Celebrating DNA Day, 2014

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dnaday_Logo2014April 25, DNA Day, commemorates the date in 1953 when James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin introduced the structure of DNA in the journal Nature. The anniversary was echoed, if a bit chronologically contrived, half a century later with the publishing of polished human genome sequences.

In celebration of DNA Day 2014, DNA Science blog honors high school students who are thinking and writing about DNA.

I was astonished to discover after my gene therapy book was published two years ago, thanks to a review in School Library Journal, that my target reader was 15 years old. In contrast to the report in this week’s Science that schooling sets back students’ knowledge of evolution, today’s teens know DNA. So here are a trio of looks at DNA-savvy high school students.

Me and March of Dimes essay contest winners: Alexi Ayrey, Molly Ottensoser, Gurjeet Johal, and Jomanda Morales, at NYU 3/25/14

Me and March of Dimes essay contest winners: Alexi Ayrey, Molly Ottensoser, Gurjeet Johal, and Jomanda Morales, at NYU 3/25/14

THE MARCH OF DIMES STUDENT CONVOCATION

For the past few weeks I’ve been traveling around New York State for the March of Dimes high school convocation, speaking about children undergoing gene therapy. The program debuted in 1971, with Jonas Salk launching the speaker series. This year I provided the question for an accompanying essay contest:

“It is possible to determine the complete DNA sequence of your genome and identify genes that may cause diseases or indicate your ancestry. Doctors are just now learning how to use the information in a person’s genome. Many genetic diseases do not have treatments. Would you want to know your genome sequence? Which genes would you like to know about, and which not?”

Answers were insightful, optimistic, and proactive, with the students realizing that knowledge of personal genetic information would enable individuals to live in ways that would minimize inherited tendencies towards certain diseases. Yet at the same time, the students recognized limitations of knowing one’s genes.

The winning essay, by Gurjeet Johal, a senior at the High School for Health Professions & Human Services in Manhattan, movingly wrote of her family’s experience with Lewy body dementia. “Having already witnessed the effects of such a disease on my grandfather’s life, I would not want to be informed of my chances of developing it. Even if my gene sequence indicates that I would develop Lewy body dementia, I have nothing within my power to prevent it and awareness would likely cause complications due to the anxiety the discovery would instill in me,” she wrote.

10224105-ashg-logoTHE AMERICAN SOCIETY OF HUMAN GENETICS

Ms. Johal chose a disease that would fit in perfectly in addressing the question posed in this year’s American Society of Human Genetics DNA Day essay contest:

“Complex traits, such as blood pressure, height, cardiovascular disease, or autism, are the combined result of multiple genes and the environment. For ONE complex human trait of your choosing, identify and explain the contributions of at least one genetic factor AND one environmental factor. How does this interplay lead to a phenotype? Keep in mind that the environment may include nutrition, psychological elements, and other non-genetic factors. If the molecular or biological basis of the interaction between the genetic and environmental factors is known, be sure to discuss it. If not, discuss the gaps in our knowledge of how those factors influence your chosen trait.”

Lewy body dementia is a complex trait – most cases are not inherited, yet mutations in several genes cause familial forms, and variants of other genes contribute to risk. Environmental influences on dementia are not well understood. So it’s possible that Ms. Johal’s risk is not as high as she fears.

The winners of the ASHG contest are Rachel Gleyzer, Adesuwa Ero, and Cameron Springer. Congratulations! “The students submitting the best essays really outdid themselves this year,” said Michael Dougherty, PhD, Director of Education for ASHG. “We continue to be impressed by the quality of their writing and their ability to master some pretty complicated science.”

I read a few of the essays, and they’re quite wonderful. Some “rounded up the usual suspects” among complex traits, such as autism, obesity, and type 2 diabetes, but a few were highly original.

One student chose Huntington disease, which would seem an unlikely candidate for a complex trait because penetrance is close to 100 percent – if you inherit a mutation, you’ll eventually get HD, unless something else gets you first. But due to gene-environment interactions, DNA is never destiny, and this student explored a very subtle manifestation of this interplay — recent findings that diet can influence age of onset of HD. That is empowering information in a traditionally helpless situation.

Another student did the opposite — chose a trait thought of as mostly environmental and discussed the contribution of a single gene: language ability and the FOXP2 gene. “Language owes its potency to its remarkable malleability; it possesses innate grammar encoded in genes and their transcriptional targets, but its phenotypic capacity is still determined by environmental language acquisition,” the student wrote.

A particularly elegant entry parsed possible causes of depression through the lens of being an adolescent. The analysis cited candidate genes, but then discussed effects of sleep deprivation from living linked to our lit devices, coupled with the academic pressures of high school. “Teens predisposed to the disorder because of mutations in genes controlling neurotransmitters may not exhibit any symptoms until confronted with burdening stress.”

