What We Don't Know About Genes
(Notes from a talk given at University of Rhode Island, April 26, 2001)

by Tom Sgouros, Jr.

April 30, 2001

So you take this little gray tree frog, and take its eggs and hatch them in a fishbowl. They turn into these little long, graceful tadpoles. But if the pond contains dragonfly larvae, which eat little long graceful tadpoles, the tadpoles get short and stout with muscular tails so they can turn faster.

Apparently the dragonfly larvae leak some chemical into the water that is detected by the tadpoles, and it triggers some change in their development.

Well, this is a case where a gene needs a trigger to be expressed, and that's not really so unusual. But the offspring of these frogs grow into little stout muscular tadpoles, even if there are no dragonfly larvae in their pond.

So where is the gene for the tadpole shape? It's in the DNA, but it requires this trigger from out there, and yet it seems to be kind of independent of the trigger, too.

I want to talk about genes. You all have learned a lot about genes, and I understand some of you already knew a lot about them, too.

What is a gene? Years ago, we would have shrugged and defined it by its effect rather than its composition. That is, we have a gene for blue eyes and a gene for brown hair and so on. But since then, we've learned about chromosomes, and then DNA, and then we've sequenced the DNA, and now we know that...

People have tried to define a gene as a little stretch of DNA that codes for a protein. DNA makes RNA makes proteins. We all know that. But RNA gets edited and proteins get combined. DNA contains "exons" and "introns" which we also call "junk" mostly because we don't know what it does. DNA makes RNA, but then the introns have to get removed -- by "spliceosomes" -- before you can make the protein. Proteins do this editing, but no one really understands how or why. Where do they get their directions? Strands of RNA get combined with other strands, and the proteins they make get combined with other proteins, and the result is that you have lots of proteins that are encoded nowhere in the DNA.

Now it may be that all the proteins you need to do this are themselves coded in the DNA, but this is not a known fact, that is, we haven't found them, and we don't know what they are or where they come from. This is speculation, based on the conviction that DNA describes how to make an organism. What if a certain spliceosome is made from DNA that must be edited by that same spliceosome? Nature is full of circularities. Chickens have eggs, for example.

Which is to say that it isn't really clear what a gene is, and after 100 years of studying them, we're back to the shrugging and the functional definition: we have a gene for blue eyes and a gene for brown hair.

You read a lot about how DNA is a blueprint. Well, fine. Let's talk about blueprints. If I'm an architect working with a builder I've never met, I need to put a lot of detailed instructions into the blueprint to answer the questions I'm sure will come up; I need to draw the bathroom doorknobs and the porch rails. But if I'm working with someone I've worked with before, making houses like ones we've made before, I don't need to do that. I can trust my friend the builder to do it right, so my blueprints can be a lot sketchier.

It's said that DNA contains information. We can dispute this -- and there are some pretty good reasons to wonder -- but it's more fun to agree with it, but then also look at all the other possible sources of information that go into building an animal. An egg contains information in its structure and its chemistry. That is, you could make it with a recipe, and that recipe is as much information as any pattern of nucleotide bases.

Ok, so genes are the ones that contain heritable information. But that's not right, either. All kinds of "epigenetic" information is heritable. Nerve cells beget nerve cells, for instance.

So genes are a fuzzy concept and mouse DNA doesn't contain all the information you need to make a mouse. But what's the harm done by assuming otherwise?

To explain that, we need to look at drawing lines. There's a big heavy line people draw between genes and the environment. The things on this side of the line are immutable and the things on the other side are dependent. Political battles rage, and public policy is made, depending on which side of the line you think things like intelligence fall. And it works the other way, too. We release genetically modified plants and animals into the world because we imagine a line between genes and the environment.

The problem is that once you've seen enough of the science, it's impossible to find a place to draw that line. Our frogs, for example, might be inclined to consider their pond both environment and part of their genome.

And you know, frogs are not the only species to have "predator-induced polyphenism". We do too. We have an immune system that takes its cues from the antigens that infect us. And we get some antibodies from our mother, that come to us unmediated by DNA. And our immune system is not so isolated from our nervous system. You can induce immune responses in mice by ringing a bell if they've been trained to associate the bell with an allergen. I can make my eyes water by thinking about cats and big soft couches covered with cat hair.

I've asked more questions than I can answer. More questions than anyone can answer, and in a way that's the point. There's not enough humility in science. Not enough acknowledgement that we really don't know what's going on inside a developing cell. When we modify a plant genome, or clone a sheep, we're just blundering around in the dark. So far, we haven't bumped into anything dangerous -- yet. Maybe.