Designer Genes

Genetic engineering involves directly altering the genetic code of an organism, generally in some way that is beneficial to us.  For example, if you want to treat a patient with diabetes, you need insulin.  Instead of going out and tapping into the pancreas of a cow, you could culture bacteria to produce insulin for you.  The procedure is relatively straight-forward: take a blood sample from a person, search the DNA for the gene that codes for insulin production, snip out the gene, make some copies of it, and put it in a bacterium.  If the bacterial cell takes up the insulin gene, you’re set!  Now you’ve got a culture of bacteria producing human insulin for all your pharmaceutical needs.

Genetically engineered organisms are actually pretty common in modern science.  Bacteria can be made to produce medically important substances like insulin, growth hormones, or blood-clotting factors; a lot of the food you buy at the supermarket has been genetically engineered in some way; some companies use algae as a source of organic fuel; a few years ago, a group of researchers in Taiwan made glow-in-the-dark pigs; and last month, a couple of Harvard scientists engineered a human cell that fires a laser.

I’ll repeat that.  A human cell that fires a laser.

Laser cell!

Okay, so the cell-laser isn’t going to be cutting diamonds or shooting down Stormtroopers anytime soon, the laser is actually pretty weak compared to most lasers used in physics and engineering, but it is in fact a concentrated beam of light produced by a cell.  Scientists think they might be able to use this biological laser to illuminate the insides of tissues for medical study.

Now, insulin-bacteria and glowing pigs are pretty impressive, but scientists are currently on the verge of taking genetic engineering to a whole new level.  For some time now, researchers have been able to produce synthetic DNA.  In nature, a cell creates new DNA by replicating existing strands of DNA, but in the lab, scientists can chemically produce the nucleotides that make up DNA and stitch them together to form a new strand of genetic material.  This artificial DNA can be produced without the need of a cell or even pre-existing DNA, using only a digital record of the structure of a gene.  That’s cool, because it means you could theoretically download a copy of the code for the human insulin gene, and then produce it artificially in your lab. 

But there’s more.  Last year, Craig Venter (already famous a decade ago due to his involvement in the Human Genome Project) and his team at the J. Craig Venter Institute took on the task of synthetically producing not just one gene, but the entire genetic sequence of a small bacterium called Mycoplasma mycoides.  And they pulled it off: an artificial copy of the entire genome of M. mycoides, but they didn’t stop there; their next step was a full-genome-transplant.  The researchers took a cell of another bacterial species, Mycoplasma capricolum, removed all of its DNA, and inserted the synthetic M. mycoides genome into the cell.  It was a success.  The M. capricolum cell accepted the M. mycoides DNA, and was even able to reproduce the synthetic DNA!  The “synthetic cell,” as they call it, not only functioned, but produced offspring, all with the same synthetic genome! 

WOW!

Many news articles jumped at the chance to call this “artificial life.”  I’m not sure I totally agree with that.  It’s more of a drastic makeover of existing life using artificial parts.  More like a cyborg, really…

So here we are, able to produce an entire genome synthetically, but so far all we can really do is make copies of existing genomes.  We still need to figure out how to make new DNA that does what we want it to do, but last week, Yale’s Farren Isaacs and his team published a paper that looks extremely promising, in which they introduce a process for editing and rewriting genetic code.

How does it work? DNA is made up of the four nucleotides adenine (A), cytosine (C), guanine (G), and thymine (T), which are arranged in a certain order along the strand.  An example might be: ACGGTC.  Each three-letter combination codes for a certain amino acid.  In this case, ACG would code for one amino acid, and GTC another.  Then those amino acids are put together to form proteins, which are used to build the structure of a cell and fuel all the cell’s functions.  These three-letter combos are called codons.  Nucleotides make up codons; codons code for amino acids; amino acids are put together into proteins; proteins make up cells; cells make up organisms.  And thus DNA is the basis of life.  Jonathan Coulton sings a fun song about it.

The nucleotides (A,C,G,T) are lined up in sets of three (codons) along the DNA strand.
Each codon codes for an amino acid, and the amino acids link up to form a protein. 
From here.

In E. coli, the codons TAA and TAG are stop codons – instead of coding for an animo acid, these codons tell the cell to finish up one protein, and start making a new one.  These codons are accompanied by release factors, called RF1 and RF2.  Put simply, RF1 makes TAG work, and RF2 makes TAA work.  Isaac’s team used a complex process to replace all of the TAG codons in E. coli cells with TAA codons.  Even though the cells no longer had any TAG codons, TAA still coded for “stop” in all the same places, so the cell didn’t suffer any adverse effects.  The team successfully rewrote portions of the genetic code.

Why do that?  Well, now that there are no TAG codons, RF1 is out of a job.  So now the researchers are free to remove RF1 from the cell, and once RF1 is gone, the cell would no longer interpret TAG as a stop codon, meaning TAG would be freed up to do whatever the researchers want.  They could program the cell to interpret TAG as coding for any amino acid of their choosing, or even for an artificial amino acid.  By reprograming the cell in this way, scientists could create completely artificial genes that code for whatever they want.  And they wouldn’t be limited to things like insulin and growth hormones, they could make genes that code for new artificial proteins for whatever use they could think of.  These biological organisms would no longer be limited to making natural biological products, but could be made to produce anything we needed!

WOW!

Of course, let’s not get ahead of ourselves.  All these researchers managed to do was rewrite one type of codon, but it’s the first step down the road to rewriting entire genomes.  Using these kinds of methods, scientists will be able to create DNA strands for entirely new “synthetic organisms.”  These organisms could be given any selection of traits.  The researchers even intone that they could create bacteria that were immune to harmful viruses.  I still wouldn’t call it “artificial life,” but it’s about as good.

And naturally, there are concerns when dealing with “new” organisms.  Ethics will of course be an issue as this sort of science progresses.  Safety is a concern, as well.  We wouldn’t want artificially created microbes escaping into the wild and doing who-knows-what to the environment.  For that reason, researchers will program cells to require a certain substance that they can only get in the lab, to prevent them from surviving elsewhere (like the lysine contingency).

But as these troubles arise, they will certainly be dealt with.  It seems to me we are on the verge of an exciting new era for synthetic biology.  Think of the possibilities!