Category Archives: Medicine

Trinity Junior in Phoenix for Summer, Doing Real Research

July 23rd, 2012

By: Nonie Arora

Sonya Jooma, Trinity '14, provided by Steve Yozwiak

Rising Trinity Junior Sonya Jooma is in Phoenix, Arizona this summer working at the Translational Genomics Research Institute (TGen) as an intern in the TGen-Duke Biomedical Futures Program. This is the first year TGen and Duke have partnered to offer a funded biomedical research internship exclusively for Duke students. Jooma and a second Duke undergrad, Geoff Houtz, are the first two students to participate in this pilot program.

The TGen-Duke Biomedical Futures Program joins the growing list of Duke programs for students excited about genomics, such as the Genome FOCUS program and the Institute for Genome Sciences & Policy Summer Fellowship. In fact, the Genome FOCUS spurred Jooma’s enthusiasm for genomics research. Last year, she worked in the John Willis lab researching plant genetics as part of the Howard Hughes Research Fellows Program.

Her project at TGen, in the lab of Dr. Lisa Baumbach-Reardon, centers on the genetic basis of Infantile Spinal Muscular Atrophy. This disease causes muscle weakness and abnormality at birth. Afflicted children often die before their second birthday. According to Jooma, there are cases of this disease for which the genetic basis is unknown. As part of her lab’s exome sequencing project, they hope to identify mutations involved in the disease.

Jooma says her TGen experience has been great so far. She finds it similar to working in a research lab at Duke because of the similar lab hierarchy. However, she appreciates that TGen has overarching specific goals that focus on translating discoveries to clinical diagnostics and therapies. Jooma also looks forward to attending professional development workshops and presenting her work at TGen’s annual intern research symposium in July.

Ultimately, Jooma’s experience at TGen will be one of many exciting research projects: she hopes to pursue a career in biology research.

CSI-House teams could make better medical diagnoses

June 28th, 2012

By Ashley Yeager

Comparing a child's DNA to his parents' could help with identification of hard-to-diagnose genetic diseases. Credit: Henrik Jonsson/iStockphoto

Dr. Gregory House, star of House, M.D., and the lab techs on CSI never fail at their jobs. But that’s Hollywood. In real life, diagnosing illnesses and sequencing DNA isn’t so straightforward. It doesn’t always lead to a happy ending either, especially for children who are sick but can’t be diagnosed, even by gifted, real-life doctors.

That’s exactly why geneticist David Goldstein has teamed with pediatrician Vandana Shashi to combine a little House and CSI to identify apparent genetic diseases and quickly end some families’ diagnostic odysseys.

So far, the team has provided likely genetic diagnoses in six of 12 children it has worked with, said Goldstein at a Cardiovascular Research Center Seminar Series talk on June 27.

The children were referred to Shashi for a pilot study where she would record their symptoms, or phenotypic behavior, much like House. Then, Goldstein and his team at the Center for Human Genome Variation collected DNA samples from the children and both of their biological parents.

Using next-generation genetic sequencers, as well as traditional DNA scanners, Goldstein and his team looked for genetic variations between the children’s and parents’ complete genome. Like looking at DNA to identify a criminal, Goldstein and his genetics team are scouring the sequences for genetic fingerprints of the diseases disrupting the children’s lives.

Once variations were identified, the entire team looked for known diseases with similar gene mutations and symptoms. Goldstein explained that the study not only pinpointed the undiagnosed congenital diseases in some patients but also presented new genes that could also be linked to the illnesses. The study’s success has led to the creation of the Genome Sequencing Clinic.

The clinic will begin to help the families of the 50,000 children (out of the four million) born each year in the US with difficult-to-diagnose genetic diseases. These types of studies will likely be the “earliest drivers for large-scale genetic sequencing,” Goldstein said.

But, he cautioned, “there’s a whole lot of junk,” or variation, in DNA. Every genome has the narrative potential for devastating diseases, and that means that House-CSI teams, like Shashi and Goldstein’s, need to be extremely careful when making diagnoses, especially if the results will influence treatment, he said.

Citation: Clinical application of exome sequencing in undiagnosed genetic conditions. Need, A. et. al. 2012. J. Med Genet. 49:6 353-361. doi:10.1136/jmedgenet-2012-100819

Rethinking science on pandemic-potential viruses

May 18th, 2012

By Ashley Yeager

Debates over experiments subjecting ferrets to modified bird-flu strains had scientists and politicians seriously questioning how to approach and publish studies on pandemic-potential viruses. Credit: J. Smalley/NaturePL.com

Making mutant forms of bird flu and publishing the results caused a major squawk in the public and in the political and scientific communities over the last year.

