Human bodies are packages of two trillion cells assembled in a very specific way. Almost all animals with bodies have a similar body plan with a front/back, top/bottom, and left/right. Generally, the head goes in front in the direction that the animal moves. For very primitive animals, like jellyfish, it is a bit harder to compare body plans. On the surface, animals like jellyfish only have a top and bottom.
No matter the different size or shape of an animal’s body, Shubin reinforces their basic similarity by focusing only on the axis of symmetry that run through bodies and none of the superficial features.
The Common Plan: Comparing Embryos. Shubin started to become really interested in studying fish and amphibians when he looked at embryos. He was amazed by the transformation that fish, amphibians, and chickens made after starting from embryos that looked so similar. Back in the 1800s, a biologist named Karl Ernst von Baer came to the same realization about embryos, and pushed further to find that all the organs in a developing embryo can be traced back to three distinct tissue layers (called germ layers). Von Baer found that all the embryos he could check had the same three tissue layers.
When looking at embryos, the basic version of the adult animal that the embryo will become, the basic similarity between all animals is much easier to see. The germ layers, even simpler than embryos, are shared by all animals. Shubin goes to the simplest versions possible to make it easier to find the things that animals have in common.
Shubin explains what happens to the “embryo” after conception. For the first few days, the embryo is just a spherical clump of cells called a blastocyst. The blastocyst implants to the wall of the mother’s uterus and cells start to rapidly divide. Tissues fold around each other to form a tube within a tube that stays a fundamental part of the human body – the stomach and intestinal system within the body.
The basic structure of the human body is already present in its simplest form a few days after conception. As a blastocyst, the complicated digestive tract is just a tube within the body – an image that helps clarify the digestive system even when Shubin brings back the nuanced structure of the human body.
Von Baer’s three germ layers are named for their position in the blastocyst. The ectoderm is the outer layer that forms the outside of the body (skin) and the nerves. The middle layer is the mesoderm, which becomes the tissue between the skin and the gut, such as skeleton and muscles. The inner layer is the endoderm, which forms the inner systems of the body such as the digestive tract and glands. For a large portion of an embryo’s life, all animals with a backbone have the same three germ layers.
Like the arches in the human head that correspond to specific head structures, the layers of the blastocyst give a simple way to think of the many various body structures in a mature animal. The logical order of the layers provides an easy way to think of the inside, middle, and outside of an animal.
The deep similarity between these animal embryos contradicts another theory that animal embryos go through the species’ evolutionary path while in the womb. Under that framework, a human embryo would be compared to an adult fish or lizard. However, von Baer’s approach (comparing embryos to other embryos) is ultimately more useful because it allows Shubin to investigate the mechanisms that might drive evolution in the first place. To do that, Shubin turns to the question of how the cells’ embryonic bodies “know” what type of cell they should become in the adult body.
Comparing embryos to embryos makes sense because it cuts out some of the variables that come from comparing animals at different stages of life. If all embryos are fundamentally the same, then the specific environmental pressures or competitions that force each species to become specialized must work at some level after the basic embryo stage. Knowing what type of cell to become means that embryonic cells must have some sort of instructions that outline what the animal has to be like in order to survive in its particular environmental niche.
Experimenting with Embryos. In 1903, German embryologist Hans Spemann investigated body-building cells in the embryo, focusing on whether all the cells in an embryo had the information to build a full body or if each cell only had a specific piece of the body-building plan. Spemann pinched apart a newt embryo (using a piece of his infant daughter’s hair) to make two separate clumps of embryonic cells. The two clumps each formed an identical newt, showing that early embryonic cells have the capacity to build an entire body.
At very early stages of life, all the cells in an embryo have the full plan to become a complete body. Spemann’s experiment highlights the often mundane concerns of scientific exploration, such as what material Spemann can use for splitting a miniscule embryo. Shubin is able to extrapolate the information Spemann found in newts to all animals because Shubin has already set up a precedent for treating all embryos as the same.
In 1920, Hilde Mangold, a student in Spemann’s lab, took that research further. Mangold was able to cut off miniscule pieces of tissue from newt embryos that contained cells from all three developing germ layers. She then transplanted that piece of tissue to the embryo of another species and found that the patch of tissue actually made a full newt body on the back of the other embryo. Mangold called the patch of tissue she transplanted the Organizer.
Mangold represents another generation of students who built on the findings of previous scientists to make truly amazing discoveries. Both Mangold’s academic prowess and her skillful physical dexterity helped her pursue groundbreaking experiments. The Organizer focuses all of the many complicated processes that make a full body into one small patch of tissue – possibly the simplest beginnings possible.
Around the same time period, another German biologist came up with a way to label cells so that the cells could be traced through the embryo to their final positions in the fully matured fetus. We can now make a map that shows where all the adult organs of an animal begin in the embryo. The Organizer somehow directs each clump of cells in the embryo to become the correct body plan for that animal.
Color-coding the cells in an embryo makes a much simpler map for an entire body, showing that body systems that may seem different actually come from the same groups of cells in the embryo. The Organizer acts as the “directions” that Shubin was looking for at the start of this chapter, when he asked how cells “know” what to become.
