Scarlet Shell (sshell@ucsd.edu)

Graduate Program:  Biomedical Sciences
Lab PI: Richard Kolodner
Undergraduate Education: Smith College
Med-into-Grad Clinical training area: Tropical infectious disease
Main clinical mentors:
Joseph Vinetz jvinetz@ucsd.edu
Carlton Evans carltonevans@yahoo.com

Quote: I was interested in Med-into-Grad because I wanted to study infectious diseases in my postdoctoral work, and I wanted to do work that was clinically relevant. Most of my training occurred in Peru, where I focused on malaria and tuberculosis in a remote lab in rural Iquitos, and a the public hospital in Iquitos. For malaria, microscopy of blood smears remains the most effective diagnostic both in the US and in developing countries. There are currently no effective drug-susceptibility tests available, and choice of therapeutics is based on what is known about resistance rates in a given region. There is a need for more robust diagnostic techniques, since microscopy is time-consuming and results can vary considerably depending on the skill of the microscopist. In very rural areas in Peru microscopy is not available, and the low case-load would make it difficult to maintain a well-trained microscopist. In these areas in particular, rapid and robust tests that do not require equipment or electricity are needed. Diagnosis of malaria is also complicated by its non-specific symptoms and by the fact that people clinically immune to malaria can nonetheless become infected and even have high parasitic burdens; therefore, the finding of parasites in a patient’s blood does not necessarily mean than malaria is the cause of the patient’s symptoms, and other etiologies may be overlooked. Along with improving malaria diagnostics there is, therefore, a need to improve diagnosis of other fever-inducing etiologies that probably cause significant morbidity and mortality that is falsely attributed to malaria. Such misdiagnoses may contribute to the development of drug resistance as well.  My post-doctoral work at Harvard will focus on tuberculosis in a manner that I hope will contribute to improvements in managing tuberculosis in poor countries, where it poses the greatest public health problem.”

Rationale for Med-inito-Grad training:
Medical training and identification of medically-relevant research issues:
Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:
Diagnostic, therapeutic, and research collaborations:
Student-specific experiences:
Long term impact.:
Advice for new trainees--autumn preparatory quarter:
Advice for new trainees--winter clinical training quarter:
Take home perspective on Med-into-Grad at UCSD:

Rationale for Med-into-Grad training: My thesis work is concerned with dissecting the mechanisms of DNA mismatch repair using genetics and biochemical techniques. I have investigated the mechanisms of mispair specificity and the functions of previously uncharacterized domains of mismatch repair factors. I was interested in Med-into-Grad because I wanted to study infectious diseases in my postdoctoral work, and I wanted to do work that was clinically relevant. The Med-into-Grad program offered a good way to learn more about the diseases that interested me and establish a framework of clinical knowledge that I could use to inform my future research.