The issue was whether the new mutants could ward off a major pandemic of bird flu or start one, explained Stephanie Holmer, a graduate student in Duke’s Department of Cell Biology.

She raised the issue during the May 18 meeting of the Science and Society Journal Club.

The row began when researchers at the University of Wisconsin-Madison and the Erasmus Medical Center in the Netherlands independently tweaked strains of the H5N1 virus, commonly named the bird flu. The strains, the teams report, are more easily transmitted between ferrets, the lab-double for humans.

“The fear was that if the mutant forms of the virus got out of the lab, bioterrorists could use them to make a super-virus and start a pandemic. But there was not any guarantee that what the scientists had was a weapon. The mutant strains weren’t even that efficient at killing a ferret,” Holmer said.

During the forum, about a dozen students and faculty from departments across campus debated whether this kind of research should have been done, if journal editors should publish the full results and what can be done to prevent future squawks about similar types of research.

Electron micrograph of influenza A virus. (Centers for Disease Control, Erskine Palmer)

Scientists want to study H5N1 to find out how fast the virus mutates and how virulent those strains are in mammals, including humans. So far, outbreaks of the non-mutant form of the bird flu in humans have been limited. The cases, about 100 to 200 from 2003-2012, have occurred most often in Indonesia, Egypt and Vietnam, according to statistics from the World Health Organization.

In two separate papers, the teams from Madison and the Netherlands reported the strains of H5N1 that seemed to be more virulent in ferrets. The Madison team submitted its paper to Nature; the Netherlands’ team submitted to Science. Both papers came under government scrutiny before they were published because the methods in each could potentially be misused to make a bioweapon.

But the researchers had already presented their data at conferences, and they had institutional approval to initiate the experiments, facts that led Subhashini Chandrasekharan, co-coordinator of the journal club, to wonder aloud why it took until the point of publication to prompt a government and scientific scuffle over the experiments and the results.

“I’m not a virologist, but I don’t find any reason that the study should not be done or that the results should not be published. The jump of this virus from birds to humans is going to happen. It’s only a matter of time. If we already understand the mutations, then we’ll be faster at finding treatments and vaccines,” Chandrasekharan said.

She added that if a bioterrorist is going to make a weapon from a virus, it didn’t seem likely that they’d need the papers, which were finally approved for publication on April 20, to make the mutations. They’d do it anyway, she said, explaining that preventing publication was probably not going to be “the wall” to stop a terrorist from plotting an attack.

That issue, of course, raises another whole set of squawks.

Varmus Encourages Provocative Questions

April 16th, 2012

By Nonie Arora

“Provocative questions,” the important but non-obvious ones, the questions to be answered by technology that doesn’t  exist yet, are one focus of Nobel Laureate Harold Varmus‘s storied career these days.

What environment factors change the risk of various cancers when people move from one geographic area to another?

Why are different tissues so dramatically different in their tendency to develop cancer?

How does obesity contribute to cancer risk?

Harold Varmus, Director of NCI Source: cancer.gov

Varmus, director of the National Cancer Institute, visited Duke April 12 to address  the Duke Medical Scientist Training Program 2012 Symposium and to share some of these provocative questions with a full house in Love Auditorium.

Varmus said we are in a period of rapid scientific change because “clinical research and basic research are mingled in a way that is extraordinary.” And while he acknowledged recently flat NIH budgets, he said, “let’s not worry about budgets, let’s worry about opportunities.”

For example, he cited one such scientist who looked for important opportunities, Renato Dulbecco (1914-2012), a virologist from Caltech who died recently. Dulbecco advocated for a systematic approach to sequencing the human genome as early as 1986 despite the many naysayers in the biology community. Varmus called Dulbecco, “a visionary who saw beyond the technology of the day” as he encouraged his audience to think in the spirit of Dulbecco: boldly.

Varmus spoke of how the “precision medicine” of genomics may lead to more accurate diagnoses and a new taxonomy of disease. He made the distinction clear between precision medicine and personalized medicine claiming that even his father practiced personalized medicine because he knew his patients well.

Cancer deaths are rising globally, especially in less developed countries, according to Varmus. He explained how open exchange of information with cancer centers around the world is important to solving new cancer challenges. He described how cancers are more frequently related to infectious agents in the developing world, like the Epstein-Barr virus’s relationship to Burkett’s lymphoma, and the implications for research.

