Homo sapiens 2.0 (pre-Alpha)

Like it or not, Homo sapiens 2.0 is here.

Last week, it came out that a scientist by the name of He Jiankui has made the first human CRISPR-edited babies. He did it in secrecy, without properly informing the parents, without any scientific review, with no animal tests, with substandard laboratory methods, and with no clear idea about what the effects of the editing would be. An excellent breakdown of the fiasco, written by Ed Yong, was published in the Atlantic. The response by most of the scientific community has been shock and disgust, although the inimitable George Church advocated restraint (and a rather odd take on the ethics involved) in an interview on the subject. It is important to note that the community is reacting to how and possibly why He did the work, not whether we should edit human genomes in the first place.

To be clear, I personally think gene editing babies is someday going to be routine and am not against the idea in principle. First off, genetic diseases like Cystic Fibrosis or Huntington's disease, could not only be prevented, but could even be (eventually) eradicated from the gene pool entirely. There is a fairly strong consensus, at least among scientists and policy makers, that such gene editing would be acceptable if the technology were developed carefully. Second, one can imagine enhancing the human genome by mixing and matching performance related traits, such as muscular build, IQ, or longevity (assuming the genetic determinants for such traits were some day carefully elucidated).

Most people are more hesitant about this latter application. At issue is nothing less than the very real risk that the human species literally bifurcates into Homo sapiens 1.0 and Homo sapiens 2.0, with the latter species arising from those who have access to and can afford the technology. I personally neither embrace or reject this eventuality, as much as I see it as a very likely and unavoidable outcome of humanity's co-evolution with the world of ideas and technology. Humanity is not and never was a static phenomenon. However, it is important to acknowledge that every human on the planet is a stakeholder in the development and use of such technology. We're not just hacking genomes, we're hacking what it means to be human.

The problem with He Jiankui's work is the reckless way in it was performed. He seems to have put about as much thought into this project as a high school student does when putting the gene for green fluorescent protein into a lab strain of E. coli. He seems to have thought: well, it will probably work so I'll give it a try and see what happens. Furthermore, He seems to be angling for recognition and personal gain. Modern science and engineering is filled with such temptations, especially as easy to use dual-use technologies like CRISPR seem to be developed almost daily. Finally, by focusing on HIV, instead of some devastating genetic disease that would have otherwise resulted in a nonviable embryo, He has blurred line between prevention and enhancement.

Unfortunately, neither society nor the scientific community have yet agreed upon any kind of process for approving a particular gene edit, other than that we should slow down. The closest rules we have are fairly rigorous processes for developing new pharmaceuticals, which (should and usually do) include years of development, animal testing, and clinical trials. But the ethical questions surrounding drug development are mainly regarding patients one at a time, and not the potential for the development of new species, and so once again, a much broader set of stakeholders are involved. And regardless or the subtle and not so subtle ethical issues, scientists like He, and probably many others, are forging ahead with the technology like it is some kind of gold rush, which to some extent it is.

He is not unique. It is likely that as with most exciting new technologies, human gene editing entrepreneurs will ask for forgiveness and not permission. It seems to be part of our culture. They will take their cues from Facebook and Uber (how exciting) instead of the Genetics Public Policy Center (how boring), and work in secret or in countries with no rules or scruples about designer babies.

I support efforts to lay out ethical frameworks and encourage discussion. I am also preparing myself for the inevitable emergence of Homo sapiens 2.0. During the rollout, there will be successes, possibly gruesome failures, public outcry, legislation, secrecy, inequality exponentially worse than it is now, and ultimately the emergence of very powerful and very precise human genome engineering. Especially given how humanity is also intertwined with technologies like AI and robotics, the effects of widespread gene editing are harder to predict than is any technology heretofore invented. I hope we manage the transition well.

DOD Funding : Part 2

In a previous post I described my position, held from about 2011 to 2016, against taking DOD funding for research into synthetic biology. Fast forward to 2018 and I find myself the PI of a DAPRA project and co-PI of an ONR project. What happened? Did I completely abandon my principles? No, I  refined them. In brief, I decided that it is much easier to assert one's values from within the system than from without. Yes, the ethical landscape is treacherous. But it is also where the conversation is, whether I am involved or not. In the process, I have come to a new understanding about the nature of technological evolution and my role in it, which has changed the way I make decisions about what to work on and who to talk to.

