Worrisome Trends in Ebola

My colleague John Brownstein just shared these worrying projections for Ebola epidemiology.

Near real-time tracking of Ebola

If you want to see just how Ebola is spreading (and soon regressing?) , this article provides the view and insight of how it’s done. Ten years ago, these data would percolate slowly, compiled by public health authorities and eventually appear in an academic or lay publication Now through the foundations of computational epidemiology established by Dr. Brownstein, we are able to directly monitor this in-progress disaster. Now that we have a good afferent circuit, let’s see hope the efferent circuit is even more robust.

Achieving clarity in cancer genomics

Approximately 3 years ago, we held a clinical bioinformatics summit to discuss with international leaders in genomics, genetic testing and clinical laboratory procedures what it would take achieve clinical grade whole genome sequencing (WGS). That is to make WGS a safe and useful component of routine diagnostic assessments in the clinic. Among the mechanisms we chose to accelerate the advent of clinical grade WGS was a competition where 3 families contributed their genomic sequence and clinical histories.  Then multiple teams assembled and competed to produce the most accurate, most clinically useful diagnostic report. The competition resulted in a lot of learning and multidisciplinary team formation but also, even though we had not dared count on it, several breakthrough diagnoses. A good lay summary can be found here from Bio-IT World and an in-depth scientific summary here. Also, the cake presented by one of the mother’s to her child, who had gone for years without a diagnosis until the leading teams converged on the same mutations in the same gene, is shown below. With generous funding from Rob and Karen Hale, we kicked off the next round of the CLARITY competition as described below.

In addition to rare undiagnosed diseases, perhaps the most clinically impactful area of genomics, in the near term,  is that of precision diagnostics for cancer. However, the analytic challenge is far deeper as it requires analyzing tumors that are often heterogeneous (i.e. different clones), comparing it to germ line sequence (i.e. non-tumor DNA). Then, how are we to determine which of the mutations found are relevant to the diagnosis or therapy selection? Integrating information from RNA sequence and epigenetic modifications (e.g. DNA methylation) may help and there are several good ideas being proffered by several researchers.  Yet, how do we begin to bring all the data together systematically and meaningfully for patients with a malignancy? Given how early we are in this new realm of medicine, we decided to first hold a workshop where several national leaders in cancer genomics gave thoughtful assessments of the best way forward. After we we synthesize the learning from this meeting, we will announce a new CLARITY challenge for patients with recurrent cancers. Shown below are some of the speakers at the meeting which included Gad Getz, Rick Wilson, Peter Park, David Sweetser, David Margulies, Isaac Kohane, Judy Garber, Sharon Plon, Steve Chanock, Marian Harris, Heidi Rehm, Levy Garraway, and Katie Janeway. Another small but important step forward in the development of a data-driven, computationally-enabled medicine.

Scholar Medical Publication DIY by Harvard Medical Students

If, as F. Scott Fitzgerald is reported to have said, action is character, then the current crop of Harvard medical students are impressive characters. Amid all the din about who controls publication, open access and shortening the loop between academia  and public dissemination, a small group of determined individuals have just come out with their premiere issue of Harvard Medical Student Review. Considerable forethought, extensive deliberations with HMS leadership and creative talent have produced what is likely to become an authoritative voice for medical students and those interested in medical education and science.  In the words of the student publishers themselves:

Today we are introducing the Harvard Medical Student Review, an online journal that will serve as a forum for students to participate in the conversations on healthcare and medicine. Our classmates here and around the world come from innumerable backgrounds, rich in thought-provoking experiences; we have much to share. Topics may range from research to reflections on training and experiences with patients. We hope that through writing and reflection, we can spark productive debate, generate innovation, and learn from one another at the beginning of our professional education and careers.

As members of the medical community, we have a duty to review the facts and communicate the truth with clarity, precision, and humanity. In his address at the 2012 Harvard Medical School commencement ceremony, Dr. Don Berwick called upon new physicians to wield their voices proudly in carrying out this duty, as each voice “can be loud, and forceful, and confident, and will be trusted.” [2] The Harvard Medical Student Review is a space for students, trainees, and professionals to answer that call.

We hope you will join us.

