A CRISPR Story: “Super Dads” Sire Super Herds

Last week, scientists announced a breakthrough in livestock breeding. Using the CRISPR genetic editing tool, they hope to create what they call “Bull Super Dads.”

Within a generation, genetic editing will touch every person on the planet. Our fruit may be picked ripe without the risk of spoiling. Vaccines for scourges like novel coronavirus may be developed in weeks, or even days. And our meat may come from super herds sired by a few Super Dads. 

“Super Dads” is a typical story of a new CRISPR application. It highlights the potential and the danger of genetic editing, including the ultimate temptation to edit the genes of human beings.  

What Is CRISPR (Briefly)?

CRISPR is a lab process for precisely editing genes, the result of decades of progressive research. Its significance is its low cost and broad availability. What twenty years ago was a twenty million dollar effort can now be done by a hobbyist. In 2015, bioethicist Hank Greely of Stanford University compared CRISPR to the Model T Ford. It was not the first automobile, but it was the one that transformed society through revolutionary advantages in cost, availability, and dependability. 

The primary actor in CRISPR technology, an enzyme called “Cas9,” is like a DNA scalpel. It evolved in bacteria over millions of years. Bacteria use it for self-defense, to cut the DNA of invading viruses to disable the attackers. Genetic scientists use it, and detailed maps of an organism’s DNA, to cut a DNA chain right at a gene they want to change. The process is finished by pasting in a new sequence of molecules to replace what was removed. 

Think of splicing a new sequence of frames into a video: it’s still the same movie, but part of the plot is different. The sterilized bulls in the latest CRISPR script have had their NANOS2 gene “knocked out,” or “KO’d” in genetics shorthand. 

The first published reports of CRISPR in 2012 sparked an ongoing frenzy to alter all kinds of organisms. Among the creations are mosquitoes whose female offspring die before they can bite, fruit resistant to disease and harsh climates, and possibly a crippled coronavirus as a vaccine. Disturbingly, two years ago, genetically altered twin human girls were born, Lulu and Nana, edited as embryos to be immune to HIV. The scientist responsible, He Jiankui, says he acted independently and with only the best intentions for the girls and their family. 

The CRISRP’d Super Dad Bull Concept

CRISPR Cas-9 gene editing has dominated biotechnology news for the past 8 years. It gives scientists and bio-hackers worldwide the power to shape life and to transform industries. 

To enable Super Dads, researchers modified the DNA of male cattle embryos to make the resulting bulls sterile in a particular way. Physically intact, these bulls have only one difference: they do not produce sperm. However, using a technique developed in the mid-’90s, when the bulls’ testes receive injections of stem cells from the testes of a donor, they start producing sperm with the donor’s DNA.  

The genetic makeup of a single bull could propagate to vast numbers of animals. Herds could be faster-growing, need less feed and water, be more disease resistant, and deliver higher-quality meat or milk.

The concept and part of the process are not new. CRISPR potentially makes it economically viable: cheaper, easier, and purportedly more humane. Labs currently castrate bulls with the chemotherapy drug, busulfan. Like humans, cattle suffer awful side effects from chemotherapy. 

The reproductively re-enabled bulls can sire sterile male offspring. Ranchers could make new super-dad DNA recipients the old-fashioned way: in the fields, with no lab required.

The researchers mention treating human male infertility as a potential future application. From the view of biology, we are highly similar to cattle: a herd of humans with a single Super Dad is just as achievable. The feasibility, benefits, and dangers of editing human DNA is literally a vital debate.  

CRISPR-ing Humans? 

The temptation to genetically improve humans is irresistible. If scientists can identify the genetic link for a desirable trait, why not exploit it? For example:

There are two grave complexities: unknown gene functions and editing errors. In the Bull Super Dads research, some altered boars suffered painful back problems (osteopathic degeneration). The researchers are unsure if the condition was an unexpected result of the NANOS2 gene deficiency, or if CRISPR cut either too much DNA or in just slightly the wrong place.

Though the first human DNA map was completed in 2003, researchers still disagree on how many genes it contains and what they all do.  The CCA5 gene that rogue scientist, He Jiankui, suppressed to deliver HIV immunity to Lulu and Nana has other functions. The edit lowered their resistance to West Nile disease and encephalitis. It may also have improved their memories and their brains’ abilities to develop and change throughout life (“plasticity.”). Did CRISPR editing make Lulu and Nana smarter?  

Exponentially-growing technologies are impatient. Already a new gene-editing too, Prime, purports to enable gene edits with far fewer errors than CRISPR. 

Regulation is Hard

Despite global government edicts, there are no robust preventions for human gene editing. The low cost and high availability of CRISPR technology, coupled with the allure of creating the better human, make it likely that quietly, somewhere, human embryos are being edited and returned to a mother’s womb.

Large government organizations are reactive entities. Months after Lulu and Nana’s births, seven years after the first CRISPR paper, the World Health Organization (WHO) issued its initial recommendation for a global registry of all funding and research toward editing the human germline. 

That well-intentioned stance will not deter a person, team, or government who doesn’t want to register. Biohackers, like Internet hackers, will create in all corners of the world. 

Unbounded Opportunity and Responsibility

If artificial intelligence is the new electricity, then genetic editing is the new fire. It can alter every living thing. It is a powerful weapon against ageless scourges of disease, hunger, and pestilence. Globally hundreds of thousands of scientists and enthusiasts, each a potential Modern Prometheus, can apply it. In 2019 He Jiankui was named one of Time Magazine’s 100 Most Influential People. And sentenced to three years in prison in China. 

$100M funding rounds for genetic editing startups are standard. The saga of the Bull Super Dads will replay indefinitely as tools become ever cheaper and easier to use. New industries will be born, and established ones transformed or eliminated.  

Here is the future. A web search for “CRISPR Unicorn” returns both billion-dollar startup valuations and ideas for editing livestock to create unicorns. Genetic editing will be an unbounded source of new money, new ethical questions, and possibly new life forms.

Cover Image:

Bull: “Betty Wills (Atsme), Wikimedia Commons, License CC-BY-SA 4.0”;

Prometheus depicted in a sculpture by Nicolas-Sébastien Adam, 1762 (Louvre): Atoma (assumed), from commons.Wikimedia.com