Easy as pie...

Once, again the past decades of developmental biology research has been forgotten amidst the layman’s limited understanding of the potential wonders of genetic technology.

It started off innocently enough: Time.com began a series of articles on “Visions of the 21st Century.”

With daily headlines on the rampant success of molecular, genetic, organismal, and evolutionary biology, it seems natural and predictable that in the wake of movies like Jurassic Park and the now perennial reports of various animal cloning successes that imaginative folks would ask “Will we clone a dinosaur?”

As one might expect, the Time article made it to the front page of Digg - where I found it.

It started off as any good article on the subject should – with sobriety:

“The short answer is no. The slightly longer answer is definitely not. The Jurassic Park idea – amber, insects and bits of frog dna – would not work in a million years, and it was by far the most ingenious suggestion yet made for how to find dinosaur genes. Cloning a mammoth – flash frozen for several thousand years – might just prove feasible one day. But dinosaurs, 65 million years old? No way.”

Sad, but true.

Unfortunately, with one illogical slight of literary hand, the next sentence erased the reality upon which the article had set itself up to expound.

“It is only when you ask the question the third time that you begin to see a glimpse of an affirmative answer.”

Huh?

“Start with three premises. First, dinosaurs did not die out; indeed there are roughly twice as many species of their descendants still here on Earth as there are mammals, but we call them birds. Second, dna is turning out to be a great deal more “conserved” than anybody ever imagined. So-called Hox genes that lay down the body plan in an embryo are so similar in people and fruit flies that they can be used interchangeably, yet the last common ancestor of people and fruit flies lived about 600 million years ago.

Third, and most exciting, geneticists are finding many “pseudogenes” in human and animal dna – copies of old, discarded genes. It’s a bit like finding the manual for a typewriter bound into the back of the manual for your latest word-processing software. There may be a lot of interesting obsolete instructions hidden in our genes.

Put these three premises together and the implication is clear: the dino genes are still out there.”

Ahh, now I see where they’re going with this…

The next part in the article makes decent scientific sense. Essentially, they lay out a path whereby over the coming decades, scientists may use the decoded DNA of birds, along with alot of computationally intensive lineage analyses to essentially reconstruct a dinosaur genome. There are many potential problems with this, but from the perspective of thinking futuristically, it’s not completely implausible (unless you consider regulatory regions – see below). We very well may be able to resurrect a close enough approximation of a dinosaur genome from DNA sequences existing in modern avians, using chunks from other types of organisms as well.

Alright, so let’s say we’ve done it – we’ve sent our text file containg the complete dino genome sequence to a high-tech DNA synthesis company and we now have a tube full of the actual DNA. What now?

To quote Reg of the People’s Front of Judea (or was it the Popular Front?),

“Where’s the fetus going to gestate? You going to keep it in a box?”

Simple, right? Apparently…

“The rest is as easy as Dolly the sheep: call up a company that can synthesize the genome, stick it into an enucleated ostrich ovum, implant the same in an ostrich and sit back to watch the fun.”

Really? Oh, well yes – if we ignore everything we’ve learned about early embryogenesis. You see, we now know that early development of an embryo is controlled by MUCH more than just the genome and gene products of the embryo itself. A mother creates an egg – a single-celled oocyte – which eventually becomes isolated from the mother’s tissues by an eggshell (unlike placental creatures). The embryo goes through most of it’s tissue and organ development inside that egg.

That means that everything the embryo needs – from nutrition to the intricate balance of hormones, growth factors, asymmetry cues, etc. – must be deposited by the mother during oocyte creation inside the egg in the exact position and concentration necessary.

So the crux of the question of feasibility is this: has the internal oocyte generation machinery inside an ostrich changed much over the last 65+ million years? I can’t imagine anything but a resounding “yes” coming from any developmental biologist.

In fact I would be more than utterly shocked if a dino DNA genome/enucleated ostrich oocyte could even make it through the first cell division, much less complete gastrulation and neurulation. The author does hint at potential developmental issues in a couple of sentences:

“Of course, there will be teething troubles – literally. Or somebody might have forgotten to cut out the song bird’s voice genes, so the first struth chirps like a sparrow. Or maybe the brain development did not quite hang together and the creature is born incapable of normal movement.”

My bet is that the defects would be far far worse than a brain not quite holding together. It doesn’t take much to perturb early development by mucking with just a gene or two. But combining this issue with the almost certain incompatibility between a 65+ million year old dino genome and a modern avian oocyte, my guess is that cloning a dinosaur is almost completely impossible.

It would be like taking a caveman and telling him to build a spaceshuttle without telling him which parts to use or how to build it – times 65 million!

This doesn’t even address another large issue with the article. It claims that scientists are discovering that DNA is far “more ‘conserved’ than anybody ever imagined.” True.  But this is largely beacuse we have learned that most organisms more or less have the same “genetic toolkit.” That is, we have the same basic genes, but what has changed is how they are expressed. Assembling the correct regulatory regions surrounding genes (or lying thousands of base pairs away in the case of many enhancers) based on extant birds seems incredibly unlikely.

But hey – I could be wrong. Maybe – just maybe – we will become advanced enough to alter the maternal contributions in the oocyte prior to or during dino DNA implantation AND somehow gain knowledge of what should be put in the egg in the first place AND assemble a genome with correct expression regulating regions.

What do you think?

Images:
ostrich: http://pro.corbis.com/images/
dinosaur http://gamewallpapers.com