Help get more women into Science

There is a problem that is well articulated by one of our students, Jean Fan. To quote her:

According to the US Department of Commerce, girls (women, females, Homo sapiens with two X chromosomes, whatever term you wish to use to refer to us) remain vastly underrepresented in STEM jobs as well as among STEM degree holders. Despite filling nearly half of all jobs in the US, girls hold less than 25% of STEM jobs. And despite the rising number of girls pursuing college degrees, girls hold a disproportionally low share of STEM degrees. So what's the problem?

After articulating the problem, she provides an ingenious kickstarter project that seeks to make a small contribution to addressing this problem. I recommend you join me in supporting this project.

Ghost stories for scientists

This report in Scientific American, just in time for the Halloween season, demonstrates that incorporeal beings take great interest in obesity, adipokines and leading laboratories at Harvard University. Perhaps they tired of the irreproducibility of their paranormal experiments.

Hat tip: Rachel Ramoni

Getting Big About Mapping Dengue

Here's a very nice application of lightly used data sources about Dengue, a scourge of underdeveloped countries. As in so many areas of public health, this huge health burden is woefully under-documented. In the absence of a vetted vaccine, understanding where it is endemic is essential for the application of scarce preventive resources. This group of investigators have cleverly used a number of public but under-used data sources, including the published literature, to create a predictive map of where 390 million infections per year are occurring.

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Epidemic or epiphenomenon?

A number of crowd-sourced infection monitors such as FluNearYou (by our own Dr. J. Brownstein) have reported an apparent upsurge in influenza-like illnesses over the last week. The CDC has not yet reported the same trend. If the CDC then confirms this early warning, it will represent a transition from proof of principle of the citizen as health monitor (see here and here) to general public health utility. If not, then we may be witnessing an outbreak of hypochondria.

No Publication Without Taxation?

I recently obtained a copy of a presentation by Elsevier representatives describing how they price their publications for different academic (i.e. university) customers. They describe how they place each institution into one of a small number of pricing tiers. How do they decide this categorization? A major component of the decision is the research intensity of the institution to which they were selling access to their publications. What was the measure of research intensity? Publication volume as measured by the SCOPUS database (an Elsevier product).

To better understand this policy, I contacted Elsevier and spoke by phone with a very cordial and clear executive. I asked why it seemed that the more we published, the more we were going to be charged by Elsevier to read these publications?

He explained that research intensity served as a proxy for the value that institutions might place on these publications. After all, if we value these publications, then we are more likely to download/use them. And pricing should reflect value.

I then asked why they were not simply measuring the download rate for each journal to directly charge for usage rather than using a proxy measure. The executive explained that their advisory board had recommended not to use the download rate as that might reduce usage thereby impeding scholarship.

So solicitous of the publisher. I knew it would be futile to bring up the effect on scholarship of inflation rates of publication prices that would make the rate of medical care inflation appear flat by comparison. A continual record of inflation that reduces every year the fraction of their own scholarly output made available to scholars throughout the world's academic institutions.

The passing of clean taxonomies.

Among the most productive constructs of the enlightenment are the modern taxonomies. These have been helpful in bringing order to the chaos of signs and symptoms and other clinical findings and were central tools in achieving our 20th century understanding of pathophysiology. They have also have an influential role to play in reimbursement for medical services. With the dawn of high-throughput molecular diagnostics many of us recognize that we are going to be able to be far more precise in our diagnostic and therefore therapeutic approach to diseases and their prevention.

Nonetheless, as we approach the systematization of medicine, we will be reminded often that nature may not hew to the simplified models that we are developing. This recent study in the New England Journal of Medicine, just does that by demonstrating directly that within a "single" tumor there exists a large multiplicity of tumor types, each with its own genomic characteristics and therefore particular therapeutic responsiveness (or lack of it). It can be argued that this is another instance of the tension between the "neats" and the "scruffies" but perhaps it is a foreshadowing of the decreased effectiveness of taxonomies as a cognitive tool for biomedical discovery and clinical care. If indeed, the underlying substructure of physiology is best represented by a probabilistic network model that can only be best grasped and managed through the use of computational tools, we have to seriously re-evaluate both our approach to disease definition and biomedical education.

Get paid to play

Earlier, I described the SHRINE distributed query system across 6 million patients with 10 billion facts. If you are a member of the Harvard Medical School faculty (with employment at one of the affiliated hospitals) you now have the opportunity to get money and glory (more the latter than the former) to spin clinical data into biomedical gold. Details on the context can be found here: http://catalyst.harvard.edu/services/pilotfunding/shrine.html

If you have questions, use this email contact.

