An interview with cancer’s ‘biographer’

This week we welcome guest writer Robert Aboukhalil, graduate student in the Watson School of Biological Sciences.

There aren’t very many scientists whose claim to fame includes writing a best-selling, Pulitzer Prize-winning and Oprah-endorsed book. A few weeks ago, I had the good fortune to sit down with one such scientist, Siddartha Mukherjee, author of The Emperor of All Maladies: A Biography of Cancer.

Siddartha is an Assistant Professor of Medicine at Columbia and a physician at Columbia University Medical Center, where his work is focused on leukemia. What follows is an excerpt from our conversation; the full transcript will be published in the Winter 2015 issue of CSHL Current Exchange.

When was cancer first described?

Interestingly, the earliest descriptions of cancer go back to the very first medical documents we have. For example, we have documents from ancient Egypt that describe cases consistent with contemporary descriptions of breast cancer.

These records are incredible because they read like contemporary medical documents. The physiology may have been wrong and the therapeutics misguided, but the organization of disease into mechanism and the treatment being driven by mechanism is an ancient idea.

Do these documents describe any treatments?

For breast cancer, the original recommendation was to do nothing because there was no treatment. Slowly, that evolved into surgery. We know there were attempts at breast surgery for cancer very early on. For example, there’s a description by Herodotus [Greek historian, 5th century B.C.] of a queen having what seems to be a breast cancer removed.

In 1971, the National Cancer Act was signed and the “War on Cancer” began. How did it start and how have we fared so far?

It started as a massive campaign organized by very prominent scientists and philanthropists. There was a feeling that tackling cancer would work like the moon landing or the Manhattan project did—that if you poured resources into a problem and made it a consolidated effort, there would be a common cause and ultimately, a common cure.

Looking back, was it too naïve/ambitious?

It was naïve in some ways, ambitious in others, but it also had many collateral advantages. The biggest advantage was that it created a landmark, which was useful for measuring our progress. On the flip side, the War on Cancer created a series of unnatural expectations around what was achievable and what wasn’t. When it was not achieved, it created a cycle of disappointment.

It was a mixed blessing, but I do think we wouldn’t be here today if it wasn’t for the War on Cancer. On the other hand, I feel as though we would be in a different place in terms of public trust if the War on Cancer had not been executed the way it had.

What prompted you to write your book?

At the time, I was a fellow in oncology and became progressively convinced that we had no roadmap for cancer. Ultimately, I was asked by a patient to explain the current state of cancer research and where we were going next. Looking at volumes of books, I couldn’t find very many that offered a bird’s eye view of cancer research; those that did were written by authors pushing for a particular direction in cancer research. They were written as polemics, whereas I wanted to write a biography of cancer.

 

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Celebrating Brain Awareness Week with DNALC’s 3D Brain – revolutionizing education in the classroom and the doctor’s office

This week we again welcome guest blogger Amy Nisselle, Ph.D. – Multimedia & Evaluation Manager for the DNA Learning Center.

Today marks the end of Brain Awareness Week, a global campaign to increase awareness about the benefits of brain research. The Dana Alliance for Brain Initiatives has collaborated with the Society for Neuroscience to host events around the world, letting us all catch a glimpse of the amazing power of our minds.

World-class brain research happens right here on the CSHL campus. Scientists have made tremendous advances in understanding the genetics of autism and other neurological disorders. Other research teams are working to understand memory and cognition, exploring how our brain processes sensory information. Still other scientists are working to map all of the neuronal connections with in the brain.

CSHL’s DNA Learning Center works to translate the science behind these amazing discoveries for the benefit of the broader public. In 2009 we produced the Genes to Cognition Online website in collaboration with the Wellcome Trust and funded by the Dana Foundation. One of our most successful tools was originally produced for G2C Online: the 3D Brain app is an interactive, three-dimensional model of the human brain. With more than 2.5 million downloads, it was created to allow students to explore 29 individual structures in the brain. Each structure also includes supporting educational materials: information on disorders, case studies, and even links to current research.

Sound like a great tool for students and educators? That’s exactly what we had in mind, and indeed, it is how the 3D Brain is most often used. But there’s another active group of users that we didn’t anticipate: medical professionals and patients.

