Finally GETting it: the 2012 GET (Genomes, Environments and Traits) Conference, Boston, 25 April 2012

As I mentioned in one of my very first blog posts, I am participating in the Personal Genome Project led by Dr. George Church of Harvard. (Read that post here to get a quick overview of the project.) For the past couple of years, they have had a one-day conference (Genomes, Environments, Traits, or GET) at Harvard Medical School to discuss progress as well as host presentations on related themes and trends. Participants in the study are invited to attend free of charge, so I stopped by to enjoy some very interesting lectures on a wide range of topics, as well as to get a full update on the progress of the project.

And OK, I admit it: I also wanted to meet Dr. Church.* I have always found the idea of ‘celebrity’ rather horrifying. With the exception of a book-signing, I wouldn’t be caught dead asking someone for an autograph, and I firmly reject the idea that just because someone (e.g. actors) is in the limelight, s/he is somehow worthy of our affection and praise. And I believe that if you admire someone for his or her convictions or policies or work, then you should admire the product (i.e. ideas), not the person (who is as fallible as you). In other words, I don’t really do hero-worship, and I don’t have any ‘rock stars’. But Dr. Church is as close as I will ever come to having a hero. His audacious project to sequence 100,000 genomes has the potential to have a greater impact than any other single scientific undertaking in medical history. I realize this doesn’t make him as fame-worthy as, say, an accomplished person like Kim Kardashian or Paris Hilton, but it’s good enough for me.

For me, the most interesting part of the day was the update on the project itself. The whole team was there, each updating on his or her area of responsibility (bioethics, legal, operations, etc.). They then fielded questions from the group of us there. The question I wanted to ask (but didn’t have to because apparently everyone was thinking it and someone else posed it first) was, isn’t the project terribly skewed towards a certain subset of the population? First there’s education and IQ: since they aren’t aggressively advertising it yet, they are getting mostly people who have a higher educational level; and since they require everyone to pass a test on the basics of genetics, risk and privacy issues at stake, it will also skew towards the more intelligent. Also, looking around the room, I saw a majority male and majority white audience (though admittedly I don’t know for sure how representative that was of the overall participant pool). Add to that the fact that one must be an American citizen to participate and it does seem a little imbalanced. There really wasn’t much of an answer for that. For the educational/IQ and American citizen issues, those are all related to legal/informed consent/privacy requirements, so they can’t really budge there for now. As for ethnicity and sex, presumably at some point they will be making a wider push for more participants and attempt to balance things then.

And that brings me to the next thing I noticed: despite the fact it’s been up and running for a few years now, it is still very early days, so patience is the key word here. There’s so much more to it than simply soliciting, receiving and processing DNA. Remember, nothing like this has ever been attempted before, so there is a very steep learning curve here: how best to collect and process so many samples, and with the best maintenance of the samples; even deciding WHAT to sample, since this is also about environment and about getting as wide a spectrum of data as possible; how to handle the interface with participants; all the legal and privacy issues; how best to process all the data to ensure it’s actually turned into something meaningful. The list goes on and on.

As for the numbers, here’s where it stands right now: there are about 2,000 of us in the project. In the first five years of the project, they sequenced 10 genomes (starting with Church’s, who led by example and released all his data); now they are up to about that many per month. The market cost for the process is down to around USD 4-5k, which is already half as much as last time I checked a year or two ago; and the price will continue to plummet as the process is improved and streamlined (which is an important secondary goal of the project).

Besides the project update, there were many fascinating presentations on other subjects, from a CEO who has the goal of achieving the 100-dollar genome, to an incredible project that is achieving the ultimate biomimickry: creating actual miniature bio-synthetic organs on which to do drug trials to ensure greater accuracy and reliability of results (not to mention saving a lot of rats!). That latter one was amazing and the implications for drug research are profound. Take for example asthma drug research. Progress in this area has been (literally painfully) slow. One of the main reasons? Animals simply don’t mimic the human version of asthma very well, so researchers often go down dead-end paths, wasting a lot of time and research money along the way. But imagine growing a biosynthetic lung and testing drugs on them directly. The researcher, Dr. Geraldine Hamilton, showed some pictures of some of the actual organs they had created. Astounding accomplishment both from a technical point of view and in light of its staggering implications.

