Well, no. Even if you could recite what each part does, you probably still have a poor understanding of how the parts work together to make a vehicle go. Let's take a more extreme scenario: you are teaching a class full of aspiring automobile engineers, and you want to teach them how to design cars. Would you teach them by just going through all the car parts one by one? Maybe you could even bring it all together at the end of the class and show them some diagrams of the parts put together: the chassis, the electrical system, the drive train. But even with the diagrams, these would-be engineers still won't be able to show up for work at Mercedes and design the next state-of-the-art engine. Parts lists and diagrams aren't enough; as any engineer can tell you, you need to get quantitative, you need to understand math and physics, and you need to be able to build model engines on computers, models which you can then test in silico without actually trying to physically build every new idea for an engine.
In many ways, molecular biologists are like that class of auto engineers. We have some very long and well-annotated lists of cell parts, and we have a lot of crude diagrams of how those parts fit together, but we don't understand a cell in the same way that an Audi engineer understands a car engine. Biologists are trying to change that, and their efforts are part of hot new field that most people have never heard of, known as systems biology. Although systems biology has yet to prove its has staying power, Harvard Medical School has such confidence in the field's potential that it has established a Department of Systems Biology, the first completely new department in over 20 years, and the publishers of Nature have created a systems biology journal.
So how is this field doing? I recently had a chance to hear the latest from some of the leaders in the field at the historic Cold Spring Harbor Laboratory. I heard some good science there, but unfortunately we're still far from understanding cells in the way engineers understand cars.
The Cold Spring Harbor Laboratory is the Graceland of molecular biology. Many of the 20th Century's greatest molecular biologists visited the Long Island lab to work or attend meetings, and the walls of the lab's buildings are hung with historical molecular biology photos paraphernalia, including a guitar signed by dozens of leading genome biologists and an enormous (and, to be honest, somewhat creepy) portrait of James Watson. (After his famous work on the structure of DNA with Francis Crick, Watson's biggest legacy is his decades-long leadership of the Cold Spring Harbor lab. He's retired now, but he still lives at the lab.)
On a recent chilly New York spring weekend, about 300 scientists interested in systems biology converged on Cold Spring Harbor to talk shop. To get an idea of what kinds of problems this scientific community is facing, let's take a look at one of the most well-understood cells: brewer's yeast. Yeast has about 6000 genes, and we have some idea of what 75% of those genes do - you can pick your favorite yeast gene, go to a database, and read about what that gene does in a yeast cell. Within a few years, we'll know what 99.9% of yeast genes do. But will we then truly understand even a simple organism like yeast? Yeast cells reproduce in a process very similar to the way human cells divide, and as a result, we have learned a lot of basic biology relevant to human diseases like cancer by studying yeast. A model of yeast cell division on par with an auto engineer's computer model of an engine could shed light on how important control systems go awry in diseases like cancer, but right now all we have are long lists of parts and some basic diagrams - not enough for any kind of engineering.
This problem crops up again in genome-wide association studies, which produce lists of genes that might be involved in diseases like diabetes, Crohn's disease, and heart disease. Do we understand these diseases better once we have such lists? Not really, because we don't know how the parts fit together in health or disease.
What are systems biologists doing about this? In truth, they are also producing long lists of genes involved in a given biological process, but many research groups are looking at how the parts list changes with time: what genes are switched on or off as a stem cell differentiates into a nerve cell? Which genes are active in which cells as an embryo develops from a single cell? Which embryonic cells give rise to the cells of muscles and nerves? Here are some highlights of what kind of science is going on right now in systems biology, at least as it was represented at Cold Spring Harbor:
Tracing which embryonic cells give rise to which mature cells is one focus of Dr. Robert Waterston's research at the University of Washington:
Waterston has developed an incredible imaging technique which tracks individual cells in a worm embryo, following an original stem cell through all of its divisions as different parts of the worm develop (click the picture to watch a movie on Waterston's site - the movie ends when the worm can start to move around):
Dr. Jeanne Loring, at the Scripps Institute, is looking at the changes that take place within single embryonic stem cells as they differentiate into other cell types. She is making good use of the human embryonic stem cell research money in California to look at DNA markings (called DNA methylation) in stem cells as they change. Understanding how those markings change over time is a key part of understanding how all of our various types of cells can have the same DNA but behave so differently.
And at Harvard, Dr. Sunney Xie is using sophisticated microscopy to study how the individual parts of biological systems behave physically inside live cells. He can look at single protein molecules inside of single cells, and measure how fast a regulatory protein slides along a strand of DNA, how quickly a cell can produce a protein in response to an environmental signal, and how many protein molecules it takes to start a positive feedback loop. (Dr. Xie has a movie as well.)
Systems biology is still an immature field, struggling to clearly define the most pressing scientific questions and to identify the most promising avenues of research. At the Cold Spring Harbor meeting, it was evident that while some people were doing tremendously fascinating research, we're still far from being able to build a computer model of the cell, or even a small cellular subsystem, with which we could simulate changes caused by a drug or a mutation. A Mercedes engineer with new idea for an engine improvement can test it on a model first; but a pharmaceutical company with a new potential drug cannot do the same, it cannot predict in any detail how a cell will respond to that drug. We may be far from that goal, but systems biology is a field worth keeping an eye on.
