What Are Scientists Made Of?

Last Thursday, the Duke Career Center, the Duke Institute for Genome Sciences & and Policy (IGSP) and Women in Science and Engineering (WISE) sponsored a screening of the documentary “Naturally Obsessed: The Making of a Scientist,” the story of three PHD candidates working to establish their careers in a Columbia University lab. The students are working to isolate proteins and determine their structures using X-ray crystallography, a difficult technique that requires a lot of luck.

The documentary, filmed over the course of three years, captures the heartbreaking failure that can follow months of work, as well as the surprising triumph that can result from a breakthrough. Each of the three students has their own reason for being there, and each approach their research in a different way. (Click here to read a review)

At the beginning of the movie, lab director Larry Shapiro somewhat controversially says that “one of the best things you can do as a scientist is suffer from Obsessive Compulsive Disorder (OCD). You become obsessed with a problem and can’t stop working on it until you find your answer.”

However, Dr. Rochelle Schwartz-Bloom, director of Duke’s Center for Science Education, argues that “you don’t have to be OCD or obsessed to love what you’re doing, you just have to have passion for it.”

Schwartz-Bloom was one of six panelists who shared their thoughts with the audience after the movie.

Grad student Vincent Chen was impressed with the film’s accuracy “in terms of the ups and downs in science. You have a lot of failures, and very few successes.”

Grad student Cynthia Tedore disagreed. “I didn’t see the repeated failure as accurate from my point of view. In any field, it’s bad to pursue one project with a small chance of succeeding. It’s better to pursue several.”

A member of the audience commented that, based on her experience in an X-ray crystallography lab, she thought the filmmakers did a good job. “I was touched by everything that happened. There are upsides and downsides. X-ray crystallography is very different from other fields, so [the movie] might not reflect what happens in other labs.”

Schwartz-Bloom said that the movie made her nervous with its emphasis on hard labor with a small chance of success. “A lot of kids today don’t go into science because they think it’s ‘too hard.’ Even people with some passion for it decide that they don’t want to do it.” She worried that the movie would only encourage this sentiment.

Fortunately, not everyone was so discouraged. My bio major friend told me that, despite the grim portrayal, she had not been dissuaded from her goal to be a scientist.

At the end of the discussion, the panelists offered their advice for aspiring researchers like my friend.

“Sometimes it is important to know when to quit, when a problem is impossible to solve. Otherwise, you can trash your entire career.” -- post-doc Rebekah Fleming

“Be a sponge. Take in everything you can, because you don’t know when you’ll need it in the future.” -- Schwartz-Bloom

“Don’t be afraid to find out what your weaknesses are, and how to fix them.” -- Tedore

“Science should be fun. If you’re doing it for your boyfriend or for your parents, you can do it for a while, but eventually it’ll break your heart.” -- panel moderator, professor Mohamed Noor of the Biology Department

What Comes After Genetics?

Guest post from James Todd, host of Duke's online "Office Hours" program.

Just when you thought you had a grip on genetics and genomics, there's this new thing called "epigenetics” that is becoming increasingly prominent.

One of the pioneers of this new field is Duke's Randy Jirtle. (visit his lab’s website)

Two years ago, the National Institutes of Health announced that it planned to provided $190 million in funding for epigenetics research over five years, as part of its Roadmap Epigenomics Program. Recent stories by NOVA, Time and the Washington Post have highlighted the importance of the field.

So what is epigenetics? Jirtle gives a definition in this video.

Curious to learn more? You can also watch Jirtle’s recent “Office Hours” interview.

Who Decides Who Lives and Dies?

As an audience filed into a Duke Hospital auditorium last week to hear Philip M. Rosoff talk about the ethical difficulties of apportioning scarce resources to fight a pandemic, a line of people waiting for flu shots in the hallway outside stretched out of sight.

Rosoff, a professor of Pediatrics and Medicine at the Trent Center for Bioethics, Humanities and History of Medicine, raised the same question as the flu shot queue: “How does one equitably distribute limited resources to as many as could benefit from them?”

Who will live and who will die? Who decides? As a result of improved technology and effectiveness of medicine, healthcare workers must make increasingly difficult decisions.

“Most of the dilemmas facing medicine in 2008 did not exist in 1918,” Rosoff said. “You either got better, or you died.”

“Our expectations of what modern scientific medicine can provide are totally different today. We expect ‘miracles’ every day and are vastly disappointed and even shocked when medicine doesn’t deliver,” Rosoff said.