Of Flies and Men. To continue the work of early embryologists like von Baer or Mangold, modern embryologists now look at the genetic makeup of embryos. Studying genetic mutations in flies that cause the flies to have organs or body parts in the wrong place can actually provide insight to the body plan genes of humans. By painstakingly cataloguing the chromosomal differences between normal flies and mutated flies, scientists can pinpoint where the mutation happens in the fly’s genome. Most wonderfully, the genes that control the body segments of the fly lie next to each other in the same order as the fly’s body plan.
Now that technology has improved past the somewhat primitive methods of early embryologists (who had to do surgery on individual embryos by hand), scientists are in the position to make incredible leaps based on the foundation that these earlier scientists provided. Genetic research has been a huge boon to many different areas of biological research, especially when full genomes such as the fly genome are catalogued.
The challenge is then to identify what is actually causing these body plan genes to mutate. Mike Levine, Bill McGinnis, and Tom Kauffman isolated a short stretch of DNA code in each body plan gene that they looked at, finding that this sequence was almost the same in each species they looked at. The sequence is called a homeobox, and the gene that includes a homeobox sequence is a Hox gene. Every animal with a body has some version of these Hox genes.
Mutations in genetic sequences happen when one letter of the DNA code is replaced with a different letter, as the genetic information from both parents forms one new set of genes for the child organism. The homeobox sequences of DNA that appear in every animal with a body are powerful evidence that the bodies of animals come from common ancestors and develop differently over time.
Animals with more complex bodies have more Hox genes, but every Hox gene is a different version of the basic Hox gene template. This similarity leads to the idea that these Hox genes were just duplicated with few changes as animals became more and more developed over evolutionary history.
Mutations actually become more likely as more copies are made (as when a person might copy a letter wrong when rewriting a document), leading to an easy explanation for the small changes in Hox genes across species.
DNA and the Organizer. After Spemann and Mangold found the Organizer, the patch of tissue was mostly abandoned by researchers because no one could figure out exactly how it worked. The discovery of Hox genes in the 1980s brought the Organizer back to the foreground. Eddie De Robertis, a professor at UCLA, looked at Hox genes in frogs, finding that a specific Hox gene was always active in the patch of tissue that contains the frog embryo’s Organizer.
Success in scientific research often comes down to whether the technology to run experiments is available or not. Scientists have to constantly revisit the work of the past to see what they can add to as each discovery leads to others. The discovery of Hox genes had huge ramifications for the organizer because Hox genes offer a way for the organizer to give instructions to specific cells.
Another researcher, Richard Harland at Berkeley, found a gene called “Noggin” that works like an Organizer gene, telling the embryo where to make a head. Many genes like Noggin interact to form the entire body of an animal. A gene called BMP-4 tells cells to make the bottom or belly side of an animal. It was found to be present in all cells that don’t have Noggin active. It seems that Noggin actually blocks BMP-4, simply telling the cells where Noggin is active not to be bottom cells and defaulting them into top cells.
At first, scientists thought that Noggin switched on in cells to form a head for the animal. Further research proved that the truth was more complicated, as Noggin actually turns off the gene that makes cells the bottom of an animal. Here is one place where Shubin must recognize the complexity of animal body formation instead of explaining a concept through the simplest means. Yet the fact that “top cell” is a default for all body cells before Noggin and BMP-4 do their work is another testament to the underlying similarity of all the cells that allow bodies to be so complex.
An Inner Sea Anemone. Moving away from the relatively easy comparison between humans, frogs, and fish, Shubin turns to jellyfish. Animals like jellyfish do not have a front/back axis, using one hole to both intake food and expel waste. Looking at sea anemones is a good way to reframe the lack of a head-to-anus line in these animals. Sea anemones have primitive versions of some of the genes that control the head-to-anus line in humans. Furthermore, anemones also have a “left” and “right” side that becomes distinctive once an anemone is cut open. The axis of the anemone is just hidden from plain view.
Shubin considers comparisons between humans frogs, and fish easy because these animals at least all have heads, spines, limbs or appendages, and body systems that act in similar ways (as in the nervous system). Jellyfish are more primitive creatures, meaning they developed earlier in the history of life before many complex body systems were possible or necessary. Sea anemones, however, show that animals that seem as simple as jellyfish might actually be complex – and therefore more similar to humans, frogs, and fish – in ways that are difficult to see at first.
Sea anemones have a version of the Noggin gene that created the bottom of frogs. Scientists injected sea anemone Noggin into a frog and found that the anemone Noggin was able to perform the same function in the frog. It seems that all animals with bodies draw from the same basic recipe, like a recipe for a cake that has been tweaked as it has been passed down generations.
It’s significant that scientists took DNA from the less complex animal (the anemone) and introduced it to the more complex animal (the frog), as Shubin’s account theorizes that the frog DNA actually came from thousands of mutations to the anemone DNA. A frog using anemone DNA is just using a primitive version of its own DNA, based on the developmental history of life on Earth.