulls and their descendants. While that may be an exaggeration, the truth is certainly that in efforts to perfect the breed very few male genetic lines are allowed to continue.

When shaved, the muscle of the Belgian Blue is even more obvious.

That’s true for all types of cattle and livestock, really. Traditional selective breeding pushes us towards a narrower gene pool. It’s unclear if that is going to get much worse or much better as modern genetic testing takes hold. We’ve already discussed how cheaper DNA tests are allowing cattle breeders to choose the absolute best bulls for line breeding. Those cheap tests mean that any rancher can now see if they have a prize bull. That may open up breeders to using new fathers, or it may simply replace the very small number of current stud bulls with a new, but equally small, generation of replacements.

Either way, what’s good for cattle is slowly becoming good for humans. Though no one seems to want to phrase it in this way, humans are starting to adopt selective breeding habits and technologies. There are now several companies that sell genetic tests in association with in vitro fertilization (IVF) clinics. With good cause, I might add. Successful testing for Tay-Sachs has helped dramatically reduce the occurence of that disease in the US. Most of these newer genetic testing companies are looking to repeat that success for more than a hundred other genetic conditions. Wouldn’t you want to know before you got pregnant if your children would be at high risk for crippling ailments? If you are a genetic carrier for such a disease then Preimplantation Genetic Diagnosis (PGD) can allow you to select fertilized embryos without the disease. IVF and PGD are giving us the tools necessary to, at least in terms of our own gametes, become selective breeders. Breeders informed with rudimentary genetic information, which is a step up from those Belgian farmers who first started propagating their mutant cows.

(Left) Trout given a mutant gene from the Belgian Blue are notably more muscular than regular trout (right).

We’ve discussed before how genetically engineered animals are on the horizon and could be on our plates in the near future. The Belgian Blue’s mutant myostatin gene variation has even been spliced into rainbow trout to give them more bulk (and thus more more worth as food). Animals are already being genetically engineered, and if work in primates is any indication, we’re slowly approaching the time when scientists will be able to waltz inside a human embryo, tinker with its DNA, and get the child to come to term. That possibility, however, scares the sh*t out of most people, and angers the rest. The chances that human genetic engineering is going to have a smooth transition into becoming a popular technology is almost nil. Expect legal and social hurdles to abound. Hell, I wouldn’t be surprised if armed conflict arose around this controversy as well. It could take decades before we accept such technology, though my bet is eventually that we will.

Meanwhile, modern sex powers on. PGD and IVF aren’t universally excepted, but they aren’t fueling riots either. Morally, they are a much more widely acceptable technology. Personally, I know a few IVF (possibly even PGD) kids and my world would be a lot poorer if they weren’t around. I’m glad it’s an option for parents.

But that doesn’t keep it from being a stepping stone to some pretty amazing selective breeding opportunities that could give us the equivalent of designer babies even without genetic engineering. See the Belgian Blue? That’s a single mutant gene that turned out to be helpful, and that simple breeding habit was propagated for more than a century. We’ve already seen human children who were born with the equivalent of the myostatin defect seen in the monstrous cattle. Picture a time when we discover other, relatively rare but potentially advantageous, genetic mutations. Imagine if everyone had the ability to comb through their sperm and find those mutant gametes with the desired traits you want. You could optimize your offspring – give yourself super babies with no genetic tampering required. Long before genetics is ready to replace it with something better, sexual reproduction is going to get more and more impressive thanks to modern technology.

I look forward to seeing all your Belgian Blue-like children in the future.

...this was not what I had in mind.

[image credit: via the Built Report, Terry Bradley via National Geographic, renatothally via DeviantArt, Barbarossa via Wikicommons]
[video credit: National Geographic]
[table via BelgianBlue.org with sources as listed]
[sources: BelgianBlue.org, Hubpages]

I have two mothers and one father! WTF?

Scientists at the Oregon Health and Science University (OHSU) were able to produce the first primates with three biological parents. Four macaque monkeys were born through an in vitro fertilization process in which the DNA of two females and one male were combined. Of the two mothers, one provided all the chromosomal DNA while the other only provided mitochondrial DNA. This technique may eventually be developed into a treatment in humans so that women with defects in their mitochondria can have healthy offspring. The successful test also raises concerns about genetically engineered babies because the new monkeys will pass on the genetic alterations to their offspring.

