Oh...you never realized I was gone?

Ah well, that's ok, because I AM back - back from a stressful few months of wondering where I would end up, how I would feed my babies (i.e. cats) and their baby-momma (my wife - yeah that does sound rather gross), and several dozen unknowns also thrown into the mix.

And after all the trials and tribulations, I can now state with certainty that I got the one job in my new future hometown (Pittsburgh) that I wanted more than anything: a post-doc in the lab of Dr. Veronica Hinman at Carnegie Mellon University.

What will I be doing you ask?

Well, I will be doing none other than studying the evolution of gene regulatory networks (GRNs). Specifically, I'll be looking at GRNs in the context of development using the wonderful sea critters in the phylum Echinodermata. For those of you not in the know, the "spiny-skinned" echinoderms are the asteroids (starfish/sea stars), ophiuroids (brittle stars), echinoids (sea urchins), holothuroids (sea cucumbers), and crinoids (feather stars, sea lillies and such).

Click for larger! Or Click HERE for super high resolution posters.

That's right folks - I am now at least an honorary marine biologist! ... kind of.  I don't know if the real marine biologists would ever deign to allow me such a title, but I can call myself whatever I want.

Many of you may know this already, but the process by which a single fertilized cell becomes a complex organism is an insanely intricate one. DNA is often called a "blueprint" for life, however in reality it's more like a cooking recipe informing each cell which ingredient to add and when, where, and how to add it - all codified into a multi-layered genetic computer program with kernels, plug-ins, sub-circuits, and all sorts of other technobabbly organic craziness.

This is where the "Gene Regulatory Network" comes in - the GRN is that central biological software controlling and allowing life itself. Not only will I be studying the structure of these networks in echinoderm development, I'll be looking at the evolutionary context of the echinoderm networks in relation to each other to suss out how they work and which parts of the networks are conserved (or not) between these amazing creatures that diverged from each other about 500 million years ago.

I'll initially be working on the "endomesoderm" network in the sea star, Asterina miniata. Down the line I'll also be contributing to the development of the sea cucumber as a new model for studying "evodevo".

In celebration, I spent a fair bit of time getting back to my art roots creating the above cladogram in the sand of the Echinoderm phylum (which you can get a poster of here if you're into echinoderms. I rendered it out in pretty high resolution, so you will definitely be getting a high quality poster. I'm pretty proud of it as it took quite a bit of work in the Blender program).

I spent a while trying to find time-lapses or animations of starfish development online, to no avail. Thus I spent a week of much needed downtime to create this computer animation: (note - you can also watch it in High Definition on youtube)

NOTE: The details of the actual metamorphosis of the rudiment into the juvenile are not accurate - it's quite hard to animate these types of changes - and to be honest I haven't actually seen these creatures in the flesh. But it's good enough to get a good idea of how the whole developmental process occurs in this type of sea star.

Anyway, I'm sure I will have much much more to say about the evolution and development of echinoderms in the future so I'll leave it at that for now.

Hopefully, I can at least be an honorary member of the cool kids club, the marine biologists: Kevin, Eric, Andrew, David, Miriam, Christie, Rick, Mark, Jason, Chris, and all the others I'm surely missing.

Remarkable Creatures: Epic Adventures in the Search for the Origin of Species

Just a couple of quick notes to my fellow developmental biologists out there:

First, due to my recent post, Science Blogging: The Future of Science Communication & Why You Should be a Part of it, I was reminded through my comments at Larry Moran's reaction post at Sandwalk that I haven't met very many developmental biologist bloggers out there.

In fact, there is only one dedicated developmental bio blogger I've found: the superb Hoxful Monsters by Nagraj Sambrani. His blog is written for scientists - and if you care about the nitty gritty details of development and evo-devo, his is a blog you should not miss. (Yes I know PZ of Pharyngula is a developmental biologist and posts on the subject as well - but I think he has "evolved" well beyond being developmental-centered - feel free to disagree)

But there must be at least a few more out there, right? If there are, please let me know.

Second, I recently started listening to Scientific American's "Science Talk" podcasts again on my long drive to work. In the February 28th episode, there's an incredibly fascinating interview with one of the premier evo-devo researchers, Dr. Sean Carroll, in which he talks about his new book, Remarkable Creatures: Epic Adventures in the Search for the Origin of Species. This is one book I will definitely be picking up with due haste.

I highly recommned the podcasts as well.

WANDERING EYES from Science News on Vimeo.

FROM FRY TO FISH from Science News on Vimeo.

The theory's thesis: "Ontogeny recapitulates phylogeny." Don't worry - it's not as complicated as the biological jargon might imply.

Ernst Haeckel's Drawings (1892 Romane copy). Note: Haeckel oversimplified these drawings. I use them here as a simple illustration of the concept of developmental similarity.

