Sequencing in polio, baseball pitching and cancer: sometimes the order of events matters

This piece originally appeared in the Timmerman Report.

What do the polio virus, baseball pitch choice and cancer have in common?

The answer, of course, is sequencing. But not in the “figure out the DNA” way (although that’s involved). Instead in the “what comes first” way. Confused? Read on!

A big perk of Seattle is proximity to great institutions of biomedical research like the University of Washington and the Fred Hutchinson Cancer Research Center. Ever since my graduate student days in genetics at UC-Berkeley I’ve enjoyed going to seminars–especially seminars that are outside my field of study. Very little beats a good seminar for giving you a quick, condensed view of the state of a field of research. A bad seminar…well…we all could use more sleep, right?

In early October, Raul Andino of UCSF came to the Hutch to talk about his work on viral evolution. His team has been examining a clever real-world system to track the evolution of viruses. The near-eradication of polio (one of the great public heath victories of the past century) has led to the curious problem that as of the middle of this year most new cases of polio arose as a result of vaccination efforts. The live, attenuated vaccine that’s used in the developing world can, in very rare cases, mutate in just the wrong ways in its host, leading to the creation of a virulent strain that can infect others. In the US we use an inactivated polio vaccine which requires several injections; in much of the developing world the oral polio virus is preferred due to its ease of administration, lower cost, and immunization profile. The Andino lab realized that by studying these isolated outbreaks, which all originated with the same, genetically identical progenitor, they could test a hypothesis about the adaptive landscape of virulence evolution. Continue reading

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Google Knows What’s in Your Inbox, But It Shouldn’t Get Your Genome Without Consent

Originally posted in the Timmerman Report

I once had an idea for a science fiction story where everyone was paranoid about their genetic information getting out because of a misguided belief that genes equal destiny and that the burden of privacy is all on the individual. People would wear protective suits and carefully guard against leaving any iota of tissue out in public—not a single follicle or skin flake. All to prevent anyone else—potential employers, rivals, even potential lovers—finding out information about their genes.

I planned the story as a satire, taking our current world where Precision Medicine and cheap genome sequencing and not-quite-as-cheap genome interpretation are real things, and extrapolating to an absurdity. I wanted to highlight the kinds of more realistic challenges we might face as we learn more about our genes and face increasing questions about privacy and access to health care services. Of course, I thought this was completely speculative; I’d just be building a straw man story to make a point. I knew something this extreme would never really happen.

But maybe I was wrong. Continue reading

Baseball, Bayes, Fisher and the problem of the well-trained mind

One of the neat things about the people in the baseball research community is how willing many of them are to continually question the status quo. Maybe it’s because sabermetrics is itself a relatively new field, and so there’s a humility there. Assumptions always, always need to be questioned.

Case in point: a great post by Ken Arneson entitled “10 things I believe about baseball without evidence.” He uses the latest failure of the Oakland A’s in the recent MLB playoffs to highlight areas of baseball we still don’t understand, and for which we may not even be asking the right questions. Why, for example, haven’t the A’s advanced to the World Series for decades despite fielding good and often great teams? Yes there’s luck and randomness, but at some point the weight of the evidence encourages you to take a second look. Otherwise, you become as dogmatic as those who still point to RBIs as the measure of the quality of a baseball batter. Which they are not.

One of the thought-provoking things Arneson brings up is the question of whether the tools we use shape the way we study phenomena–really, the way we think–and therefore unconsciously limit the kinds of questions we choose to ask. His example is the use of SQL in creating queries and the inherent assumptions of that datatype that objects within a SQL database are individual events with no precedence or dependence upon others. And yet, as he points out, the act of hitting a baseball is an ongoing dialog between pitcher and batter. Prior events, we believe, have a strong influence on the outcome. Arneson draws an analogy to linguistic relativity, the hypothesis that the language a person speaks influences aspects of her cognition.

So let me examine this concept in the context of another area of inquiry–biological research–and ask whether something similar might be affecting (and limiting) the kinds of experiments we do and the questions we ask.

Continue reading

Genetic counseling at Illumina

All opinions of the interviewer are my own and do not necessarily reflect those of Novo Nordisk.

Illumina is the industry leader in high-throughput sequencing platforms and over the past decade has employed a fascinating mix of innovation, creativity in approach, community engagement and aggressive exploration into different business areas. I recently had the opportunity to interview Erica Ramos, who works as a clinical genomics specialist and certified genetic counselor in the professional services group within Illumina’s CLIA lab, about Illumina and genetic counseling.

Kyle Serikawa:  Can you describe what Illumina is doing in the field of genetic counseling? That is, are you creating a genetic counseling service, or advocating an increase in training of genetic counselors, or creating materials to facilitate counseling?

Erica Ramos: So Illumina has four full time genetic counselors as part of their services group. We don’t provide direct services to patients; Illumina’s model is to provide support to the providers, the physicians. We support what’s being done in the genetics core at Illumina. As for training, we offer opportunities for that. Every year we welcome a second year student in genetic counseling for a 10 week, part time rotation. We’ve done about 5 of those so far. It’s an opportunity for those students to see how genetic counseling skills can be applied to a non-clinical setting. We see the internships as a way to engage these people who will go on to become genetic counselors. Illumina is also a very active in the genetics community, including membership in the American College of Medical Genetics and other organizations.

KS: Given the current landscape of, for example, exome and whole-genome sequencing, it seems like genetic literacy will become an increasingly important skill—both for understanding how genetic variants can be interpreted and also how genetic information will be communicated. How is Illumina thinking about educational needs in genetics?

ER: The genetics community as a whole is concerned about the need for wider understanding of genetics to help inform medical practice. From Illumina’s standpoint, one of the things we can do is to support the internships I’ve described as a way to provide exposure to non-clinical roles for genetic counselors, which broadens the potential market. Also, we’re providing a training option that maybe not all academic programs can support. At the same time, the universities themselves can see the developing need, and through supply and demand we hope to see an increase in the number of genetic counselors being trained.

There is also need for the education and updating of other professions. Physicians, nurse practitioners and others. Illumina has put on the “Understand Your Genome” symposia to work with providers who don’t currently have as deep an understanding as they would like.

KS: How do you see genetic counseling as synergizing with Illumina’s business interests? Continue reading