So what does the future of genetics hold for us? The possibilities are practically endless. As Dr. Church said, we all have some ‘superpower’ in our genes (large or small, whether we are aware of it or not). This can be anything from harder-than-average bones to HIV-resistance. Now imagine identifying thousands of such ‘superpowers’ through large-scale genomic research. Then imagine leveraging that knowledge of individual genes to create therapies for others who lack that particular ‘superpower’. You don’t need much of an imagination to realize that the implications for the future and well-being of humanity are profound.

The future is a wild place, folks. Hold on.

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*For the record, I did get to meet him and speak with him for a few minutes, and was quite proud of myself for not gushing overly much. I think I might even have been relatively coherent.

Gene-ious

I said yesterday that I had gotten my genome 'partially sequenced' at 23andme.com. That is not technically accurate: I got genotyped, which is just taking one's DNA and looking at genetic variants (as opposed to sequencing the genome, which is of course far more involved, though in principle it's the same idea). As noted in an earlier post, I have also volunteered for Dr. Church's PGP (Personal Genome Project), which in fact would lead to having my genome entirely sequenced. They are looking for 100,000 total volunteers, but I think that their eyes may be bigger than their wallets on that, at least in the short term.

So why did I do the genotyping? I had a number of motivations:

1) Sheer curiosity. I just wanted to learn more about the process and its efficacy and results.

2) There was probably some morbid curiosity as well: it's not every day one gets insight into what will ultimately kill one. Of course, no one knows for sure how one will die (insert cliché about getting hit by a bus tomorrow yada yada), but genotyping can give you a pretty good picture. For the record: stroke and Alzheimer's are my two most likely means of exiting the stage. Neither came as a great surprise given family history.

3) A peek into my children's future. What I have as genetic predisposition or as recessive carrier trait can of course impact future generations. Interestingly, as far as carrier traits, I had...zilch. From Alpha-1 Antitrypsin Deficiency to Torsion Dystonia, I seem pretty much devoid of any unfortunate recessive carrier baggage.

4) Taking control of my health. Knowing that I am 25% more likely than the general population to suffer from stroke or other events or maladies stemming from atrial fibrillation, I am certainly going to be more careful about heart health. Knowing that I am twice as likely as others to develop Alzheimer's means I am certainly going to figure out a more obvious place to keep my keys. And on the other side of the coin, I am going to relax a little bit about type II diabetes: while it may be present in my family, I am far less likely than most people to develop it myself. And most interestingly, I even have some insight into the efficacy of certain drugs in the event I do fall ill. Plavix, for example, is less likely to help me should I need it, which is a very good thing to know for someone with the aforementioned predisposition towards atrial fibrillation. Knowing in advance that other alternatives might work better, could make all the difference. (On the sunnier side, should I ever need interferon, I am more likely than others to respond well to it.)

Another very useful bit of information was about diet. I am very physically active, but all my adult life I have had to work hard to keep the spare tire of 10 pounds or so off my stomach. I have usually combated this through exercise and a low-fat diet. Turns out that might not be the right approach for me; it might even be the problem. I have a gene that not only makes a low-fat diet ineffective, but actually makes things worse. With this gene, I am MORE likely to have extra pounds if I have a low-fat diet. Mind you, this isn't a licence to go and raid McDonald's every day: while I will benefit from much higher fat intake, it has to be high in just one variant of the good kind of fat, mono-unsaturated. So it's good-bye low-fat foods, hello nuts, poultry and oils like olive, canola, etc.

5) Genealogy. It confirmed what I already knew about my paternal side: Irish origins. Interestingly, on my mother's side it's a bit murkier than expected. I could be anything from Druze Muslim to Ashkenazi Jew to Basque (or something as prosaic as British origins, which is certainly the case going back the past few centuries, as my genealogical research confirms). Makes me wonder about the long path my ancestors took in their journey after Africa.

6) Getting an understanding for what I am fighting with v against. There are two possible attitudes one can take here. I can see a genetic predisposition towards not being a sprinter as an excuse not to run. Or I can take the attitude that I must try all that much harder, and note that the same trait leaves me more favorably disposed towards endurance running.