The idea boils down to a simple one - one that seemed to make sense in light of the fact that the science of developmental biology had only just begun from a systematic standpoint. The idea: if you watch an organism develop from an embryo to an adult, you can watch it slowly move through the evolutionary steps that had created it. That is: development repeats evolution.

So a human embryo would first look like a fish, then a reptile, then a mammal, and finally a human. Of course, we now know that in a literal sense, the theory is completely and utterly wrong. No stage of human development, or of any other organism, correlates with a discrete step in evolution.

We are never fish. (Though we do have embryonic tails).

However, that doesn't mean that there aren't kernels of truth to the idea, if applied loosely. Take the most famous and classic example: embryonic human gills. You may have heard yourself that humans have gills as embryos. Unfortunately this claim arises from misconception and incomplete understanding of developmental biology. Humans do not - ever - have gills. But as embryos we do have "pharyngeal arches." These are little bumps around what you might consider the neck area of a developing embryo (see Haeckel's drawings above). And these little mounds of tissue do in fact remarkably resemble similar mounds found in fish - mounds that in fish develop into gills (Note: Haeckel vastly oversimplified these drawings. I use them here as a simple illustration of the concept of developmental similarity. See: http://zygote.swarthmore.edu/evo5.html. Thanks Bjørn!).

One of the amazing aspects of developmental biology that much of the public does not generally understand is that evolution does not occur by adding new organs, appendages, or tissues to adult animals (whether through gradual steps or not). Evolution works by slowly sculpting the early embryonic clay of an organism.

Fish evolved these gill pouches as embryos - pouches that could then be sculpted into gills. As evolution waltzed and hopped along at its geological pace, genetic mutations began to change how these little mounds were sculpted, such that now in humans, these arches are sculpted into various parts of the face and head. A genetic program was already in place to control the shaping of the pouch. All that natural selection did was slightly tweak that program. For example, instead of a group of cells moving one direction, they moved another. Instead of becoming blood vessel cells, they became cartilage or bone cells.

Thus, while we now understand that we are not witnessing evolution in miniature during development, we are seeing pieces of our evolutionary history - little remnants that remind us of our relationships to our ancestors and also help inform us on what morphogenetic processes underlie evolution.

Which brings us to our adaptation of the week: the freaky asymmetric eyes of the flatfish.

Flatfish (www.seawater.no)

Most people have probably seen a flounder - one member of the flatfishes. They have adapted to lie amongst the silty ocean bottom, hidden from predators and prey, flat on their sides. For a normal fish this might be maladaptive - they would constantly have one eye buried in the sand. Of course the negative of being one-eyed might be offset by being much more camouflaged and undetectable.

Luckily for the flounder, the eye that should be buried in the sand has moved around its forehead so that both eyes are on one side.

The flatfish eye served as one line of attack against natural selection back in the day - and Darwin himself didn't quite know how to answer the charges. Evolutionary gradualism would predict that through successive steps, the eye slowly moved upward toward the forehead and eventually to the other side of the face. But what advantage could a slightly moved eye give, if it still was on the wrong side? Alternatively, as Richard Goldschmidt postulated in the 1930s and 40s, perhaps a single monstrous freakfish was born with both eyes on one side, and this allowed it to lie flat without losing half its vision. It could have then survived and had lots of little freak fish babies of its own.

So how did the flatfish become the strange creature it is now? Let's first look at the developmental biology of the flatfish eye.

WANDERING EYES from Science News on Vimeo.

FROM FRY TO FISH from Science News on Vimeo.

Flatfish Metamorphosis (Schreiber 2006)

It's been know for quite some time that flatfish larvae look like perfectly normal, symmetrical, and upright fish. The picture to the right is from a study by Alexander Schreiber in the Journal of Experimental Biology from 2006. As you can see, at early stages the larvae are normal, but progressively tilt and become horizontal as one eye moves across the face. He also showed in this study that eye movement and flattening behavior occur independently during development - but that's a much longer story.

Alright, so one eye gradually moves across the skull during development. What about during evolution? Do we have any clues as to the steps involved? Well, as many biologists know, the fossil record has now answered the question for us.

In a well-known study that was published last summer in Nature and received much media attention, Matt Friedman showed findings from a series of fossils delineating a clear gradual evolution from symmetrical to asymmetrical flaltfishes. (For excellent in-depth coverage looking at this study and the debate over flatfish evolution, see one of my favorite science bloggers, Ed Yong at Not Exactly Rocket Science, and also see the popular science writer Carl Zimmer at The Loom, and GrrlScientist at Living the Scientific Life).

