Gene-editing public discussions: looking ahead

By Jon Holmlund

Passing along word that the National Academies of Medicine and Science are planning an international commission on human gene editing, the editorial board of the New York Times has issued a welcome call to make the public discussion of the issues as broad as possible.  Read the whole thing, but this key graph is particularly important (emphases mine):

“As gene-editing technology advances toward the clinic, scientists will need to do more than listen to the concerns of bioethicists, legal scholars and social scientists. They will have to let these other voices help set priorities — decide what questions and issues need to be resolved — before theory becomes practice. That may mean allowing questions over societal risks and benefits to trump ones about scientific feasibility.”

See the 29 March 2018 post on this blog regarding two calls—the Times linked to one, and quoted from the author of the other—for broader discourse.  This discourse is urgently needed, but must go beyond risk-benefit discussions to the broader meaning of, and issues raised by, heritable human gene editing in particular.  (Somatic human gene editing, to treat a known disease in an existing individual in a way that cannot be passed on to the next generation, is less troublesome ethically, except insofar as it enables the heritable version of gene editing.)

The challenges to effective public deliberation of heritable human gene editing are formidable: getting truly wide participation; getting the scientists to inform and educate non-scientists without trying to lead them to a set of preferred conclusions; engaging the developing, as well as the developed, world; obtaining “religious input” that is more than token; and sustaining the conversation as long as necessary to hold attention in our short-attention world.

It seems that to execute on that will take a pretty large group of dedicated people engaged in a focused, full-time effort to make it happen.  Existing science and ethics groups, like the National Academies, may be the default nominees, but it also seems like a broader group of facilitating entities is needed.  The “global observatory” mentioned by the Times editorial would, as proposed, be established by an “international network of scholars and organizations…dedicated to gathering information from dispersed sources, bringing to the fore perspectives that are often overlooked, and promoting exchange across disciplinary and cultural divides.”

Hear, hear.  One hopes that this happens—and that individuals can find a way to help make it happen.  Spread the word—people should be encouraged to set aside time, energy, and mental space to consider this revolution for the human race.

Roundup Ready® Humans

Everyone is familiar with Roundup®, arguably the most well-known of any herbicide in the world and my favorite gardening tool. What may be less well known is that Monsanto has created a line of genetically modified organisms (GMOs), which are resistant to their famous herbicide. Called Roundup Ready®, soybeans in this product line can essentially take a bath in Roundup and still grow up to be healthy soybeans. Monsanto charges a lot more for these soybean seeds but farmers apparently make up the difference in their yields, as they can use Roundup to kill off competing weeds. Farmers also agree not to use the new growth seeds without paying Monsanto a royalty for their technology or resign to simply buy new seeds the following year. As such, Monsanto effectively controls a large swath of soybean production, and the herbicide market that controls soybean weeds.

One farmer attempted to skirt Monsanto’s royalty scheme. He went to his local grain silo and cheaply and legally bought random soybean seeds, gambling that at least some of these random seeds were descendants of the Roundup Ready® soybeans. He treated his random soybean seed field with Roundup®, effectively killing off all the non Roundup Ready® soybeans. Having no contractural obligation preventing him from using the new seeds, he eventually developed a supply of Roundup Ready® soybean seeds without ever paying Monsanto for their technology, arguing that the he was not responsible for soybeans doing what soybeans do naturally – making more soybean seeds. Monsanto naturally disagreed and the patent case went all the way to the Supreme Court, with the Court siding unanimously with Monsanto. The Court’s opinion stopped short of applying their verdict to all self-replicating entities, limiting the decision in this case to preventing individuals from replicating patented products (nice NPR summary article)

Fast forward to humans. John Holmlund provided a nice summary of a recent closed-door meeting at Harvard Medical School of a group of leading genetic researchers whose reported goal would be to synthesize (make from scratch) an entire human genome in the next 10 years, perhaps even creating novel sequences of human DNA resistant to various (or all) diseases. The novel sequences come close to a Roundup Ready® human. Who will own the disease-resistant human DNA sequences?

To move this closer to the Monsanto soybean example, suppose the Harvard group formed a private company called Humansanto and they developed a human antiviral drug that effectively disabled any virus, at the cost of unavoidable continuous low-grade, flu-like symptoms in the humans that took the drug. Humansanto then invented a human genome sequence that made an individual and her descendants resistant to the side effects of their antiviral. While it seems reasonable for the individual receiving the initial genetic treatment to pay Humansanto, should all of her descendants pay as well? Following the current Monsanto ruling, the answer would be yes.

It would not take too much imagination to turn this into a good genetic terrorism novel or movie where the side effects of the antiviral drug are intentionally far worse, or the evil corporation develops the actual deadly virus, all preventable, of course, with their modestly priced DNA sequence.

It seems unfair that Monsanto (or Humansanto) is not equally obligated to pay a similar royalty to the Original Holder of the patent on soybeans (or humans).

Genetic Prime Patterns

Last month, Science published the results of an ongoing experiment conceived to determine, among other things, the minimum number of genes necessary for viability in a mycoplasma bacterium. Calling their engineered result Syn 3.0, scientists at the J. Craig Venter Institute (JCVI) rearranged and reduced the number of genes on the single chromosome of a M. mycoides bacterium and inserted it into a different mycoplasma called M. capricolum, whose genetic material had been removed. The new genetically rearranged mycoplasma had just 473 genes, 52 fewer than the 525 found in the naturally occurring smallest cousin M. genitalium. Starting with their first artificially rearranged viable mycoplasma, Syn 1.0, which had 901 genes, the JCVI scientists divided their artificial chromosome into roughly eight sections and began trial-and-error substitution and rearrangement until they arrived at the current frugal collection of possibly necessary but certainly sufficient genes for viability. While the bacterium successfully reproduces itself, I am not sufficiently skilled in taxonomy to determine whether or not the resulting organism is still a mycoplasma or something else altogether.

Regardless, the project has many benefits, the most significant of which is to learn which genes do what in the life of this bacterium. Out of the 473 genes in Syn 3.0, scientists are confident of the function of 324 of those genes. This means that the remaining 149 genes are necessary but mysterious as to what role they play in the life of this particular mycoplasma bacterium. Efforts continue in an attempt to gain a more detailed understanding of the function of these genes and to eliminate any remaining genes to arrive at the fewest genes necessary for viability, what I am calling the genetic prime pattern for this particular mycoplasma.

Wondering out loud: Is there a similar genetic prime pattern for human viability? Humans are estimated to have between 20,000 and 25,000 genes so any process to investigate this question is going to take infinitely longer than fiddling with 473 genes of a single-celled organism, not to mention the ethical prohibitions (currently) from conducting similar experiments on human chromosomes. Regardless, what would a genetic prime pattern human look like (genotypically and phenotypically speaking)? For instance, while such a human could, by definition, reproduce, would he or she seem human?

The last question is begging for a definition of humanity. Knowledge of an organism’s genetic prime pattern gives genetic engineers a viability starting point. Experiments such as Syn 3.0 point to our growing ability to rearrange and reduce genetic material, literally creating new genetic patterns (at least in mycoplasma) that are viable. Would the equivalent human genetic prime pattern be an adequate minimal definition of humanity?

After all, aren’t we just the sum of our parts?