Faster, cheaper and in control

Let's say you have a problem (e.g aligning the world's literature to defining the phylogenesis of the components of the current world-wide written corpus for scholarly attribution and automatic detection of plagiarism) that requires a computational solution. But it's taking days for the software to run. Buying a faster, bigger computer might provide some speed up, but what if you could get a 1000 fold improvement through a better implementation of the algorithm at the core of your software? Here's your chance to see if it can be done through a contest hosted by the Harvard Catalyst. Will the Overmind answer your most difficult computational questions?

Libraries are going to the dogs

Yale Law School has gone for the full monty, so if your medicolegal liability is getting you down, we are pleased to present Cooper as a prescribed cure. Please observe the maximum dose of 30 minutes.

Many happy returns

This twitter feed of returns of items borrowed from the Countway Library provides a glimpse of the vibrant engagement of our community with the scholarship of the present and past. These include The Anatomy of madness : essays in the history of psychiatry, Calories don't count by Herman Taller, Tachycardias--mechanisms, diagnosis, treatment, and Observed brain dynamics by Partha Mitra. One could presume that these were not all borrowed by the same patron, but if they were, what questions were they asking?

Stuffed full of information

That bird rendered by taxidermy in a museum is not only of visual interest. This report by an enterprising undergraduate points to some unexpected public health insights gleaned from the feathers of these museum specimens about the trajectory over centuries of mercury contamination in seabirds. Perhaps needless to say, this could not be done with a purely virtual collection.

Deadly Medicine

We are hosting a sobering exhibit about what happens when medical science loses its moral compass. More details can be found here.

Let the games begin!

Do you think that you can create the new software app that will revolutionize healthcare? Do you agree that substitutability will allow us all to innovate healthcare practice? As detailed on the challenge.gov website, there is now a very short term opportunity to "walk the talk" for a modest prize and immodest glory.

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We, the librarians

As Harvard University reorganizes its extensive library system, it is worth reconsidering where library activity occurs and who drives it. This effort in Finland (hat tip David Osterbur) is a reminder that although professionally trained librarians with a mission and institutional memory are central to the curation, preservation and dissemination of scholarly materials, there is no sharp demarcation as to where expertise, time and effort can be found in our collective efforts. If individual scholars do not curate their own, increasingly electronic, notes, their messages, and other residua of the scholarly process, there will be very little for institutional librarians to work wit and a gaping hole in the scholarly record. But first, academic institutions will have to provide them with a easy to use process that can last their entire careers. This is a first class opportunity for entrepreneurial, techno-librarians who can think at the scale of the Internet. Conversely, libraries must reach out the to network of distributed expertise in all areas of academic endeavors which is populated by experts often well outside the walls of organized academe. Literally tens of thousands of precious modern and ancient scholarly archives remain in the dark, queued up, waiting for an overworked archivist to provide even the most cursory cataloguing. Shotgun mass annotation, leveraging external expertise will have to become the norm and, again, there is a large opportunity for those who are able to provide such capabilities at scale and with the appropriate legal and institutional framework.

Graduation in Five Years

from a doctoral program in the life sciences is a reasonable goal, under most circumstances. For some unfortunates, it is not. Prospective students should make sure that they have the key bits of information required to decide if and where to proceed with a specific graduate program. If you are already in graduate school at Harvard University, you might want to consult with some of the faculty who are knowledgeable mentors.

Genome-wide clinical-grade interpretation

We are getting very close to the point that genome-scale sequence is available for clinical use. But will we know how to process and interpret it for such clinical applications?

Harvard Medical School, Children’s Hospital Informatics Program, and Harvard Medical’s School Center for Biomedical Informatics, the Partners Center for Genetics and Genomics, and the Harvard Medical School Center for Computational Genetics will hold a working meeting on December 7th and 8th, 2010 at the Countway Library on the Harvard Medical School campus. The purpose of this meeting is to directly address the challenges of providing consistent and clinically useful information to physicians and their patients based on large-scale genome sequencing. This meeting will focus on developing a "pre-competitive space" where industry collaborates earlier and more often to accelerate the clinical benefit from next-generation sequencing. Attendees are from clinical laboratory, sequencing, electronic health record companies as well as governmental and academic groups. This is a free but limited attendance meeting so please contact me if you are interested.