Flatfish Evolution (Friedman 2008)

The evolution of the flatfish eye seems to mirror what we see during development. Thus, here we have a case of ontogeny appearing to recapitulate phylogeny quite wonderfully. There are many excellent examples of this throughout the biological world, though few that show such incredible similarity between the two processes of development and evolution. Nonetheless, this isn't really evolution we're watching during flatfish development - we're merely seeing how slight changes of the developmental programs are themselves responsible for the changes we see over time through evolution. Generally speaking, earlier developmental processes appear much more similar across varied species than later processes.

Development is in fact one of the primary constraints against evolution.

So while you were never a fish, you still showed remnants of fishy development during your own development. For it was these fishy developmental process that allowed the evolution of your own.

Scientific References:

• Schreiber AM. Asymmetric craniofacial remodeling and lateralized behavior in larval flatfish. J Exp Biol. 2006 Feb;209(Pt 4):610-21.
• Friedman M. The evolutionary origin of flatfish asymmetry. Nature. 2008 Jul 10;454(7201):209-12.

Previous Adaptations of the Week:

1. Timber Rattlesnake Camoflage
2. The Aye-Aye’s Freaky Finger (I’ve Been Cursed by an Aye-Aye!)

Happy 200th birthday, Charles Darwin!
Happy 200th birthday, Abraham Lincoln!
Happy 150th anniversary, On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life!
And here's to a happy Darwin Day and upcoming Valentine's Day to everyone else.

As a part of my own contribution to the Blog for Darwin campaign, I present to you "Darwin and the Heart of Evolution."

What do all four of the above events have in common, other than being events of celebration? The answer will become obvious, but as a clue, I will begin with an appropriate Valentine's question:

A Frog's Heart

Why do humans have hearts?

I can see it already – you’re rolling your eyes thinking, “Well duh…because we need a way to circulate oxygen, hormones, immune cells and other signals, and transport waste compounds and gases.”

Ahh, but you would be wrong. For the above describes only what a heart does – not why we have one. As I wrote a few days ago, evolution pays no attention to "needs." Species don't evolve because they "need" to adapt or change some trait. Natural selection is blind to all intention and desire.

Before Charles Darwin (and his buddy Alfred Russell Wallace) gave us the theory of natural selection, the above "necessity" explanation would have sufficed – with an added “because God designed it that way” just for good measure.

The genius, beauty, and simplicity of Darwin’s big idea was in how it utterly reshaped the manner in which all “why” questions about reality are posed and how their answers are understood. The Origin of Species laid the foundation for the complete upheaval of the very word “why.” In fact, when it comes to describing biology, astronomy, physics, geology, and every other empirical look into reality, the word “why” now means nothing more than the word “how.” The how is the why.

So again, I ask - why (how) do humans have hearts?

To answer this question we need to jump back about 500 million years ago into the ancient ocean. Based on the fossil record, this is a good date to pick, considering that worms don’t make great fossils; however, the exact date is not at all important for this discussion. Nor does it matter the exact species of worm-like creature we consider, or the exact details of the hypothetical time-traveling adventure upon which we will now embark.

Imagine it - we’re swimming now in the ancient ocean sometime after the massive explosion in the evolution of all sorts of strange ocean-dwelling invertebrate body forms (the Cambrian explosion). One of the many advantages that certain individuals of various species find is that their larger body sizes makes them better able to compete – up to a point. Once a small early worm-like species reaches a certain size, it finds that it cannot grow any bigger with its current body plan. This is because at this point, our hypothetical creatures do not have circulatory systems. They must absorb all their oxygen from the surrounding water. Any individuals born larger than a certain size can no longer get enough oxygen due to the oxygen not reaching deep enough into their tissues, and so they die (or are our-competed).

The Vertebrate Family

Now imagine an individual of this species is born with what others of its species would consider a defect (if they had brains with which to consider such a concept). This individual has certain cells that have formed a small simple tube-like structure. Perhaps it is only a vague cavity – or some extra space between its cells. Now when this individual swims around, contracting its primitive muscles, the fluid within its body spreads a little bit more and a little bit faster through this cavity or space.

Our little worm leads a happy life, finding mates (or perhaps reproducing asexually) and leaving an ocean full of cavity-containing offspring. It seems self-evident to us now, but Darwin found himself surprised at the amount of variability in traits throughout the animal kingdom. All populations vary; thus, some of our worm’s children are a little bit bigger than their siblings. And some of these worm children will have inherited papa worm’s fluid cavity, which meant that they could survive with a slightly larger body than those without the primitive vessel, due to the oxygen distributing power of the fluid filled vessel.

Thus began the evolution of the heart. By a series of easy to imagine steps through thousands or millions of generations, the cavity became slightly more developed, eventually forming an actual tube. I would like to note here that the above scenario is strongly supported by much embryological, anatomical, and genetic data. However, I would like keep this simple and vague for the layperson.