For some background: In 2010 and 2011, a few opportunities to fund synthetic biology, mainly from DARPA, had come up. My experience with DARPA funding in control systems and robotics as a graduate student and a postdoc led me to believe that the DOD's interest in synthetic biology may result in potentially dangerous military applications. I did not want to be a part of that. I stood by this position for years, refraining from submitting proposals and having to turn down offers from colleagues to collaborate. I became known among certain very small circles of synthetic biology researchers and students as somewhat outspoken on the issue. I enjoyed stimulating and interesting conversations with people, some aligned with my position and some quite opposed. Sadly, I also endured conversations in which my position was openly mocked. Those conversations for a time reinforced my own arguments against DOD funding for synthetic biology as I dug in my heels in an attempt to justify my position.

In any case, for about five years, DARPA programs in synthetic biology came and went, and I did not participate. Many new technologies were developed by researchers for whom I have the utmost respect. Students were funded, companies were spun-out, papers were published, and new applications developed. At the same time, the community discovered just how difficult it is to reprogram cells, refining its expectations and developing new questions. In reality, these DARPA programs were a success. And they were essentially the only major source of funding for synthetic biology outside of the NIH, which only recently has begun to be interested in the area, and only for very focused, health and longevity based applications.

What about the military applications that concerned me? Indeed, there are now national labs doing research in synthetic biology to which the broader research community (including me) is not privy.  Students who "grew up DARPA" are now working for the DOD, having taken their knowledge of synthetic biology with them. Going forward, DARPA is doubling down on synthetic biology, investigating a broad range of applications from genetic circuits to neuro-engineering. For example, a recent call for proposals supports technology for "temporarily and reversibly tuning gene expression to bolster the body’s defenses". On the face of it, this looks a lot like gene therapy. When funded by the NIH, gene therapy is focused on genetic diseases, for example. But funded by the DOD, the technology would be clearly intended to build hyper-resilient soldiers.

Did first generation of DOD funding for synthetic biology spawn these ideas? Partially, yes. But the ideas also grew out of NIH funded research, private sector research, and the creative minds of researchers, students, and futurists everywhere. But in another sense these applications feel inevitable. Funding aside, people talk about immortality, curing cancer, neural prosthetics, hyper-nutritious food, green chemical synthesis, terraforming Mars with synthetic microbes, and on and on. The Pandora's box was opened a long time ago, in the 1970's, with the development of recombinant DNA.

These days, most view technology as arising from a living, evolutionary, mimetic process. New technological memes, whether practicable or not, arise from creative effort, building on existing science and technology. A technological meme can be realized as a real technological artifact through the research and development process. Crucially, once the technological precursors to an unrealized meme are worked out, the meme may become quite virulent, potentially infesting the brains of engineers all over the world, especially if it co-evolves with a story about increased convenience, health, security, or power. Eventually, someone builds the thing. If not you, someone else.

Society, alas, has little control over technological evolution. Most of the population does not understand most of the technologies that are currently being developed. And as the recent explosion of social media problems demonstrate, next to nobody can predict the outcome of unleashing a new technology on the world. Governments can steer technological evolution to some extent, by either pouring funding into an area, like cancer research, or by actively legislating against an area, like human cloning. But life (by which I mean the evolving world of technological memes) will find a way.

As engineers, what control, if any, do we have over this process? Very little, it turns out. Unless you are a Jeff Bezos or an Elon Musk, we can really only choose where to spend our time. We can also choose what conversations to have and with whom. For me, I choose to spend my time on building a reliable framework for engineering genetic circuits and systems. I do this because I believe that both individual lives and entire ecosystems on this planet are quite fragile. I think we we ought to not only understand life, but intervene where necessary to preserve it and make it more robust. In my work, I have come to the conclusion that synthetic biology is a potentially powerful technology that may redefine what it means to be human, and that can be used for both useful and nefarious purposes. And I see it as completely inevitable, given the current intellectual, fiscal, and moral climate on our planet. Thus, I believe that since I am an expert in this area, I should spend whatever extra time I have available working to make sure the technology is developed responsibly. 

