"...genetic determinism of disease is a reductionistic fallacy that is now collapsing."

I received an interesting email today as part of a loose group of geneticists, statisticians, epidemiologists, and molecular biologists that my mentor participates in regularly. It was a forwarded rant, pasted in its entirety below, from Jonathan Latham, Executive Director at the Bioscience Resource Project.

Dear Friends and Colleagues

In the eighteen months since we published (to some scepticism) The Great DNA Data Deficit: Are Genes for Disease a Mirage? there have been important developments in human genetics that are relevant to the food and environmental movements worldwide, and that deserve to be very widely known.

In particular, two scientific publications, the first from Jan 2012:

The mystery of missing heritability: Genetic interactions create phantom heritability by O. Zuk, E. Hechter, S. Sunyaev and E. Lander in the Proceedings of the US National Academy of Sciences.

This can be found at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268279/

and even more recently, from April 2012:

The Predictive Capacity of Personal Genome Sequencing by NJ Roberts, JT Vogelstein, G. Parmigiani, KW Kinzler, B. Vogelstein and VE Velculescu in Science Translational Medicine.

This can be found at: http://www.biostat.wisc.edu/~kbroman/hgjc/hgjc_2012-04-13.pdf

These papers have powerfully vindicated the scientific conclusions of our article. We draw your attention to three noteworthy aspects:

1) the lead authors of each (B. Vogelstein and E. Lander) are among the most highly cited biomedical researchers in the world

2) that their analyses, though new, are based on data that has been available since the human genome was sequenced. It is a rethink, not new data.

3) these papers demonstrate that leading medical geneticists no longer have realistic expectations that most human disease occurrence can be explained by inherited genetic predispositions.

In other words, genetic determinism of disease is a reductionistic fallacy that is now collapsing. Geneticists now face a long retreat from Moscow and the interesting question of who will rewrite the textbooks and tell the public.

We would also like to point out some others who have stuck their necks far out and predicted these events long before we did.

Joseph D Terwilliger and Kenneth M Weiss Linkage disequilibrium mapping of complex disease: fantasy or reality? Current Opinion in Biotechnology 9: 578-594 (1998)

Jay Joseph (The Gene Illusion, 2004) http://jayjoseph.net/the_gene_illusion

Helen M. Wallace (2006) A model for gene-gene and gene-environment interactions and its implications for targeting environmental interventions by genotype. Theoretical Biology and Medical Modelling 3: 35-58.

One last point is perhaps worth making. It is important to appreciate that, with a few exceptions, research geneticists have not merely been wrong in this matter, but that they have actively and grossly misled society as a whole. They could have and should have known that genetic predispositions might after all explain very little in the way of disease, but they routinely failed to make clear that possibility and went far beyond the actual evidence in order to obtain public funds and prestige. Caveat emptor.

yours sincerely

Jonathan Latham and Allison Wilson

What I find interesting, both in this casual email and in some of the linked articles, is the accusation of deception. I'll grant that in a research landscape that promotes harsh competition and limited rewards only for those at the very top, the "significance" section of many grant proposals may be often overblown in order to try to secure funds. However, this exaggeration is done with the completely transparent knowledge that the reviewing committee is not stupid. We are scientists communicating with our peers (other scientists) and it is not likely that this exaggeration is fooling anyone. 

There is also the fact that many geneticists, rife with excitement, have communicated regularly with popsci and lay press regarding the possibilities that lie ahead in genetics. Here, though, is where I raise the question of intent. Latham's email says "research geneticists have not merely been wrong in this matter, but that they have actively and grossly misled society as a whole." I find this statement to be grossly misleading, itself. When the Human Genome Project was completed, yes, you couldn't take ten steps in any direction without tripping over an article about how genetics was going to solve all of our medical problems. But in more recent years, I've been hard-pressed to find statements by respected geneticists that still make such claims. Heck, I even wrote about this myself over two years ago (cliff's notes: we don't have enough knowledge or genetic information to actually give someone a definite measure of their likelihood for developing diseases.) What you're more likely to find, in my opinion, are statements like mine from geneticists that are optimistic but that are representative of the theme that there is still so much we don't know, and THAT'S why continued research is important. It's absolutely not because we think we are trying to convince anyone that we already have the answer, and just want more money ... just because.