With scarce resources in the emergency room, how would you choose between a 21-year-old honor student and an 86-year-old nursing home resident? Not a difficult choice for most in the audience. But how would you choose between a 21-year-old honor student and a 40-year-old mother of three young children? Between two 21-year-old honor students? Or between an honor student and the child of a colleague? The audience grew solemn as he went down the list.

“Everyone was happy to knock off granny,” Rosoff joked.

Planning for a potential epidemic reveals some critical problems. “Even during a regular flu season, about 100,000 medical ventilators are in use. In a worst-case human pandemic, the country would need as many as 742,500,” Rosoff said.

Duke Hospital has a supply of 150 ventilators, of which 90% are in use or in repair in any given time. Of those, a number are suitable only for infants or young children. The Strategic National Stockpile has 4,900 ventilators in strategic locations across the country and hospitals nationwide have about 105,000 ventilators.

“People will still get cancer, will still have heart attacks, acute appendicitis and premature babies and thus need hospitalization: what happens to them if we have a pandemic? Do we send the 65-year-old cancer patient home so we have a bed for the 35-year-old with influenza?”

Rosoff said some allocation systems have been proposed:

• Minor adaptations of standard emergency department triage systems for assigning ventilators
  
• The “life cycle principle” for rationing vaccine, privileging the young over the old (with the idea that each person should have an opportunity to live through the different cycles of life)
  
• A variation of the organ transplant distribution system, which is already widely accepted

“We should not ration care based on morally arbitrary and irrelevant features about people, such as skin color, ethnicity, religion, age, gender, etc. ... Social worth -- however you feel about people -- should not play into it.”

“Decision making and planning should be transparent and reasons for decisions should be available and defensible,” Rosoff said. “We should apportion care based upon substantiated and justified evidence of its efficacy. We can make societal decisions that anyone over a certain age, or anyone with certain types of disabilities or people not in the country legally will not be eligible for curative care, but this has to be a consensus decision.”

Most importantly, “we must be prepared and have thought through many of these issues ahead of time.”

His proposal for North Carolina, once a healthcare emergency has been declared and resources are scarce:

• Initiate the Hospital Emergency Incident Command System to coordinate resource allocation.
  
• Pre-existing conditions will exclude some patients from consideration for life-preserving care. For example: severe cognitive impairment, heart failure, liver disease, metastatic cancer with less than a year life expectancy and severe burns.
  
• Life preserving resources will be allocated to patients based upon a modified SOFA score with age component (younger patients privileged).
  
• There will be an appeals process available to patent families 24/7 to contest a decision.
  
• Healthcare workers with influenza would not be privileged to receive resources ahead of other patients (colleagues and coworkers do not jump to the head of line -- this is to bestow legitimacy for the public)

“We must reaffirm our moral commitments to serve as a guide for our actions,” Rosoff said. “Hard choices must be public, acceptable and justifiable.”

Preemies' Intestinal Microorganisms Surprising

A research pediatrician and an ecologist are joining forces at Duke to improve the prospects for very premature infants by exploring which bacteria first colonize their intestines.

"We hope this will allow us to ask if there are organisms that, when acquired early, provide early warning or reduce the risk of serious disease," said Patrick Seed, an assistant professor of pediatrics, molecular genetics and microbiology at the Duke Medical Center.

"We're examining which microbes are there, what's their relative abundance and how quickly do pathogenic organisms appear," added Robert Jackson, a Biology and Nicholas School of the Environment professor of biology and global climatic change. He provided Seed with DNA detection tools originally developed to identify which species of microorganisms live in soil samples.

While all babies are thought to be sterile in the womb, they are immediately exposed to their mother's microbes during delivery and through nursing as well as via tender loving handling by relatives, Seed said.

As a result, by the time researchers can assess them, these recent arrivals already have thriving microbial mixtures living in their intestines.

"Living with microbes is a fundamental part of the human experience," Seed said. The growing microbe collections are generally user-friendly species needed for digestion. But bad actors can quickly be acquired in some cases, sometimes causing problems such as diarrhea.

By contrast, the tiny very premature infants arriving months too early are immediately isolated and treated with antibiotics to ward off infections. Even nursing is delayed. Instead, they are initially nourished through a catheter. Thus protected, preemies should enter the world as blank slates for microbes.

So Seed is applying Jackson's molecular toolkit on preemies' stool samples to establish which bacterial varieties are first taking up residence in their immature intestines. As a result, perhaps treating physicians would better know which problem species to anticipate. "Or perhaps we can identify which kinds of organisms could form cornerstones for healthy bacterial communities," Seed said.