With these goals in mind, where are people (a) talking about futuristic applications of synthetic biology and (b) talking about responsible innovation? Among other venues, they're talking about it at DARPA. This is not to say that DARPA actively facilitates these conversations. Rather, the researchers they fund talk about it among themselves, with their program managers, and with their students. And I would like to think they talk about more when I am around, because I am always bringing it up. For example, at a recent meeting, we were brainstorming DOD applications of synthetic biology. An administrator (not a biologist) running the meeting suggested we consider offensive, defensive, and civilian applications. Somewhat flabbergasted, I reminded him that biological weapons are illegal. "Oh. I didn't realize that," he said! In other less extreme conversations, the issues were more subtle, involving the risks of dual-use technologies, issues of access, reminders of who are the stakeholders, and a fair amount of extrapolation of current technologies into the future.

So, I have come to believe that I am doing some good getting involved with DOD funded research. I maintain that in 2005-2010 I would not have been able to hold my own in conversations like the above, and was wise to stay away. I was a more junior researcher, less confident, and less informed. Now I feel like I have better tools with which to navigate the landscape. I feel confident enough in my own value system and ethical decision making framework to steer the development of new technologies toward uses that I believe will do the world good. Furthermore, I have found that many of my colleagues who also work with the DOD are doing the same thing, seeing themselves as responsible stewards of new technological memes that, for better or worse, infest the brains of humanity. I still draw the line, and can confidently say there are many technologies I will not under any circumstances work on. But the line is not drawn arbitrarily along a funding boundary. Rather, it is actively drawn by me, by trusting in my own judgement and my ability to mostly do the right thing.

To the students who feel betrayed by my seeming reversal, I invite you to chat with me about the subject. I have much to learn and I expect my position will continue to evolve. Please bear with me as I work through these issues and help me do the right thing from a compassionate and empathetic point of view. I will strive to do the same. 

Ideas

As an scientist, your job is to find new ways of thinking. You are often wrong, and even when you are right your ideas can easily be misunderstood, as new things often are (even by you). In the best of worlds, your ideas will be respectfully and supportively critiqued by friendly colleagues and collaborators. However, just as often your ideas will be attacked, ridiculed, dismissed, and actively discouraged. Some people just feel it is their job to shit all over other people's work, and because your ideas seem like your brain children, such treatment might feel intensely personal. As a result, many academics carefully guard new ideas, keeping them safe, nurturing them in private, building up rebuttals to common attacks, and testing their ideas with preliminary studies. However, there are many situations where you have to make your ideas semi-public before they are mature: seeking ethical approval, funding proposals, PI meetings, research talks, working with or trying to find collaborators, or writing up papers exploring preliminary steps.

Without a framework to understand ideas and the various criticisms to which they will be exposed, you can become overwhelmed and shut down. Sometimes the critics will be right; your ideas are flawed, and a project will fail. After enough failures, you might begin to doubt you have any good ideas at all, which can lead you to question your own worth as a researcher or engineer. Failure is part of the process of course, and all successful researchers fail more often than they succeed mainly by trying many ideas while quickly weeding out the bad ones. In any case, you can avoid obvious pitfalls by thinking about ideas differently.

I believe that the foundation of "idea management" is to understand that, in fact, none of these ideas of which we speak are in fact your ideas. Sure, an idea may have occurred to you and feel like your personal invention. But just like a child, it is its own entity. Your job is mainly to challenge it and possibly to protect and nurture it. An idea is a kind of meme, and therefore subject to the dynamics of evolution. Ideas infect brains, are mutated through transmission, and are slightly modified for new applications. They form symbiotic or parasitic relationships with other ideas, institutions, communities, and people like you. Because so many researchers are working in similar fields, going to the same conferences, socializing, and reading the same papers, it is very easy for an idea to occur to two or more people almost simultaneously. Many times have I thought of something, made a mental note of it or even started working on it, only to see it published a year or two later. The idea will have been picked up by someone I don't even know who happens to have been readier to receive or better prepared to instantiate the idea than I.

