How Genetics Is Revolutionizing Cancer Research
Harold Varmus is an American Nobel Prize-winning scientist and the 14th and current Director of the National Cancer Institute, a post he was appointed to by President Barack Obama. He was a co-recipient (along with J. Michael Bishop) of the 1989 Nobel Prize in Physiology or Medicine for discovery of the cellular origin of retroviral oncogenes. He also serves as one of three co-Chairs of the President's Council of Advisors on Science and Technology.
From 1993 to 1999, he served as Director of the National Institutes of Health. As the NIH director, Varmus was credited with nearly doubling the research agency's budget. From 2000 to 2010, he served as President of Memorial Sloan-Kettering Cancer Center in New York City.
Beginning during his tenure as NIH director, Varmus has been a champion of an open access system for scientific papers, arguing that scientists should have control over the dissemination of their research rather than journal editors.
Siddhartha Mukherjee: Tell us a little bit about what the Cancer Genome tells us about the genetics of cancer and what we have learned from the Human Genome Project followed by the Cancer Genome Project. Do you want to start and then we’ll go around?
Dr. Lewis Cantley: Sure, well, as I said earlier the first thing the Cancer Genome is beginning to tell us is that there are many, many more subdivisions of cancers than we previously could predict based on pathology alone, and I think that is going to be extremely informative. The goal now with target therapies—first of all, it’s telling us what genes are likely driving the cancer, so if you find that in lung cancer 30% of the people get a particular mutation in a gene called RAS, 90% of pancreatic cancers have exactly that same gene, and you see that those are exactly the subgroups that don’t respond to any of our existing therapies. Then you realize that we need to have drugs that target RAS in some way. All the approaches we’ve made thus far have failed for that particular target, so people are trying to figure out ways to do that; it turns out to be a difficult gene to target. So the first thing that is going to come out and has already come out is the identification of what we call drugable oncogenes, things that are mutated in the cancer EGF receptor in lung cancer for example. So those opportunities hopefully we already know a lot about those and drugs are being developed and we’re hoping to get a lot of success out of that. In some ways I think on the other hand it has been somewhat disappointing in that most of the things we’re finding from the cancer genome sequencing are things that we already knew. In some ways retroviruses that cause cancers in mice and chickens, things that Harold actually worked on as a post doc and helped develop the field; they’ve essentially done the experiments in other animals and identified the oncogenes for us, so we’re finding relatively few oncogenes that we didn’t already know about from these mutational events, but I think it’s still going to be extremely valuable.
Dr. Siddhartha Mukherjee: Do you share the disappointment about the Cancer Genome Project Harold?
Dr. Harold Varmus: No, but I would point out a few things building on what Lou just said. First we knew about the RAS genes of course well before the Cancer Genome Projects, but we knew about RAS genes and the mutations that arise in them very frequently in pancreatic, lung and colon cancer even before there was a Human Genome Project because we knew about that in the early 80s, so I think it’s useful to remind people of that because here is a tremendously attractive target for developing drugs, even for thinking about ways to diagnose cancers early and we really have had a hard time capitalizing that over the last 30 years and that is a good reminder of how difficult this all is.
The second point I’d make is that, yes, I agree that we have of course rediscovered in the Cancer Genome Atlas Project and other efforts of genomics of cancers that the oncogenes we knew about because they’re relatives of the retroviral cancer genes, sure, they’re involved quite frequently as our well know so called tumor suppressor genes. But we’re getting a much better picture of what the real complexity of cancer might be. Secondly, there are new methods that extend our ability to analyze a genome well beyond just looking for small mutations. There are some very important rearrangements. We were talking earlier about prostate cancer and one of the things that I think is a pretty good indicator of the danger of a prostate cancer can be seen by finding a rejoining of chromosomes that generates a new gene that seems to be a driver of prostate cancers and that's the kind of thing that would have been very difficult to discover without this concerted effort that is going on.
Third, there are actually changes in the genome that are not mutational. They affect the way DNA is modified by chemical processes and the way in which DNA is expressed because of changes in the proteins that coat DNA and allow genes to be expressed. Very recently there have been a surprising set of mutations that govern what we call the methylations, a kind of chemical addition to DNA that governs gene expression that is regulated by a series of enzymes and coated by genes we would not historically have thought of as oncogenes and it’s clear from some recent work about an adult leukemia called acute myeloid leukemia that these genes are playing a very important role in that disease and represent another kind of target for therapy and a way to think about diagnosis, so I think there are a lot of rather surprising things that are coming out of this and the picture, the full picture of genomic change is really very dramatic and quite wonderful.
