Part I
Brushing Up on Biology
In this part . . .
Stem cell research has a long history, but it has come under intense public scrutiny only in the past decade or so. Research involving human embryonic stem cells is at the root of most of the controversy surrounding stem cell science. (Research on fetal tissue and fetal stem cells also is controversial in some circles.) In this part, we provide an overview of stem cell research, as well as a primer on cells and tissues and how they work in the human body.
We also explore the history of stem cell science, revealing what the ancients knew about regenerating body parts in humans and other animals and what scientists have discovered about how cells operate in living organisms. We show you how understanding DNA and other cellular mechanisms have helped researchers combat diseases like leukemia and how todayâs scientists are building on that body of knowledge to tackle other health issues.
Chapter 1
Painting the Broad Strokes of Stem Cell Science
In This Chapter
Exploring the foundations for stem cell science
Understanding what researchers know now
Looking at what scientists still need to discover
Some stem cells researchers shake their heads in bemusement at the sudden public interest in their field. Thirty years ago, no one outside the scientific community had ever heard of stem cells. Today, stem cell scientists are sort of like the overnight singing sensations who have been performing at local nightclubs for years and suddenly has a No. 1 hit on the national charts. The general public has no idea how much work that singer put in before she was âdiscovered.â Similarly, many people arenât aware of how much stem cell researchers have discovered about normal biological development and disease, or how those years of research have led them to the experiments and discoveries that are touted in the headlines today.
Finally, many people are unaware of how far stem cell research still has to go. Although scientists know a lot about human development, the workings of various genes, and the behavior of certain diseases, a lot of questions remain unanswered. And these arenât esoteric questions, either; theyâre questions like why some cells in the bodyâs tissues never become specific cell types, what signals or mechanisms direct those cells to become active, and how cells malfunction in disease.
In this chapter, we provide a brief overview of what stem cell scientists have been doing all these years before their work generated such widespread interest. We explain why scientists do so much work with mice, fruit flies, and other animals, and how they translate their findings in animal studies into predictions (and subsequent testing to confirm those predictions) about what happens in humans. We also inventory the things that researchers think they know about various kinds of stem cells, as well as the things theyâre still trying to figure out.
Working with Animals and Other Organisms
Humans are a lot like yeast. No, this isnât the start of one of those joke e-mails your coworkers send you on a quiet Friday afternoon; itâs a biological fact. Humans also are a lot like fruit flies, mice, and other animals and organisms that have eukaryotic (pronounce you-CARE-ee-ah-tic) cells â cells that have a distinct nucleus encased in a membrane. (Prokaryotic cells, such as those in bacteria, donât have a compartmentalized nucleus, but rather a less-defined nucleoid region that contains their DNA.) Amazing as it sounds, at the cellular level, many of the pathways and functions of eukaryotic cells are the same no matter what organism the cells are in.
Scientists have shown that some of the genes in yeast will function in human cells, and vice versa. This interchangeability of genes among different organisms is called conservation; that is, nature uses many of the same blueprints and mechanisms, at least at the cellular level, for a wide range of living creatures. In fact, different organisms are so similar at the cellular level that many of the genes that cause certain kinds of cancer were first discovered and studied in yeasts and fruit flies. When it comes to fruit flies and worms, not only are the pathways inside cells very similar to those in humans, some of the pathways for communicating between cells or for instructing a cell to specialize are similar. For example, scientists know what genes are turned on in order to make a human neuron and wire it so that it communicates properly with other cells and tissues in part because theyâve studied these genetic mechanisms in fruit flies and worms.
Just because fruit flies donât look like humans â or just because fruit flies are insects and humans are mammals â doesnât mean they donât share some characteristics. From a scientific perspective, fruit flies, mice, and humans are like different motorized vehicles. Fruit flies are motorcycles; mice are compact cars; and humans are luxury sedans. The details of how you put each of these vehicles together differ greatly, but many of the basic mechanisms are the same, and a lot of the parts are the same (although they may not be the same size). And, in some cases, some of the parts are even interchangeable, as in the case of yeast and human genes. Obviously, you canât take the throttle from a motorcycle and install it in a luxury sedan. But when the throttle on the motorcycle breaks, sometimes it can tell you a lot about how the Cadillacâs acceleration mechanism might break. The same principle is what leads scientists to spend so much of their time working with yeasts, worms, fruit flies, and mice. These approaches are important because, in many cases, experimenting on human beings is unethical; the risks are too great.
Understanding the mouseâs role in stem cell research
The mouse has arguably been the most important animal in stem cell research. In the early 1960s, Canadian researchers James Till and Ernest McCulloch were the first to prove that bone marrow contained stem cells. They exposed mice to high doses of radiation to kill the mouseâs blood- and immune-forming system and then injected bone marrow cells into some of those mice. The mice that didnât receive new bone marrow cells died; the mice that received the transplants lived because the new bone marrow cells rebuilt their blood- and immune-forming systems.
Till and McCulloch also noted that the mice that received transplants developed small but visible nodules, or lumps, on their spleens, and that the sizes of the nodules were directly proportional to the number of bone marrow cells the mouse received in the transplant. The scientists theorized that these so-called spleen colonies originated with a single cell from the bone marrow transplant â perhaps a stem cell. They later proved that theory and, as their work continued, also proved that some cells in bone marrow are capable of reproducing themselves as well as generating specific cell types.
Till and McCullochâs work on mice is the basis for human bone marrow transplants, which are routinely used today to treat leukemia and some other kinds of blood disorders (see Chapter 13). Embryonic stem cells also were first isolated from mice. In the early 1980s, researchers learned how to extract the inner cells from mouse blastocysts â a hollow ball of cells that forms a few days after an egg cell is fertilized â and grow them in Petri dishes or other containers. When these cells are grown properly (a process called culturing), they reproduce themselves â or self-renew; they donât adopt the characteristics of specialized cells until theyâre exposed to the appropriate biochemical signals. That work formed the foundation for isolating human embryonic stem cells in 1998, which in turn led to the âovernight sensationâ phenomenon the field is experiencing today. (See Chapter 4 for more on embryonic stem cells.)
Using mice in todayâs labs
The mouse is still a critical component of many stem cell laboratories. Researchers manipulate mouse genes to see how specific genetic changes affect normal development or the progression of a disease. They create mice with defective immune systems so that they can inject them with human tumors to study different forms of cancer (see Chapter 8). And researchers focusing o...
