Sunday, April 3, 2016

The Augmented Human Being

I worry about a lot of things. I encourage people to worry about a lot of things, but worry in the sense of taking action, doing something about it and being cautious as you do something about it—doing safety engineering. Every field of engineering has a safety component, eventually. You have civil engineering, aerospace, and so forth; huge amounts of their budgets go to safety components, and biology is no exception. Certainly in pharmaceuticals a huge fraction of the budget for bringing a new drug to market is not the research and development that produces the first prototype drug; it’s all clinical trials—toxicity efficacy testing. (...)

Some of the things that we want people to worry about, in an enabling way these days going forward, are a lot of new applications of a new technology: CRISPR. (...)

Basically, there is no organism on the planet that I know of that somebody has tried that it doesn’t work in now, which is not true for every editing method. This editing method, you could say, is just a little more efficient and a lot cheaper. That makes it sound like it’s increment, but every now and then if it’s a sufficiently large increment, it’s transformative. Most people who are familiar with it are classifying it as transformative.

When you look at the applications of it beyond engineering human stem cells, which we showed first thing, you can do gene therapy with greater precision; that’s the most obvious thing. A little less obvious is you can engineer agricultural species in such a way that many governments are now classifying it as not a genetically modified organism. This is a big deal, and it shouldn’t be a big deal; it should be a minor bureaucratic footnote.

Because of people willfully ignoring scientific studies on safety, they draw this sharp line between genetically modified and not, especially for foods. Even the most ardent anti-GM are still pro-GM if it’s life and death; like genetically modified insulin, where you grow human insulin in bacteria. But we’ll come back to that. Those two things are the more obvious ones: human gene therapy that's more precise and efficient than ever, and agricultural.

Less obvious and fewer groups working on it is gene drives, which can be used to eliminate any vector-borne disease—malaria, dengue, lime disease—as well as invasive species like rodents that are killing off precious, endangered species on hundreds of islands worldwide and mainlands. That’s gene drives.

Then transplantation: going from pigs to humans. There are a million people in need of transplants, which are not limited just by incompatibility between people; there are just not enough people. Even if we were all compatible, there are not enough donors. Pigs offered that possibility, but there were two problems. One is the immune incompatibility, and the other is they had endogenous viruses. We have used CRISPR to solve both of those problems.

Then there is ecosystem manipulation. In addition to gene drives, you can address the isolation of a species’ elements: territories shrinking, getting divided by roads and other human artifacts—farms, and so forth, so that they become inbred. When species are inbred, they become less robust, less fertile, and that can be found by another revolution we’ve been involved in, which is "next generation sequencing," or reading the genome. You can now insert, using CRISPR, the proper more fertile and more robust version of the genes, or generate greater diversity.

Some of that diversity you can bring in not only from adjacent populations that are separated by manmade structures, but also diversity separated by time. You can bring in DNA from the ancient, extinct versions of these animals, near relatives, because this amazing next generation sequencing is so inexpensive and powerful that we can reach back up to 700,000 years into the past and get accurate sequences of long-extinct species, but with potentially very valuable lessons for modern ecosystems.

New technologies do change our perception of ourselves. It used to be new discoveries, and it still is; it’s integrating. If you have a new technology like a telescope, it can cause a discovery about where our planet sits in the universe—whether it’s at the center or not—but more and more frequently in the present, we have new technologies.

Sometimes people ask me why everybody is so worked up about applying CRISPR to the germline of humans. They’re not worked up particularly about applying it to the germline of animals. We just got approval for genetically modified salmon, and plants have been genetically modified for many years now. Even though some people will eat it and some people won’t, the fact is it’s a multibillion dollar business.

Why are humans special? You could say we have the Food and Drug Administration (in multiple countries) that makes sure every new medical technology, whether it’s a medical device or pharmaceutical has to be safe and effective. It does you no good to have a drug that’s safe but does nothing, nor having one that’s very effective but kills people.

What is it that makes germline manipulation of humans special? It's what you were just getting at—our perception of ourselves. If we feel that we can change any aspect of ourselves, where do you begin and where do you stop? and who sets those rules?

When you’re in a more primitive phase of the technology, you don’t have to ask that question because it seems so far off. We can only make minor changes: a little nip-and-tuck, cure a few vaccines; it doesn’t fundamentally change human nature. But if you ever did get a tool where you could fundamentally change human nature to anything you wanted—any hybrid with any animal properties that you like, hybridization with your inorganic machines that’s more intimate than it is now—that changes our view of ourselves. I guess that’s why people not only want more caution than ever before, which I would concur. They want maybe so much caution that it can never happen. There are many technologies that get banned at one point or another; it’s not unusual. Railroads were banned because trains were colliding with one another, sometimes in the middle of towns. (...)

There are now 2000 gene therapies where you’ll take a little piece of engineered DNA, put it inside of a viral coat so all the viral genes are gone, and you can put in, say, a human gene or you can have nonviral delivery, but the important thing is that you’re delivering it either inside of the human or you’re taking cells out of the human and putting the DNA in and then putting them back in. But you can do very powerful things like curing inherited diseases, curing infectious diseases.

For example, you can edit out the receptor for the HIV virus and cure AIDS patients in a way that's not dependent upon vaccines and multidrug resistance, which has plagued the HIV AIDS story from the very beginning. You’re basically making a human being which is now augmented in a certain sense so that, unlike most humans, they are resistant to this major plague of mankind—HIV AIDS.

There are now people walking around who are genetically modified. There are some that are resistant to AIDS because they have had their T cells, or more generally, their blood cells modified. There are children that have been cured of blindness by gene therapy. None of this is CRISPR, but it’s in the same vein. CRISPR is overtaking it very quickly and it’s drafting behind all the beautiful work that’s been done with delivery of DNA, delivery of genetic components to patients. (...)

Some of the questions that come up with Revive and Restore, of using cutting edge molecular technologies for ecosystem conservation and preservation, some of the same questions come up as come up with using these molecular technologies in medicine, which is who gets to choose? who decides? Are people not being heard or not being invited to sit to talk? (...)

The question of who decides ultimately with these kind of transparent and open projects, where it’s not being done in secret like the Manhattan Project, is —society decides. We vote with our wallets, we vote with the free enterprise system, with our politics, the power of the pen, and in some cases, we may change our mind later. There's an emphasis on things that are reversible—those get higher priority.

But eventually, we do irreversible things.

by George Church, Edge |  Read more:
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