Dr. Lewis Cantley: So if I could just add one additional thing. I don’t want to leave the impression I'm disappointed or we shouldn’t have done that, and of course the mutations that Harold was talking about I think are very exciting. It really has opened up the field, but it’s still a relatively minor subset of cancers that are involved in gliomas and AMLs.
Dr. Harold Varmus: Well I think we don’t know yet.
Dr. Lewis Cantley: Well there is- Yeah, anyway, that is definitely helping us out, but I think the other thing that we’re going to get from this is biomarkers that will allow us to do much smarter clinical trials, so that we do a clinical trial and 15% of the patients respond. If you don’t have thousands and thousands of patients it’s hard to prove that that 15% is actually relevant and the drug may fail to be approved even spite of a huge investment in the trial and many, many years and there is examples of that that we know of where it was very clear to the clinicians the drug was working, but it still didn’t get approved, so if we can design trials where we tease out early on who is going to respond and who isn’t then that 15% becomes the 100% because you only do the trial on them. They’re defined by their mutational status, the so called biomarkers that- these are biomarker-driven trials, so I think that is going to be a tremendous advantage coming out of this.
Dr. Harold Varmus: If I can make one comment about the clinical trials because this is of great interest to the public. One reason we were so successful with pediatric cancers, developing chemotherapies that cure a large fraction of pediatric cancers is because virtually every kid came to a cancer center, was entered in a clinical trial and over the course of many years a lot of disappointments, heartache, and a lot of loss of life because these cancers are very, very difficult to treat, we finally emerged with a set of principles and operating procedures for treating these kids effectively. We’ve been much less successful with adult therapy and one of the reasons I think is because the heterogeneity of the tumors as Lou is describing. The Cancer Institute is currently reorganizing its clinical trial system in a way that is designed to take advantage of the point that Lou is making. For example, in treatment of lung cancer we know that a small fraction are susceptible to inhibitors of mutant kinases and one of the drugs erlotinib just barely squeaked through its first clinical trial because they were enough patients with that mutation in their tumors. Another very similar drug didn’t squeak through because it had too many people who didn’t have that mutation and now that the Cancer Genome analysis is giving us the tools to so called stratify these patients I think all of us believe there can be much smarter trials set up, faster trials, trials that give us much more effective information about how to treat.
The Cancer Genome Atlas project, already several years underway, is transforming the way scientists think about and treat cancer.
Subscribe to our Weekly Video newsletter
A study looks at the ingredients of a good scare.
Catching fear in a bottle<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDYyNzg1Ny9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyOTQwMTcyMn0.WtpJ1E_dhK2o09fBpKARynj4_p5NXeklgsXsbd7xr9w/img.jpg?width=980" id="8ff51" class="rm-shortcode" data-rm-shortcode-id="f10dd9188b173f4a36e85e9325507c6b" data-rm-shortcode-name="rebelmouse-image" />
Credit: Photo Boards/Unsplash<p>Previous studies have tracked physiological signs of fear arousal, but none have established a one-to-one correlation between that arousal and specific, actual fear events.</p><p>Andersen says that much of the research has been conducted in lab settings with weak fear stimuli, observing subjects as they experience things like scary videos. Scares in these situations tend to be weak and difficult to measure. Even harder to track in these situations is the link between enjoyment and fear. </p>
Eyes everywhere<iframe src="https://player.vimeo.com/video/109695164" width="100%" height="480" frameborder="0" scrolling="no" class="rm-shortcode" data-rm-shortcode-id="267ba87cfb8591ed5830499574d2272a"></iframe><p>Andersen and his colleagues conducted their experiments at <a href="https://dystopia.dk" target="_blank" rel="noopener noreferrer">Dystopia</a> Haunted House, a commercial attraction in Vejle, Denmark constructed in an old, run-down factory. The Recreational Fear Lab has a long-standing partnership with the spook shack.</p><p>They outfitted 100 volunteers with heart monitors and sent them on their terrifying way through the 50-room horror mansion. The facility incorporates a number of fright mechanisms including frequent jump scares in which a sudden threat takes a visitor by surprise.</p><p>Researchers surreptitiously observed their participants on closed-circuit video as they made their way through the attraction. They tracked each individual's scares, scoring them for intensity according to their visible reactions. After exiting the attraction, individuals self-reported their experiences in the haunted house.</p><p>Combining these self-reports with observer notes and each participant's heart-rate data gave the researchers subjective, behavioral, and physiological insights into the ways in which fear is experienced, and when it's a good thing or not.</p>
A pair of inverted U-shapes<p>In analyzing their data, the researchers saw two separate inverted u-shape curves. One depicted participants' enjoyment based on their self-reports and observed behavior. A similar u-curve was detected in their heart rates showing that just the right amount of heartbeat acceleration is associated with fun, but too much is too much. It's the terror Goldilocks zone.</p><p>Says Andersen, "If people are not very scared, they do not enjoy the attraction as much, and the same happens if they are too scared. Instead, it seems to be the case that a 'just-right' amount of fear is central for maximizing enjoyment."</p><p>The research suggests that being scared is enjoyable when it represents just a quick minor physiological deviation from one's normal state. When it goes on too long, however, or triggers too severe a physiological change, it becomes disturbing. Game over.</p><p>Andersen notes that this is not dissimilar to the factors known to make interpersonal play enjoyable: just the right amount of uncertainty and surprise. These are, maybe not coincidentally, also the ingredients of a successful joke.</p>
A meteorite that smashed into a frozen lake in Michigan may explain the origins of life on Earth, finds study.
