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Gene research has made incredible leaps in the last decade. A physician/Pulitzer-prize winning author explains what our new knowledge means for our immediate medical future, given our struggles with genetic knowledge in the past.

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Dr. Siddhartha Mukherjee, Asst. Prof. of Medicine, Columbia Univ. and author, The Gene: An Intimate History.

For more information: http://authors.simonandschuster.com/Siddhartha-Mukherjee/49784674


16-28 Our New Genetic Knowledge

Nancy Benson: Some people believe our fates are predetermined. Not in a religious or cosmic sense, but a biological one. We’re stuck with the genes we’ve inherited, our destiny determined by our DNA. For example, they might say that if a woman inherits so-called breast cancer genes, she’s extremely likely to develop the disease. However, experts point out that her chances are not absolute.

Mukherjee: As we learn more about genetics, we are learning that genes are not the only thing that dictates our current state or our future state as humans. But a very important feature is we now know that it’s a combination of genes plus environments, plus interactions with genes or intersections between genes and then some chance.

Benson: That’s Pulitzer Prize winner Dr. Siddhartha Mukherjee, assistant professor of medicine at Columbia University and author of the book The Gene: An Intimate History. He says that the influence of genes on what happens to us runs in a spectrum, sometimes determined by how many genes are involved. For example, whether we’re male or female.

Mukherjee: That’s really dominated by one gene really. And you know, it’s an astonishing fact that we’ve learned over the decade that that is dominated by one gene. And yet of course if you think about what it means to have gender identity, it’s very clear it’s not dominated by one gene and there’s many, many variations. There’s a wide spectrum in between and I think that’s important to realize that it depends on what you’re talking about.  If you’re asking the question, you know, what is the chance that the color of your hair is determined by genetics, it’s strongly influenced by genetics. And we now know that we can even spot out or clarify or identify the genes that play a major role in that.

Benson: However, other traits have a more mixed genetic influence. Environment and culture count, too.

Mukherjee: The analogy that I like to use, and it’s a useful analogy, is that genes form like a canvas. And that if you change the shape or the structure of the canvas itself, obviously what comes out of the painting that comes out as it were will change. But it still remains the case that genes are a canvas in which many, many things can be painted including the environment and including chance.

Benson: So on one end of the spectrum, if you inherit the mutated form of the Tay-Sachs disease gene, you’ll very likely have that disease no matter what your environment is. On the other end? The way we respond when we’re attacked by a flu virus or many other infectious diseases. Mukherjee says our genes still play a role, but a smaller one.

Mukherjee: Here you are looking at an interaction not only between your genes but your genes in the microbe, whatever the microbe genes might be. And some examples of that might be tuberculosis or malaria. Our genes have a role in that disease. But it has to do also with the genes of the microbes and the interaction in between those two.

Benson: However, most chronic human diseases fall somewhere in the middle.

Mukherjee: Diabetes, hypertension, schizophrenia, these lie in the middle in which clearly genes play an important role. Mostly there’s not one gene but multiple genes. We really have to understand that idea. There’s no gene for most of these diseases, but the multiple genes interacting with each other. In multiple cases, of course the environment plays a role. A classic example is diabetes. We know that if you change one’s eating habits, the course of the disease gets changed and the mechanisms are fundamentally affected. So that gives you a sense of the wide spectrum.

Benson: Cancer susceptibility is similar. While environmental factors such as cigarette smoke can actually change genes, others have a strong family history of one or another type of cancer. Genetic tests can reveal whether a person has an increased risk, but in most cases, Mukherjee says it’s not worth it yet to test to see if you’re affected.

Mukherjee: Right now I would say that technologies or the genetic testing for cancers without family history are not that successful. If you do have a family history, I would advise you to speak with the genetic counselor or your doctor obviously, and then make a decision about whether this is worth genetically testing or not, because some of them we don’t know the gene’s force. We wouldn’t know exactly what we’re testing for. Certainly, if it’s breast cancer there’s a familial variant of breast cancer. In other words, if breast cancer happens to run in your family, if breast and ovarian cancer happens to run in your family, and the other such things, other such overlaps as well, breast ovarian cancer, pancreatic cancer, then it’s worthwhile again talking to a genetic counselor and potentially testing for BRCA1 or BRCA2.

