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When Will We Cure Cancer?
Siddhartha Mukherjee is the author of The Emperor of All Maladies: A Biography of Cancer, winner of the 2011 Pulitzer Prize in general nonfiction, and The Laws of Medicine. He is the editor of Best Science Writing 2013. Mukherjee is an assistant professor of medicine at Columbia University and a cancer physician and researcher. A Rhodes scholar, he graduated from Stanford University, University of Oxford, and Harvard Medical School. He has published articles in Nature, The New England Journal of Medicine, The New Yorker, The New York Times, and Cell. He lives in New York with his wife and daughters.
Siddhartha Mukherjee: The former NCI director, Dr. Andrew von Eschenbach established an ambitious goal of eliminating the suffering and death due to cancer by 2015. Dr. Varmus will this happen?
Harold Varmus: You’re putting me in a different position. Politically, I don’t want to bash a previous director, but I will because this was a claim that just has no reality. The argument was we’re going to banish death and suffering from cancer, not that we were going to abolish cancer, but that is just not going to happen in such a short timescale, and it creates first of all, a false aspiration, one that we clearly cannot succeed in achieving and secondly, it provides too much optimism in a setting that is—as you’ve heard around this table—a very complicated set of diseases and we are not going to conquer all those diseases and prevent death from them in such a short timescale.
Lewis Cantley: Yeah, I completely agree and I would add that I'm optimistic because I think with these target approaches and as we break cancer into more and more sub fractions we figure out how to cure the sub fractions. Every year we’re going to see another few percent get if not cured, at least have treatments that allow people to live without extensive chemotherapy approaches and so if you do that, if you project it and say we’re only going to cure 2% this year, well if we started curing 2% in 1970 today we’d be almost finished because in 50 years at 2% we could get them all.
Siddhartha Mukherjee: I'm reminded of the advertisement that came out in 1969 which said, “Mr. Nixon, you can cure cancer”, in the New York Times and the Washington Post and of course the advertisement says you can cure cancer as if it was one disease and of course the word cure. And in fact, the goal was set at that point of time by 1981, and 1981 has long passed as you know.
Harold Varmus: Yeah, I think the discussion though needs to be enlarged slightly so we remind ourselves that while it’s attractive to think about curing an advanced cancer with drugs that there are many other things we can do to reduce the burden of cancer. One of course is to prevent it and we’ve had some brief discussions about that, but we can make great- in fact, most of the reduction in mortality from cancer in this country is due to smoking cessation. Secondly, I would point out that drugs are only one of many things we do to treat cancer and perhaps the most effective thing we can do is remove a cancer, so surgery is a very important tool here, surgical methods, not much talked about, have improved. When we detect cancer early before it has spread we can cure it more frequently, so early detection, prevention and conventional therapy used early on are very important steps.
The other thing I would go back to is Dr. Von Eschenbach’s term suffering. We tend to forget that while cancer is still a terrible disease we have reduced suffering from cancer already dramatically, much better pain control, control of nausea and vomiting. Chemotherapy has gotten more tolerable. We can restore bone marrow function fairly quickly with really very superb science using hormones to stimulate the way the marrow functions after chemotherapy. These are major changes.
Deborah Schrag: And the fact that it’s no longer something that people need to keep a secret, the fact that there are many public figures who have cancer who are open about their cancer diagnoses and the numerous strategies people use to cope.
Doug Schwartzentruber: I think our strategy somewhat has changed. Yes, we continue to search for a cure, but the other C word, control and so many of our trials right now that are publishing results talk about cancer control as opposed to the term cure and getting that disease to stabilize and not progress and if we can do that it becomes an elegist to some of our other chronic diseases.
Siddhartha Mukherjee: Dr. Schrag, can lifestyle choices alone prevent cancer?
Dr. Deborah Schrag: Lifestyle choices alone can’t prevent all cancers, but they can enormously decrease the incidence, particularly of some cancers, so lung cancer would be the best example. Some of the things Harold was talking about, getting vaccinated for hepatitis B, getting vaccinated for the human papillomavirus, getting 11 year-old girls- we could probably eradicate or come close to eradicating cervical cancer. The challenge is here we’ve got a cancer that is caused by a virus and we know that just as our genes are changing and evolving so are the genes of viruses, so right now we have a vaccine that seems to work against most strains, but is it possible that we’ll have new viral strains that this vaccine will no longer work? Absolutely, that's possible, so this is going to be an ongoing process.