- A new paper reveals a meteorite that crashed in Michigan in 2018 contained organic matter.
- The findings support the panspermia theory and could explain the origins of life on Earth.
- The organic compounds on the meteorite were well-preserved.
Meteor streaks through Michigan sky<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="80b7f30820153b35fc515592d7475f53"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/EPu2qnqMYBo?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span>
The meteorite that smashed into Strawberry Lake carried pristine extraterrestrial organic compounds.
Credit: Field Museum
A Mercury-bound spacecraft's noisy flyby of our home planet.
- There is no sound in space, but if there was, this is what it might sound like passing by Earth.
- A spacecraft bound for Mercury recorded data while swinging around our planet, and that data was converted into sound.
- Yes, in space no one can hear you scream, but this is still some chill stuff.
First off, let's be clear what we mean by "hear" here. (Here, here!)
Sound, as we know it, requires air. What our ears capture is actually oscillating waves of fluctuating air pressure. Cilia, fibers in our ears, respond to these fluctuations by firing off corresponding clusters of tones at different pitches to our brains. This is what we perceive as sound.
All of which is to say, sound requires air, and space is notoriously void of that. So, in terms of human-perceivable sound, it's silent out there. Nonetheless, there can be cyclical events in space — such as oscillating values in streams of captured data — that can be mapped to pitches, and thus made audible.
Image source: European Space Agency
The European Space Agency's BepiColombo spacecraft took off from Kourou, French Guyana on October 20, 2019, on its way to Mercury. To reduce its speed for the proper trajectory to Mercury, BepiColombo executed a "gravity-assist flyby," slinging itself around the Earth before leaving home. Over the course of its 34-minute flyby, its two data recorders captured five data sets that Italy's National Institute for Astrophysics (INAF) enhanced and converted into sound waves.
Into and out of Earth's shadow
In April, BepiColombo began its closest approach to Earth, ranging from 256,393 kilometers (159,315 miles) to 129,488 kilometers (80,460 miles) away. The audio above starts as BepiColombo begins to sneak into the Earth's shadow facing away from the sun.
The data was captured by BepiColombo's Italian Spring Accelerometer (ISA) instrument. Says Carmelo Magnafico of the ISA team, "When the spacecraft enters the shadow and the force of the Sun disappears, we can hear a slight vibration. The solar panels, previously flexed by the Sun, then find a new balance. Upon exiting the shadow, we can hear the effect again."
In addition to making for some cool sounds, the phenomenon allowed the ISA team to confirm just how sensitive their instrument is. "This is an extraordinary situation," says Carmelo. "Since we started the cruise, we have only been in direct sunshine, so we did not have the possibility to check effectively whether our instrument is measuring the variations of the force of the sunlight."
When the craft arrives at Mercury, the ISA will be tasked with studying the planets gravity.
The second clip is derived from data captured by BepiColombo's MPO-MAG magnetometer, AKA MERMAG, as the craft traveled through Earth's magnetosphere, the area surrounding the planet that's determined by the its magnetic field.
BepiColombo eventually entered the hellish mangentosheath, the region battered by cosmic plasma from the sun before the craft passed into the relatively peaceful magentopause that marks the transition between the magnetosphere and Earth's own magnetic field.
MERMAG will map Mercury's magnetosphere, as well as the magnetic state of the planet's interior. As a secondary objective, it will assess the interaction of the solar wind, Mercury's magnetic field, and the planet, analyzing the dynamics of the magnetosphere and its interaction with Mercury.
Recording session over, BepiColombo is now slipping through space silently with its arrival at Mercury planned for 2025.
A heated debate is occurring at the University of Miami.
- Students say they were identified with facial recognition technology after a protest at the University of Miami; campus police claim this isn't true.