The ASHG essays weren’t all gloom and doom. A student wondered why the ability to relate a wavelength of light to perceiving a specific color is taken for granted (color vision), yet the ability to do the same for a sound and a musical note is regarded as a talent (perfect pitch).

Dr. Yuval Itan supervised Benjamin and Mark Mazel last summer as they made the human gene connectome more accessible. (Rockefeller University)

Dr. Yuval Itan supervised Benjamin and Mark Mazel last summer as they made the human gene connectome more accessible. (Rockefeller University)

THE HUMAN GENE CONNECTOME REVISITED

High school students aren’t only writing about DNA science, they’re doing it.

About a year ago, I posted about the human gene connectome, the physiology-based network that is the brainchild of Rockefeller University postdoctoral researcher Yuval Itan. Two of the co-authors of his new publication at BMC Genomics are in high school, twins Benjamin and Mark Mazel.

“These two very talented students made a web interface for the human gene connectome, which now enables everyone to easily use it. I think that it’s a great example that could give motivation for young students to participate in science and for investigators not to be intimidated by age,” Dr. Itan said.

The connectome uses a “new metric” – a “biological distance” calculated from shared function rather than shared DNA sequence. But originally the database required downloading too much information, inducing what Dr. Itan calls “terminal command line phobia.” So his two young protégées spent last summer applying their computational skills to improving the interface.

Which gene variants are clinically relevant? And for whom? (NHGRI)

Which gene variants are clinically relevant? And for whom? (NHGRI)

A DISCONNECT BETWEEN THE STATE OF THE SCIENCE AND PUBLIC PERCEPTION

Coincidentally, an article published yesterday in Nature ties together the student experiences above: the uncertainty of genetic information that can impact health (March of Dimes), the complexity of many traits (gene:environment interactions; ASHG), and how genes interact (the human gene connectome.)

The Nature paper reports recommendations based on a workshop held at the National Human Genome Research Institute (NHGRI) in September 2012 to discuss ways to assign meaning to gene variants for individuals. It’s all about context.

“Mistakes are happening in the clinic based on questionable evidence of an association. People are jumping to the conclusion that if a patient has the same variant as was previously implicated in a disease, then they must also have the same disease. Medical treatment decisions are then being based on this information, sometimes to the detriment of the patient,” said one of the authors, Teri Manolio, M.D., Ph.D., director of the Division of Genomic Medicine at NHGRI.

I have a broad perspective on the issue from writing and revising my human genetics textbook over the past two decades. And I’m convinced the genetics community has known all along that the human genome sequence itself was only a beginning, despite the hyperbole at the various milestone announcements. Using all of the information in a genome would require understanding not only every gene’s function, but identifying the nuances of every possible variant (base changes and copy numbers), and then the implications of all possible gene-gene and gene-environment interactions. The expectation that knowing the sequence could automatically lead to cures always was a huge oversimplification – a little like reading a novel by speaking each letter aloud, from page 1 until The End, and somehow understanding the story.

(NHGRI)

(NHGRI)

Yet it appears that the oversimplification has persisted, judging from a disconnect I sensed in the essays responding to the question I posed. For at the same time that geneticists are rightly warning physicians that incorporating genomics into their practices will not be straightforward, some students think that day is already here. I only read a few of the essays, the top ones, but these ideas emerged:

1. Doctors sequence and interpret genomes. Already. Regularly.
2. There was one human genome project, the government one.
3. All genetic testing stems from the human genome project.
4. Each individual has his or her own genetic code.
5. Gene therapy, including the germline variety, is already being done.

Where are these ideas coming from?

I don’t think it’s from teachers, who only spend a few weeks on genetics and are probably happy just to get through Mendel and DNA structure. A more likely source is the media’s constant barrage of breakthroughs and advances. The uncertainty of using DNA information in diagnosis does not make as compelling a story on the nightly news.

Double Helix with StethoscopeThe difficulty of translating genomics into the clinic IS the story that will ultimately affect most if not all of us. Summed up James Evans, M.D., Ph.D., Bryson Distinguished Professor of Genetics and Medicine at the University of North Carolina at Chapel Hill and co-author of the Nature paper, “Deciding which genomic variants are important players in disease is probably the most difficult challenge that we face in trying to implement genomic data in medicine. It’s difficult to implicate specific variants as having an effect on disease because there are millions of variants in the human genome, and most are rare and do not have a big impact on health. This will likely be a long-term challenge.”

It sure will be, making me wonder what DNA Day will celebrate ten years from now. And twenty years from now.

DNA Day is a terrific tradition. It’s important to acknowledge the past, while realistically projecting where DNA science will take us in the future.

(Many thanks to Mike Dougherty of ASHG for the DNA Day image)

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Celebrating DNA Day, 2014 by DNA Science Blog, unless otherwise expressly stated, is licensed under a Creative Commons Attribution 3.0 Unported License.

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