The linked January 2012 paper from Zuk and Hechter presents the idea, as if it's a novel one, that interactions and pathways between genes, as well as interactions between genes and the environment, are more likely to explain complex disease pathology than genetic heritability alone. Allow me to remove my 'serious hat' for a second when I say: Well, duh! Labs have been exploring GxG (gene-gene) and GxE (gene-environment) interactions for years, but the problem? It's hard. At present, the mathematical and statistical models available to us cannot adequately address these interactions, but tons of labs are working on it. 

I have long been frustrated by the way that science research as a whole is portrayed and reported on in the popular media. I think that these misrepresentations of more responsible research are at fault for any misconceptions that society at large has regarding genetic research or biomedical science in general. I do not believe that the blame lies at the feet of geneticists, who are constantly adapting their work and techniques to incorporate and address the newest ideas and knowledge in the field.


Now, my whole response here is an OPINION piece, so, as with anything op-ed, citations needed.

Book Review: Interview with the Vampire by Anne Rice

I have always harbored an interest in canonical vampire stories, and yet I’d never read any of the Rice Vampire Chronicles. Interview with the Vampire is the first of the Chronicles, and it’s the first of the three that I plan to read (having heard that they decline in quality after Queen of the Damned.) But that’s a discussion for another day.

Interview is written as a memoir of sorts, an account of vampire Louis’ life as he tells it to a mortal boy who records his narrative. The basic outline of Louis’ story is that he is turned in New Orleans by the vampire Lestat, and Louis hereafter searches New Orleans and Europe for answers regarding his vampire nature, and vampire origins. His adventure has several phases that are largely determined by who his immortal companion is at the time: his time in New Orleans is primarily spent with Lestat, and then after turning a young girl, Claudia, Louis begins to love her deeply and the two of them travel to Europe. In Paris, they meet the oldest living vampire, Armand, with whom Louis then shares a powerful mutual attraction.

Throughout the tale, Louis grapples with love, loss, vampire morality, immortal existentialism, and the separation of human nature from vampire emotion and being. Interview is a very philosophical novel, as Louis is constantly questioning spirituality, good and evil, loyalty, and many questions surrounding these themes that were never answered for him as a human. At times, the novel comes off as kind of mopey and histrionic, particularly if you like your vampires cheeky and darkly humorous (think Spike or, for a recent example, Damon Salvatore.) It was also kind of slow at times, and it took me a bit longer to get through it than I should have been able to do had I really applied myself.  Overall, though, I did like this book, and I liked that it stayed true to traditional vampire mythology — these vampires do not go out in daylight, and there are telltale signs about their appearance that clue humans into their supernatural nature. I’ve started on the second book in the Chronicles, which allegedly is a bit more “fun,” so I’ll see how that goes.

I got a tumblr

It's wholly unnecessary since I post short, context-free crap here too, but since some of the funniest things on the internet as of late are on Tumblr, I wanted to get one to re-blog all of that stuff and also maybe just post really frivolous pictures that haven't found a home here on this blog. So...

http://mandoir.tumblr.com/

It's not very pretty or anything. I may fix that if I choose to care more.

Happy birthday Punk!

My baby sister (of Punk Says the Darndest Things) is finally turning 21 today, so it's time to do the birthday dance!

Here are some scattered thoughts.

-- Ack! Totally different Blogger format! Deep breaths. Okay. It just looks like the rest of Google now. Freakout averted.

--I made a Mad Men GIF of Peggy's "WTF? ...nm" face

-- So, Coachella. I went. I'm going to do a more in-depth write up later (mostly so that I can remember my life when I'm old) but I wanted to address a lolworthy comment here really quick. So, it's kind of obvious that Coachella is in a bit of a Brochella phase and that, well, there are a lot more douchey people there than in years past. But what's funny is when people say "Coachella got too mainstream. People who are there now only care about the image. I don't want to go any more because I care about the music." Let me make it clear: only people who do, in fact, care about image would choose not to go to a music festival because of the other people who go there.

-- If you're interested in beer write-ups, don't forget about my other blog at http://alwaysanswerbeer.blogspot.com !

