YouSaid · the spoken record

Russ Altman

lines on the record: 10
first: 2017-03-07
most recent: 2017-03-07
sittings or episodes: 1
sources: podcast

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“The themes in our lab, everybody in the lab works at a different scale, but the best projects are the ones that integrate these scales because a signal that you get at the molecular level may or may not be true as noise in all data sets. However, if you're seeing a signal at the molecular level, that gives you oodles more confidence that this might be a real signal and not just a weird artifact of the data. And so”
2017-03-07 · a16z Podcast · a16z Podcast: The Genetics Of Drug Delivery · IDENTIFIED FROM THE TRANSCRIPT · source
“The electronic medical record and other and wearables, which you're going to hear a lot about in seven minutes and 50 seconds, these are all unbelievably useful sources that we can use to characterize drug response fully. And then we can get to the population level. We can look at population level databases and say when we give a drug to a million people, yes, it does what we thought it would do based on the approval, but it probably does lots of other things as well. And we can mine public databases to figure out what's going on.”
2017-03-07 · a16z Podcast · a16z Podcast: The Genetics Of Drug Delivery · IDENTIFIED FROM THE TRANSCRIPT · source
“The second level we can think of is the cellular response. Whatever's happening at the molecular level, it will lead to a sequence of signals that has the cell change its physiology. The reason we're giving the drug is we want to shift the cell's kind of, if you think of it as a network, you want to get it into a new basin of interactions that's more healthy than wherever it was before. And so we're very interested in fully understanding how a small molecule or large molecule drug changes the cellular milieu, the expression of the genes. Which genes are turned on, which genes are turned off, how that cell is working. But we're informatics people and data scientists, so we're not limited to scale. This is the one, I should say, this is the one advantage we have over experimental colleagues. They're awesome, but they tend to be, I'm a cell person, or I'm a molecule person. We can go over all magnitudes of scale and just integrate the data, and this is, I think, the important theme. So the next level after cell is tissues and complete organisms.”
2017-03-07 · a16z Podcast · a16z Podcast: The Genetics Of Drug Delivery · IDENTIFIED FROM THE TRANSCRIPT · source
“In order to optimize their production and use of drugs. So when I talk about drug responses, they happen, one of the things that makes this, I wouldn't say easy, but one of the fortunate situations is because it's a biological phenomenon, drug response can be characterized at multiple levels. I can talk about the molecular level. How does this small molecule drug interact with its target physically? It forms all kinds of chemical connections, and if there's changes in this protein because of differences in genetics, it might change how tightly it binds and other molecular properties. So we have a big interest in looking at the low-level molecular interactions to get the full set, for example, of molecules that might interact with a drug, even some of the molecules or targets that were not anticipated by the people who develop the drug.”
2017-03-07 · a16z Podcast · a16z Podcast: The Genetics Of Drug Delivery · IDENTIFIED FROM THE TRANSCRIPT · source
“Very limited. And it's not because anybody is doing anything wrong per se, but the companies, when they develop these drugs, have a very focused view of what they're hoping the drug will do, and they design their trials to prove that it does or doesn't do that. If the drug is on the market, it means the trial was relatively successful. And so they'll say, this drug does X. It treats hypertension, it treats diabetes. And that is true. But because of their focus, they sometimes have blinders to the other things that the drug might be doing, which we might put under the bin of side effects or other idiosyncratic effects that are not understood. But if I'm in charge of understanding the genetics of drug response, I need a full picture of the drug response. So this project over the last 16 years has given me the excuse with my lab to really look at drug response at many levels to try to fully understand what drugs do. And I'll try to argue with you that this is what the pharmaceutical companies of the future are going to have to do.”
2017-03-07 · a16z Podcast · a16z Podcast: The Genetics Of Drug Delivery · IDENTIFIED FROM THE TRANSCRIPT · source