Medical training and identification of medically-relevant research issues: Most of my training occurred in Peru, where I focused on malaria and tuberculosis. In Iquitos under the supervision of the malaria lab of Joseph Vinetz, my activities included the following: attend infectious disease or pediatric rounds at a public hospital; accompany nurses employed by the project to enroll patients in studies at local hospitals and health posts in conjunction with attendance to their illnesses or complaints; go to villages near Iquitos with teams conducting surveys or performing GPS mapping as part of transmission dynamics studies; accompany teams collecting mosquito larvae from village sites for transmission dynamics and infectivity studies; accompany teams performing door-to-door surveys of malaria symptoms and infection to determine rates and dynamics of infection. In Lima under the supervision of the tuberculosis labs of David Moore and Carlton Evans, my activities included the following: attend case presentations at a public hospital; attend rounds in an HIV ward of a public hospital; observe at a free clinic for street children; accompany nurses employed by the projects to enroll and collect samples from patients newly diagnosed with HIV in a tuberculosis diagnosis study; accompany nurses enrolling and collecting samples from patients with multi-drug resistant TB for second-line drug susceptibility studies and contacts of patients for diagnostic studies (in clinics and home visits); observe lab procedures for diagnostic and susceptibility testing of clinical samples; perform lab experiments assessing the use of colorants as indicators of mycobacterial growth; perform analysis of data collected from clinical studies of colored indicators.
         Through observation at clinics and hospitals I not only learned about prevalence, diagnosis and treatment of specific diseases, but I also gained an understanding of the clinical atmospheres in a diverse group of health care settings in Peru and of the effects of poverty and severe resource limitations on how health care is delivered. Observing the living conditions and daily life of Peruvians from different socioeconomic classes was also an important component to understanding the complexities of public health in this country. From discussion with doctors and nurses involved in attending patients and performing research, principal investigators, students, lab technicians, and ordinary Peruvians, I learned about topics including disease prevalence, diagnosis and treatment, the effects of resource limitation on health care and public health efforts, design of research projects to address identified needs, techniques and challenges of actually carrying out clinical research projects (including finding patients, working with government authorities, and developing productive relationships with the communities involved), and the challenges of incorporating the products of research into a real-world health care system.
         In the field of tuberculosis, it is now clear to me that there is a need for faster, more effective diagnostic and drug susceptibility testing techniques that are cheap and simple enough to be used in resource-limited and often physically isolated environments. There is also a need for more rapid techniques for evaluating response to treatment, so that patients who are not responding can be quickly identified and switched to other treatment regimens. Investigation of transmission dynamics is also important to identify people at greatest risk of disease and appropriately direct resources for screening. Additionally there is a need for new drugs to shorten and simplify treatment, as well as effectively combat drug resistant strains, thereby allowing higher treatment completion rates and decrease both fatality rates and transmission. Of course there is also the obvious need for continued vaccine research. In the field of malaria, there is a need to investigate the dynamics of transmission and development of immunity, so that candidate vaccines (which due to the complexities of immunity to malaria may be designed to prevent infection, illness, or transmission) can be appropriately tested and their effects on target populations can be accurately predicted. There is also a need for simple diagnostic techniques that do not require a microscope for use in very sparsely populated rural areas.

Research collaborations: I developed a collaboration with Dr. Carlton Evans while I was in Lima. I did some experiments in his laboratory to complement a larger project that his lab had already undertaken, and since returning to the US I have done data analysis for this project and plan to participate in writing the manuscript.

Long term impact: Learning about the context in which tuberculosis diagnosis and treatment occurs in a developing country like Peru has affected my choices by leading me to seek a post-doc in which I will be able to perform research that I hope will contribute to improvements in managing tuberculosis in poor countries, where it poses the greatest public health problem. More broadly, understanding the medical realities of malaria and tuberculosis has broadened my perspective as a researcher. I have also learned about how productive collaborations are formed between healthcare providers and researchers, which I hope to have the opportunity to put into practice when forming my own collaborations in my future research.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:       For tuberculosis, state-of-the-art diagnostics currently consist of automated culture systems that allow for relatively rapid detection of mycobacterial growth and determination of susceptibilities to first-line drugs. These systems are supplemented by sputum-smear microscopy and molecular tests that allow for quicker diagnosis and susceptibility determination for some patients. Unmet needs include the need for faster diagnostics for smear-negative patients, and more rapid drug-susceptibility tests, particularly for second-line drugs. However, in developing country health care systems the unmet needs are somewhat different. In Peru the automated culture systems are unaffordable, and slower manual culture techniques are used. In countries that have even poorer infrastructure, culture may not be performed at all, and sputum-smear microscopy may be the sole diagnostic tool available. The needs in these countries are for simple and inexpensive diagnostics and drug-susceptibility tests that are highly robust, don’t require extensive training or equipment, and ideally, that have minimal need for electricity. With respect to therapeutics, the needs in rich and poor countries are similar: drugs are needed that can effectively treat TB in a shorter period of time than the currently required six months to two years, and drugs with new mechanisms of action are needed to combat resistance. In all countries, co-infection with HIV is common in TB patients and leads to unique challenges in diagnosis and treatment; strategies designed to circumvent these challenges are needed.
            For malaria, microscopy of blood smears remains the most effective diagnostic both in the US and in developing countries. There are currently no effective drug-susceptibility tests available, and choice of therapeutics is based on what is known about resistance rates in a given region. There is a need for more robust diagnostic techniques, since microscopy is time-consuming and results can vary considerably depending on the skill of the microscopist. In very rural areas in Peru microscopy is not available, and the low case-load would make it difficult to maintain a well-trained microscopist. In these areas in particular, rapid and robust tests that do not require equipment or electricity are needed. Diagnosis of malaria is also complicated by its non-specific symptoms and by the fact that people clinically immune to malaria can nonetheless become infected and even have high parasitic burdens; therefore, the finding of parasites in a patient’s blood does not necessarily mean than malaria is the cause of the patient’s symptoms, and other etiologies may be overlooked. Along with improving malaria diagnostics there is therefore a need to improve diagnosis of other fever-inducing etiologies that probably cause significant morbidity and mortality that is falsely attributed to malaria. Such misdiagnoses may contribute to the development of drug resistance as well.