The previous director of the National Cancer Institute wanted to banish suffering and death from cancer by 2015. Current director Harold Varmus says this claim was not based on reality, but huge strides in prevention, detection, and treatment are being made.
Andy Samberg and Cristin Milioti get stuck in an infinite wedding time loop.
- Two wedding guests discover they're trapped in an infinite time loop, waking up in Palm Springs over and over and over.
- As the reality of their situation sets in, Nyles and Sarah decide to enjoy the repetitive awakenings.
- The film is perfectly timed for a world sheltering at home during a pandemic.
The multifaceted cerebellum is large — it's just tightly folded.
- A powerful MRI combined with modeling software results in a totally new view of the human cerebellum.
- The so-called 'little brain' is nearly 80% the size of the cerebral cortex when it's unfolded.
- This part of the brain is associated with a lot of things, and a new virtual map is suitably chaotic and complex.
Just under our brain's cortex and close to our brain stem sits the cerebellum, also known as the "little brain." It's an organ many animals have, and we're still learning what it does in humans. It's long been thought to be involved in sensory input and motor control, but recent studies suggests it also plays a role in a lot of other things, including emotion, thought, and pain. After all, about half of the brain's neurons reside there. But it's so small. Except it's not, according to a new study from San Diego State University (SDSU) published in PNAS (Proceedings of the National Academy of Sciences).
A neural crêpe
A new imaging study led by psychology professor and cognitive neuroscientist Martin Sereno of the SDSU MRI Imaging Center reveals that the cerebellum is actually an intricately folded organ that has a surface area equal in size to 78 percent of the cerebral cortex. Sereno, a pioneer in MRI brain imaging, collaborated with other experts from the U.K., Canada, and the Netherlands.
So what does it look like? Unfolded, the cerebellum is reminiscent of a crêpe, according to Sereno, about four inches wide and three feet long.
The team didn't physically unfold a cerebellum in their research. Instead, they worked with brain scans from a 9.4 Tesla MRI machine, and virtually unfolded and mapped the organ. Custom software was developed for the project, based on the open-source FreeSurfer app developed by Sereno and others. Their model allowed the scientists to unpack the virtual cerebellum down to each individual fold, or "folia."
Study's cross-sections of a folded cerebellum
Image source: Sereno, et al.
A complicated map
Sereno tells SDSU NewsCenter that "Until now we only had crude models of what it looked like. We now have a complete map or surface representation of the cerebellum, much like cities, counties, and states."
That map is a bit surprising, too, in that regions associated with different functions are scattered across the organ in peculiar ways, unlike the cortex where it's all pretty orderly. "You get a little chunk of the lip, next to a chunk of the shoulder or face, like jumbled puzzle pieces," says Sereno. This may have to do with the fact that when the cerebellum is folded, its elements line up differently than they do when the organ is unfolded.
It seems the folded structure of the cerebellum is a configuration that facilitates access to information coming from places all over the body. Sereno says, "Now that we have the first high resolution base map of the human cerebellum, there are many possibilities for researchers to start filling in what is certain to be a complex quilt of inputs, from many different parts of the cerebral cortex in more detail than ever before."
This makes sense if the cerebellum is involved in highly complex, advanced cognitive functions, such as handling language or performing abstract reasoning as scientists suspect. "When you think of the cognition required to write a scientific paper or explain a concept," says Sereno, "you have to pull in information from many different sources. And that's just how the cerebellum is set up."
Bigger and bigger
The study also suggests that the large size of their virtual human cerebellum is likely to be related to the sheer number of tasks with which the organ is involved in the complex human brain. The macaque cerebellum that the team analyzed, for example, amounts to just 30 percent the size of the animal's cortex.
"The fact that [the cerebellum] has such a large surface area speaks to the evolution of distinctively human behaviors and cognition," says Sereno. "It has expanded so much that the folding patterns are very complex."
As the study says, "Rather than coordinating sensory signals to execute expert physical movements, parts of the cerebellum may have been extended in humans to help coordinate fictive 'conceptual movements,' such as rapidly mentally rearranging a movement plan — or, in the fullness of time, perhaps even a mathematical equation."
Sereno concludes, "The 'little brain' is quite the jack of all trades. Mapping the cerebellum will be an interesting new frontier for the next decade."