“They experience will be because they felt good about getting a prescription from the doctor and not because it was having any activity. There are other people who turn codeine into morphine super rapidly. So they, for example, get 20 great minutes of morphine and then they have three hours until their next dose of continued pain. So codeine is a great example, one of hundreds where knowing a little bit about your genetics will allow us in the future to implement this vision of an information system with knowledge of your genome securely, which can then help your prescriber make decisions about the drugs that are most likely to work and the least likely to cause side effects. But that's not what I came to talk about. What I came to talk about is because we're building the Farm GKB, which is the genetics of drug response, it's really critical that we understand drug response. And actually, even for drugs that are on the market and have been used for many years, our ability to really describe what they actually do is”
2017-03-07 · a16z Podcast · a16z Podcast: The Genetics Of Drug Delivery · IDENTIFIED FROM THE TRANSCRIPT · source
“But there's usually not a family lore about drug response. We all remember grandpa's big ears, but we don't remember that grandpa had terrible side effects when he took coding. So we have to depend on the genome to make measurements. And over the last 15, 16 years, we've actually accumulated quite a large knowledge base of genetic variations in humans and how they can affect the response to drugs. One quick example, codeine. Codine is in tylin number three. Any of you have had a minor procedure may have gotten tylenol number three. Codine is actually biologically inactive. It goes through the liver. This is where your liver is. I should say I'm an internist as well, a general practitioner. Coding goes to your liver and there's an enzyme in your liver that transforms it into morphine. And morphine is active. Very popular. 7% of people of European descent don't have a version because of genetic differences in that enzyme. They can't turn codeine into morphine. So codeine is a placebo for them. Any pain relief”
2017-03-07 · a16z Podcast · a16z Podcast: The Genetics Of Drug Delivery · IDENTIFIED FROM THE TRANSCRIPT · source
“Impacts drug response. So you might not think about this, but your response to drugs was inherited from mom and dad and grandma and grandpa just like your height and your hair color and your eye color.”
2017-03-07 · a16z Podcast · a16z Podcast: The Genetics Of Drug Delivery · IDENTIFIED FROM THE TRANSCRIPT · source
“Thanks very much, and I would be Russ Altman from Stanford University. So, let me just tell you quickly that I get most of my funding from the National Institutes of Health. I also have collaborations with Pfizer and Genentech and Carius and second OM. And I am a founder of Personalis, which does immuno-oncology. So at Stanford, my laboratory focuses on informatics, biomedical informatics, and data science for understanding drug response and optimizing it. And so I think the reason I'm talking to you today is maybe some of the things that we're doing is form the basis of the next generation of pharmaceutical discovery and development. And I have some confidence in that because we're working with these companies that I mentioned who are thinking about how they might change their way of doing things. So I got into this because we're building a database called FarmGKB, Pharmacogenomics Knowledge Base. We've been doing this for 16 years. And PharmGKB is a simple idea. It's a database or really a knowledge base of how human genetic variation”
2017-03-07 · a16z Podcast · a16z Podcast: The Genetics Of Drug Delivery · IDENTIFIED FROM THE TRANSCRIPT · source
“I am Vijay Ponde, journal partner A16Z. This episode of the A16 podcast is on the genetics of drug response. This was recorded as part of our A6 and Z inaugural summit. It gives a great deep dive by Stanford Professor of Bioengineering Genetics and Medicine Russellman, and his work, especially around building pharma GKB. Professor Altman gives a window into how data science and bioinformatics will change the future of drug discovery and drug response. In this case, it turns out that when we think about inheritance, we might think about inheriting your grandmother's eyes or your grandfather's ears. But it turns out there's a lot more to generics than just that. How you respond to drugs will be similar to your parents as well. Moreover, we can now see how building a large bank of human genetics variations will transform our understanding on optimizing of drug discovery and response both for understanding side effects and toxicity as well as making better drugs and going after new indications. Professor Altman gives up really fantastic overview of the space.”
2017-03-07 · a16z Podcast · a16z Podcast: The Genetics Of Drug Delivery · IDENTIFIED FROM THE TRANSCRIPT · source