Can we make a dinosaur?

                I’m not saying that we should do it, all I’m saying is that maybe we could do it. This is obviously just a thought experiment. Legality aside, most of the options I’m going to mention would be highly immoral and probably deadly for the animal. Basically, what I’m saying is don’t try this at home. Now that I’ve got my disclaimer out of the way, let’s get into it.

Image: Dinosaur eggs hatching in Jurassic Park (1993).

                The first and most important question here is “Could we make a dinosaur?” The short answer is no, but actually yes. The Jurassic Park movies popularized the idea of cloning dinosaurs, so we can look into that prospect first. In order to clone an organism, the bare minimum requirement is that you have some of its DNA. Prehistoric mosquitos frozen in amber would probably just give you mosquito DNA, so dinosaur fossils would be a better place to look. There have actually been a few attempts to extract DNA from dinosaur fossils, which Paleontologist Jack Horner explains well in his TED talk, but none of them have been successful. One attempt even involved building a portable lab at the fossil dig site, so that the DNA could be extracted as soon as the fossil came in contact with the air. Even this elaborate setup resulted in failure. It seems like cloning a dinosaur wouldn’t be a valid option, so it may be impossible to make a perfect replica of a dinosaur exactly as they lived millions of years ago. However, it might be possible to reverse engineer a dinosaur-like creature using developmental biology and genetics. Let’s walk through the steps.

                Because we aren’t building a dinosaur from scratch, we need a starting animal to base everything off of. At this point there is no debate that birds evolved from a dinosaur group called the theropods, which included most of the two-legged dinos like velociraptors and t-rexes. Since birds are the closest living relatives to dinosaurs, we’ll use them as our template. Chickens are often used in developmental biology research, so we’ll stick with chickens for this example, but if you want a bigger, badder dino you could swap the chicken out for something like an ostrich or a cassowary.

                Now that we’ve got our starting material, let’s begin changing it up. The first feature that needs modification is the beak. The distinct shape of a bird beak is made of a material called keratin (the same material as fingernails and hair), but we want the more rounded snout shape of a dinosaur. There have actually been some studies that found a way to do this exact thing. The scientists in this experiment showed that a gene called fgf8 is turned on more than usual in the face/beak area of developing chickens.1 When this gene is experimentally turned off during face development, the chicken instead forms a snout-like feature, more akin to an alligator or a dinosaur. So, in order to give our chicken a snout, all we have to do is turn off the fgf8 gene in the beak area.

The effects of inhibiting the fgf8 gene during snout development: the beak of a chicken (Control) begins to look a lot more like the snout of an alligator. (Bhullar et al. 2015)

                We have a functional snout now, but what’s a snout without teeth? The ancestors of modern birds lost their teeth a long time ago (about 100 million years ago), and no birds alive today have teeth.2 Geese have a serrated, tooth-like structure called tomia, but this is made from the same material as the beak. Luckily, scientists have discovered a chicken mutant called Talpid that seems to cause chickens to go back to their ancestral ways of growing teeth.3 The idea of a single mutation changing 100 million years of evolution seems too good to be true, and in a way it is. The Talpid mutation is most likely lethal for the chick, so our experimental dinosaur wouldn’t survive. There are probably a lot of other genes that would need to be changed as well (for example, it seems that restoring enamel to hypothetical bird teeth would be near impossible),4 but this is just a thought experiment so I’m only focusing on the larger structures.

                Apart from probably being dead from a lethal tooth mutation, the front side of our dino is starting to look pretty good, so let’s move on to the back. The next feature that we’re going to build is a tail. Ancestral birds lost their tails to help with flight but looking at chicken embryos shows that birds actually develop a full tail, and then completely lose it before hatching.5 This means that we don’t have to build a tail from scratch and instead just have to prevent the tail from being lost. This will take a couple of steps. First, we would need to stop the Hoxb13 gene from being active in the back of the bird. Experiments show that turning this gene off in the tail region causes chickens to keep two more vertebrae than usual. That’s good, but we’ll need about 13 more vertebrae in order to match what many theropod dinosaurs had. Studies have also shown that a chemical called retinoic acid (RA for short) is what causes normal chickens to lose their tails. Blocking this chemical in the embryo would allow the bird to keep its tail after hatching.

