China Genetically Engineers Dog to Have More Muscle

It’s the stuff of comic book lore. A young woman who was a former professional athlete gave birth to a baby with unusually developed muscles. She did not give the identity of the boy’s father, but several members of her family have been known to have unusual strength. She was muscular, herself, although not as remarkably strong as her son.

All tests showed that the boy was healthy and normal except for his unusual muscle mass. When the child was four years old, scientists did genetic and biological studies to determine the cause of his unusual features and found that he lacked a gene related to muscle building called myostatin. At four he was able to hold 3kg (~6.6 lbs) dumbbells in each hand with his arms extended horizontally. The child had twice the muscle mass and half the body fat of other children his age. His parents keep his identity a secret to maintain his privacy.

It sounds like the back story to the next Marvel movie, but this isn’t fiction. Scientists published the results of their genetic study of the boy in the New England Journal of Medicine in 2004.

Before the muscle baby came on the scene, researchers had been studying a certain breed of cattle that had unusual muscle mass as well as “bully whippets” which is the muscular version of the whippet dog breed. The hope was to find a way to help people with muscle wasting diseases, such as Duchenne muscular dystrophy. Scientists discovered, using mouse studies, that their abilities to amass muscle had to do with inhibiting myostatin.

That’s when the athletes started calling.

David Epstein reports in The Sports Gene that Se-Jin Lee, one of the scientists who discovered the effects of myostatin, was concerned about talking to sportswriters. He said Lee “is troubled by the apparent willingness of athletes to abuse technology that isn’t even technology yet, and that is meant for patients with no other options.”

At the time, though, tinkering with genes was dangerous and difficult. While the muscle baby’s naturally occurring mutation provided a glimpse at the possibilities of engineering a myostatin mutation, this was not particularly feasible at the time. Things changed in 2013.

Think of it like writing. Anything published before 1980 was likely hand-written before it was handed to a typist or clerk. Writers typically hand-wrote their first drafts and if any changes needed to be made after it had been typed, rather than changing the “file,” which was saved on tapes, it was easier to just re-type the whole thing. Also, prior to handing the hand-written draft to a clerk, there was undoubtedly a lot of crossing-out, re-writing, and literal copy and pasting. Getting a document submission-ready was an arduous task.

Now, one can “think” through their fingers with relative ease on a personal computer with word processing software. The backspace button is used almost as often as the space bar. CRISPR/Cas9 is the word processor of gene editing.

To be clear, just as word processing didn’t make coming up with a story any easier, CRISPR/Cas9 doesn’t mean we magically know which genes to edit to get the results we want. It was prior studies by Lee and others that demonstrated how myostatin mutations lead to increases in muscle bulk. CRISPR/Cas9 just made the actual process of knocking out a gene easier to execute.

China has invested much time and effort into exploiting CRISPR/Cas9 technology, making headlines earlier this year for genetically editing a human embryo. The authors pointed out that their research does not violate human subject protocols because the embryos were non-viable, but that did not stop the firestorm of media coverage on the ethics of modifying the human embryo.

Now Chinese scientists have made headlines again, reporting on the creation of muscular beagles with a myostatin mutation using CRISPR/Cas9. As Regalado reports in MIT Technology Review this is part of a research endeavor to modify several types of animals and a larger effort for China to become a world-class player in scientific research.

If science is nothing more than a race to see who got there first, then China is winning by shear tenacity. But, when world class means “I got here first,” there is no impetus to take the time to find elegant solutions that are less ethically problematic. I’ve written before about the difference between the elegant solutions and the bulldozer solutions. China’s beagle experiment involved 67 embryos of which 27 puppies were born and 2 had some myostatin mutation, but only one showed myostatin knock out. That beagle will likely pass the mutation on to its offspring.

With the CRISPR/Cas9 research, 25 beagle puppies did not have the mutation. What isn’t said is what did happen. They may or may have had genetic deformities and they likely did not survive. The two puppies with the mutation may or may not be healthy. We’ll have to see.

Soft spot for puppies, aside, two out of twenty-seven live births is not terribly efficient, and certainly would be inappropriate for genetically modifying a human being. Even if it is used for therapeutic purposes, as proposed, and even if the technology was more efficient such that it was feasible for IVF purposes, there would be no way to know if it worked without doing it. Someone has to be the first and that first person would have no say in their germline modification or the modification of their progeny. This is why many countries have called for a moratorium on human embryo modification using CRISPR/Cas9.

Will people try it anyway? The only group of people more adamant about winning-at-all-costs than scientists is athletes, or more appropriately, the sports industry. On the global competitive level, athletes are groomed from a young age to not only compete, but to represent their country. Just as winning the research race is as much about international clout as it is about helping cure disease, athletic competition on a global level is more than the individual’s desire to be world-class, it is about national pride. Historically, many countries have put their athletes through hell in order to churn out the best product. This research ought to have them salivating.