"We have learned nothing from the genome." That's the grim message that J. Craig Venter recently gave Der Spiegel in an amazing interview. Venter, decoder of the human genome and creator of the world's first fully synthetic bacteria, doesn't pull any punches when describing the medical benefits we've derived from sequencing the human genome. They are "close to zero to put it precisely." The Der Spiegel interview catches Venter in a blunt mood and we're given a rare insight into how one of the foremost scientists in the field (probably the foremost scientist) see our progress thus far and our hopes for the future. To paraphrase: we haven't really accomplished anything yet, people don't want to believe that at all, and we're finally taking the first steps to really understanding things now. Some of Venter's juicier statements have me rethinking the current state of genomics. Check out the quotes below.
As we recently discussed, the 10 year anniversary of the Human Genome Project (and Venter's competing and more successful Celera Genomics) has raised serious questions about what we have really learned from our foray into genomics. We've had success with in vitro screening for certain genetic illnesses, and we've used genetics to craft a few new medications, but the public at large has not seen a lot of benefit. Why?
Because we have, in truth, learned nothing from the genome other than probabilities. How does a 1 or 3 percent increased risk for something translate into the clinic? It is useless information.
We've seen personal DNA testing become a burgeoning product, with companies like Pathway Genomics, 23andMe, and Navigenics offering to scan your genome for important genes (SNPs) and tell you what their presence may mean. Such tests are all about probabilities, and many have raised the same concerns as Venter - that we what we learn from such studies is practically useless. I for one, enjoyed my DNA test, but mostly for the educational merit. I've haven't changed a single habit in response to the data I was given. Why?
we need a lot more information: Information about your body's chemistry, your physiology, your complete medical history, your brain and your entire life. We would need to do that a million times on different people and correlate that data with their genetic information.
Essentially we have more DNA than understanding. Until we can correlate massive amounts of genetic data with real-world effects we really don't know what to tell people when we give them results to personal DNA tests. Even those that have had their whole genome sequenced (not just SNPs) don't really have much insight into their lives. As Venter says about his own experience with sequencing: "We couldn't even be certain from my genome what my eye color was."
But efforts are already underway to correlate medical histories with DNA. We've already discussed biobanks of hundreds of thousands of patients that are being created over the next decade. With cheaper whole genome sequencing it will eventually be possible for us to examine this rich pool of data and perhaps discover meaningful and useful insight into how genes affect our bodies and health. What happens then?
It's not, 'Oh, we know your genome, we're going to make this drug for you.' That will never happen. It is more important that you use the information in the genome about your personal risks and reduce them through intelligent behavior.
I heartedly agree on the last part, but object to the first. We don't know if it will be practical to tailor drugs to individuals (probably cost prohibitive) but I think it is likely that we'll be able to customize treatments. Doctors already do that for every patient without a lot of knowledge about genetics. In the future we may not create entirely new medications for each patient but we're very likely to use fast chip processing to give doctors an idea which drugs will react poorly with the patient due to genetic predisposition. Given enough possible combination of medications the difference between custom making drugs and custom designing a cocktail of them will seem slight. In my opinion.
If you think that Venter's comments in Der Spiegel are unbearably gloomy, you haven't read enough of the interview. Yes, the first third is mainly Venter trash talking about Francis Collins, and the second third chastises everyone for thinking that genetics was some magical cure-all or some dreaded infringement on God's turf. The last bit, however, reveals where Venter's hopes seem to lie: in creating new life from scratch.
We don't even know how the simplest bacterial cell works. We want to learn what the minimum cellular components are, so we're going to be taking out all the non-essential genes.
He's already assembled bacteria from the building blocks of DNA, and now he has his sights on using that technology to really advance our understanding of genetics. He and his team plan on building a 'minimal cell' - the simplest form of bacterial life you can make and still have survive. The hope is that this will lead to a greater understanding of what it takes to be an organism - to understand the basic components and operating system of cellular life.
From that understanding could come the ability to truly design organisms from the ground up. We could design bacteria that produce complex carbon compounds and reduce our need for oil. Exxon Mobile has invested $600 million with Venter in the hopes of creating these new life forms which could radically alter the availability of resources all over the world. Think of what the organisms we design may be able to produce.
Not only gasoline. Plastic, asphalt, heating oil: Everything that we make from oil will at some point be made by bacteria or other cells. Whether that is in five, 10 or 20 years is unclear. Why don't we have fuel now other than alcohol from microbes? It's because nothing evolved that can produce great amounts of biofuel out of CO2. That's why we have to make it.
Venter's vision of the future seems to be as hopeful as his vision of the past is disdainful. There is so much power in genetic engineering and synthetic biology that it's hard to fully grasp both its limitations and its potential. If there is one message to take away from Venter's comments I think it is this: we need more understanding. Thankfully there are many, including Venter and his colleagues, who are pursuing that understanding with a fiery passion.
All quotes are J. Craig Venter,2010 as taken from Der Spiegel. The full Der Spiegel interview with J. Craig Venter conducted by Rafaela von Bredow and Johann Grolle can be found here. It is awesome. Read it.
[source: Der Spiegel]