With which, the fidelity which we can change this human generation was surprising to me. Rose we conclude with cyber warfare and talk to alex gibney the filmmaker and david sanger the New York TimesNational Security correspondent about a new film from alex gibney called zero days. So many people refuse to talk to me about it and refuse to admit their role in the operation. And this is after the race was blown. We now know that the u. S. And frankly israel were responsible for this attack. I want to talk about the attack. I didnt have to know the code for the attack but nobody will engage on this issue. Its also relentlessly secret and no one will engage on the issue why its so secret. Rose a conversation about the future. First about the genetic revolution and then about cyber warfare possibilities when we continue. Rose funding for charlie rose has been provided by the following and by bloomberg, a provider of multimedia news and Information Services worldwide. Captioning sponsored by Rose Communications from our studios in new york city, this is charlie rose. Rose the mapping of human genome in 2003 created as many questions as it answered, how much of the Human Experience is determined by the environment. What happens when we learn to read and write our own Genetic Information. Is biology destiny. A new book seeks to answer these fundamental or life defining questions. It is called the gene an intimate history. Joining me now is the books author siddartha mukherjee. He is a physician, hes a scientist, hes a writer. In 2011, he won the Pulitzer Prize for his biography of cancer, the emperor of all maladies. Im pleased to have him back at this table. Welcome. Thank you so much. Rose what drove you to this. You are an enencologist by training. This came out of three strands if you will. The first strand is professional. Im an oncologist. Cancers a genetic disease and i was watching in the period of time since ive written emperor the word of cancer being redefined by genetics. We were sequencing cancer genomes in greater and deeper ways. I mean it was powerful. Number one. Number two, which is the idea that its also a very personal story. The book begins with my own history, my own familys history of mental illness. Schizophrenia and bipolar disorder affect more than one generation in high family. The question of, the defining question is what is it. What is that thing that crosses over generations. Why isnt everyone affected. Why are only some members affected. And then the third strand, which is probably very very topical is that during this period of time we had begun to invent technology that is said to read and right the human genome. And that was praising to me, the felicity with which the fidelity which we could do this, change Genetic Information was totally surprising to me. So this came together in the book. Rose did you decide you want to go into medicine. I knew distantly. I was interested in biology, cell biology. I was studying cells, i was interested in viruses. It was a time when were discovering new things about cancer. You know, this was the early 1990s. And then all of a sudden, it became clear and clearer to me that what i had to do was to be a physician, a physician scientist. Rose if youre making the choices again, would you make the same choices based on what you know now. Based on how you know the worlds exploded and changed and evolved. I would, yes, i would. I find myself in medicine is the profession remains so dynamic partly because its become so science driven. So much of it has become. I mean of course theres the humanist ic part of it. I write about it. But you know the capacity to understand the Genetic Information just to give you one example has really changed our practice of medicine and im enjoying it. I find it exhilarating and i think most doctor scientists are relating. Rose tell us about the definition of a gene and a definition of a genome. So, a gene, well first thing is interesting is the definition is changing. But the gene used to be a unit of information that moves from cell to cell or from parent to offspring that defines a particular series of traits, a feature. Now we know that, you know, one gene can define more than one feature. We also know that one feature can be defined by more than one gene. But it is really a unit of biological information. Thats the simplest way to think about it. Its the unit of biological information. A genome, the best way to describe a genome is to make an analogy. The genome is the encyclopedia of all the genes we possess of humans, tell the gene when to turn on and off. Some of the enough in between some we know the function of and some we dont know the function of. But its an encyclopedia. Whats amazing, and thats part of the reason for writing this book, if it was really an encyclopedia if you imagine it as an object, it would be 66 full sets of the encyclopedia britannica. We would be sit in this room and every inch of this wall would be volumes of the encyclopedia britannica. If you open one of them it would read actgctgc. And whats astonishing is that your embryonic cells can take that encyclopedia thats your genome and build you and me with our similarities and differences. And thats whats astonishing. Thats whats astonishing to me about that. That code, you know, written three billion letters just four alphabets, actg can create ultimately through processes were beginning to understand, the complexity of you and me. And altering that code. Rose see thats the point isnt it. Thats where the future is. En i say we the community ofly scientists. In the last five to ten years charlie, weve discovered ways to alter the human genetic code within the fidelity, with the efficiency and the accuracy that wouldnt exist, just hadnt existed. I mean, ill tell you rose repeat the words, fidelity, accuracy. And efficiency. But fidelity we mean again reminding us again 66 sets of the enencyclopedia britannica. You can go find one volume, volume 17 of set four open up that volume, find one word in it, actgcc and change that last c into a g. Now you could say well what does that mean. That last g could be the code that say increases your risk to have autism. Or that last g could be one of the nucleotides that increases your risks to have a certain form of cancer. So, that