The mitochondria organelle often gets called the power house of the cell because of its role in creating energy releasing molecules. However, it could also be called the ticking time bomb of the cell because as many as 1 in 4000 people develop illnesses due to defects in their mitochondrial DNA. Sometimes these defects can be passed on from a mother who has no outward signs of the condition. Those people with this type of genetic problem have risks for certain kinds of epilepsy, cancer, diabetes, heart disease, liver disease, deafness and blindness. The work at OHSU demonstrates that a carrier could pass on the 99% of her DNA that is healthy (chromosomal) and use a donor to fill in the missing 1%.

Shoukhrat Mitalipov from the Oregon National Primate Research Center lead the study. The four healthy macaque monkeys (named Mito, Tracker, Spindle, and Spindly) are a good first step in his plans to eventually bring the technique to humans. However, Mitalipov is quick to point out that a technique is not a treatment, and it will likely be several more years before human clinical trials could be considered. Additionally, he would need to see how the new monkeys produce offspring to see if there are any problems with the passing of genetically altered DNA to offspring.

Twin monkeys, Mito and Tracker, are the result of a mitochondrial DNA swap between mothers.

The passing on of genetic alterations, called germline engineering, has raised a lot of interest for medical ethicists. Mitalipov’s work is a remarkably specialized case of germline engineering: only mitochondrial DNA was swapped out, and its goal is purely to avoid known defects. In the grander scheme of things though, germline engineering could lead to designer babies if applied to chromosomal DNA. Currently, the hoops it would take to produce an engineered human baby are many: USDA approval, using only private or state funds, and bypassing laws which forbid clinical trials using genetically modified embryos.

Similar laws are in place in the UK where Newcastle University is pursuing results closely related to the work done at OHSU. Scientists there have a similar technique (though it is reputedly less efficient and has DNA swaps occurring after insemination). And some British scientists are working to get exemptions from their Human Fertilization and Embryology Act (HFEA). That law prohibits implanted altered embryos into a womb.

The fact that four baby monkeys are raising such concern shows the importance of germline engineering. The OHSU work, which focuses on one day helping to cure a certain kind of DNA defects may also reveal how designer babies eventually find their way to market. Parents want the best for their children, genetically as well as environmentally. If their exists a way for them to avoid giving their child a few bad genes, they are likely to take it. As we’ve said before, parents are already selecting embryos for that very reason. It’s only a matter of time before swapping DNA between mothers stops being just monkey-business.

Could you say no to a face this cute? Nope, and that's why we'll have designer babies.

[photo credits: Nature]

Designer Babies - here they come!

The Fertility Institutes recently stunned the fertility community by being the first company to boldly offer couples the opportunity to screen their embryos not only for diseases and gender, but also for completely benign characteristics such as eye color, hair color, and complexion.  The Fertility Institutes proudly claims this is just the tip of the iceberg, and plans to offer almost any conceivable customization as science makes them available.  Even as couples from across the globe are flocking in droves to pay the company their life’s savings for a custom baby, opponents are vilifying the company for shattering moral and ethical boundaries.  Like it or not, the era of designer babies is officially here and there is no going back.

For decades now a technology called preimplantation genetic diagnosis, or PGD, has enabled In Vitro Fertilization (IVF) clinics to screen embryos for more than 100 potentially debilitating and often deadly diseases before the embryo is implanted into the mother.  A medical revolution has thus unfolded, enabling literally tens of thousands of couples and their babies to sidestep some of the world’s most terrifying diseases.

Take the case of Cindy and John Whitley.  Their first child died at the age of 9 months from a deadly genetic disorder called spinal muscular atrophy.  Genetic analysis uncovered that the Whitley’s statistically had a 1 in 4 chance of creating a child with spinal muscular atrophy each time they conceived.  Unwilling to risk having another child with the deadly disorder, the Whitley’s used PGD to conceive three children, all healthy.

Yet PGD allows scientists to screen embryos for much more than just genetic diseases, and therein lies the promise – and the peril – of designer babies.

Gender was the first major genetic trait beyond genetic disease to be widely manipulated through PGD.  The Fertility Institutes is a leader in the field, claiming nearly 100% success in providing couples with a baby of a predetermined gender.  Completely healthy and fertile couples from all over the world are coming to The Fertility Institutes everyday to confront the risk, the expense, and the discomfort of  conceiving their baby in a test tube, all for the ability to choose the sex of their baby.

Gender selection is a big business.  Dr. Steinberg, Director at The Fertility Institutes, claims that they are performing on the order of 10 gender selection fertilizations every week, each for a fee of $18,400.  Although In Vitro Fertilizations were originally designed to help parents that were unable to conceive children naturally, Steinberg says that a staggering 70% of their clients have absolutely no difficulty conceiving children, coming to the Institute purely for opportunity to choose the sex of their baby.