Part of your job as a researcher is to attempt to create new ideas from old ones. You can do this by brainstorming, writing, having conversations, or taking long walks. It is very difficult to come up with a truly new idea. You might think you have one, but it turns out that you heard it from someone else and merely restated it in your own words. More often you will work to find, identify and evaluate the new ideas you read about in "future work" sections of papers or hear about in the late night conversations at conferences. Really, when we say "your ideas", we mean those ideas with which you have decided to associate yourself. Some of them may truly be your brain children, but most are probably infesting your brain because you happen to have the expertise to understand them. Some of these ideas may be good, some bad, some premature, and some hopelessly flawed. Somewhat alarmingly, the virility of an idea may be independent of its quality, utility, and even soundness. This is because it is likely human nature, or at least academic nature, to become emotionally invested in ones ideas. Something has to motivate you to follow through on an idea. Seen this way, ideas are really just using you. We researchers are like cells, mindlessly copying DNA, sometimes changing it, and sometimes benefitting from doing so.

Within the evolutionary framework of idea management, you will do well to dissociate yourself from the ideas that infest your brain. You want to see them for what they are and to be able to easily dislodge them if you need to. Within this framework you might also begin to see that your efforts to market ideas to others (in proposals, abstracts, and talks) are just more ideas that become symbiotically associated with the original idea. Thus, your job becomes less personal. A criticism of an idea is not a criticism of you. It is just a criticism of the idea. The focus of your job as a researcher is instead to learn all you can about every idea in your field, the old ones, the new ones, the bad ones, and the good ones. Learn the underlying theories and conceptual frameworks. Read voraciously. Teach and be taught. In this way, your brain becomes ready for ideas. It develops a healthy "immune system" to avoid being infested by flawed ideas. It is ready to understand subtle and immature new ideas. And it is able to nurture ideas by testing them, challenging them, modifying them, and marketing them. Take seriously valid criticisms of your abilities to perform these tasks. But if someone criticizes an idea that you happen to have latched on to, evaluate the criticism. Maybe it isn't something you've thought of. Use it to improve the idea, to improve your explanation of it, or to dismiss it as flawed.

In a future blog entry I plan to attempt to categorize the kinds of criticisms that people will launch at "your" ideas. Understanding these categories, you can dismiss illogical criticisms and take seriously the valid ones. You can even try these criticisms on your ideas yourself in relative safety as you work to refine, justify, and support your positions. Hopefully, you'll develop a healthy relationship with the various ideas that infest your brain.

Beginnings

In the beginning there were no blogs, only basic particles, energy, space, and various other stuff about which cosmologists speculate. Blogs came later, and when they did, many people thought "I know, I'll start a blog". And they did and you would meet people at parties who would say they had a blog, and it would sound similar to when people used to say they were writing a novel or starting their own business. Some of the blogs were good and still are. Other blogs were not so good because they didn't really say anything interesting. How many pictures of your food and stories about traveling does the world really want to see? The biggest problem was that starting a blog was the easy part. Adding content week after week was the hard part, and many blogs languished after an initial flurry of activity, and a pronouncement of the blog's existence at parties. That's embarrassing for that same blogist at the next party where the he or she is asked "So how's the blog going?" and the answer is a disappointing "Oh, I haven't posted in a while, but I'll get back to it soon."

So it is with trepidation that I start this blog. I am taking a risk. Certainly, until I have posted enough content and gotten into a rhythm with adding new content, I am not going to tell a soul. Eventually though, I'll post something amazing, and I'll mention that I did so on Facebook, and people will read it, and then they will notice other posts, and the next time I see them they'll say "Oh, I didn't know you had a blog. Why didn't you tell me?". And I'll refer them to this, the first post, and it will become clear. I didn't want the pressure. I didn't want readers. Not yet anyway. Its too delicate. Too new. What if I get discouraged? What if some evil troll is overly critical? It could burst my bubble.

So I'll keep this to myself for now!