What happens if we consider welfare programs as investments?
- A recently published study suggests that some welfare programs more than pay for themselves.
- It is one of the first major reviews of welfare programs to measure so many by a single metric.
- The findings will likely inform future welfare reform and encourage debate on how to grade success.
Welfare as an investment<p>The <a href="https://scholar.harvard.edu/files/hendren/files/welfare_vnber.pdf" target="_blank">study</a>, carried out by Nathaniel Hendren and Ben Sprung-Keyser of Harvard University, reviews 133 welfare programs through a single lens. The authors measured these programs' "Marginal Value of Public Funds" (MVPF), which is defined as the ratio of the recipients' willingness to pay for a program over its cost.</p><p>A program with an MVPF of one provides precisely as much in net benefits as it costs to deliver those benefits. For an illustration, imagine a program that hands someone a dollar. If getting that dollar doesn't alter their behavior, then the MVPF of that program is one. If it discourages them from working, then the program's cost goes up, as the program causes government tax revenues to fall in addition to costing money upfront. The MVPF goes below one in this case. <br> <br> Lastly, it is possible that getting the dollar causes the recipient to further their education and get a job that pays more taxes in the future, lowering the cost of the program in the long run and raising the MVPF. The value ratio can even hit infinity when a program fully "pays for itself."</p><p> While these are only a few examples, many others exist, and they do work to show you that a high MVPF means that a program "pays for itself," a value of one indicates a program "breaks even," and a value below one shows a program costs more money than the direct cost of the benefits would suggest.</p> After determining the programs' costs using existing literature and the willingness to pay through statistical analysis, 133 programs focusing on social insurance, education and job training, tax and cash transfers, and in-kind transfers were analyzed. The results show that some programs turn a "profit" for the government, mainly when they are focused on children:
This figure shows the MVPF for a variety of polices alongside the typical age of the beneficiaries. Clearly, programs targeted at children have a higher payoff.
Nathaniel Hendren and Ben Sprung-Keyser<p>Programs like child health services and K-12 education spending have infinite MVPF values. The authors argue this is because the programs allow children to live healthier, more productive lives and earn more money, which enables them to pay more taxes later. Programs like the preschool initiatives examined don't manage to do this as well and have a lower "profit" rate despite having decent MVPF ratios.</p><p>On the other hand, things like tuition deductions for older adults don't make back the money they cost. This is likely for several reasons, not the least of which is that there is less time for the benefactor to pay the government back in taxes. Disability insurance was likewise "unprofitable," as those collecting it have a reduced need to work and pay less back in taxes. </p>
What are the implications of all this?<div class="rm-shortcode" data-media_id="ceXv4XLv" data-player_id="FvQKszTI" data-rm-shortcode-id="3b407f5aa043eeb84f2b7ff82f97dc35"> <div id="botr_ceXv4XLv_FvQKszTI_div" class="jwplayer-media" data-jwplayer-video-src="https://content.jwplatform.com/players/ceXv4XLv-FvQKszTI.js"> <img src="https://cdn.jwplayer.com/thumbs/ceXv4XLv-1920.jpg" class="jwplayer-media-preview" /> </div> <script src="https://content.jwplatform.com/players/ceXv4XLv-FvQKszTI.js"></script> </div> <p>Firstly, it shows that direct investments in children in a variety of areas generate very high MVPFs. Likewise, the above chart shows that a large number of the programs considered pay for themselves, particularly ones that "invest in human capital" by promoting education, health, or similar things. While programs that focus on adults tend to have lower MVPF values, this isn't a hard and fast rule.</p><p>It also shows us that very many programs don't "pay for themselves" or even go below an MVPF of one. However, this study and its authors do not suggest that we abolish programs like disability payments just because they don't turn a profit.</p><p>Different motivations exist behind various programs, and just because something doesn't pay for itself isn't a definitive reason to abolish it. The returns on investment for a welfare program are diverse and often challenging to reckon in terms of money gained or lost. The point of this study was merely to provide a comprehensive review of a wide range of programs from a single perspective, one of dollars and cents. </p><p>The authors suggest that this study can be used as a starting point for further analysis of other programs not necessarily related to welfare. </p><p>It can be difficult to measure the success or failure of a government program with how many metrics you have to choose from and how many different stakeholders there are fighting for their metric to be used. This study provides us a comprehensive look through one possible lens at how some of our largest welfare programs are doing. </p><p>As America debates whether we should expand or contract our welfare state, the findings of this study offer an essential insight into how much we spend and how much we gain from these programs. </p>
Richard Feynman once asked a silly question. Two MIT students just answered it.