Doctor-patient communication has historically faced significant challenges. Just think of the last time you visited a doctor. When chatting about your condition and possible treatments, it’s likely your doctor explained everything verbally. But, research suggests most people promptly forget up to 80 percent of the information they are given in such exchanges. Sometimes doctors use a model like this one to show patients some part of their anatomy. It may be helpful in the moment, but once a patient leaves the office, they must rely on memory.

No wonder, then, that the 3D Brain has taken off in medical communities, and was even featured in a recent article about how doctors can use apps to make patient education more effective. By enabling patients to visualize where different structures are in the brain the app gives patients a sense of “ownership” – a spatial awareness of where certain structures are inside their own head. This and other mobile apps present an opportunity for doctors to connect with patients both during and after consultations. Because the app was initially designed with students in mind, it is written at a level that isn’t highly technical.

The 3D Brain is available on Apple, Android, and Windows platforms, and has been downloaded by medical professionals, patients, educators, and students. Reviews on app stores even indicate that parents of children with neurological conditions have used the app to explain to a new caregiver what’s going on with their child’s brain. The need for education extends beyond the classroom, and the 3D Brain and similar apps are proving to be an asset wherever there’s a need for educational resources.

Download your very own 3D Brain right here:

Apple Istore
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What makes a great scientist tick?

Professor David Spector, a cancer biologist, is Director of Research at Cold Spring Harbor Laboratory. He and his lab team are explorers of the nucleus, the compartment in every cell that holds DNA, the genetic material. Dr. Spector has discovered new structures inside the nucleus, demonstrating that it is in fact home to much more than DNA. Recently, he published work that demonstrates unexpected flexibility and variability in how genes are activated in cells. On April 4, Spector will be at SUNY Purchase discussing the bestselling book, The Immortal Life of Henrietta Lacks by Rebecca Skloot. Decades ago, Henrietta Lacks, a cancer patient, unknowingly donated some of her tumor cells to science. They would become one of the basic tools of modern biomedical research. Dr. Spector will discuss the impact of her story on research, ethics, and informed consent. Below, a talented local high school student, Skyler Palatnick, profiles Dr. Spector and his work.

What makes a great scientist tick?

CSHL Professor David Spector

Bright lights. Tall buildings. Busy New York streets. This is where it all started for one of Cold Spring Harbor Laboratory’s (CSHL) most valuable players: Dr. David L. Spector, cancer researcher, head of the Laboratory’s microscopy resource and the institution’s Director of Research. 

I’m Sklyer, a sophomore at Cold Spring Harbor High School and I had a chance to interview Dr. Spector and find out some things that I don’t believe most people ever get to learn about scientists like him. Most people are interested in the great accomplishments of scientists, but I wanted to know more about where Dr. Spector came from, how he got to where he is, and what he enjoys outside of science. Here’s what I found out. 

I got an in-depth look at Dr. Spector’s early years, dating all the way back to when he was a little city kid who loved to play stickball with his friends. They would play in the alleyway next to his apartment house, and Dr. Spector says he has “many good memories” of these days. Softball was another popular sport among his friends. When not playing sports, you might have found him walking around downtown Manhattan, especially around Rockefeller Center. He always loved to shop back then, and nowadays too. He even called himself “the ultimate shopper.”

Even as a child, he was always interested in the sciences; especially biology. Dr. Spector’s “breakthrough moment” that really kicked off his pursuit of the sciences was a science fair in elementary school!  Looking back, he said:  “The prize I won for coming in first was all of ten dollars, but in that science fair I won so much more than that: the keys to a successful life and career.” Since that science fair victory, Dr. Spector has pursued research. In his senior year of college, it was one of his professors who really kick-started his interest in microscopy.

Dr. Spector gathered experience at three colleges: City College of New York, Lehman College, and Rutgers University. He says that City College and Rutgers were the places where he gained the most valuable assets for what he does now. City College was where he earned his bachelor’s degree and major experience with microscopy. Microscopy plays a huge role in his own research. He earned his Ph.D. at Rutgers, and that required a broad knowledge of chromatin and chromosome structure. This knowledge has been key to his past and current research.

Highly motivated. Passionate. Very organized. Dr. Spector said these are the aspects of being a researcher that have contributed to his overall success. He stressed that these are the qualities researchers and scientists just starting off need to have in order to achieve great things. He also stressed one other quality as possibly even more important. “Always come back fighting whenever a setback or problem occurs,” said Dr. Spector. “When a research grant that you apply for doesn’t get funded you might feel upset, angry, or frustrated, but you just have to keep working hard and don’t let it get to you.”