Now, we move forward in time, though how far is unclear. Our little worms are now bigger worms, insect ancestors, and a myriad other small invertebrate species. Some of these species have evolved their tubes to have contractile regions - that is, a region of the tube than can actually squeeze and pump. Some, like our modern earthworm, have seven of these pumping “hearts”. Others, like the Drosophila fly, have only one heart - called a "dorsal vessel" (see the Drosophila larvae movie below).

The Fish Heart

We swim forward to 525 million years ago, just as the first fish appear in the fossil record. A lineage of the invertebrates has slowly morphed through primitive chordates (organisms with a nerve cord) to become the most primitive fishes. Along with the changes in many other body structures, the basic contractile heart and vessel system has itself become more complex. Instead of one contractile chamber, the fish heart has divided into two chambers: an atrium and a ventricle (and a stretchy region called the conus that isn’t contractile). The fish themselves then radiate over time, each lineage slowly accumulating many small changes, resulting in the gradual evolution of an ocean teeming with fish species – all with two-chambered hearts (see image at right).

Eventually, some fish species start shacking up near shorelines or in shallow ponds and lagoons. Some are born with thicker fins, which allow them to push along the bottom of the pools a little more quickly or lithely than others. They mate, and the process continues. Finally, one of them decides to just get it over with and leaps out of the water to land as a frog on four fully-formed legs.

The Amphibian Heart

Not really, but you get the picture.

We now see amphibious creatures roaming the shorelines like beastly salamanders. Their hearts have changed even further as other aspects of their bodies evolved to take in oxygen through lungs. Why did this happen? Because the changes that make it possible did happen. These shallow water-dwelling creatures began to develop vessel-filled outpockets on their esophagus, giving them the advantage of pulling oxygen from the air. In addition, the individuals with slightly better circulatory systems found their bodies better at all sorts of other things, such as regulating their bodies with hormones and getting rid of cellular wastes.

At this point, a series of further changes occurred in the amphibian heart. The atrium became two separate atria, either through a physical division of the one atrium, or through a duplication of the vessels coming into the heart. Thus, the frog ancestors developed three-chambered hearts, which were subsequently passed down to every frog currently inhabiting the earth (see image).

The Reptile heart

As time passed, the frogs began drying off their slime, sprouting scales and forked tongues, and inspiring instinctive reptilian nightmares in their prey. They became lizards. As the lizards moved fully to land and grew even larger, certain inherited variations in their hearts naturally worked a little better – thus natural selection continued the continuous sculpture of life. The ventricle began to separate into two chambers, much like the atrium had done in the amphibians. However, the ventricles didn’t fully divide. As one can see in almost every reptile on earth today, the ventricular division is incomplete – almost like a four-chambered heart, but with a hole between the ventricles (see image). However, I said that almost all reptiles have the pseudo four-chambered cardiac morphology; in fact, one branch of the reptiles went on to develop a fully-featured, true four-chambered heart: the crocodile - but that's a side story.

From some of the lizards the dinosaurs then sprung forth, populating the land from the small dark corners to the open plains. A short while later (a paltry 170 million years) most of the dinosaurs died off. Along with their distant crocodilian, lizard, and snake cousins, at least one dinosaur lineage and one reptilian lineage survived. We now call them birds and mammals, respectively.

Both the bird and mammalian lineages mirrored the path of the crocodile, completing the division between the ventricles (probably prior to their divergence). Natural selection has continued to sculpt our own mammalian hearts, resulting in marvelous structures such as the multiple different valve types, chordae tendenae ("heart strings"), and trabeculae (fibrous strings in the ventricle's interior).

The Bird and Mammal Heart

And with that, we have answered our initial question, in a massively oversimplified fashion. We have hearts because each change leading to our hearts conferred some small advantage to the individuals that inherited them (or at the very least, were not disadvantageous).

Of course, all of these cumulative small changes in the shape of the vessels and hearts, ultimately involved millions of small changes in the genes that controlled the behavior, shape, and functions of the circulatory cells. Scientists have now discovered an incredibly large and complex network of such genes controlling development of the heart.

One of the most astonishing yet completely expected facts we have garnered through studying organisms from Drosophila to the African clawed frog (Xenopus) to humans is the discovery that every organism on this planet with some version of a heart contains the same or a similar set of genes to control heart development.

That’s right. Read it again.

Many of the genes involved in the formation of the relatively primitive “dorsal vessel” in a fly are versions of the same genes that initially form our own hearts. Think about that! Think about how massively more complex we are compared to flies (which are themselves insanely complex in their own rights). Think about the hundreds of millions of years that separate us from our most recent common ancestor with a fly. Yet your heart still uses many of the same genes and in the same ways during early heart development. Of course flies and humans have continued to evolve in parallel ever since our lineages split those hundreds of millions of year ago – we have both made countless changes and tweaks to our own cardiac programs and networks. Nonetheless, our hearts remain related.