7) Having a laugh. In theory, I should more likely be a blue-eyed man of shorter than average height, with a balding head. (My eyes are hazel, I am 189cm tall and as of age 39, all the hair's still there and the shower drain is clean, knock on wood.)

All in all, I would certainly recommend the 23andme.com service. I have spent USD 99 on far stupider things. A word of warning, though: they do make you explicitly request to have certain results revealed to you, and you should consider that carefully. For example, when you log on for the first time after they finish your kit, most results are right there on the page; but for, say, Parkinson's, you have to click through a warning that basically asks, 'Are you SURE you want to know this?' It could be devastating. I was required to go through the same process for the Alzheimer's one. I opted to look because I figured it couldn't be worse than what I feared. (It wasn't. It was actually better: there's a 75% chance I will never develop it; worse odds than most people, but far better than I had feared.) But give that some careful thought before clicking through.

Great Books, Part I of ∞ : An Optimist's Tour of the Future

I've no experience at all with book reviews. Giving my opinion is hardly problematic, as I warned in my inaugural post. But summarizing is not my forte. If anything, I tend to do the opposite of summarizing: give me a paragraph and I will give you a book. When trying to review an entire book, then, well....I just hope blogspot doesn't charge by the word.

Nevertheless, here I am trying to do a book review. Why? Because I am suffering from an embarrassment of riches of late. I have come across so many wonderful books in the last couple of years that I am bursting to share them all. I haven't come across such a wealth of wonderful reading since I was a very young man*, back when ALL wonderful literature was new to me. So, over the coming months, I will share some of these titles and my thoughts on their content and worth.

Among the most recent is Mark Stevenson's An Optimist's Tour of the Future, an insightful and inspiring (if occasionally mildly terrifying) book about the latest trends in all the technologies and ideas that will shape the world to come. I was fortunate enough to read an advance copy of the book, which is being released in the US on 3 February 2011. After I read it, I began a correspondence with the author, who is one of the most genuinely kind people I have had the pleasure to 'e-meet', the electronic nature of our acquaintanceship notwithstanding. I mention this only in the interest of full disclosure: I am reviewing a book of a person whom I have come to know (albeit to a necessarily very limited extent). But to be clear, reading and admiring the book came first and my reflections are thus free of any bias: I would not have reached out to the author had I not already respected his work. So with all the disclosures out of the way...

Think back over the past few years and think about the books you've read on the current state of the world and/or its fast-approaching fate. Then, when you get back from the pharmacy and take your copious amounts of anti-depressants needed to cope with those books, pick up a copy of this book and throw out the pills. Amid all the doom and gloom, here's a blossom of hope. Mind you, Mr. Stevenson is no naïf in rose-colored glasses: he approaches his subjects - among them some of the world's most brilliant people - with an intelligent skepticism, challenging their assumptions and never letting them off the hook when they try to wiggle out of the tough questions.

To get a sense of Stevenson's style and approach in this book, think about the motivations behind "What Are You Optimistic About?: Today's Leading Thinkers on Why Things Are Good and Getting Better", combine it with the probing intelligence and never-say-die quest for creative answers behind "Freakonomics", then dash in the wit and wisdom of a Bill Bryson.

Each section of the book covers a specific topic, with subjects ranging from transhumanism to robotics to the environment to genetic engineering (to name but a few). But more interesting still are the people working at the cutting edge of these fields. In each section, we follow Mr. Stevenson around the world as he visits some of these leading minds of our time, visionaries like Ray Kurzweil, George Church and Vint Cerf. Through wit, charm and intelligence, he elicits a level of frankness that you will not witness in any other interview format. (In that sense, the book is worth the price for the biographical components alone.)

I think the biggest selling point of this book, though, is the way it alters the reader's whole way of looking at an exciting future that is so much closer than most of us might think. Stevenson calls it a 'reboot', and that's a very apt descriptor: the reader finishes the book with a sense of awe (and yes, some trepidation) about a future in which everything we have taken for granted for so long, is suddenly washed away in favor of very new definitions of things as fundamental as success, happiness, relationships, even mortality.

So put down the doom and gloom for a while, turn off the 24/7 parade of dismay and pick up this reason to be optimistic. The future is going to be a wild ride, and Stevenson's book is a good road map.

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Footnotes:

*1938-ish?