is the kind of again, fidelity accuracy, efficiency, that were trying to understand. And of course, the question is, i mean can we use this technology in a way thats responsible. It is technology that is to me at least, comparable to the greatest Tech Technologies that we have thats fundamental to human history. The capacity to read and write genomes, i know as a cancer geneticist as someone who sees Cancer Patients every week, the capacity to read and write genomes changes who we are. Changes the conception of who we are as human beings. Rose and so what are the implications of that in terms of if someone can use it not just for good but for bad. Well the words good and bad are the words that are on the table right now. What is good. I mean on one hand of course we could use these technologies to do amazing things. Cure diseases. I mean you know, outside, this book doesnt talk about the biosphere but of course there are several books about changing crock, changing pests. You can have a dramatic impact not only on human beings and the biosphere but you can imagine transformative things, you can cure diseases with it. You can do gene therapy. The bad is, you know, will someone use it to enhance the way the human genome looks right now. Rose build some kind of new order. Try to build a different kind of human being, different kind of organism, different kind of crop that will change the way, that will change our relationship with the biosphere, change the relationship with have with ourselves. In the case of humans, theyre still strong in this country, theyre strong constraints on this. This isnt sort of free for all technology. Its relatively complicated. You cant sit in your garage and change the human genome. Its complicated technology. Whats important is the pieces are all there. The in principle all the pieces are there and thats what makes it a definable. We need to have the vocabulary to be able to ask the question, you know, what should we do next. Rose do we need rules and regulations. Absolutely, we need rules and regulations. Rose coming from government. Advised by science. Advised by science and patients and family and you and me. This is not something that will be figured out in the laboratory somewhere. This is not something that we will figure out the questions. And i hope the book raises these questions clearly. But the questions are so fundamental. Who are we. What defines us. Whats normal. When are, what are the boundaries of normalcy which is abnormal see. What if you could read. Ill give you a particular example. Weve now had technologies to be able to read the genomes of eggs or embryos before they are implemented. Preimplantation genetic diagnosis. So you can read the genome, you can sequence the genome. And what if i told an individual human being that their future unborn child carried a risk of a lethal disease, fatal disease but only by 10 . 90 the chances to be perfectly fine because obviously genes dont determine biology doesnt determine destiny. Genes interact etcetera etcetera. What if i told you i now have that information that theres a 10 risk. What would you do with that information. How would you act on that information. It gets to the question of who we are, what do we think we are. What risks are we willing to take. Rose and that choice will be up to the individual to make that choice. That choice. It should be up to the individual to make that choice but on the other hand of course the technologies that are being invented are being invented as a community. We are inventing technologies altogether to try to figure out how to advise, how to think about that number 10 . I mean what if i increase that number to 20 , you know. Is there a magic threshold where all of a sudden if i were to say to you again as a parented that the parented that the risk of your child have been a neuro degenerative disease 35 as a child how would you act on that information. This information is reading the genome. This is what reading the genome means. We havent been able to do it in a particular, you know its not as if we can prepare a report card that gives grades but we are beginning to prepare report cards that give probabilities. Its like reading a report card of probabilities. Rose how much of it is used now . Well, for mono genic diseases, and by that i mean single genes, and theres a high degree of penetrants. If you have that gene mutation or gene variation you will likely have that disease. Rose what takes the high probability. Is there a number that makes high probability. It just depends on the kind of gene it is and kind of interaction it is. Ill give you an example. A disease. Weve had programs in hospitals for a while that screens you for that disease. Not you but your children for that disease. Down syndrome is another example. Ultimately its a genetic syndrome. Its a extra chromosome but you can sample as you know, you can sample tissue. And again those are examples where as i said the pen transae very high. As a society, if the disease is a suffering is great enough weve decided thats okay to do. Weve made that decision. The question now as we read the genome in more deep ways as we read individual genomes in more deep ways are we entering arenas where the moral uncertainties are so great we dont know what to do, we need to have a conversation about. Rose is there an urgency to have a conversation. Theres an absolute urgency to have a conversation. Just to give you a couple examples. In about four or five weeks before i finished writing the book, in china there was an attempt to make a genetic, define genetic change in making an embryo. Now these were nonviable embryos, they were chosen. So there were some natural limits to the experiments. You couldnt have carried out this experiment but it was nonetheless an experiment that was formed and the chinese performed an experiment. Rose what was the result of the experiment. So again, early days they found that when they used these techniques, they found there were lots of errors. They often, they didnt hit the right gene. The efficiency was lower than they had probably expected. Again remember fidelity accuracy efficiency, those were not at the level that was expected. But those seemed to be technical challenges. Rose and those seemed to be the kinds of problem