Future Ben

First off I want to be clear that I didn’t expect to win the young investigator’s award. OK, I am still bitter about it, but I am bitter about lot’s of stuff. So while I am not particularly upset about not winning, it was the finalists who really irritated me.

All three featured commercial products some with affiliation to the “judges.” That really set the tone. Sure there is no point in reinventing the wheel, but using something you bought as directed by the manufacturer is not exactly ground breaking. To her credit the winner was actually collaborating with a chemist to improve the agent. La di frigging da.
None of the finalists used any methods other than imaging. Sure it’s an imaging conference, but if you are going to claim your labeled differentiated into a particular type of cell, you are obligated to back that up with some staining. “We injected some bone marrow, it did aomething, you can see it, isn’t that awesome?” Wow, mail that back to 1988 when it wasn’t taught in first year immunology!

So what was the judging criteria. judging from the abundant use of the RGD peptide for labeling avbeta3 integrin, it was mostly based on FDA approved nonthreatening tech. By nonthreatening I mean it doesn’t challenge anybody’s research. To set such a conservative standard for grad students and post docs is a travesty. This is the point in our careers where we should be challenging the status quo or at least looking at biology in a new way. Sadly, medicine is too parochial and corrupt to allow real creativity to flourish.

I am back in construct design mode, and a deeper lesson just dawned on me. I have been playing with a human protein in a human cell. It’s the metal transporter DMT1 that I will be talking about in Kyoto next week. Not surprisingly, this protein is tightly regulated at every level. How do I get around that problem?

I could edit out parts of the sequence and figure out what parts are regulatory, but that could take a long time. It turns out that a long time ago E.coli picked up the gene for DMT1 through horizontal gene transfer. All the regulatory parts have long since mutated away. Thanks for the help. I am going to use the Bacterial protein as a starting point, but of course it’s not that simple. First off bacteria prefer to use different codons for proteins. you can still get bacterial genes to express, they just don’t do it very efficiently. i have to synthesize the gene for mammalian expression. That’s not so tough these days. A trickier problem is the membrane. E.coli have a different thickness of membrane than a mammalian cell. I will have to do some serious sequence gazing and mental modeling to fix this problem. Sadly there is no structure to work with. If there was somebody else would have done this already.

Damn I have to geek out here for a minute. I am listening to this dude give a tlk on the lambda repressor. It’s been 20 minutes of rambling about how life is just mass action and kinetics. He has the smug confidence of a man who doesn’t know how dated he is. Denying Systems Biology is the new Inteligent Design.

Seriously, just because you figured out that the Cancer field is mostly bullshit doesn’t make you Linus Pauling!

Now Len Girrenti is talking about Sirtuins. Makes sense that Sir2 in year and worms points to a working Sir2 in humans.
“I don’t know of caloric restriction will make you live longer, but it will sure feel like it did”. Ha!

I guess the whole point of taking resveratrol is to pretend like you are living like a yogi. Awesome!

Sirt1 stimulates BDNF production. Who is taking a systems approach? There must be a bunch of people.

It makes me think about going all out on aging. That field is never going away.

It’s a rainy day. When it’s like that outside I find little things to do around the lab.

I have a series of surgeries next week so I better get all my scissors sharp and organized!

I finished running all of the gas lines for a new oxygen enriched anesthetic system. Once the last part was in place I had to step back and get a picture.

Techically not steampunk, but all the gauges and pneumatic hoses next to the superconducting electromagnet reminded me of a panel from Girl Genious.

Next I will install a tesla coil and a giant knife switch.

After months of failure. I finally succeeded in electroporating my novel reporter gene into the brain of a newborn mouse. As it turns out the equipment I was using was crap, and since I don’t know anything about unipolar square pulses with exponential decay, I was unaware of its shortcomings. So after ~250 mice injected that sacrificed. Here is the result.

The champagne doesn’t pop just yet however. This wasn’t what I was going for. Getting GFP to express like this was an achievement a few years ago, but it is just the control for my real experiment. The question is, does this correlate to an MRI? I have a whole litter of these pups, and hopefully the other 9 have the same kind of expression as the 3 who were sacrificed so far.

But, if they really do correlate, suddenly it is endgame for my thesis and I can start doing some cool stuff with the my new technology.

I presented a talk to the NYU Biotechnology club today, Metabiotechnology: or Why Biotech Sucks Right Now. Attendance was low but the crowd was more bemused than offended at the title. Often as you put a presentation together your thesis develops. And feedback from your audience is even better for that purpose. Drew and Dusan were particularly helpful but I was surprised at what did and did not resonate.

I will try to post the talk if I can figure out how to get powerpoint into wordpress. Basicly my thesis is that the current hegemony of Biotechnology is Biobusiness. While there is nothing inherently wrong with a free market the system is monolithic and there are huge needs that are very poorly served. The most prevalent being the needs of developing nations.