To fund important but non-obvious questions in cancer research, he has launched the “Provocative Questions” Project. These questions are meant to build on specific advances and address broad issues. Because researchers can be more risk-averse when funding levels are lower, this project hopes to fund intriguing questions that would otherwise remain unfunded and unanswered.

These questions need answers. Who better to answer them than the Duke MD/PhD candidates in the audience.

Students Discuss Property Rights to Excised Tissue

April 3rd, 2012

By: Nonie Arora

While students from Duke, UNC, Wake Forest and UVA enjoyed lunch at the first Duke-UNC Bioethics Symposium, Neby Teklu, a Duke sophomore, spoke on property rights to excised tissue.

The circular relationship between people who contribute and benefit from medical research. Credit: Neby Teklu

According to Teklu, when deciding who owns the property rights, the conflict is between the patient — the source of tissue — and the physician or researcher — the possessor of the tissue. Teklu said she is concerned about whether some profits should be returned to people who serve as the source of cell lines when monetary gains are made from pharmaceutical research.

Teklu referenced the Belmont Report, a 1978 document created by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research to address ethical guidelines for human subjects research. The report stresses respect for patients, beneficence and justice.

Essentially, patient autonomy must be maintained. Patients should not be harmed, while benefits are maximized and harms are minimized, and there must be fair distribution of costs and benefits to research participants.

Still, the question remains whether patients have intellectual property rights over their bodies and should be financially compensated for profits from cell lines. Teklu argued that requiring consent for procedures done with excised tissue would hinder medical research.

Neby Teklu speaks at the Duke-UNC Bioethics Symposium. Courtesy of: Nonie Arora.

In the case of Greenberg v. Miami Children’s Hospital Research Institute, Inc., the United States District Court for the Southern District of Florida found that “the research participant’s property right in blood and tissue samples … evaporates once the sample is voluntarily given to a third party.” The Supreme Court upheld this precedent in William Catalona v. Washington University, when they decided that the university, not the researcher nor patients, had rights to the tissue samples. The university could sell, license or use the samples any way it saw fit.

Clearly, there is a trade off between social benefits of science using samples from human subjects and individual patient rights, Teklu explained. She said she believes that medical research depends on the altruism of individuals and that requiring additional measures of consent for use of tissues would be harmful for the progress of medicine.

Other students also presented including Duke Research Blogger Pranali Dalvi and Wake Forest undergraduates Elizabeth Stuart and Muhammad Siddiqui. Topics ranged from health care rationing to post-trial access for expensive medications

Informed or uninformed consent?

March 29th, 2012

By Ashley Mooney

Patients giving consent for medical research often do not know what they are getting into, said Christine Grady, chief of the department of bioethics at the National Institutes of Health Clinical Center.

In a March 28 lecture entitled “Ethics in Global Health Research: New Data on Enhancing Informed Consent,” Grady presented the results of her quantitative study on informed consent in the developed and developing countries. As low as 10 percent of patients understood the studies they were participating in, she said, adding that patients in the first and third worlds showed no statistical difference in understanding.

Hospital Corpsman 1st Class Dennis Gamad from Leaitle, Wash., questions a patient who is waiting to see a doctor from the 31st Expeditionary Unit (31st MEU). U.S. Navy photo by Photographer's Mate 1st Class Winston C. Pitman, via Wikimedia Commons.

Using results of 49 studies of the quality of consent—31 in developing countries and 18 in developing countries, Grady compared the quality of informed consent based on patient understanding and voluntariness.

“Informed consent is an ethical, a legal and a regulatory requirement in most healthcare and research with human subjects, but it’s not the only thing that makes research ethical,” Grady said. “There should be a lot of attention to the purpose of doing it, the value of doing it, how the studies are constructed [and] what the risks and benefits are.”

She noted that literacy rates, lack of familiarity with research, cultural-specific patterns of decision making and socioeconomic factors did not prevent informed and independent consent.

“Written documents are increasingly becoming longer and more legalistic, making it impossible for people to understand what they’re getting into,” she said.

Several patients did not understand the use of placebos in research trials, or that they might be randomly selected as members of a control group and not actually receive the treatment.

To improve informed consent, Grady noted that researchers can use tests and feedback, multimedia, enhanced consent forms and extended discussion with a research team member or neutral educator. These methods, however, are based on Western models that do not work in developing countries, she said.