In fact, if you watch heart development in an embryo, such as in the Xenopus movie below, you can almost see the course of heart evolution itself. Of course this isn't really ontogeny recapitulating phylogeny - but some of the evolutionary history behind cardiac development is at least evident.

Tbx20 expression in a frog larva heart

One example of a cardiac gene that I’m particularly familiar with, having received my doctorate studying it, is a gene called “Tbx20”. For this discussion, its exact function does not matter. Suffice it to say that when I began my studies, we had a clue that this gene was important in heart development. Why? Because flies have a copy of this gene, as do humans, mice, and every other heart-bearing organism we’ve looked at; furthermore, in each of these organisms this gene is “turned on” in the developing heart tissue.

I went on to show that when you prevent frog larvae from making the Tbx20 protein, they develop incredibly malformed hearts (see the videos below). This means that the Tbx20 gene is indeed important in making a heart. Other researchers later went on to show similar results in mice and flies. Finally, about two months before I finished graduate school, another group of researchers found that some humans born with congenital heart defects have mutations in the Tbx20 gene.

Normal African Clawed Frog (Xenopus) heart

African Clawed Frog (Xenopus) heart lacking Tbx20 protein

So here we have found in only a few years of research a single gene that supports the entire model of evolutionary theory. To rephrase the famous quote from Theodosius Dobzhansky, the existence of Tbx20 in controlling the development of the heart in organisms from flies to humans does not make any sense – except in the light of evolution.

Due to the rich evolutionary history behind the development of this complex organ, the genetic network has become incredibly complex, involving hundreds of genes in thousands of cells all working, moving, and functioning in precise coordination. The higher the complexity, the more things that can possibly go wrong. Unsurprisingly, congenital heart defects are among the most prevalent of all inherited diseases, resulting in about 9 babies out of every one thousand being born with some sort of cardiac abnormality.

I’m sure many of you were wondering how I would manage to tie Abraham Lincoln tie into all this. Although still hotly debated and unproven, at least some researchers believe that Abraham Lincoln may have been afflicted with a disease called Marfan Syndrome, a connective tissue disorder affecting the heart and many other organs. Other researchers believe that he had an unrelated disease. Regardless, it remains at least possible that President Abraham Lincoln was the inheritor of one of the billions of less advantageous variances in heart development that have presented themselves throughout the heart’s evolutionary history.

In summary, the heart of Darwin's theory of natural selection is the idea that evolution comes not through the "why." It comes through the how - through the accumulation of minute individual variations that spread like wildfire when they contribute an advantage.  There remains no better demonstration of this principle than the myriad heart morphologies and functions we can trace today.

Each of you has most certainly inherited a cardiac variation, whether it be a major mutation in a gene, or a tiny change in one letter of your genetic code (a "single nucleotide polymorphism").

Who knows...perhaps yours is the one upon which an entirely new evolutionary history will be built.

So here’s to your own personal variation, and to the man who made our understanding of it all possible. We would have gotten there without him – but I doubt anyone could have rivaled the combination of his incredible intellect and beautiful prose.
Happy birthday Darwin!

_____________
Image credits

Frog heart photograph: Me
Phylogenetic tree: McGraw-Hill and Biology Corner (links to original source broken)
Drosophila heart tube movie: unknown
Heart diagrams: Oracle ThinkQuest Education Foundation
Cardiogenesis animation: Me
Frog heart movies: Me
Lincoln photograph: Visiting DC

Lincoln photo:

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

Check out the next two images. They are the same cells viewed in two different ways (normal light, and epifluorescence).

Long neuronal axons stretch across the dish below.

Two beautiful connected cells.

1. What exactly makes us different from our animal cousins?
   With the completion of the human genome project, we now know that at the DNA level, we are 96-98% identical to our closest cousin, the chimpanzee. Scientists around the world are now scrambling to decipher what exactly in that DNA defines us as human and what separates us from the rest of our animal brethren. We have far yet to travel. It appears now that only about 1.5% of our genome encodes for proteins; the rest of it is often (and inappropriately) called “junk” DNA. We have deciphered the function of only a fraction of the protein-coding genes. Furthermore, many of the differences between chimps and humans lie within this non-coding DNA. The coming years and decades will yield much knowledge as to exactly which genes have evolved in the hominin line, which regulatory regions within the non-coding sequences have changed, and which structures in the brain and other organs define our differences. We already have a sizeable list of genes that putatively separate us from apes. However, there is still much work to be done.

