EditorialMedical Education

From Dissecting Cadavers to Dissecting Genomes

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Science Translational Medicine  11 Sep 2013:
Vol. 5, Issue 202, pp. 202ed15
DOI: 10.1126/scitranslmed.3007091

Eric J. Topol

CREDIT: JOHN ARISPIZABAL

When William Harvey, the physician-anatomist known as the father of the circulatory system, dissected the bodies of his deceased father and sister in the early 17th century, it foreshadowed the future of medicine. Harvey found that his father’s colon and sister’s spleen were remarkably large, which might have raised concerns about unspecified heritable conditions. For centuries, the dissection of cadavers has been a fixed (as in formaldehyde) part of the medical school curriculum and is certainly one of a medical student’s most memorable experiences. Many medical educators believe that the human face of dissection fosters professionalism by promoting respect for the human body.

But today’s physicians and medical scholars have transcended Harvey’s era of postmortem diagnostics; instead, they inhabit a world in which physicians are connected electronically with distant patients and massive amounts of biomedical data. In the current era of molecular medicine, intricate analyses of a patient’s genomic data are destined to become an integral part of routine medical practice.

Although gross anatomy with cadaver dissection remains inculcated in the educational programming for most of the 138 medical schools in the United States, an increasing number have moved away from this ritual to computer simulation, now with enhanced three-dimensional features. Just as new imaging and modeling technologies are challenging the continued need for cadaver dissection, modern genomics technologies make it possible for medical students to learn about the human body through another form of dissection—that of one’s own genome—as part of the standard medical curriculum.

GOOD TIMING

In the past few years, increased speed and sensitivity have facilitated the translation of exome and whole-genome sequencing (WGS) technologies to the clinic, and the enhanced power of genomic medicine has saved the lives of individuals with undiagnosed, life-threatening conditions by identifying the causative mutation (or mutations) and the apposite intervention. WGS and exome sequencing are emerging as valuable tools in precision therapy for cancer. By paired sequencing of tumor DNA and germline DNA, cancer driver mutations can be delineated along with the relevant biological pathways. Other informative -omics technologies, such as RNAseq, can also be used to guide the therapy matched to the underlying biology of an individual’s cancer. With a single tube of maternal blood, WGS of a fetus is now possible even as early as week 8 of a pregnancy, which forecasts that, one day, fetal WGS may be as commonplace as determining an unborn baby’s sex is now. Virtually every prescription medication likely has a heterogeneous response related to DNA-sequence variants, even though just over 100 drugs currently carry a genomics-related label mandated by the U.S. Food and Drug Administration. As millions of individuals with myriad phenotypes have their genomes sequenced, WGS will become increasingly informative for predicting susceptibility to medical conditions. WGS of pathogens has become an important tool for understanding the root cause of epidemics and will likely become the primary method for determining optimal antimicrobial treatment in the future.

In addition to the medical and scientific bases for using WGS as a teaching tool for future physicians, there is an economic argument as well. In 2004, it cost more than $28.8 million to sequence a human genome. In 2013, that cost has already dropped to less than $3500—a 99.8% reduction. Projections that the cost will hit the long-anticipated $1000 mark in 2014 appear to be on target. It typically takes years to change a medical school’s curriculum, so the economic case for WGS will only become stronger over time. Indeed, WGS is approaching a level of affordability that represents only a tiny fraction of the average medical school’s tuition and is minuscule when compared with the cost of acquisition, storage, and maintenance of cadavers for anatomical dissection.

State-of-the-art WGS consists of sequencing an individual’s DNA an average of 40 or more times (so-called deep “coverage”) to assure accuracy, and this feat can usually be accomplished in a couple of days. There are freeware programs that provide a preliminary annotation of the number of variants as compared with a reference human genome, and each of our genomes house ~3 million single-nucleotide polymorphism (SNP) variants and a lesser number of structural variants. All of these variants can currently be displayed on an iPad with free or very inexpensive apps (for example, 99 cents), such as Genome Wowser (Children’s Hospital of Philadelphia) or My Genome (Illumina). The displays set up hyperlinks to the U.S. National Center for Biotechnology Information that immediately provide relevant articles that describe what is known about a sequence variant. Many medical schools now supply their students with iPads for the convenience of having a uniform way to display, archive, and update course materials; adding a student’s WGS is a natural extension of using wireless mobile devices in education.

PHYSICIAN, KNOW THYSELF

A student’s access to his or her DNA sequence would undoubtedly have a profound, lifelong impact. WGS is instructive about maternal and paternal ancestry, one’s proportion of Neandertal genome, carrier states for a wide variety of Mendelian conditions that become crucial when conceiving or screening children, drug interactions for efficacy and major side effects, and susceptibility to or protection from hundreds of diseases and medical conditions. Students will gain an understanding of the physiological importance, nuances, and complexities of the regulatory genome—the 98.5% that comprises the non–protein-coding DNA sequence. Perhaps most importantly, dealing with one’s own massive data set of 6 billion nucleotides and ~250 billion data points (assuming 40X coverage) will provide a student with an excellent grounding in the essential challenges in bioinformatics.

Although a strong case can be made that all medical students should be dissecting their genome sequences, until now, no medical school has altered its curriculum to have each student undergo WGS or even less informative (and less expensive) -omics investigations, such as the cataloging of one’s gut microbiota or a genome-wide scan (for example, 23andMe $99 limited SNP genotyping). Several schools have incorporated teaching about the biomedical uses of WGS in their medical genetics courses, and a few offer an elective that includes the potential for obtaining a very limited peek at one’s genome via a genome-wide scan. Only one medical school, Mount Sinai, initiated, in the autumn of 2012, an elective course in which each student receives and interprets a whole-genome sequence (1). The course is open to only 20 students from the medical, graduate, and genetic counselor training programs. A student can choose whether to work with his or her own genome sequence or that of an anonymous individual. Only when opportunities for students to annotate and decipher their own genomes become widely available will medical schools create a new generation of physicians fully capable of rendering genomic medicine for their patients.

References

  1. Funding: This work was supported by NIH/National Center for Advancing Translational Sciences grant 1U54AI108353. Competing interests: E.J.T. is a cofounder of Cypher Genomics.

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