Book review: The Knife of Never Letting Go by Patrick Ness

Todd Hewitt is the only boy in a town of men. Ever since the settlers were infected with the Noise germ, Todd can hear everything the men think, and they hear everything he thinks. Todd is just a month away from becoming a man, but in the midst of the cacophony, he knows that the town is hiding something from him — something so awful Todd is forced to flee with only his dog, whose simple, loyal voice he hears too. With hostile men from the town in pursuit, the two stumble upon a strange and eerily silent creature: a girl. Who is she? Why wasn’t she killed by the germ like all the females on New World? Propelled by Todd’s gritty narration, readers are in for a white-knuckle journey in which a boy on the cusp of manhood must unlearn everything he knows in order to figure out who he truly is.
 
Where do I start? Well, I guess right off the bat I’ll say that I was disappointed. I expected great things, both because everyone seems to love this AND because I usually fall hard for dystopian YA. Coming off of The Hunger Games and hearing all the buzz around this series, I was ready to accept a new obsession into my life. Unfortunately, I don’t think the Chaos Walking trilogy will fill my void.

The rest is going behind a cut because there will be SPOILERS and because I want to invite everyone who has read this and loves it to prove me wrong and tell me why I should pick up the next book.

Book review: The Hunger Games by Suzanne Collins

I don't think there is a lot of uncovered territory with this one. Two tributes from each of twelve districts are ordered by the Capitol government to fight each other to the death in a booby-trapped arena. Our heroine is Katniss Everdeen, who volunteers to fight in place of her initially selected younger sister Primrose. We're also introduced to Haymitch, District 12's Hunger Games mentor, Peeta, Katniss' friend and competitor in the Games, Gale, Katniss' hunting partner (and yes -- those latter two are the points on the Love Triangle, which I totally don't want to talk about.)

I also totally don't want to talk about the Battle Royale comparisons. I haven't done my book review on that one yet, so I don't want to talk too much BR in my HG review, but I'm just going to say that they both draw from the same premise, but it's not like BR invented the premise either. So to say that HG ripped off BR is, in my opinion, really silly and willfully ignorant of a long tradition of gladiatorial stories in literature.

Anyhoo, this book became an instant favorite. It's quickly-paced and I found the characters immediately compelling. The writing is not super sophisticated, but it's completely serviceable and probably a pretty accurate representation of the internal monologue of a 16 year-old. I'm not going to wax sociological about the heavy themes here, either, because honestly, that's everywhere on the Internet. I'm just going to blithely add my voice to the chorus of those who loved this book.

Book review: Stranger in a Strange Land by Robert A. Heinlein

This is me slowly making me way through the venerable science fiction classics! Stranger in a Strange Land is about a human of Terran origins who was raised on Mars, and his return to Earth. The plot is really simple; it’s mostly the Man from Mars — Valentine Michael Smith — re-acclimating to our society and, eventually, teaching some of his Martian ways to other humans who are willing to learn.

The novel is much more character-driven than plot driven, and the differences between Michael’s perspectives and abilities vs. ours comprise the impetus for most of the character arcs. As Mike adapts to Earth via the instruction and guidance of his companions, they adapt to his customs as well. Eventually, by the end, Mike’s gospel reaches many more people outside of what was, initially, a rather tight group of people who initially enabled his freedom on Earth.

It’s my understanding that, at the time of its publication in the early 1960′s, this was a pretty controversial novel. It’s easy to see why, as it lampoons religion and includes very favorable portrayals of polyamory and group sex. There is some pretty heavy philosophizin’, too, that justifies its position on these topics. All in all, it made for an interesting read, and in many cases was pretty ahead of its time.

In other cases, though, it is pretty pointedly indicative of when it was written. The imagined universe here, unfortunately, despite all of the liberties it takes with sexual relationships, delivers a pretty disappointing facsimilie of  heteronormative 1950′s gender roles. Where some science fiction novels enjoy their ability to challenge social roles, and others deftly side-step them, this one seems to rather revel in its sexism and homophobia. Expect all of the men to be experts in everything, and always delivering their expertise to the women, whose responses are primarily “That’s interesting, dear. Can I pour you a drink?” And for all of the pontificating about brotherly love, and eschewing modesty, and sharing everything and loving everyone and deeply understanding and empathizing with everyone on a molecular and spiritual level, sex — the pinnacle of understanding each other — only happens between men and women. Also, brace yourself for when one of the female characters says “Nine times out of ten, when a woman is raped, it’s her fault.” It’s, as I said, disappointing.

Still, this is a classic, and as far as sci-fi goes, it’s nice to see a venture into character study. I’d still recommend this one overall, with the caveat that there is some potentially upsetting cognitive dissonance with regard to the gender and sexuality content.