2. What is the nature of the mind? How do the emergent properties of consciousness arise from the underlying interactions of synapses and neural pathways in our brain?
   This one is going to take a while. Eventually, however, we must assemble a complete working knowledge of all genes and all of their functions and interactions. We will combine our knowledge of molecular biology with our knowledge of cell biology. Over this synthesis, we will layer our understanding of neuroscience and cognitive psychology. We must take into account the existence of memory, emotion, learning, sense perception, and every other integral process or function of the brain. The question is: will the underlying structures and functions of all microscopic and macroscopic aspects of the human brain allow us to predict and explain the emergence of consciousness? Only time and science may tell.

3. What is love, hate, and emotion?
   Scientists have largely answered this question already, but as with most neuroscience, the details remain fuzzy. It is quite clear from decades of research that everything we feel, whether it be sensation or emotion, is mediated by the release of molecules, largely neuropeptides, between synapses in the brain. Dopamine, serotonin, epinephrine, and a large cadre of other small molecules act as the signals between our brain cells. Our understanding is growing by piecemeal, but as with the emergence of consciousness, soon we will hopefully be able to synthesize a complete model of emotion, including not only happiness, anger, sadness, joy, fear, and courage, but also spiritual experiences, amazement, and euphoria.

4. Who am I? What is the self?
   This may be seen as more of a philosophical question than a question that science can answer, and there are obviously huge aspects of this question that are inherently untouchable by science. However, I think that if we can understand all aspects of neuroscience and cognition, and if it turns out that we can predict and explain the emergence of consciousness from the underlying levels of complexity, then a full understanding of what defines the “self” may be a natural outcome. We will have a full synthesis of all aspects at all levels of the human brain, and it seems likely that we will then be able to define the “self” as a construct containing everything within the model. That is, you are the sum of all your parts, biochemistry, memories, senses, experiences, feelings, and the emergent properties themselves.

5. Can artificial intelligence have consciousness?
   No doubt, this question may be answered sooner than we think. The field of artificial intelligence is ever expanding, and as the complexity of our computing systems and programming grow, so too may that complexity lead to emergent properties that we may define as consciousness. A better question is perhaps: how long will it be before a computer or robot passes the Turing test (a conversation in which the human cannot tell whether he or she is talking to a human or a machine)?

6. Can a single human consciousness be replicated or simulated by computer or another organic form?
   This is almost the same question as number five, though it has a slightly different focus. This question could be reworded: if we can understand all aspects of consciousness and “self,” and if we have the computing power or organic synthesis power, could we theoretically “download” a human consciousness into another brain or into a computer. It’s the classic sci-fi dream. Who knows whether this is even theoretically possible? It would certainly take an almost unfathomable level of complexity of circuitry. In all likelihood, any specific consciousness or self would be too defined by the molecular and perhaps even quantum properties of its own constituent parts. I cannot really conceive of humanity becoming so adept at manipulating the physical world that we can completely mimic every neuronal connection and interaction in the brain. But then again, this very thought may be considered small minded several generations from now. There are also the philosophical issues of whether the “self” would truly be transferred. Nonetheless, I think this is a mind boggling question that may just be answered by science. Who wouldn’t want to be made virtually immortal?

7. What is the nature of memory? How is it stored in the brain?
   Here’s what we know: certain structures such as the hippocampus and amygdala are integrally involved in memory. In addition, much research is going on at this very moment in an attempt to define the method in which memories are encoded. Current results have shown that memories are likely encoded by the formation and connections of specific synapses (neural connections). There are an estimated 60 trillion (that’s 60 million million) synaptic connections in the brain. Hopefully, we will soon understand exactly how information of our perceived reality is stored in these connections. Just as importantly, we hope to discover how this information is retrieved and processed, parsed, and associated with other memories and senses. Why are smells so often vividly linked with memory?

8. How did life evolve?
   Although this is a question we will never be able to definitively answer (unless Number 18 becomes possible), I think we will one day be able to demonstrate practical ways in which life can evolve from non-life. In 1953, Miller and Urey demonstrated the formation of essential amino acids by simply electrocuting boiled methane, ammonia, hydrogen, and water – compounds believed to be abundant on the early Earth. Since then, many researchers have uncovered many specific conditions that can result in the formation of compounds necessary for life as we know it, including the formation of nucleic acids. It is very conceivable that in the near future, scientists may demonstrate the formation of self-assembling, replicating molecules in such an experiment. Perhaps they will then show how these replicating molecules can acquire membranes, like the phospholipid bilayers of our own cells (which are already known to be self-assembling). A wide variety of theories exist concerning the abiotic origins of life, too many to debate here, and I think that we may in our own lifetimes find practical methods that our own molecular ancestors might have used to become life.

9. What is the exact evolutionary lineage of all life on Earth?
   As above, historical events are by definition inherently unknowable, from a definitive standpoint. However, as the fossil record continues to accumulate, and more importantly, as more and more genomes are sequenced, we will be able to use compare the specific DNA codes of all life on Earth (or as much as we want) to calculate the ultimate Tree of Life on Earth. There will always be holes, and specific areas of fuzziness in the data. Many organisms have been show to transfer genetic material between species, largely due to things like retroviruses and bacteria, which can muddy our understanding of specific lineages. Nonetheless, we will eventually construct a tree of evolution that comes close to outlining the entire history of natural selection on Earth.