1985. This is the year that Dr. Spector came to CSHL. Little did he know back then that he would become not only a Professor but also the Director of Research for the entire institution. His own research evolved, too. Before starting at CSHL, he had studied tiny organisms known as dinoflagellates. Some of these are known more simply as plankton, and others are part of coral reefs. They are known to cause paralytic shellfish poisoning and red tides. Dr. Spector worked on trying to understand their chromosomes and genetic makeup. Next, he moved to mammalian cells and began to study messenger RNAs (RNA that carries messages from genes that contain information about making proteins). At CSHL he added research on chromatin (a combination of DNA and proteins that is found in the nucleus of a cell) to his repertoire. For a while he worked with the small RNAs in the nucleus that are involved in processing messenger RNAs, and eventually that evolved into working with long non-coding RNAs.

Much time has passed since Dr. Spector first joined CSHL but his mindset remains the same. His motivation to accomplish big things has carried through all the way from the time he was a student trying to win the science fair competition. “The reason that you keep interested in science is that you just never know what to expect,” he explained. In the future, he sees himself and his team of researchers working to stop a certain type of breast cancer. They are making great progress toward this goal. The professor explained to me that each one of the eleven team members in his lab has his or her own small project that’s related to one big goal. “With each person working on a piece of the pie,” he says, “we can make big strides toward beating breast cancer.”

When he’s not fighting cancer with research, Dr. Spector can still be found walking around Manhattan with his wife and best friend Mona and enjoying all that the big city has to offer. He’s also interested in exploring the world and recently visited Hamilton Island in Australia on the Great Barrier Reef. He believes that there should be a balance between work time, family and fun time. I learned a bit about what makes this man tick — you can take the professor out of the city, but you can’t take the city boy out of this professor.

If you can’t attend Dr. Spector’s lecture at SUNY Purchase, you might want to watch a similar lecture at CSHL here.  A recent profile of Dr. Spector appearing in the Harbor Transcript can be read here.

 

 

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Students step into teachers’ shoes in innovative DNA Learning Center program

by Amy Nisselle, DNA Learning Center

Program students from I.S. 059 Springfield Gardens show their classmates how to extract DNA back at school.

The Laboratory’s DNA Learning Center (DNALC) is inspiring the next generation of science teachers by giving local students the opportunity to show off their new biotechnology skills. The intent is to provide students with the opportunity to do meaningful hands-on experiments, and then to have those students teach their peers the same experiments.

In a collaboration with the North Shore-Long Island Jewish health system (NS-LIJ), every year the I.S. 059 Springfield Gardens school in Jamaica, Queens, sends selected 8th–11th grade students to DNALC West at Lake Success to learn the latest biotechnology and bioinformatics techniques over nine sessions. The Learning Center’s West location was established 11 years ago, the beginning of a now even broader effort to extend the reach of CSHL’s pioneering programs in hands-on genetics education.

Those “seed students” who are taught at DNALC West then get to teach part of what they learned to classmates back at I.S. 059.  Since 2008, 125 students have been through the program.

“We had tons of fun – learned, taught. Thanks for giving us gifts that will keep on giving,” commented Marcia Young, an I.S. 059 science teacher who brought 16 students to DNALC West as part of the program.

Dr. Christine Marizzi, DNALC West Manager and plant biologist, said the students absolutely loved being able to use ‘real’ equipment and experience what it’s like to do actual research. “They had lots of fun, but also concentrated and took notes to make sure they understood everything and could explain it to their classmates.”

The larger aim of the program is to give underrepresented and less-fortunate students an opportunity to experience the laboratory environment and gain exposure to a variety of career choices, says Donna Manchisi, Director of Marketing and Education, NS-LIJ.  She intends to track students involved in the program on their decisions to work in specific STEM careers, such as healthcare and medical research.

Find out more about CSHL’s DNA Learning Center and the programs it offers for 5th-12th graders (and their teachers) across Long Island, NYC and online at www.dnalc.org

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Making the case for preprint publishing in biology

written by CSHL QB Fellow Justin Kinney

This week, Cold Spring Harbor Laboratory Press launched bioRxiv, a preprint server for the biological sciences. This is very exciting for those of us who have moved into biology from physics (as well as other quantitative disciplines, such as mathematics and computer science). Scholarly publishing in physics has changed dramatically as a consequence of a service introduced by Paul Ginsparg at Cornell in 1991 that users call the arXiv (see also http://en.wikipedia.org/wiki/ArXiv). Many of us are hoping that bioRxiv will motivate similar changes in biology.