Diagnostic & therapeutic collaborations:  I do not have any specific ideas for diagnostics or therapeutics that I am planning to pursue. My immediate plans are to study the mechanisms of pathogenesis of tuberculosis, with the goal that a better understanding of TB can lead to novel insights about how we can shorten the length of chemotherapy required for treatment.

Student-specific experiences:  This unique experience taught me lots of things I didn’t even expect. I would advise all graduate students to pursue this opportunity if they are able. Graduate training rapidly becomes very focused, and Med-into-Grad provides an unusual opportunity to get a broader sort of training that gives a very valuable perspective.

Advice for new trainees--autumn preparatory quarter:  I recommend studying anatomy and medical terminology. For students going to Peru, I recommend working hard on their Spanish, because the amount they can get out of this experience will be proportional to how much Spanish they can speak and understand.

Advice for new trainees—winter clinical training quarter:  For a student going to Peru, advice on this topic would be highly dependent on their focus. My experience focused more on clinical research than on patient care, and my role in clinical settings was strictly observational. I think there is room for further development of the clinical training aspect for future students going to Peru by recruiting Peruvian physicians to act as mentors to Med-into-Grad trainees.

Take home perspective on Med-into-Grad at UCSD:  I think this is a terrific training opportunity and I highly recommend it to other students. The single most interesting part of my experience was simply seeing what life is like in a very different country, which is something inherently fascinating to me. Visiting hospitals, health posts, and even the homes of people in impoverished areas gave me an insider’s view that visitors to foreign countries don’t easily get. I believe the most important thing was seeing the wider context of the seeking and provision of health care, which allowed me to develop an understanding of how treatment of disease is much more complex these than simply having a good diagnostic test and an effective drug. The effectiveness of health care depends on myriad factors including what kinds of care are available, what they cost, how difficult it is for people to access them, how difficult it is for people to access follow-up care, people’s beliefs about the risks and dangers of various behaviors, illnesses, and treatments, healthcare providers’ attitudes towards patients and vice versa, conflicts between complying with treatments and fulfilling people’s everyday obligations at home and work, and so many more. I think an understanding of these contextual issues is important for anyone trying to make an impact in the health care field, even in strictly lab-based research, because it’s all interconnected and the more one can see the bigger picture, the more effective one can be.

Unsolicited communication:

Dear Dr. Kamps,

I want to give you an update on how Med into Grad is continuing to influence my career in very positive ways. Last week I went to the American Society of Tropical Medicine and Hygiene annual meeting and I presented a poster on the TB project I got involved in while I was in Peru. The principal investigator on this project is Carlton Evans, a colleague of Joe Vinetz. I did a lab experiment for the project while I was in Lima, and since then I have been involved in analyzing a large clinical data-set and I will be taking a lead role in writing the manuscript.

I have also been applying for post-doctoral positions at TB labs in Boston and New York and I have been getting very good responses and will be going back east to interview at 5 or 6 labs next month. Everyone I have talked to mentions my experience in Peru, so I think it has been a key factor in demonstrating that my interest in TB is serious and that I am coming to this field with some experience and knowledge. And the education I got in Peru really does inform my thinking on TB in important ways. My experience there taught me things that can't be learned from books. I am so grateful that Med Into Grad exists and that I had the opportunity to participate, because it already is having a meaningful impact on my career. I hope the program continues so that other students can have these opportunities as well!

Thanks so much for all your support and giving me this opportunity. I am so happy and excited with the direction my career is going. It's like a dream coming true.