10. Can we engineer our own evolution?
    The trajectory of current molecular and developmental biology places us squarely in line to eventually understand the contributions of all genes within human development and physiology. We are already at the point where embryos can be screened for genetic defects, such as Trisomy 21 (Down Syndrome), before being implanted into a woman’s uterus. Our tools for genetic manipulation are improving, though we are still far from using gene therapy as a routine treatment. It seems likely that we will one day be faced with the opportunity to engineer our own evolution. The current state of civilization seems to suggest that at least a macro level, humans are not experiencing selective pressure to evolve, other than negative selection against disease (see my article on human evolution below). However, we may one day be able to direct the course of our own evolution. We would need the currently unimaginable computing power necessary to simulate potential genetic changes, and superb genetic tools. Perhaps with enough knowledge of developmental biology, physiology, anatomy, and with the necessary computing power and tool, we could make our species happier, adapted to undersea life, more intelligent, free of disorder and disease, or any number of things we can imagine for our species. Of course, there are enough moral and societal issue with this possibility to fill a Wikipedia. Then again, who knows what kind of world humans will live in many generations from now.

11. What is are the costs and benefits to specific changes in the brain?
    An interesting issue has been brought up by the fields of clinical psychology and cognitive psychology, and it is the issue of the cost/benefit of deficits or enhancements in the brain. Many have speculated a growing list of artists, geniuses, and creative thinkers from our history to have been autistic, or at least have had personalities on the autistic spectrum. In addition, creativity has been positively linked with bipolar disorder (formerly known as manic depression). The study of neuroscience and neuropsychology will likely discover some interesting links between gaining certain abilities or traits, while displaying deficits of others. We have all heard of the rare “savants." If do get to the point of self-directed evolution or even personal enhancement with drugs, it may be interesting to define the interplay between these different traits in the human psyche.

12. How does a single cell turn itself into a thinking, breathing organism?
    How does a fertilized egg regulate its own genes and control the timing and three dimensional growth of cells to form tissues and organs? The field of developmental biology is currently in an explosion of data. What at first seemed only insanely complex, now seems near-infinitely more so with the discovery of the roles of things such as microRNAs, epigenetics, maternal contribution on development, on top of the role of protein-coding genes. It seems like it will take centuries for us to parse out the different factors, interactors, and processes involved in the construction of an organism. However, time is something we’re not concerned with here. Assuming all remains right with the world, science will almost definitely explain exactly how a sperm and an egg can come together to create someone like you.

13. Is there a maximum human life span?
    The human body did not evolve to be particularly long-lived. As we age, our somatic telomeres shorten (which degrades genes at the end of a chromosome), we accumulate mutations, oxidative damage, and cellular debris, and we develop diseases. How many of these things can we overcome? As of this moment, there is only one proven method of extending life spans in mammals: caloric restriction. Eat less, live longer – at least on a population level. It remains to be seen how long we can extend the human life. Even if we can extend it further, we will have to address issues of quality of life as well. Nevertheless, I have much optimism that science could extend the human life dramatically, given the time and knowledge.

14. Can we save our planet?
    How much power can we wield over mother earth? Will we learn to alter climate? Will we learn to utilize renewable energy? Can we cure hunger? To me, it seems that we may always remain as ants when compared to the larger forces of this planet. I cannot foresee large scale engineered climate change and weather control. Then again, who could have conceived of gene therapy two hundred years ago? I think that science has already provided at least rudimentary answers to both renewable energy and hunger. The main issues with these seem now to be cultural and economic, which I don’t want to get in to here. Bioengineering is almost assured to produce a new revolution in energy production. I predict that we will soon have microbes producing ethanol or other hydrocarbon fuels from cellulosic material. We already have solar technology. And bioengineering is also in the beginning stages of creating more nutritious foods that are easier to grow. These will have negative effects and issues of their own (such as the loss of biodiversity and increased susceptibility to sudden disease), but these are issues that I believe we can overcome.

15. Can humans survive on other planets?
    Scientists have already discovered over 300 extrasolar planets (planets around other stars). Right now, our technology is limited to inferring planets by the wobble their gravity induces on nearby bodies, so most of the discovered planets are enormous Jupiter-like planets. However, mounting evidence suggests that earth-like planets orbiting “habitable” zones, which are areas of proper temperature ranges, may be much more common than initially suggested. Thus, I think it’s easily conceivable that with new detection technologies, we may discover watery earth-like worlds in our own lifetime, or our children’s. Now can we get there?

