For the 12 Days of “The STEM Chicksmas” we’re highlighting 12 scientists who have contributed something innovative and exciting to their field. It is the season of giving, and these brilliant minds have given incredible gifts to the scientific community! This year we’re looking at 12 Nobel Prize winners from the past 15 years in the fields of Physics, Chemistry, and Physiology or Medicine.
Day Four: The 2012 Nobel Prize in Medicine or Physiology.
Can time run backwards? Maybe not, but cell development can, at least according to the 2012 Nobel Laureates in Medicine or Physiology, Sir John B. Gurdon and Shinya Yamanaka. There are three main types of cells in mammals: germ cells (related to reproduction), somatic cells (the flesh and bones of mammals), and stem cells. Stem cells are cells that are not differentiated but are capable of dividing by mitosis. When a cell is differentiated, it makes a new, more specialized cell type. Mitosis is the process by which a cell splits itself into two new identical cells. That means stem cells can not only make more of themselves, they can also differentiate into other types of cells!
There are three types of stem cells: totipotent, pluripotent, and multipotent. An important totipotent cell is the zygote, which is the result of a sperm fertilizing an egg. Totipotent cells can become any type of cell, including those in the amniotic sac and placenta. They differentiate into pluripotent cells, which can become any type of cell except those in the amniotic sac and placenta. Essentially, pluripotent cells give rise to all the cells in an adult, whereas totipotent cells also give rise to those in fetal development. Pluripotent cells differentiate into multipotent cells, which can create cells in certain families. For instance, the hematopoietic stem cell eventually gives rise to blood cells. Pluripotent stem cells are mainly found in embryos. In adults, most stem cells are multipotent. These adult stem cells play important roles in areas such as repairing damaged tissue.
Pluripotent cells are important for research and medicine, because they can be used to make any other type of cell, outside of the amniotic sac and placenta. However, harvesting them from embryos has been historically controversial. But Gurdon and Yamanaka demonstrated that cell development is not a one way street, and they made it possible to get pluripotent cells from adult stem cells. Gurdon made the first “clone” in 1962. He destroyed the nucleus of a frog’s egg and replaced it with an intestinal cell from a tadpole. This cell, with all the genetic information stored in the nucleus, ended up giving rise to tadpoles! This demonstrates two things: one, it’s possible to take the genetic information of a creature and make a new creature of it (the new tadpole was genetically identical to the one the intestinal cell was taken from). The first mammalian clone was the sheep Dolly in the late 90s. Two, it demonstrates that development can run backwards. The intestinal cell he used was already differentiated, yet it still resulted in a whole tadpole. This means that certain conditions experienced by the modified egg cell caused the nucleus of a fully differentiated cell to dedifferentiate to a stem cell and from there differentiate into all other cell types!
Yamanaka was inspired by this work more than 40 years later. He wanted to find out which conditions cause gene expression to induce pluripotency. In Gurdon’s clone, the specialized cell must have made pluripotent cells, but this is only seen by the resulting tadpole. Yamanaka decided to pick apart the process from the inside. He identified the genes associated with pluripotency and injected them into fully differentiated fibroblast cells from mouse skin. Eventually, he narrowed it down to four specific genes responsible for dedifferentiation to pluripotency.
Yamanaka’s induced pluripotent cells were a breakthrough. Scientists all over the world started using his technique to make pluripotent cells in their own labs. There was no longer a need for difficult to obtain embryonic cells when pluripotent cells were now so easy to grow. And like Gurdon demonstrated, the genetic material in these cells could be controlled. Researchers studying diseases can take a cell sample from any patient and make pluripotent stem cells from that. The resulting cell has the patient’s genetic information. This is especially useful for studying hereditary diseases and for looking at genetic predisposition to disease. Research is also being done to look at using pluripotent cells for transplants. A person with diabetes, for example, could receive insulin producing cells instead of having to take insulin injections. Some research also suggests that if the induced pluripotent stem cells cultured from an individual’s own cells, they are not rejected by the body, doing away with the need for immunosuppressants! There is a lot of research still to be done, but it is a promising field for medicine and research.
To read more, check out the Nobel Prize site or the award winning work here (Gurdon) or here (Yamanaka).