Now, in the latest twist in the march towards designer babies, The Fertility Institutes says they will soon be able to offer couples the ability to screen their embryos for eye color, hair color, and complexion.  The Institute cannot change the DNA of the donating couple — if neither the mother nor the father has genes for green eyes, for example, then the Institute cannot give them a baby with green eyes.  Yet within the constraints inherent in the DNA of the donating couple, The Fertility Institute is willing to screen embryos for these traits.  The Fertility Institute wants to offer several other customizations, and many more are sure to be released in the coming years as the science behind screening for them is developed.

In many countries around the world PGD is heavily regulated and designer babies are strictly out of the question.  Yet in a strange paradox, even as the United States is one of the world’s most regulated nations in several areas of medical research and development, PGD is completely legal and unregulated in the United States.  Hence, even as the United States is hindered by regulation in areas such as stem cell research, the country seems poised to be a world leader in the designer baby revolution.

At the moment, The Fertility Institutes carries the mantle as the company at the forefront of this revolution, and as such they are a lightning rod for the praise and adoration, but also the bitter and severe anger, of those on both sides of this great moral debate.

The genie is officially out of the bottle, in fact it probably has been for a long time.  There is no stopping the designer baby revolution.  Even as some countries try to clamp down on it, others will allow it.  Progress, if we call it that, will continue unabated.  A similar phenomenon has unfolded with embryonic stem cell research  in recent years.  Even as the Bush administration almost completely strangled US investment and research in this promising field, other countries invested heavily and advances continued.

A new generation of genetically enhanced designer babies is inevitable in the coming decades.  Yet for those of us that are merely “normal”, do not despair.  Even as we are outmatched by the next generation genetically, a host of new technologies from chip implants to gene therapy may allow us to keep up, allowing us to enhance ourselves in equally transformative ways.  The future will indeed be interesting.

Want to know more? Below are some excellent videos and articles that served as much of the source for this story:

60 Minutes Story Focused on The Fertility Institutes:

The Wall Street Journal: A Baby, Please. Blond, Freckles — Hold the Colic

Image: source

“CHILDREN with three parents might sound like monstrous chimeras, but they are among us already. In the late 1990s, an American team created the first genetically engineered humans by adding part of the egg of one woman to the egg of another, to treat infertility. When the US Food and Drug Administration got wind of the technique it was promptly banned, though related methods have been used in other countries.”

Although almost all of our DNA resides in the nucleus of our cells, there is a tiny portion of our DNA that resides separately in the mitochondria, and this mitochondrial DNA is passed down only from the mother, not from the father.  It turns out that there are several seriously debilitating diseases that the mother can pass on to her child if she has defective mitochondrial genes, such as Leber’s hereditary optic neuropathy and Leigh syndrome.  Unless the mother’s mitochondrial DNA can be changed the mother’s child is doomed to inherit the these potentially debilitating or even deadly genes.  This of course presents the mother with a terrifying dilemma – choose to have a child, but then face an unusually high risk that the child will suffer from severe disease.

Lane writes about a research team at the University of Newcastle in the UK that is attempting to help mother’s with these defective mitochondrial genes avoid passing them on to their children.   The trick is to replace the defective mitochondria in the egg from the mother with healthy mitochondria from a donor mother.  According to this article, the procedure works as follows:

The procedure would involve fertilising a woman’s egg by in-vitro fertilization outside the body and transplanting the fertilised nucleus to an egg from another woman which has had its nucleus removed.

Any child born following implantation of such an embryo would have cells containing a nucleus with genes from both parents, and mitochondria from a woman other than their mother.

The ability to save a child from inheriting these dreadful diseases will be a great triumph for science, but this triumph comes with the usual moral baggage of genetic engineering.  If mitochondrial dna modification becomes successful then it is one more step of many that are bringing mankind down the path of designer babies.  At the Hub we think the choice is clear: as long as mitochondrial dna modification can safely protect a child from inheriting a debilitating or deadly disease, then it should be done.  The moral implications will just have to come along for the ride.

Morals and hope aside, the technique still requires much research before it will achieve its goals.  There are several safety issues associated with mitochondrial transfer that must be addressed to ensure that even as one disease is avoided, other diseases and complications are consequently introduced.  The relationship between mitrochondrial dna and nuclear dna is complex and researchers need to ensure that changing one does not have an unintended incompatibility with the other.

More on the status of this research can be found here and also at the University of Newcastle website for mitochondrial research.

Image: source