that trial and error. Thats right, trial and ear. If you read the major scientific jurndle, every week there are more and more reports about how the technology is improved, the accuracy is improving. More and more you can go into that one volume, volume 7 edition 6 of the encyclopedia and change one word and find the rest of the enencyclopedia is untouched. Theres an urgency about it. I was telling you earlier, that experiment generates over night, i think, 1500 comments in the New York Times asking questions. Rose from the first new article. From that first new article. Rose 1500 over night. Yes. I read them the next morning, i dont know how quickly they came. But the astonishing thing was the range of opinion. It ranged from some people saying if the chinese are doing this, we have to. We have to start. To there are absolute moral constraints in the west that allow us obviously not to stop any intervention. Rose what do you think of the idea that if, that you cant stop science. Theres always someone who wants to push every frontier and they will not be reigned in by any government or ethical considerations. I think thats an overblown fear. I think we visited these fears before with recombinant dna. I was a student with paul burg one of the inventors. Paul and i spoke yesterday on the phone. And he was a great mentor, has been a great friend. Obviously this technology was invented not only by him but several people, you know, added to the technology. And paul won a nobel prize for this invention. But as many of us remember, he was one of the organizers along with several other people of a large convention. I talk about that meeting in which they put a moratorium on being able to, you know, snip and paste pieces of dna. They had invented technologies taking a viral gene with a rabbit gene or cow gene and put it in a bacterial cell. Because the code is universal, the thing, the machine would start ticking as it were as if nothing had happened. So theres that one example. Theres a famous example as you know the atomic, about the atomic bomb and the famous viard letter in which again there are powerful limits being played. This is not garage technology yet. I dont believe it will become garage technology. Theres always a question will there be a Hacker Movement. Will there be a Hacker Movement that will come and you know start making human or genetic changes in animals or pets or crops. I personally dont think thats going to be the case and i think the regulations will have to be strong. Rose you dont think its going to be the case because . Because its not a garage technology. For one. There are some natural thresholds. You cant just do it. Rose at the same time ive always been influenced by the notion in history, a lot of smart people. Thats absolutely true and people are getting smarter. Rose they do a lot of dangerous things. There is a danger, yes. Theres absolutely a danger. Theres absolutely the danger and thats why i think we need the vocabulary. That is why this conversation cant be a conversation thats happening in the medical board room alone or in a laboratory alone or in a closed circuit universe alone. You need to participate, i need to participate, we need to figure out what we can do with it because like the atom, this is technology that fundamentally changes the conception of technology itself. It is one of those kinds of parts of technology. Rose is it possible that we are approaching the time that we can in a sense create a diseasefree perfect human. No. I think what we now know about genes is rose what does perfect and diseasefree mean. Yes, first of all what does perfect and diseasefree mean. Disease intersects with environment. Theres a strong rose biology is not destiny. No but it plays a powerful role in destiny. As youre pointing out, the question that were being asked to ask ourselves is what does perfect mean. I mean you know, evolution creates by virtue of, you know, its processes creates organisms that are adapted to particular circumstances. If you change the circumstances, what was sickness in one circumstance becomes illness in another circumstance. A hairless man in the antarctica is fit in one sense and ill in another. So the question of what perfect means is always changing. Of course there are some diseases where, you know, under no circumstances can we imagine that there will be sickness. They are devastating diseases. Rose so success has been found when you can identify one gene much more difficult if they are multiple genes. Typical human diseases are multiple genes. Rose especially cancer. Especially cancer. Rose so where are we in cancer today. Put on your oncology hat and your gene hat. We all know about immunotherapy. We now know at Duke University using polar vaccine. Brain disease. We know biden has a moon shot, this sort of moon shot. To eliminate as much cancer as possible. Weve made dramatic with more knowledge of genetics and human genome with more knowledge and more powerful technology. Yes. Rose and within increasing sense of shared information, although biden speaks about the silos that exist in this word. He does and hes right about most. Rose its not a sharing of information because everybodys in their own race. Yes. Rose were we, though, in terms of cancer getting back to your other question. Its an important because its a contiguous hat. These are contiguous questions. Let me tell you about immunotherapy. Ill give you two examples. One, the idea that cancers could resist being killed by the immune system through by activating certain genetic pathways is an idea that came out of genetics. So here again you have an example in which cancers can create a kind of cloak around themselves. So that the immune system cant really recognize that cancer and then kill the cancer as a kind of object or cell thats growing in the wrong place at the wrong time. That cloak as it were is really a genetic cloak. It is through genes, it is through by toggling with genes that cancers do this. Thats one great example of how genetics is illuminating and it continues to illuminate how Cancer Therapies work. Thats one example. You heard about these amazing trials which you put in t cells, modified immune cells. Guess what youre putting in that. Putting in genes that would now allow these t cells that previou