16. Is interstellar travel possible?
    This would obviously take a revolution in the world of physics. Light seems to be the limit right now. The closest star to Earth is Proxima Centauri at 4.2 light years distant. However, our current technology cannot even hit 0.004% the speed of light. Perhaps we will one day be able to accomplish a more sizeable proportion of the speed of light and reach the nearest star within a lifetime (10 years at about 50% c), though the energy required for such speeds boggles the mind. Science fiction writers and theoretical physicists are always theorizing that there may be loopholes in the way reality actually works. Perhaps we can figure out a way to circumscribe the peed of light conundrum (a wormhole anyone?). Only science will tell.

17. Are we alone in the Universe?
    Will SETI (Search for Extra-Terrestrial Life) one day finally receive that long awaited telephone call? Will the Phoenix lander discover microbes beneath its microscope (albeit very tiny ones)? Will future craft find beings inhabiting the oceans of Europa that make whales look like shrimp? Our own galaxy contains roughly 100 billion (yes – 100 thousand million) stars. In addition, there are about 100 billion galaxies in our observable Universe. That’s 10,000,000,000,000,000,000,000 stars (assuming our galaxy is average). Considering the frequency with which we are discovering new planets, it seems more than possible that many planets are habitable and may harbor life. The question boils down to the likelihood of life making that first step from non-life, which is a complete unknown. But it is a question sure to be at the forefront of human thought and scientific curiosity. Perhaps we are already being visited. Scientific evidence is lacking, but it doesn’t seem so unlikely to be impossible. See the Drake Equation to play with more astronomical number on alien life.

18. Is the Universe inherently deterministic or is there “true randomness” in nature?
    Do steadfast laws underlie quantum physics? At the macro level, all physics seems deterministic; i.e. every action is causally linked and predictable in theory based on the events preceding it. Current quantum theory seems to indicate an inherent randomness in the behavior of quantum particles. Some claim that this is due to an incomplete understanding of nature – that there are hidden variables and even at the quantum level, causality holds true. The question remains: is there “true randomness” inherent in nature at the subatomic levels? I have read that most physicists currently lean toward true randomness. If there is no “true randomness,” then every event in existence was determined by those before it, thus eliminating the possibility of free will. However, if there is randomness, this at least leaves open the possibility of true free will. Obviously, we are edging into philosophy here – and a topic which we could debate for years, no less. Nonetheless, if physicists can reconcile quantum physics with Newtonian physics and relativity, and all the other weird quantum stuff I am light years from understanding, perhaps they may answer the question of the nature of the existence.

19. What is the maximum carrying capacity of the Earth? Will we enact global population control measures?
    Just how many people can live on the Earth? Some would argue that we have already surpassed the carrying capacity, while others believe we have a ways to go. Given current birth rates and ever-expanding life spans, it seems inevitable that we will be forced to enact population controls on a world scale. It is science that will have to tell us exactly what our resources can handle. No doubt, technology can increase our carrying capacity, if utilized properly.

20. What is the Ultimate fate of our Universe? Will our observable Universe eventually cease in a frozen motionless entropic heat death? Or will the dark matter and energy pull all matter back into the singularity from which we exploded (The Big Crunch or Gnab Gib? This is still a hotly debated topic. We lack much crucial data. However, current measurements indicate that the Universal expansion is accelerating and not decreasing in its rate of expansion. How much dark matter is actually out there? And…

21. What is dark energy and dark matter, anyway?
    I don’t have much to say about dark matter or dark energy, and I’m not sure that physicists have much more. Actually I’m sure that they do – I am probably just avoiding them. Something seems to be out there, swirling within galaxies, holding them together, and pulling groups of galaxies into clusters and superclusters. We have inferred its existence from its effect on other mass. More than that I cannot tell you. I hope that science will tell us much much more in the coming years.

22. Is time travel possible? Yes. Forward at one second per second. I jest. Again, theoretical physicists have come up with scenarios in which some form of time travel might be possible. They all seem baffling to me. I had high hopes for the Time Traveler Convention of 2005, but unfortunately it seems that humans will not eventually discover time travel, or that when they did, they will have never heard of the Convention and so failed to show up.

23. What is the true nature of existence? Parallel Universes, multiple dimensions, strings?
    Physicists – I leave this one to you. I have tried on many occasions to wrap at least a few brain cells around string theory (may those neurons rest in peace). If science ever comes to grips with the nature of our physical reality and devises the Grand Unified Theory of everything, I sure hope the math can be translated into more conceptual terms. If it turns out that we live in only one (or four) of 13 dimensions or some other such craziness, we prove it, and I still cannot understand it, it will be a sad and anticlimactic day.

Well, those are the best questions I have to offer. Again, please feel free to leave your own two cents. I am sure there are worlds of interesting and important scientific questions left to be answered.