As I was preparing and during the presentation I realized that it was worse than that. The science supporting Biotechnology is often undermined by profit motivation. My case study on this was the “Green Revolution.” Initially plant breeding and ecological management through pesticides and herbicides seemed like a good idea. It has become pretty clear in the past 20 years that this is not the case and that there are much more sound and sustainable practices. Yet people with access to all of the data pointing to the failings of previous generation technology continue use ultimately damaging methods. In fact they have subjugated Biotechnology to continue even farther down this destructive path. (Hence the subtitle.)

So the evils of greedy corporations aren’t all that new, as several people pointed out. But what surprised me was the audience response to my proposal. If Biotechnology is currently monolithic and profit motivated then the weaknesses of that system opens up the possibility of Biotechnology that is dynamic and either need, OR profit motivated.

Maybe I didn’t express that clearly enough, but I got a lot of knee jerk capitalism. “Technology has to have a product,” or “that system works a lot better than government funding.” Both true statements, but not in anyway an argument against need motivated Biotech. And I acknowledge that there are government grants to encourage people to develop need based technologies, but there has to be something more, something new.

I am glad I used the agriculture case study because the great weakness of current agriculture is that it is monoculture based. And that is exactly the problem with Biotechnology and Big Pharma. Sure there are a lot of little Biotech companies, but they are all playing the same game. Especially since they all presumably follow the FDA rulebook. A true disruptive Biotechnology would bypass this whole system. Is paradigm shift old enough to be retro? It sounds stupid, but there were very intelligent people in the audience who couldn’t imagine that there could be an alternative to our current system.

If you equate it to other paradigms, Biotechnology is ready for it’s own version of the personal computer, model T, cotton gin. I think sequencing was the equivalent to the printing press or early computer. Biotech is fortunate in that it can take all of the lessons from the electronic and information technology fields. Open source, distributed systems and other meta-technologies. The question is, what will that technology be? If history is any teacher we won’t know until it becomes pervasive.

I try not to repost boing boing material, but sometimes it’s to topical to pass up. Wired contributer Quinn Norton has posted her slides from her talk on Body Hacking. Body Hacking is admittedly just a catchphase that doesn’t really capture the embryonic state of post humanism we live in, but I can’t think of anything better so OK. So what makes body hacking different from piercings and tattoos? Ms. Norton makes the point that body hacking goes beyond the aesthetic and into enhanced functionality.

Already Lasik and ligament replacement surgeries are being used for enhacement in sports, and drugs like Provigil Aderol and Xanex enjoy vivrant trade on the black market. So what is the future of body hacking?
I would guess that surgical enhancements will grow as quickly as creative drug use and biological theraputics like viral gene transfer. I am waiting for somebody to use the Adenoviral treatment for CF on themselves to enhance their breathing capacity. I doubt it would do anything, but I still hope they try.

I have been appointed the task of naming my first foray into synthetic biology/ protein engineering. I have never invented anything substatial enough to name before so I am having some trouble.

The protein is a new reporter for MRI. It binds paramagnetic Manganese and it creates a brighter signal than background tissues when imaged properly. What the hell do you call something like that?

My coleague and friend Yousef had this to say.

your construct could
termed as MP’s standing for either “magnetic protein”, “manganese protein”,
“metal protein”, “MRI protein” (a lot to stand for) to parallel the FP field
(fluorescent protein). Since there is no color such as in GFP and RFP
etc….Your enhanced MP (EMP) are reduced to 2 tone: darkening (DMP)and
brightening (BMP)proteins. In DMPs Ferritin would be one of them and in BMPs
yours would fall in this category…

BMP? I’m not sure it has pizzaz. Although I agree that an acronym would be appropriate. How about Manganese Enhaced Magnetic Resonance Imaging Protein? MEMRIP. Maybe MRI can be collapsed and I could just call it MEMP. If I did and Iron one it would be FEMP.

I have to figure this out before starting the patent.

I said we were going to Boston first, but the future starts here in New Yok. This spring will be the groundbreaking of a project to create nearly 1 million square feet of Biotechnology lab space in NY right next to the NYU med center. Apparently they hemmed and hawed about it for years and then Guiliani got cancer and suddenly became very interested in Biomedical sciences. (Funny how that works.) NYU had tried to get the project rolling, but had only managed to get the area rezoned before NYC took the project away from them. Now it looks like it is acutally going to happen.
In addition to providing labspace at rates competitive to Boston, SF and La Lloya, the city is also putting together a sizable investment fund for startups. Hopefully this is the kickstart that NYC needs to catch up to other areas in Biotech. I didn’t plan on staying in New York after grad school, but this might be an opportunity that I should stick around for.