- Over 60 universities nationwide have banned facial recognition; a few colleges, such as USC, regularly use it.
- Civil rights groups in Miami have called for the University of Miami to have talks on this topic.
Arthur Holland Michel: The Future of Surveillance Technology<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="8c330ab8c4df396f5313be796c0d96da"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/hIC-kaYcq34?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Americans don't always agree with that assessment, especially on college campuses. Over 60 universities—Harvard, MIT, and UCLA are on the list—have banned facial recognition. Of the few schools that utilize it, USC lets students enter their rooms via face scans; the software also ensures intruders cannot access buildings.</p><p>These are great uses of this technology. You could argue it's how any progress with our devices should work: in service of people. The problem, of course, is that those in power don't tend to stop when they have a little taste of the possibilities.</p><p>University of Miami is the <a href="https://www.forbes.com/sites/rachelsandler/2020/10/27/human-rights-groups-call-on-the-university-of-miami-to-ban-facial-recognition/#a11c8bf2965a" target="_blank">latest school</a> to be embroiled in a battle over facial recognition. The ACLU of Florida was joined by 21 other groups when requesting that the university hold an open forum so that students can express their concerns. A piece of their letter is below. </p><p>This call for action was inspired after a September incident in which students <a href="https://www.miaminewtimes.com/news/university-of-miami-tracked-protesters-with-video-surveillance-11712139" target="_blank">protested</a> returning for in-person classes during the pandemic. The students, concerned about their health, predominantly wore face masks. Still, a number of them were identified, leading to concerns that facial recognition was used. Campus police denied it—the chief even claimed the tech "doesn't work," though that notion <a href="https://www.cnn.com/2020/08/12/tech/face-recognition-masks/index.html" target="_blank">has been refuted</a>—yet civil liberties groups are worried that an invasion of privacy occurred.</p><p>Lia Holland, a member of the digital rights nonprofit <a href="https://www.fightforthefuture.org/news/2020-10-27-20-human-rights-organizations-call-on-university-of-miami-to-ban-facial-recognition-and-meet-f6f2119fd41b/" target="_blank">Fight for the Future</a>, wants answers from school administrators. </p><p style="margin-left: 20px;">"UMiami is struggling to answer to their creepy surveillance practices, and clarify whether they are using their own facial recognition system, or Florida's state facial recognition database."</p>
Credit: Pixel Shot / Adobe Stock<p>The police chief in question, David Rivero, claims overhead surveillance cameras provided identification at the protest. Yet speaking of another case involving facial-recognition software, he's <a href="https://www.miaminewtimes.com/news/university-of-miami-tracked-protesters-with-video-surveillance-11712139" target="_blank">on the record stating</a>, "We were able to [easily] identify and arrest him. We've [detected] a few bad guys that way."</p><p>The letter sent to the Board of Administrators <a href="https://www.fightforthefuture.org/news/2020-10-27-20-human-rights-organizations-call-on-university-of-miami-to-ban-facial-recognition-and-meet-f6f2119fd41b/" target="_blank">includes the following demands</a>: </p><ol><li>Issue a campus-wide policy banning non-personal use of facial recognition technology, and issue a statement that you have done so.</li><li>Immediately schedule an open forum with students and faculty/staff to discuss community concerns and clarify how student activists who participated in First Amendment protected protest activities were identified by campus police.</li><li>Immediately schedule a meeting with the UMiami Employee Student Alliance (UMESA) to address their COVID-19 safety concerns, the subject of the original protest.</li></ol><p>There's no doubt facial-recognition technology has a place in law enforcement. Victims of unsolved crimes are relieved when the perpetrators are brought to justice, regardless of the means. As Michel writes, some police forces are already surveilling large regions of their districts using the Gorgon Stare, a camera used from airplanes. Cameras are ubiquitous, and that's not going to change. </p>As a society, we need honest discussions regarding the application of surveillance. Nearly every citizen in China has <a href="https://www.cnet.com/news/in-china-facial-recognition-public-shaming-and-control-go-hand-in-hand/" target="_blank">already been logged</a> by facial recognition software, which has led to human rights abuses. While the stated intention of this tech by American police is pure, good intentions are known to pave the way...well, we know how that ends. <p>--</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a> and <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank" rel="noopener noreferrer">Facebook</a>. His new book is</em> "<em><a href="https://www.amazon.com/gp/product/B08KRVMP2M?pf_rd_r=MDJW43337675SZ0X00FH&pf_rd_p=edaba0ee-c2fe-4124-9f5d-b31d6b1bfbee" target="_blank" rel="noopener noreferrer">Hero's Dose: The Case For Psychedelics in Ritual and Therapy</a>."</em></p>