We know there's some genetic determinants ... that are involved. When people have gone to look for those genetic determinants, the hunt has come up quite not so clear. ... The summary is, basically, that thus far we have not found, as I said, I don't like the word or the phrase, we have not found a "gay gene," and it's unlikely that we'll find one. ... Like many phenomena in human identity, there will be multiple genetic determinants interacting with environments, but it's very important to be clear about these ideas, because otherwise we fall into language that's all incorrect and wrong, and then you just foster nonsensical controversy.
On understanding how some diseases are more genetic than we originally thought
There's a spectrum, so I'll start with one end of the spectrum and work my way to the other end. So let's start with cystic fibrosis or Huntington's disease, where we know that the influence of genetics is extremely strong, almost autonomous. This means that if you inherit the abnormal version, or the mutated version, for one of these two diseases, the chances that you will have that disease are very high. In genetics we use a word for this called "penetrance," these diseases are highly penetrant.
In the middle somewhere are diseases like diabetes orheart disease. Here there's still a powerful influence of genes. In fact, we know some of these genes, but it's an interaction between multiple genes and the environment.
Then, on the far end of the spectrum there are things that one might imagine, things like infectious disease where ... there's clearly an influence of genes. We now know that if you have certain genetic combinations or if you inherent certain genes, your susceptibility to HIV, for instance, might change, or your susceptibility to influenza might change, even though these are infectious pathogens. But these lie in sort of a different area, where the interaction between you and the pathogen, or you and the environment is much, much more acute.
On how genetics is changing how we think about and treat cancer
There's a substantial degree of reorganization in the way we fundamentally think about cancer that's going on right now, some of it related or a large part of it related through genetics. If you look at the mutations in individual cancers, you might find actually that a lung cancer carries a mutation that it shares with, let's say, breast cancer, or it shares a mutation that it shares with leukemia.
The question that's being asked right now in the field, which is an important question, is ... should we reorganize this old anatomical classification of cancer, you know, lung cancer, breast cancer, and base it a little bit [more] on a kind of mixed classification? Yeah, you say "breast cancer, which has these following mutations."
My overall impression is that the anatomical classification isn't going to go away. I think there are very important things that the anatomy determines — there are genes that are particular to breast cancer, there are genes that are particular to lung cancer. But it's going to be vastly refined, and we're seeing this already with genetics. So we're going to say, "lung cancer, but with genetics or genes that share some things with leukemia." We might, in fact, treat these two cancers similarly.
On targeting pathways of cancer
The simple analogy that I like to make is, we now know from cancer that even when a single gene is mutated, it rarely causes cancer. There's some instances, but it rarely causes cancer. You need multiple mutated genes in a single cell for it to become cancerous, and these mutated genes make products, proteins, and they co-opt the normalcy of a cell, and they kind of create a kind of whisper campaign, in which they co-opt the behavior of the cell, and now the cell begins to behave abnormally, divide abnormally, metabolize abnormally, ultimately leading to cancer.
The idea of a pathway is that if you think of these individual mutations by themselves, you can think that there's infinite numbers of combinations, in infinite different ways. One person has one combination, another person has another, but the point here is that what I've called a "whisper campaign," the internal network of these is often quite common between diverse individuals. And so rather than focusing on individual mutations, which can be very diverse and can cause us to get confused, we can focus on ... the core things, core networks, as it were, that are leading the abnormal behavior of a cancer cell, and target that using a drug.
On the new technology that allows doctors to make changes to cells
Making genetic changes in cells used to be very complicated. We used to be able to use viruses and deliver some genes into the cells. We used to be able to make mutations by exposing cells to, for instance, X-rays. But if you were to ask me 10 years ago, "Can you change this one particular gene in a cell?" I would say, "I could do it, but it's pretty hard to do."
What's happened in the last five years [is] ... this technology has allowed us in an astonishing way, to go into a normal cell or a cancer cell, even potentially an embryonic stem cell, and essentially directionally or intentionally make a mutation in a single gene, in an intentional manner.
I've likened this technology to saying, you know it's like saying if you imagine the human genome as a vast encyclopedia ... what this technology allows us to do, essentially, is to go into that 66 entire sets of the Encyclopaedia Britannica and identify one word in that and change that word and leave most of the rest of the encyclopedia untouched. I'm saying "most of the rest," because there are still some collateral effects ...
But what it allows you to do is you can erase one word and replace it with a slightly different word. That's how powerful the technology is, and so therefore you could now ask me, which you couldn't ask me five years ago, "Is it easy to make a directional or intentional change in a cell?" The answer I would say, "infinitely easier today."
On the ethical considerations related to working with the human genome
The biggest ethical questions are should we be tampering with the human genome when we don't know very much about it still? Should we be changing human genes? And that leads to the question of what is disease? What is a genetic disease?
In Gene, I offer up a simple formulation that we might be able to think about ... one question you might think about is, "We're going to change some genetic material, are we sure that the benefits outweigh the risk? Is there truly extraordinary suffering associated with that disease?" ...