So far, Seed has surveyed 11 infants, two of those in great detail, several weeks after their premature deliveries and after they were taken off antibiotics. While Jackson's DNA tests are revealing some diversity in bacterial populations, each baby's gut seems to be harboring the same "predominant organisms," according to Seed.

"I'm just surprised that the infants' immature systems wouldn't give more organisms a chance to move in, he said. "However, this also seems like a real opportunity. We may have more of a chance in the future to help babies develop 'healthy' groups of microbes that promote growth and development while keeping the particularly dangerous players out," Seed said.

Decision Making, of the worst kind

A top-flight research hospital like Duke has the ability to pour tremendous resources and technology into saving the lives of newborn children who might otherwise have died within days, weeks, or months.

And it often does.

How does a family torn between hope, grief, guilt and despair sort out all the probabilities and technicalities? Do faith and hope make a difference? How do they live with the choices they've had to make?

Duke nursing professors Sharron Docherty (pictured here) and Debbie Brandon are trying to understand this complex, enormously stressful situation by doing a long-term study that they hope will help other parents and health care providers make these wrenching decisions in the future.

Funded by a 5-year, $2 million grant from the Institute of Nursing Research in the NIH, their study will enroll as many as 40 families with newborns who are extremely pre-term (before 26 weeks), have serious heart abnormalities, or genetic conditions requiring a stem cell transplant. Health care workers will be part of the data too, since they're part of the decision-making.

Probably 40 percent of these children won't make it to their first birthday, Docherty said. The survivors will likely face continued illness.

Doctoral candidate Kimberly Allen, RN describes one study case of a child who had cardiac arrest at 9 days of age, surgery on day 10, an abdominal surgery for another condition at 28 days, and again at 30 days, whereupon the baby died.

"How do you decide to go back in (for additional surgery)?" Allen asks. When -- and how -- do you make the excruciating decision to simply keep the baby comfortable and let it pass? "We tend, at a hospital like Duke, to do everything we can," Docherty said. Even though it may be a lost cause.

Families and caregivers are interviewed and given questionnaires at regular intervals for a year in an attempt to measure their thoughts, fears, hopes, and feelings throughout the roller coaster ride. The data are more qualitative and subjective than a statistician might like, but "this is the only way to do it," Docherty said at a recent research open house in the School of Nursing. "We've looked at decision-making for decades and haven't really got at this. We've been able to see a tree, but not the whole forest."

The team is working on ways to visualize their complicated findings with the Renaissance Computing Institute (RENCI). Read the abstract of their pilot study. (PDF file)

Flipping through the chronicles of a Nobel Prize winner

"I want to share my time as a scientist by turning the pages in my scientific notebook", Oliver Smithies, 2007 Nobel Laureate for Medicine, said in front of a packed Love Auditorium in LSRC at Duke.

Oliver Smithies, a graduate of Oxford University, is the Excellence Professor of Pathology and Laboratory Medicine at University of North Carolina.

On Thursday, as part of The Duke MD-PhD Program Annual Symposium, Smithies delivered the keynote address "On Being a Scientist for 60 years."

"Science is a matter of chance, opportunity and planning. However, hardly anything ever happens as planned," Smithies noted. He said science has ups and downs. For example, his thesis paper for his PhD on the development of an extremely precise osmometer, "has the dubious distinction of never being cited by anyone."

"So what is, or what was, the point of all the work?" he asked. "It's how you learn how to do science."

Smithies has developed and pioneered numerous techniques in medicine and genetics over the past 60 years that are now universally used in all research work. Early in his career at the Connaught Medical Research Laboratory in Toronto, he developed a technique known as starch gel electrophoresis, which utilizes the properties of starch to act as a molecular sieve, allowing separation of proteins by size. Using this technique, he was able to isolate previously undiscovered protein components of the human serum.

"In my job at Toronto, I worked under David A. Scott, the first person to crystallize insulin. When I asked him 'what am I supposed to do here,' he acted like a true scientist and told me to do anything, as long as it was connected to insulin. That inevitably led to the development of starch gel electrophoresis. This was the chance- the chance invention."

In the mid-1980's , Smithies started to work on gene targeting, and he exploited the naturally occuring phenomenon of homologous recombination to introduce DNA at a defined position in the mammalian genome. "My opportunity here was the inherited differences in plasma proteins. The planning was to try and use the method of homologous recombination to modify the genes. It worked!" Smithies won the Nobel Prize for Medicine in 2007 for this seminal work.

Currently, even at the age of 83, Smithies continues to explore the field of medicine, and his lab at UNC currently focuses on the role of genetics in the development of high blood pressure.