The effects of knocking out the Hoxb13 gene (right) in comparison to a normal chicken (left). The experimental chicken has a few more vertebrae in the tail, making it that much more dino-like. (Rashid et al. 2014)

                This is a pretty good looking theoretical dinosaur at this point. It’s got a snout, teeth, and a tail. But it feels like something is missing… Scientific consensus at this point is that dinosaurs (or at least the theropods) had feathers.6 And while it would be scientifically accurate to keep the feathers on our theoretical dinosaur, it would also look way cooler if we gave it scales. And this isn’t a perfect dinosaur replica anyways, so why not try to make it look awesome? I’ll at least entertain the idea and look at some ways to make scales. Giving birds scales won’t be nearly as difficult as giving them teeth because unlike teeth, which have been completely gone for millions of years, modern birds still have scales. If you don’t believe me, take a look at a chicken’s feet. In fact, many birds still have scales on their legs.  There has been a lot of research into how scales evolved into feathers, but not many experiments have been tested to cause the reverse. Studies show the chemicals β-catenin and retinoic acid (among others) play big roles in turning scales into feathers.7 If the reverse holds true, maybe blocking these chemicals would cause scales to form all over the chicken, instead of just the legs. Then again, biology is rarely that simple, so only time will tell if this is the best way to give our experiment cool looking scales.

And there we have it: a dinosaur (-like creature). Obviously this isn’t a perfect replica, and it wouldn’t take an expert to know something is off. In reality our dino’s appearance would probably horrify people rather than amazing them. But it is a cool thought experiment. To me, the most incredible thing about this is that we can break down the major structural evolution from dinosaurs to birds in a few simple steps.

References:
1. Bhullar, Bhart-Anjan S., et al. “A Molecular Mechanism for the Origin of a Key Evolutionary Innovation, the Bird Beak and Palate, Revealed by an Integrative Approach to Major Transitions in Vertebrate History.” Evolution, vol. 69, no. 7, 2015, pp. 1665–1677., doi:10.1111/evo.12684.
2. Louchart, Antoine, and Laurent Viriot. “From Snout to Beak: the Loss of Teeth in Birds.” Trends in Ecology & Evolution, vol. 26, no. 12, 2011, pp. 663–673., doi:10.1016/j.tree.2011.09.004.
3. Harris, Matthew P., et al. “The Development of Archosaurian First-Generation Teeth in a Chicken Mutant.” Current Biology, vol. 16, no. 4, 2006, pp. 371–377., doi:10.1016/j.cub.2005.12.047.
4. Sire, Jean-Yves, et al. “Hen’s Teeth with Enamel Cap: from Dream to Impossibility.” BMC Evolutionary Biology, vol. 8, no. 1, 2008, p. 246., doi:10.1186/1471-2148-8-246.
5. Rashid, D.J., Chapman, S.C., Larsson, H.C. et al. From dinosaurs to birds: a tail of evolution. EvoDevo 5, 25 (2014). https://doi.org/10.1186/2041-9139-5-25
6. Xu, Xing. “Feathered Dinosaurs from China and the Evolution of Major Avian Characters.” Integrative Zoology, vol. 1, no. 1, 2006, pp. 4–11., doi:10.1111/j.1749-4877.2006.00004.x.
7. Wu, Ping, et al. “Multiple Regulatory Modules Are Required for Scale-to-Feather Conversion.” Molecular Biology and Evolution, vol. 35, no. 2, 2017, pp. 417–430., doi:10.1093/molbev/msx295.

