I think most laypeople understand that academic scientists, in order to keep their jobs, have to publish new findings.  I assume most people also intuitively understand that not all venues for publication are equal.  Not to malign my hometown newspaper, but it’s less impressive to write an editorial for Bloomington’s Herald Times than the New York Times.

In the research world, journals are ranked by “impact factor.”  At the top of the heap are journals like Cell, Nature, and Science; these have “impact factors” in the 30s.  The Journal of Cell Biology, where I published my thesis work, has an impact factor around 10.

And the Journal of Assisted Reproduction & Genetics?  Its impact factor is slightly below 2.  My local university’s medical library doesn’t even subscribe.

So I was puzzled: why did the research paper with one of the flashiest single-sentence summaries land in J Assist Reprod Genet?

 

journals
Research journals: tiny nudges to the frontier of human knowledge, & a whole lotta people who got to keep their jobs.

Here’s the summary, in case you missed it: a new genome editing technique was used to insert an HIV-resistance gene into human IVF embryos.

To my mind, that’s a pretty big deal.  It’s not that genetically-modified organisms are anything new.  The big difference is that the technique this group used, CRISPR, makes the whole process incredibly fast, precise, and cheap.  The difference is that sculpting the genome of a human embryo will be easy soon.

CRISPR-Cas9_mode_of_action
A charming schematic of CRISPR from Wikipedia. To use CRISPR for a new gene modification, only the short blue / orange targeting strand in the schematic above needs to be synthesized. Eazy-peezy, right?

At the moment, nobody understands the human genome well enough to propose the sort of editing that shows up routinely in science fiction movies — probably the best way to convince you quickly, without getting into too much detail, is to slap up the title of a recent paper: “Most reported genetic associations with general intelligence are probably false.”  We know that many aspects of human physiology and personality are partially controlled by genetics, but we haven’t yet decoded which genes in which combination give any particular effect.

superman_autism_by_sircle-d5zm8k8
Not all differences are detriments.  Clever image by sircle on Deviantart.

I don’t think we even understand fully the trade-offs inherent in human personality.  We’ve recently begun to understand that many traits designated “mental illnesses” exist on a spectrum and that the challenges are inextricably linked to good qualities — creativity and schizophrenia, puzzle solving and autism, awareness and ADHD.  It’s unlikely that any recipe for a “perfect” human brain exists.

Still, there are traits that parents prefer.  Male height.  Facial symmetry.  Disease resistance.  We’ll soon know which genes modulate these.

Which was why, I assume, Xiangjin Kang et al. wrote their paper, “Introducing precise genetic modifications into human embryos by CRISPR/Cas-mediated genome editing.”  They may have felt a moral imperative to draw attention to these issues.

As far as I can tell, this is also the explanation for why their super-flashy experiment landed in a low impact factor journal.  It’s not a typical research paper.  They wrote an opinion piece about scientific ethics with a somewhat-unsuccessful experiment grafted on in order to get the thing published.

I don’t mean that as criticism.  I think they’ve done the right thing.  If anything, the problem is with scientific publishing; I assume their paper was rejected by a higher impact factor journal.  This paper, with its focus on ethics, is not what fancy journals typically publish.

For instance, the reason why their experiment was somewhat unsuccessful?  Kang et al. were using CRISPR to introduce HIV resistance into a human embryo.  But, because they think that using CRISPR on human embryos is unethical, they specifically chose polyploid embryos — these are non-viable cells produced when two sperm fuse with a single egg.  They have too much DNA and can’t possibly become people.

Because CRISPR uses a DNA-reading guide strand to direct a DNA-modifying enzyme to a particular location, and because the experiment would be “successful” only if all copies of a gene were modified, using a polyploid embryo with more copies of each gene increases the chance of “failure.”  In basketball, making three free throws in a row is obviously more difficult than making two in a row.  That’s what they were trying to do.

Which is why, even though the typical way to read a research paper is to look at the pictures, then read the captions, then maybe read the results section — to wit, ignoring the bulk of the text — the most important part of Kang et al.’s paper is the discussion section.  From their paper:

Because human in vitro fertilization methods are well established and site-specific nuclease technologies are readily available, it is foreseeable that a genetically modified human could be generated.  We believe that any attempt to generate genetically modified humans through the modification of early embryos needs to be strictly prohibited until we can resolve both ethical and scientific issues.

That’s a sentiment a lot of people probably agree with.  But I think it carries more weight in a paper that demonstrates just how easy this process is.

And, sure, they did not sequence the full genomes of their modified embryos.  One risk with CRISPR genome editing is that you’ll have “off target effects” — you might change more of the genome than you were intending.  But there are plenty of very smart people working to make the technology more precise.  Within five years, I’d guess, you’ll be able to change single target genes reliably.

Gattaca chillingly illustrates the dystopia of unregulated genetic manipulation, but even that film understates what we’ll soon be capable of.  The premise of Gattaca is that, by sequencing IVF embryos, parents can choose what sort of child they want.  From hundreds of options, parents pick one.

Scary, sure.  But not this scary.  CRISPR could let parents sculpt the child they want.

GFP_Mice_01
Not that you’d want this, but it wouldn’t be that hard to make your kid glow in the dark.  Maybe you’d want your progeny to be eight-feet tall and brilliant, too.  You could do it.  But, should you?