Engineering Solutions for the World's 21st Century Challenges

Engineers and scientists -- including social scientists -- need to work together and urgently to address 14 engineering challenges identified as crucial to Earth's future last year by the National Academy of Engineering, said academy director Charles Vest in a March 2 kickoff address at the Durham Performance Arts Center during the first session of a summit on those problems.

Panels of experts have compartmentalized those challenges into six broad areas, Vest said at the two-day event, hosted by Duke University, the University of Southern California's Viterbi School of Engineering and Franklin W. Olin College of Engineering. Those include energy use, addressing global warming, maintaining sustainability, delivering health care, security against human and natural threats, and developing ways to enhance human capability and joy.

Speaking as a snowstorm was moving up the East Coast and the stock market continued to nosedive in a face of dire and worldwide economic news, Vest remained upbeat. "I believe this is the most exciting time in human history to be engaged with science and engineering," he said. But to harness that excitement, engineering educators also need to revamp curricula to lure more socially committed youth to major in engineering, he added.

A. Paul Alivisatos, the interim director of the Lawrence Berkeley National Laboratory, said he has noticed a startling turnaround of student interest in helping resolve such issues as climate change and such consequences as the potential for geopolitical conflict due to competition for water, land and other resources.

Alivisatos concentrated on another hot button issue, energy use, which he said contrary to public perception does not always increase as nations get wealthier. For example, the State if California's overall energy use actually held steady when compared to domestic outputs after new state standards stimulated new industry innovations in refrigerator efficiencies.

Alivasatos, who replaced Nobel Laureate Steven Chu at Lawrence Berkeley after Chu became Energy Secretary, also described new research efforts to boost efficiencies of collecting the sun's energy by developing solar cells made of nanocrystals or plastics and temporarily storing that energy in molecules like Nature does in photosynthesis.

Robert Socolow, a professor of chemistry, materials science and nanoscience at Princeton University, said successes at building large scale power grids are considered the number one grand engineering achievement of the 20th century. But the goal for the 21st century is not to significantly expand that power capacity but rather improve the efficiency of what exists now with techniques such as recycling waste heat. Tapping nuclear fusion will be a "century-long challenge," and building more nuclear fission power plants a shorter one, Socolow predicted.

Meanwhile, technology is already being developed to remove carbon dioxide from industrial exhausts and store it underground so it can't contribute to global warming, he said. A new challenge will be to regulate the proliferation of nitrogen in a way analogous to CO₂, perhaps by engineering more plants to produce it instead of relying on industrial fertilizers.

Medical Fiction That Rings True

A guest-post from Andrea Fereshteh, senior writer in Duke's office of news and communications:

Re-reading physician-turned author Abraham Verghese’s first book My Own Country last month, I was struck by his raw, revealing look at treating AIDS in East Tennessee during the late 1980s.

My father went to work with Verghese when I was just seven years old and though I identified them as doctors by their white coats and the stethoscopes draped around their necks, I now appreciate Verghese’s graphic illustration of the daily challenges they faced confronting the space between life and death, witnessing humanity laid bare.

Verghese continues to usher readers into the intimate world between patient and physician with his debut novel Cutting for Stone.

He read excerpts from the book and spoke to an audience of physicians, medical students and local fans at the Searle Center last night. (Read a New York Times review and the first chapter of the book)

The story follows twin brothers born of a secret union between an Indian nun and a British surgeon named Thomas Stone in a hospital in Africa. The circumstances are familiar ground for Verghese; he was born in Ethiopia to Indian parents. The twins in the story later find themselves drawn to the medical profession, as did Verghese.
He read aloud two excerpts from the book, including a humorous exchange between two doctors -- one teaching the other how to do a vasectomy -- that had the audience laughing out loud.

He then spoke candidly to the audience about his journey from medicine into writing, and how he continues to straddle both worlds today as professor of internal medicine at Stanford University

Marking a departure from the two non-fiction books he has written in the past, fiction writing, Verghese commented, was a challenge.

“People have an inherent interest in non-fiction because it actually happened,” he said. “For fiction writing, you have to work harder to make the reader suspend disbelief from the moment they begin reading through the last page of the book.”

Describing how he felt drawn to medicine after reading Of Human Bondage by William Somerset Maugham, Verghese says he writes in order to “find out what I’m thinking.”

Writing this book, he said, reminded him that the most important function of a physician is not just scientific or technical, but Samaritan.

“The act of sitting down to write is important,” he said, noting that he keeps a journal and finds time to write whenever he can. “Writing this novel reaffirmed my faith and love for medicine. It is more than a profession, it’s a calling.”