An Introduction to Monster Biology

Officially, I study the evolution of development (evo-devo for short). Personally, I would rather consider myself a monster biologist. A standard reaction to a statement like that would be something like “But monsters aren’t real! How could you research something that doesn’t exist?” And my response to that would be “Of course monsters are real! You see them every day!” To prove this point, I’ll propose a thought experiment. Which of the following seems more plausible:

A. A horse with a horn or
B. A 20 foot tall spotted horse with a 6 foot long neck and a 21 inch long tongue

I’m going to guess that most people would pick option A. Strangely enough, the laws of developmental biology forbids unicorns from existing, yet we take for granted the miracle that is a giraffe. With access to the internet, we’ve become so exposed to all types of creatures, that we’re numb to the marvels of the natural world. But go back a few thousand years and the description of a rhinoceros was probably just as awe inspiring as a dragon.
History is filled with examples of humans discovering creatures that they had never seen before, and many of the best documented accounts come from European explorations of other continents. Quotes from European explorers in the 1600s and 1700s can be found describing a variety of creatures for the first time in their language, including penguins, bison, and crocodiles. My favorite description, however, is John Fryer’s discovery of my own research organism, the cuttlefish. Upon seeing a cuttlefish for the first time, Fryer portrayed it as a “monstrous figure… all one Lump with the Head, without scales; it was endowed with large Eyes, and had long shreds of Gorgon’s Hair, hung in the manner of Snakes, bestuck with snail-like Shells reaching over the body; under these appeared a Parrot’s Beak, two Slits between the Neck are made instead of Gills for Respiration.” (Fryer 1698) The way that Fryer describes the cuttlefish with elements of other animals reminds me of the ancient Greek myth of the chimera, a monster with the head of a lion, the body of a goat, and a snake for a tail. I think that Fryer’s account perfectly reported how truly strange the form of a cuttlefish is.


I research Cephalopods (octopus, squid, and relatives) because I think that they are some of the most fascinating monsters that the world has to offer. There are so many stories to be discovered from these ancient, aquatic invertebrates. They’ve evolved suckered arms and tentacles, camera-like eyes, the ability to change color and texture, jet propulsion, and advanced intelligence, yet they descended from the same common ancestor as slugs and snails. The alien-like nature of Cephalopods inspired the incomprehensible horrors of H.P. Lovecraft and the brain-eating Illithids of Gary Gygax. For me, the opportunity to study such incredible creatures is like living out a childhood dream.
Myths and stories make it clear that humans have always been captivated by monsters. The diverse array of concepts for fantastic creatures in folklore bring new meaning to Darwin’s idea of “endless forms most beautiful”. (Darwin 2004) Many of these stories go about explaining the origin of certain animals, like how a turtle got its shell. In essence, that is the same job as a developmental biologist. I look at animals and ask “How did this happen?” Whereas Aesop of ancient Greece might explain a turtle shell by saying the Greek god Hermes cursed it to carry its home everywhere it goes, Dr. Scott Gilbert of Swarthmore College would say the turtle’s shoulders moved inside its rib cage during development (Gilbert 2001). I would argue that both explanations are equally interesting.
When most people think of developmental biology, I would guess they picture a scientist hunched over a microscope, performing lonely and tedious work. This image makes me sad, because it takes the story out of the research. The story isn’t the fact that “snakes are missing a 17 base pair section of the ETS1 transcription factor.” (Kvon et al 2016) The story is answering the question of “how snakes lost their limbs.” The fun of developmental biology is in discovering answers to these types of questions.
My experience as a developmental biologist has helped me see all organisms through a different lens, but you don’t have to be a biologist to appreciate the creatures living in the world around you. All you have to do is ask questions. Next time you see Spanish moss hanging from a tree, ask yourself how a plant can live without roots or leaves. Or when you see an armadillo on the side of the road, ask yourself how a mammal got an armored shell. All it takes is a little extra thought, and you too can live in a world full of monsters.

Works cited:
– Darwin, Charles. The Origin of Species. Barnes & Noble Classics, 2004.
– Fryer, John. “A New Account of East-India and Persia, in Eight Letters Being Nine Years Travels Begun 1672 and Finished 1681.” R.R. for Ri. Chiswell, 1698.
– Gilbert, Scott F., et al. “Morphogenesis of the Turtle Shell: the Development of a Novel Structure in Tetrapod Evolution.” Evolution and Development, vol. 3, no. 2, 2001, pp. 47–58., doi:10.1046/j.1525-142x.2001.003002047.x.
– Kvon, Evgeny Z., et al. “Progressive Loss of Function in a Limb Enhancer During Snake Evolution.” Cell, 2016. doi:10.1016/j.cell.2016.09.028.