Benson: However, for most diseases today, family history tells doctors as much as they can expect to find out. We’re still in the dark on the genes that create that family history of disease. But Mukherjee says that will change in our lifetimes. Researchers are now to the point that they can edit some genes and may someday be able to correct defective ones.

Mukherjee: These involve various mechanisms to change the structure of DNA, the code of the genome. I’ve likened this to saying, the human genome that builds you and me, has three billion letters. They come in the four alphabets, A, C, T and G. And you could imagine the human genome as an enormous encyclopedia. And if it were actually written as an encyclopedia, it would be 66 full sets of the Encyclopedia Britannica. So you could imagine walking into a room and finding every wall, one of these volumes of the Encyclopedia Britannica. But most importantly, in the last five or 10 years, scientists have begun to gather technologies that allow us to go into that code, that master code of instructions, pick out one volume of the encyclopedia, pick out one word in the encyclopedia, erase it and change it.

Benson: Scientists can do this in the test tube for a few genes now but it’s extremely new technology. And while gene editing could someday be an incredible way to eradicate genetic diseases, we don’t know the cost.

Mukherjee: We don’t know what its side effects are. But the capacity to change the human genome in this way is obviously of great significance because potentially it could change the way we’re exposed to breast cancer, say if you had BRCA1 mutation or BRCA2 mutation. All of this is being evaluated now, but my book is just a reminder, this is the precipice that we’re on and that we really should be careful about moving forward as we answer some of the fundamental questions of what all of this means.

Benson: First of all, Mukherjee suggests that we should figure out the ultimate purpose of the use of these technologies.

Mukharjee: Being a doctor, I think that the first kind of standard is that we should be really using this if at all to ameliorate extraordinary suffering and this should not be used casually, there’s no casual role for using or intervening on the human genome. The ultimate role is to eliminate extraordinary suffering. Number two, I think it’s important to realize that we should only do these kinds of invents or interventions when we understand to a large extent what the genes do. In other words, there should be a good correspondence between the gene and the disease. We’re not trying to, you know, intervene on things that affect disease 10 percent of the time. Or may have a large role of chance in them. And the third and probably most important piece of this is that all of this has to be done with freedom and with choice and with the big public conversation around it. So by freedom and choice, I mean that they cannot be a state mandate to change someone’s genome or to forcibly look at your child’s genome before you decide to do anything about it.

Benson: However, some have challenged the ethics of this kind of research. They worry that scientists have indeed gotten to the point where they can play god. But Mukherjee doesn’t believe it’s unethical to research how to edit the human genome, at least on cells in the lab. Beyond that, though, it gets murky.

Mukhargee: The main ethical boundary is if you have the possibility of doing this in a human embryo or even potentially in something that can become a human embryo in the future. So that’s where the barricades are the most stringent because we do not want to change the human gene pool in a way that might have unintended consequences or side effects that we have not understood yet. So it’s very strictly barricaded, but it’s really barricaded right now, particularly human embryo. I should emphasize and it’s important, that this barricade may not apply to all countries. So in China, for instance, there’ve been attempts to take nonviable human embryos, importantly nonviable in the long run, but nonetheless human embryos and the attempt was made to try and edit the genes of human embryos. And that’s unleashed a kind of spectre of worry across the world and the realization that we might be able to potentially intervene a human embryo in the way that we hadn’t been able to before.

Benson: Mukharjee says we’ve been down the dangerous road of genetic manipulation before. It was in Vogue in the early 1900’S when it was called eugenics… And Nazi Germany used it as an excuse for extermination of an entire race. Mukhargee says it’s a reminder that we can never be too cautious.

Our production director is Sean Waldron.

I’m Nancy Benson.



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