Developmental Biology and Modern Medicine

An Essay By Hannah D. // 6/1/2017

When life begins, it starts as a zygote – a single cell with genetic material from two parents. The first job of that cell is to divide. Then those cells divide, and those cells divide, and on and on. As they divide, they get smaller and smaller, and the embryo remains the same size as the original zygote.

At this point, the embryo looks like a tiny blackberry – a little sphere composed of lots of littler spheres. We call this bundle of cells a morula. From here, some big changes are about to take place. The cells start migrating into a new type of structure called a blastocyst. When the blastocyst has fully formed, the cells are now arranged in a hollow sphere, and one corner of this sphere has a nice little pile of cells called the Inner Cell Mass (ICM). This is what will eventually grow into the adult animal.

After the cells in the ICM have sufficiently divided, the cells will migrate again into what is a more recognizable fetus. By this time, the cells have started to differentiate. That means that the cells, which up until now have been pretty much identical to each other, will begin to take on new forms and shapes. What will become the skin cells need to organize around the outer part of the fetus, the soon-to-be stomach cells needs to come near the center, and future heart cells needs to settle just off-center, closer to the top and slightly towards the left.

How do these cells know where to go? Well, the embryo is awash in an array of chemicals. Some of these are chemicals like Retinoic Acid. Others are proteins transcribed from the genome. DNA contains genes that are translated into proteins. DNA has the instructions; proteins carry out the task. HOX genes are especially important for embryonic development. The proteins from HOX genes also surround the embryo to help organize cell differentiation.

Each of these exists in a different type of gradient – some concentrate towards the head, and get rarer and rarer as you move down towards the bottom; other gradients orient left from right; still others form a gradient from the stomach to the back. The cells in the embryo sense how much of each chemical surrounds it. In doing so, the cell “knows” where it is - up or down, left or right, front or back - so it knows whether it should differentiate into a skin, heart, or stomach (smooth muscle) cell.

This process, one can imagine, requires a very delicate balance of concentration of each of these chemicals and proteins. If a mom takes Retinoic Acid while she’s pregnant, the delicate balance of Retinoic Acid already inside the embryo will be completely thrown off balance. The embryo will then develop with some tragic deformities. When a substance causes deformities, other problems, or death in an embryo, we call it a teratogen. Teratogens are dangerous for embryos, so moms must avoid them at all cost. Retinoic Acid is a serious teratogen, as is alcohol. For frogs and fish laying their eggs in freshwater streams, steroids and hormones from sewage runoff can infect the embryos and act as a teratogen as well. These all act in different ways on the embryo, and their effects can vary based on exposure, but the important thing to remember is that they are very dangerous to the embryo.

Once all the cells have found their place and differentiated into heart, skin, nerve, bone, etc. cells, the last major step is simply growth! The animal grows until it is ready to hatch or be born. Development very often continues into adulthood, and even afterwards – aging is technically a part of development – but the embryonic part is over. A baby has been born.

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Developmental Biologists have become increasingly relevant in the study of medicine. In particular, they have been consulted as scientists try to find cures for cancer or tumors. Why is that the case?

Let’s consider what cancer is, for a moment. Cancerous cells are cells that won’t stop dividing. In normal cells, there is a genetic “switch” that tell the cell if it needs to stop duplicating itself. In cancer cells, this switch has been turned off. Tumors are basically the same thing. These cells divide, divide, and keep on dividing. Then suddenly, they spread.

If you think about it, this process kind of mirrors what an embryo does, when it moves from a zygote, to a morula, to a blastocyst, to a fetus. The zygote’s cell replicates, the morula reorganizes into a blastocyst with an ICM inside, and that ICM starts migrating and moving around to form the fetus. In a similar way, a cancerous cell starts dividing, forms a lump called a tumor, and – if this isn’t caught on time – the cancerous cells will start to spread.

If that is the case, then what if you exposed these cancer cells to a teratogen? The tumor is basically acting like the ICM. If teratogens harm ICM's, couldn't they harm tumors too? This has gotten Developmental Biologists curious, so they are researching the effects of stuff like Retinoic Acid on tumor cells. More needs to be researched on the topic, but so far, results have looked promising.

Now let’s consider another medical application of Developmental Biology: the use of Embryonic Stem Cells. Embryonic stem cells are taken from the ICM of an embryo. Now, in a natural setting, the ICM can differentiate into every single cell that that organism needs. By understanding how that differentiation process works, scientists can manipulate the stem cells to differentiate into whatever cells they want. This has become a sort of gold-standard-ideal for some medical treatments – what if we could grow tissues for a new kidney, instead of requiring a specially matched donor? Perhaps a new eye? A new heart? Replenish skin cells on a burn victim? This can all be done, theoretically, with embryonic stem cells.

What a fascinating area of research! However, one word needs to be underlined, boldened, capitalized, and otherwise emphasized above all else: the word THEORETICALLY . Scientists have been trying to use embryonic stem cells for a while now, and they are not getting promising results. The reason?

Even after being differentiated and transplanted into a patient, the stem cells are behaving like tumors. The risk of cancer goes up dramatically in studies where embryonic stem cells have been used. This is a risk most doctors (and patients!) are not willing to take. The ICM can transform into a beautiful baby sea urchin or tadpole or person, but when taken out of context, it has the potential to turn to the dark side. This is one major risk of medical treatments with embryonic stem cells.

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Our final exploration here of the field of developmental biology will be a glimpse into an experiment done on pregnant mice.

It is well known that when an animal – specifically, a mammal – becomes pregnant, Mom shares a lot with her baby. She feeds and nourishes it, and some of the embryo’s stem cells enter into her blood. What kind of effect does this have on her?

Developmental Biologists wanted to find out, so they inflicted wounds onto the hearts of pregnant mice. The scientists tracked the movement of embryonic stem cells in the moms’ bloodstreams, and they kept tabs on their hearts as well. What they found was downright remarkable.

Not only had the embryonic stem cells concentrated to the region around her heart, but they had actually begun to repair the hearts. The mouse moms were nearly healed by the time of their babies’ births.

This aspect of a mammal’s pregnancy is thought to help support the mother and prepare her for labor. However, the embryonic stem cells remain in Mom’s system long after her kids have been born. In human women, embryonic stem cells have been detected decades after her last pregnancy. In all likelihood, those embryonic stem cells are doing the same thing the stem cells did for those mice - finding tissue that needs to be repaired and healing them. If that is, indeed, the case, then moms have health benefits that no one else in society has access to.

Perhaps the most remarkable fact about all this is that studies have never shown any correlation between pregnancy and increased cancer risk. Now, money and research has been poured into the possibility of using embryonic stem cells for medical treatment (and tiny human lives have been destroyed in the process). Despite all this, they have not been able to separate the use of embryonic stem cells from increased occurrences of cancer in patients.

Mammalian moms, however, gain this health benefit naturally from their babies, without increased risk of cancer, and for decades to come. Modern medicine is incapable of carrying out what their bodies can accomplish.

Sources:

Gilbert, S. F. (2014). Developmental Biology. Sunderland, MA: Sinauer Associates, Inc.