The synthetic human genome could be around the corner

synthetic biology

In biology, more than any other science, there is quite a lot of restraint. Whether it’s a banned, deadly super-virus or a taboo experiment with a human embryo, there are countless avenues of biology that can be pursued, but which shouldn’t be. Just where the line lies, separating the “weird-but-necessary” experiments from the “hold-on-there-Mengele” experiments, is a constant debate. We’ve seen controversial proposals for cloned human beings and three-parent children, mostly in pursuit of fixing some horrible genetic disease — but now, scientists are starting to rumble about the possibility of creating an all-new human genome from scratch. And that could bring up all new legal and ethical concerns, making the already muddy waters all the more treacherous.

What separates this proposal from the sorts of things we’ve been doing in molecular biology for a long time is simply where the genome comes from. Usually, scientists who wanted a genome with particular characteristics would start with an adult genome and modify it by deleting, inserting, or changing a gene or genes within it. This genome can then be the basis for a single cell or, if put into a sperm or egg cell, to create an engineered animal. The human genome is more touchy, but we can genetically engineer cultures of human cells, and take individual human genes and put them into similar organisms to see what they do.

dna storage 7

A synthetic genome is different, because it is built entirely from scratch. It’s the difference between touching up a painting, and actually painting it. You might be able to come in and add a few strokes here and there, perhaps even improve it a bit. But none of that implies that you could have painting the original in the first place, and you until you paint something yourself you can never really be sure you understand the techniques. Diving down into existing content is a great way to learn — but building up from nothing is the only way to master.

Scientists can control DNA in amazing ways -- but genome-length strands are still beyond current technology.

Scientists can control DNA in amazing ways — but genome-length strands are still beyond current technology.

In more concrete terms, scientists are starting to think about the prospect of literally building a human genome from individual bases of DNA; that is, designing and synthesizing a combination of genes that can support viable human cells, and theoretically allow proper development and functioning in the animal. They’d create individual genes and whole regions of DNA individually, then link those regions together, then link those new regions together until they had theri full chromosomes of DNA.

In this case, our final load-out of genes is determined by some ungodly-long TXT file generated in a linoleum-floored computer lab. It’s about as unnatural as you can get — but does that matter?

There’s no proposal to actually develop these synthetic genomes into viable embryos, and the research will be useful to creating any large synthetic bunch of DNA, not just the politically touchy human genome. The aforementioned three-parent children arise from a medical tech designed for use in real patients, while this is a pure research initiative that would impact people’s lives only indirectly.

CRISPR

CRISPR allows direct editing of the human genome, making worry about direct synthesis a bit redundant.

Right now, scientists are on the look-out for genetic freaks. It sounds cold-hearted, but the reality is that some of the most unfortunate individuals in history have been the basis of incredible medical advances, usually to help alleviate that person’s own disease in others. With a synthetic genome created directly from a genetic plan, researchers wouldn’t need to wait for tragedies to provide them with a whole human being’s-worth of diseased cells, but be able to create just a single such cell, directly. They could create an array of many different gene-combo variants and do statistical analysis on the resulting cells to see which genes are necessary, in which patterns.

Plus, creating genomes from scratch is a great way to learn how they work. The recent attempt to make the simplest possible genome is already paying dividends in terms of revealing the function of certain genes, even those that we thought we understood quite well. Creating a human genome from scratch would obviously be much more difficult from a mechanical perspective, just snapping together that much DNA without making mistakes or getting it all tangled up in itself. But unlike a hypothetical simple genome, we have the human genome available to use as a guide. The question of which of our genes are indispensable is an old one, and synthetic biology is the most plausible way to actually answer that question in the near futrue.

syn cell head

The simplest cell ever known to exist is a man-made organism.

However, many are worried about the safety of biological experiments involving human DNA, and in particular many observers worry about the potential to put human genetic material inside living cells, develop our genome in an embryo and grow a human being according to the compliment of genes we designed on a word processor. That’s obviously not actually what these experiments propose, but it is so clearly the endpoint of this sort of research that the discussion has basically skipped all the way to the end. How can scientists ethically justify experiments that could create horribly deformed humans? Well, they can’t, and don’t.

At its heart, this is a chemistry experiment. It has to do with snapping together nucleic acids, handling long chains of DNA so we can keep working with them even as they get unmanageably long, and keeping it all in working order until it gets inside the cell. What people are keying off is the very obvious question that follow this explanation: Why? It’s one thing to say you’re specifically looking to advance a core science, but what about the long-term application of that new ability?

At the end of the day, there’s nothing stopping scientists from doing horrifying Frankenstein experiments without this technology. What this tech will do is make a lot of that sort of tinkering much more tantalizingly possible — and thus, in some direct sense, more probable to actually occur. We shouldn’t oppose these early steps in the mechanics of bioengineering, but we should be very aware of where they’re headed, and how far in that direction we’re really willing to go.

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