What is a “preprint server” and why are people like me so excited about it?  The original arXiv is a website where researchers can post manuscripts for free and without any peer review. Physicists typically post newly written papers directly to the arXiv even before submitting to a journal. The authors benefit from being able to immediately claim priority on their discoveries. The physics community as a whole benefits by being able to read new research without the lengthy delay often caused by the peer review process. And a much larger community of interdisciplinary scholars across the globe benefits from having free access to everything that is posted.

One might worry about the effect such a preprint server would have on the peer-review process. But in the physics community, the arXiv is widely believed to have strengthened the peer-review process. When physicists read an article that makes questionable claims, or is hard to understand, they often just email the authors and (politely) say so. And after the authors have received feedback, either from such emails or from the formal review process at some journal, they will post a revised manuscript.

What about the bad research or pseudoscience that remains on the arXiv? Frankly, people just ignore it. For instance, every weekday morning I get an email from the arXiv listing the abstracts of all the papers that were posted to the q-bio (quantitative biology) section the previous day. Most are not of any interest to me, and not infrequently I see a manuscript that is obviously pseudoscience, but so what? It doesn’t take that long to read the email, and whenever I do see something that might be interesting — either from some author whose research I like, or on a topic I’m interested in — I add it to my reading list.

There has been a lot of hand wringing lately about how to improve scholarly publishing in the biological sciences — how to improve the quality of papers, how to prevent lengthy delays in publishing, how to avoid the unnecessary experiments often asked by reviewers, how to reduce delays in the publication process, how to guarantee free access to research that, after all, was likely paid for by taxpayer dollars. I would argue that physics has already solved this problem: freely accessible preprint servers. This is why I believe the bioRxiv is such an exciting development.

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A Brave Genius

by WSBS graduate student Kristen Delevich

On Monday October 28th, the Cold Spring Harbor Laboratory community filled Grace auditorium to hear noted biologist and author Sean Carroll discuss the role of chance and circumstance in the life of the French scientist Jacques Monod. While many in attendance were familiar with Monod’s Nobel Prize-winning research about how organisms tune their gene expression to respond to the environment, few knew about his prominent and dangerous role as a member of the French resistance in Nazi-occupied France.

In his introduction, James Watson described Monod as biology’s “only true movie star.” Indeed, as Carroll chronicled Monod’s life during WWII, events unfolded like a historical thriller. In early 1940, Monod was an ordinary doctoral student who directed choral groups in his free time. Everything changed with the shocking Nazi occupation, which threatened his family. Monod (a Christian by birth) sent his Jewish wife and children to the countryside and joined one of France’s most militant Resistance groups. As an officer, he carried out covert cross-border missions into neutral Switzerland and orchestrated a network of anti-Nazi saboteurs who operated in the streets of Paris – all the while carrying out biological experiments that laid the groundwork for his 1965 Nobel Prize.

Through firsthand accounts and newly uncovered documents, Carroll discovered just how close Monod came to capture during the war. In his book Brave Genius, Carroll explores how the chance encounters and lucky breaks that carried Monod safely through WWII instilled in him a sense of urgency and purpose that ignited his scientific genius. Monod believed that the most important science could change the way people viewed themselves in relation to the world. The transformative truth he found in Darwin’s theory of evolution and the early discoveries of molecular biology was that humankind is the product of an incalculable number of fortuitous events.

As Carroll’s remarkable story suggests, the same could be said of Monod himself.

*******

The lecture was part of an annual series held in memory of Gavin Borden, the late publisher of the influential Molecular Biology of the Cell textbook. The series is intended to enhance the educational experience of graduate students at Cold Spring Harbor Laboratory and annually includes a roundtable discussion with the visiting Gavin Borden fellow. Carroll, whose research has focused on how genes control animal development as well as the evolution of animal forms, is vice president of science education at the Howard Hughes Medical Institute. He directs initiatives to increase the public’s understanding of science by educating and inspiring its youngest members. You can read more about Brave Genius at here.

