Synthetic Biology

My dear friend Zara has shared a fascinating article on Synthetic Biology. Basically one could call it the beginning of “real-life” programming (and engineering), or even scientific creationism. James Collins is a pioneer in the field. After looking around a bit, I came across another interview with the man where he talks not just biology, but also delves into education, psychology and politics, and explains the importance of failure.

DMM is an Open Access biomedical research journal.

 

The way we approach projects that are creative and high risk is to fail fast. What we find is that if we are going after a project where we need to develop a new technique, we assume that we need ten good ideas to find one that will work. The odds are stacked against us even more when we delve into the basic science realm. Out of 100 new ideas, only one will probably be correct. We try to very quickly triage out the bad ideas. My feeling is that our willingness to fail, and to fail quickly, will get us to that one idea that will work. One proposed definition that I’ve heard is that a scientist or engineer is someone who can go from failure to failure with undiminished enthusiasm. We do not want to avoid failure, but rather to use the experience to steer us toward success.

 

I think an unwillingness to teach kids to learn from mistakes is a big problem. Increasingly, educators cater to kids rather than teaching them how to learn. Students get A or B grades for regurgitating spoonfed information. This environment may be fine for a few really smart kids who will challenge things on their own. Many of the kids I see are really smart and many are willing to work hard. Still, when they move into research or any real-world area that includes intelligent peers and competition, the environment they face becomes largely unforgiving. The reality of their future is that their own close colleagues may expose their bad ideas or reject their manuscripts. It is important to know how to handle this criticism. I think we are doing a great disservice to our young people because they are not prepared to fail and to use the experience to learn. I like to give young students two messages. First, I hope they fail. This idea usually makes their mouths open agape. I explain that what I mean is that, although they may be protected from failure in their studies, I hope that they venture beyond this and challenge themselves. Second, I hope that they become comfortable with doing nothing for at least some period of each day. By this, I mean that they should allow themselves to be unconnected from their phone, text or computer and actually spend time thinking about their ideas. This could include discussing ideas or introspectively ruminating about them. This activity is too largely ignored. To move the world forward requires thinking about new ideas and then trying a few, even though some will not work. […] You have to be comfortable with failing. You don’t have to accept failure but you have to be willing to fail and you have to have the coping mechanisms to handle it. Many of my scientific colleagues focus on the most obvious question that they can identify, a question that will guarantee them enough results to secure their next paper or grant. This ‘safe’ science is often important, but real advances require innovation and risk. Failure is hard on the ego and can definitely diminish your spirits. It is sometimes hard to keep going if you are constantly thwarted, but this is the reality of moving forward into innovative space. Kids need to be encouraged to develop the skills to withstand it.

 

They can ask questions without being intimidated by the notion that multiple geniuses may have already thought of everything. I like to present historical cases where a seemingly innocuous and simple question was asked that changed the way that people thought about significant issues. Most people would have assumed that the answer to the question would be known by the time the question was ever asked. In many cases, I think that young people have very good questions that they automatically assume have been asked and either answered or dismissed altogether. I encourage them not to put the simple questions aside so quickly.

 

An effective mentor is someone who is really candid. If they think that you’re not working as hard or working in the right way, they tell you. A mentor is someone who is going to challenge you to take the risk but is going to be on your side when it seems like the outside world is attacking you. If you get tough reviews or grant rejections, you want a mentor who’s going to be there to tell you that it’s going to be okay. You want a mentor who can really help you identify your interests and know your strengths. A mentor should help you find your path to success. Many students today seem almost paralyzed by the number of choices that they have. They become so fearful that they are going to move in a direction that is irreversible. I think a good mentor will tell them to look at life like a Woody Allen film; when you come to a fork in the road take it. You have to make decisions that affect your career, but almost none of them are irreversible.

 

My first student in synthetic biology and microbiology, Tim Gardner, was an engineer who brought an engineering approach to his biological questions. He considered multiple possible answers to a scientific question in parallel. Instead of just considering how one construct might interact with a gene, he would consider ten or 20 and was then able to pick out the ones that were the most significant. Using this approach, he was able to design one of the first synthetic gene networks in a relatively short period of time.

 

What I see at more traditional places, whether it be the Ivy League schools or established tech institutes, is an almost institutional reluctance, either in the department at chair level or dean level, to take on risks. At these places, if you take a risk and fail there is a serious fear of losing rank or status.

 

We started with physicists, engineers and mathematicians because these groups were immediately enthusiastic. Increasingly we are recruiting bona fide molecular biologists and cell biologists who want to apply systems approaches to organisms. In the past, I’d say starting in the mid-1990s, I had great success recruiting what I call ‘the misfit toys of science’. This might be the physicist who was drawn to biology but could not get collaborative interest from biologists because they did not have a biological background. Physicists were equally resistant to train them because of their biological leanings. I was able to bring them into my lab since they had backgrounds that jived with my background and interests. They tended to be really smart amateurs who, by both their intelligence and their freedom from conventional thinking, were able to make very innovative contributions. Their work has had a pretty big impact. Although it is initially different, work from people who think between fields is more rapidly understood and accepted than it used to be. When we moved into the antibiotic space, a little over two years ago, with our discovery that all bactericidal antibiotics induce a common death mechanism in bacteria that involves damage from oxidative stress, many in the field were highly skeptical. Several of the initial skeptics have now reluctantly come to believe the findings as an increasing number of groups build on them, extending them rapidly. Soon, I think our idea will become an accepted notion. This is an amazing time scale since, in the recent past, it was generally thought that in order to get a truly innovative scientific idea accepted, you had to literally wait for the established members of the field to die. We are moving on a much faster time scale in modern science. There are so many studies coming out that you don’t have to wait for the old guards to die, you can just overwhelm them.

 

James Collins (Disease Models & Mechanisms 3, 403-406, 2010)

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