Science Fact: Stem cells have many stories to tell. Depending on the teller, you may hear:
– a tale of politics interfering with life-saving medical research;
– of babies saved because scientists were not allowed to use fetal tissue;
– of politicians co-opting tenets of religious faith for personal gain.
Today’s post frames the story differently: Researchers, supported by both saints and sinners, work within society’s constraints and yet create life-saving miracles. As a scientist I like this story better than a political or cynical one. But of course I have biases of my own…
To give a Goldilocks amount of detail (not too much, not too little) it seems best to break this post into two parts. Today’s Part 1 tells of the discovery of stem cells and the tremendous excitement over their potential for medical treatment. Thursday’s Part 2 describes how political restrictions, rather than stifling research, instead caused a burst of productive creative work.
The Background of Stem Cell Research
The fascination with stem cells comes from a fascination with life itself. Before recorded history, humans marveled that a bird’s egg, consisting of a very un-bird-like blob of yolk and albumin, could if left in the nest turn into a living being, which in turn would grow to an animal of the same type as its parents. The mysteries built into this simple observation were profound:
– how does the robin’s egg know to turn into a robin rather than a hawk?
– how do the parts of the robin get correctly assembled, so that the beak is on the head rather than at the end of a wing? And especially,
– how could an undifferentiated blob evolve into all the different structures that make up the total animal?
This third question, concerning differentiation, led directly to the concept of stem cells.
The optical microscope was probably invented in the late 1500s. Robert Hooke used it for up-close study of many materials and organisms. In 1665 he reported that cork and other plants were made up of millions of very similar chambers that he named “cells” by analogy to the small identical living spaces used by monks.
Stem Cells Get a Name
Other scientists started looking at blood, skin and tissue and found cells everywhere they looked. By the late 19th century it was believed that some cells could differentiate into many different types of cells. In 1908 the biologist Aleksandr Maksimow named these flexible precursor cells “stem cells.” The term “stem” was used in the sense “originate from” just as a plant originates from its main stem.
Stem cells weren’t too interesting at first, since if they existed they were thought to be simply a fleeting stage in the life of the cell; they always turned into something else that was the true purpose of the cell’s development. However, in the 1960s important discoveries were made by Canadian doctors Ernest McCulloch and James Till, work that earned them the prestigious 2005 Albert Lasker Basic Medical Research Award.
Stem Cells Can Reproduce and Thrive
McCulloch and Till were studying bone marrow transplantation as a means of treating bone marrow cancer. Basically, you used radiation to kill the cancer cells, but the radiation also killed the bone marrow cells that were essential to replace worn-out blood cells. So the patient (in their work, a mouse) was saved by a transplant of bone marrow from a healthy subject. Through a series of detailed experiments, they were able to show the existence of stem cells that could reproduce and maintain themselves as a continuing colony, but that could also differentiate to produce red cells, white cells and platelets for blood. Moreover, they showed that stem cells would thrive and reproduce only in just the right tissue environment.
The research community was astounded. Now you could visualize maintaining a colony of stem cells with the magical ability to become any kind of cell. Here was the possibility to replace diseased body parts with healthy ones, grown by persuading the stem cells to differentiate in just the right manner. Not just blood cells, or tendons, but perhaps nerves and even organs could be grown and implanted as needed.
Challenges in Applying Stem Cells
Of course, nothing is easy. Or better stated, all the easy stuff was done a long time ago, so the problems that remain are always very difficult.
For example, some stem cells form tumors when they are implanted. After all, cancer arises from cells that start dividing when they shouldn’t, and the ability of stem cells to reproduce and to change is closely allied to processes that occur in cancer.
In addition, not all stem cells are completely flexible. There’s a wide range of types of stem cells ranging from totipotent cells, which can produce any kind of cell in the human body, all the way down to stem cells that can produce only one or a very few types of cells. It’s tricky to maintain a culture of stem cells since stem cells have a tendency to turn into something else unless they are kept in exactly the right environment, including temperature, atmosphere, growth medium, geometry and biochemical signaling molecules.
Finally, the signals that coax a few fetal cells to form body parts are complicated and not well understood. Therefore, if you want to grow a replacement trachea or, more ambitiously, a heart the most efficient approach is to develop a framework or “tissue scaffold” to guide the stem cells into forming the right structure. As described in an earlier blog, some projects are assembling groups of organs for testing new drug therapies.
On Thursday we’ll continue with Part 2 of this post, discovering how political restrictions on stem cell research served to stimulate a great deal of creative and valuable work.
Stem cells found their first clinical application in bone marrow transplants. Do you know anyone who’s had that procedure?
Drawing Credit: tbi39, on openclipart.org