 

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SCIENCE SHORTS: The Social Brain and Autism

Check out this SCIENCE SHORT – “The Social Brain and Autism” – in which postdoctoral researcher Yongsoo Kim, Ph.D., of Associate Professor Pavel Osten’s laboratory helps us understand more about how we are using mice to study behaviors associated with autism. Statistics from the U.S. Centers for Disease Control and Prevention (CDC) identify around 1 in 88 American children as on the autism spectrum –a ten-fold increase in reported cases over the last 40 years.

In the Osten lab, researchers focus on the analysis of brain regions and how brain cells connect and communicate with each other to drive behaviors. This communication between neurons may be disrupted in disorders like autism and schizophrenia. The lab uses the latest technologies to image entire mouse brains and to map brain-wide neuronal activation evoked by various behaviors, including social behavior. Dr. Kim and his CSHL colleagues try to identify the specific cell types in the brain regions involved, and test the role of different cell types and brain regions in mediating specific aspects of the behaviors. The goal is to identify targets for therapeutic development.

Congratulations to Yongsoo, recent winner of a coveted NARSAD Young Investigator Award, which he will use to pursue research on the hormone oxytocin in a mouse model of autism. Because oxytocin has been associated with certain behaviors including social recognition, bonding, anxiety and maternal behaviors, it is sometimes referred to as the “bonding hormone.” Yongsoo is looking at which brain regions respond to doses of intranasal oxytocin, and how administration of this hormone alters brain activity in response to social stimulation. Read more about the award here.

About SCIENCE SHORTS: Each short talk of approximately 5 minutes explores a topic or area of research at CSHL. They were designed for non-scientific audience and given by a CSHL Ph.D. student or postdoc. So far we have covered the question “Why haven’t we cured cancer yet?“; the beautiful imagery generated by the important scientific technique of florescence microscopy; and, how protein structures are determined using “molecular photography.”

A 3-D Diagram of a new microscopic technique which shows every brain cell within a mouse's brain. Image taken from video.

 

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The Single Cell Analysis course – at the cutting edge of science

 

Instructors and participants of the single cell analysis course at CSHL June 2013

Instructors and participants of the single cell analysis course at CSHL, June 2013.

In June I had the chance to sit down and talk with Professors Jim Eberwine (University of Pennsylvania) and Cynthia McMurray (University of California, Berkeley/Lawrence Berkeley National Laboratory) about the Single Cell Analysis course they co-direct, held here at Cold Spring Harbor Laboratory (CSHL). The course, currently in only its second year, was a natural branch from a meeting and concurrent workshop on Single Cell Analyses. I wanted to know what made this nascent course so special. Jim and Cynthia enthusiastically recounted how the course got started, where it is going, and just what makes this area of science and the course they have put together so unique.
Continue reading

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SCIENCE SHORTS: Molecular photography

Following on from our last SCIENCE SHORT about fluorescence microscopy imaging, postdoc Jonathan Ipsaro, Ph.D., of Professor and HHMI Investigator Leemor Joshua-Tor’s laboratory, takes us even deeper into the molecular world as he talks about what he calls “molecular photography.”

This 5 minute SCIENCE SHORT delves into how scientists determine the structure of proteins and build pictures of them in order to design therapeutic drugs for malaria for example, amongst other important questions. The malaria protein shown decorates the surface of the malaria parasite and enables it to bind red blood cells. Jonathan presents the 3D structure of this protein in order to show just how much information they can get from “molecular photography.”

About SCIENCE SHORTS: Each short talk of approximately 5 minutes, explores a topic or area of research at CSHL. They were designed for non-scientific audience and given by a CSHL Ph.D. student or postdoc. So far we have covered the question “Why haven’t we cured cancer yet?“, the beautiful imagery generated by the important scientific technique of florescence microscopy, and, in this current installment, determining protein structures using “molecular photography.” Coming soon, the final one in this year’s series.

Jonathan Ipsaro SCIENCE SHORT molecular photography malaria

Malaria surface protein 3D structure; determined in the laboratory of Professor and HHMI investigator Leemor Joshua-Tor

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The DNA60IFX genome sequencing contest draws 1000 competitors worldwide

by Michael Schatz**

This past April 25th was the 60th anniversary of the publication of Watson and Crick’s famous paper describing the double helix structure of DNA. Many events were held around the world to celebrate the historic day, including a contest organized by James Taylor of Emory University and myself, and sponsored by the journal Genome Biology.

DNA60 IFX color puzzle

The contest consisted of a series of 5 DNA-related analysis problems released over 4 days, organized so that the solution to one stage was needed to unlock the clues to the next. Continue reading

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