Using Broader Knowledge in Different Ways

Interview with IdeaConnection Problem Solver Chris Cullis Chris Cullis is the Frances Hobart Herrick Professor of Biology and Chairman, Department of Biology at Case Western Reserve University. An eminent and widely published scientist, his main work focuses on the regulation of the variation of the plant genome in relation to the interaction between the genome and stress environments.

Here he talks about his work with IdeaConnection and as a scientist working on ideas that go against mainstream thought about genetics.

What attracted you to your field?

That's a long, long time ago but I was finishing up doing a PhD and looking to do a postdoc and the problem that I'm working on, and have been for almost forty years, sort of arose at that point. So it sounded like an interesting thing that'd keep me occupied. I think my wife laughs because I said, "Ah, it should keep me busy for about three years" and some forty plus years later I'm still working on it.

I always wanted to work with DNA and I kind of went a slightly circuitous route. My first degree was a double major in math and physics. Then I did a Master's in biophysics and a PhD in genetics when I was trying to work a bit on DNA when it was still a trendy thing to do. Then I got this postdoc to work on this problem and I then worked in a research institute with that for about fourteen years and then I came here twenty-six years ago.

And you're looking at DNA changes or rapid DNA changes in response to what happens in the external environment?

So flax is the example we use and if you grow it under different growth conditions with different nutrients you actually get DNA changing while the plant is growing. And those changes can be transmitted to the next generation. Not all of the varieties do that so I'm trying to understand what controls it and what is the mechanism by which that occurs.

With the aim of understanding better how plants may respond under stress situations or to modify plants for a particular end?

So there are a couple of different possibilities. One is if you understand the process – my assumption is that the plant does this so that it actually winds up generating something that's better adapted to the environment. It doesn't know just what it wants to do, but there's a whole range of things that change and there's been a selection of which pieces work better in that environment.

Theoretically if we could understand that, we could either see whether other plants have it or introduce it so that you could breed for stress tolerance with the plant making the changes rather than you trying to understand what changes you might have to make in order for it work better.

The other part has nothing to do with plants but because not all plants respond like this, one of the speculations that I have is that it's possible that the genes that control this are in fact the same genes that are the cancer susceptibility genes in humans for example. So why do some people get lung cancer when they get second-hand smoke and they hadn’t smoked and why do some not get it when they smoke three packs a day for forty years?

There's a difference in their responses to that and some of the DNA rearrangements that you see in particular cancers are relatively specific and that's the same kind of change you can see in some of these plants. So it's possible that there is a link in that sense, that those environmental susceptibilities, in humans for example, may well be controlled by the same process.

At this point I’m trying to understand how the system works because it's still a reasonably controversial one even though there have been publications on it for more than half a century. There are still a lot of people who are very sceptical that this isn't real, or if it is real it's really just restricted to this particular plant because this is not supposed to happen.

Epigenetics is starting to breakdown some of those prejudices but it's not an acceptable way to say that the environment can really cause this kind of massive restructuring of genomes. It's not supposed to happen that way. So it really is trying to understand what is going on and why, and what is the control of it because it's a very different process.

How does it make you feel to be working on something that doesn’t follow a conventional line of thought?

Well it makes life interesting. It also makes life quite difficult because everything that you do gets scrutinized in a very different way. So manuscripts are much more difficult to publish, grants are much more difficult to get because you get really odd comments coming back that you can tell that the reviewer simply is sufficiently uncomfortable with the idea that they are clutching at straws. I think the closest universal comment is, "All the work you do is really good and there is nothing wrong with it but you understand it can't be right?"

Moving onto IdeaConnection, how did you get involved?

Well it seemed like it was an interesting idea. I mean I do think about lots of different things. So what I've been talking about now is a line of research that I have carried through for forty odd years but I've also worked on lots and lots of other things during that time. And this seemed to be a way that one could use some of that broader knowledge in different kinds of ways and maybe even broaden that knowledge.

You have a depth of knowledge and experience in your own field; did you find it difficult to join a group where perhaps you didn't know as much as other people?

That's fine. I mean I'm perfectly happy to listen. If I'm not a primary research resource there then I think I can offer a certain amount of help in formulating answers and making the final product a reasonably good product.

Do you think crowdsourcing, open innovation, whichever label you want to give it, has something to offer scientific research?

I think so. So it's not actually that different from a conference. Most of the time if you go to a meeting you hear some talks and you talk to people about what you're doing and what they're doing and those are often relatively focused conversations on a problem as it stands at the moment. They're very rarely the grand scheme of things. They're much more detailed questions. It's those conversations that allow you to identify a new approach you want to do.

I think explaining your reasoning out loud to somebody else is an incredibly good way of deciding whether there's a basic flaw there. When you talk out loud you certainly hear yourself and say, "I'm not saying that, am I?" whereas if you think it, it sounds perfectly reasonable. So I don't think it's really very different.

It's different in the sense that you've got a group of people who are tackling a very specific problem and asking about a solution but if you're in a lab that has a couple of graduate students, a couple of postdocs, then there are four or five or you who are doing that all the time, but only on the problem on which you're working, but that's what you're doing. So I don't think it is really very different.

I think the difference is that the challenges at IdeaConnection tend to have a group of people who probably wouldn't be working together in the sense that they have complementary rather than overlapping expertise. So you're now putting people talking together who think differently and also have a different primary dataset on which they're basing what they're talking about. So you have a much more widely read community in lots of ways at that point.