“Informed consent can be improved everywhere. There’s no logical reason to insist that informed consent be identical in countries with different cultures,” Grady said. “We need to be creative in terms of our methods of giving people information, asking them about their understanding [and] enhancing their ability to make decisions.”

CITATION: “The quality of informed consent: mapping the landscape. A review of empirical data from developing and developed countries,” Amulya Mandava, Christine Pace, Benjamin Campbell, Ezekiel Emanuel, Christine Grady. Journal of Medical Ethics, online Feb. 7, 2012. DOI: 10.1136/medethics-2011-100178. Full text.

Catching the Space Bug

March 13th, 2012

Prachiti Dalvi

Robert Satcher, MD, PhD –the first orthopedic oncologist to orbit the Earth –discussed his interest in telemedicine and telesurgery during a school of medicine seminar last month.

Growing up not to far from Duke in Denmark, South Carolina, Dr. Satcher developed a profound interest in science and chose to pursue chemical engineering at MIT. After graduating at the top of his class, he entered the MD/PhD program just across the river at Harvard Medical School and returned to MIT to complete his PhD in chemical engineering.

Then, he followed the more conventional route of interning in general surgery and spending his time as a resident at UCLA. Deciding to further specialize, Dr. Satcher proceeded with an orthopedic oncology fellowship at the University of Florida. For a short time period, Dr. Satcher was an assistant professor at Northwestern before he caught the space bug. Satcher successfully completed a rigorous application and interview process and was elected to begin space training at NASA.

Although his interests span chemical engineering and orthopedic oncology, he is particularly interested in bone mineralization, nanomaterials, and bone metastasis in cancer. At the MD Anderson Cancer Center he is exploring telesurgery and telemedicine. In November 2009, Dr. Satcher went into space as a mission specialist on Atlantis, spending more than 200 hours in space and engaging in more than twelve hours of spacewalk.

“Medical knowledge comes into play when people are going through adaptation in aerospace,” Satcher said. While in space, Satcher performed maintenance and conducted research on how the human body reacts in space. His own research interests resonated through when he was able to study how bone density and skeletal muscles are affected by zero gravity. Dr. Satcher likened walking in space while inspecting the station’s outside equipment to surgery: attention to precision is vital. To complete this task, he was able to use his surgical skills to navigate a robotic arm to scan the shuttle for damage.

Although space exploration comes with some dangers and difficulties, Satcher believes space exploration is important because there is a lot we still do not know. According to Dr. Robert Satcher, the common thread of curiosity for the unknown ties space exploration and medicine.

Raiders of the Lost Blood Spots

March 2nd, 2012

By Nonie Arora

Blood Spots Assessed by CDC

Almost every newborn in the United States is pricked on the heel within hours of birth for a few drops of blood that are then tested for conditions like PKU, sickle cell anemia, and cystic fibrosis. But then the sample is often put on small piece of blotter paper and filed away by the state. Few parents know about these millions of residual dried blood spots.

Alex Kemper, Duke professor of pediatrics and community and family medicine, spoke at the Genomics and Personalized Medicine Forum on the “raiders” of these lost blood spots, researchers who might use them to improve public health. Along with issues of science, he addressed the negative public reaction to research using stored blood spots. “Why does the government have my DNA?”

Dried blood spots have many uses beyond early detection of diseases. They can be used to improve quality of current screening tests and new screening approaches. In a few cases, dried blood spots have been valuable in forensic analysis to identify an abducted child. In this era of increasingly personalized medicine, being able to use blood spots for genomic analysis would provide answers to new research questions, Kemper said.

However, the differences in the way blood spots are stored present research challenges. Kemper is very interested in how environmental toxins affect children’s health. When his research team attempted to use dried blood spots to study how flame-retardants affect thyroid problems, they ran into a major problem. Because blood spots are often stored in an environment more like the warehouse from Raiders of the Lost Ark than a controlled lab environment, the specimens were too contaminated to use for research.

Besides the inherent quality concerns, the public is wary of researchers using blood spots because of the lack of consent and confidentiality. (See “Texas Newborn Bloodspot Saga”) Should researchers be able to use blood spots from infants without consent from parents? Should the blood spots be anonymized to protect privacy even though anonymization limits the types of research that can be performed?

These questions do not have easy answers.

States differ on legislation about the retention, confidentiality, and parental control of blood spots. Some states have no rules at all. Kemper claimed that many of these laws are currently in “a state of flux” because of pending lawsuits and changing public perceptions. As the rules change, one thing is almost certain: improving the genetic literacy of the public is essential to advancing uses of dried blood spots.