Here's a fun experiment to try. Go to your pantry and see if you have a box of spaghetti. If you do, take out a noodle. Grab both ends of it and bend it until it breaks in half. How many pieces did it break into? If you got two large pieces and at least one small piece you're not alone.
But science loves a good challenge<p>The mystery remained unsolved until 2005, when French scientists <a href="http://www.lmm.jussieu.fr/~audoly/" target="_blank">Basile Audoly</a> and <a href="http://www.lmm.jussieu.fr/~neukirch/" target="_blank">Sebastien Neukirch </a>won an <a href="https://www.improbable.com/ig/" target="_blank">Ig Nobel Prize</a>, an award given to scientists for real work which is of a less serious nature than the discoveries that win Nobel prizes, for finally determining why this happens. <a href="http://www.lmm.jussieu.fr/spaghetti/audoly_neukirch_fragmentation.pdf" target="_blank">Their paper describing the effect is wonderfully funny to read</a>, as it takes such a banal issue so seriously. </p><p>They demonstrated that when a rod is bent past a certain point, such as when spaghetti is snapped in half by bending it at the ends, a "snapback effect" is created. This causes energy to reverberate from the initial break to other parts of the rod, often leading to a second break elsewhere.</p><p>While this settled the issue of <em>why </em>spaghetti noodles break into three or more pieces, it didn't establish if they always had to break this way. The question of if the snapback could be regulated remained unsettled.</p>
Physicists, being themselves, immediately wanted to try and break pasta into two pieces using this info<p><a href="https://roheiss.wordpress.com/fun/" target="_blank">Ronald Heisser</a> and <a href="https://math.mit.edu/directory/profile.php?pid=1787" target="_blank">Vishal Patil</a>, two graduate students currently at Cornell and MIT respectively, read about Feynman's night of noodle snapping in class and were inspired to try and find what could be done to make sure the pasta always broke in two.</p><p><a href="http://news.mit.edu/2018/mit-mathematicians-solve-age-old-spaghetti-mystery-0813" target="_blank">By placing the noodles in a special machine</a> built for the task and recording the bending with a high-powered camera, the young scientists were able to observe in extreme detail exactly what each change in their snapping method did to the pasta. After breaking more than 500 noodles, they found the solution.</p>
The apparatus the MIT researchers built specifically for the task of snapping hundreds of spaghetti sticks.
(Courtesy of the researchers)
What possible application could this have?<p>The snapback effect is not limited to uncooked pasta noodles and can be applied to rods of all sorts. The discovery of how to cleanly break them in two could be applied to future engineering projects.</p><p>Likewise, knowing how things fragment and fail is always handy to know when you're trying to build things. Carbon Nanotubes, <a href="https://bigthink.com/ideafeed/carbon-nanotube-space-elevator" target="_self">super strong cylinders often hailed as the building material of the future</a>, are also rods which can be better understood thanks to this odd experiment.</p><p>Sometimes big discoveries can be inspired by silly questions. If it hadn't been for Richard Feynman bending noodles seventy years ago, we wouldn't know what we know now about how energy is dispersed through rods and how to control their fracturing. While not all silly questions will lead to such a significant discovery, they can all help us learn.</p>
Finding a balance between job satisfaction, money, and lifestyle is not easy.
- When most of your life is spent doing one thing, it matters if that thing is unfulfilling or if it makes you unhappy. According to research, most people are not thrilled with their jobs. However, there are ways to find purpose in your work and to reduce the negative impact that the daily grind has on your mental health.
- "The evidence is that about 70 percent of people are not engaged in what they do all day long, and about 18 percent of people are repulsed," London Business School professor Dan Cable says, calling the current state of work unhappiness an epidemic. In this video, he and other big thinkers consider what it means to find meaning in your work, discuss the parts of the brain that fuel creativity, and share strategies for reassessing your relationship to your job.
- Author James Citrin offers a career triangle model that sees work as a balance of three forces: job satisfaction, money, and lifestyle. While it is possible to have all three, Citrin says that they are not always possible at the same time, especially not early on in your career.