Fourteen years

Lab Note #15
Jun 06, 2015

On July 2nd I will put an end to more than fourteen years of lung cancer research in the lab. I will start a new job, related to cancer research, but no more bench work. No more experiments running and no more rushing to see the results. Is this a final end or just a pause? I cannot answer that right now. But it will be difficult to come back, at least to come back to the same setting, a small lab in academia, fighting for grants.

On these fourteen years I've focused on one single protein: hnRNP A2/B1. A protein involved in mRNA processing: alternative splicing, mRNA stability and transport. So, it's a fundamental protein in the processing of genetic information. It was completely unknown to me back in February 2001 when I first sit down on our office shared space at NIH. I've learned a lot in this process. And it is possible, as I a former mentor said, that at this point I am a worldwide expert on this protein in cancer and more specifically in lung cancer. I don't know. Maybe it's true. In any event, one of the first things that I can conclude from these 14 years is that deep knowledge is irrelevant in academia. It's useless. You read, you study, you think, you hypothesize, you talk and discuss but it's useless. At the end this fascinating process leads to not having any institutional support in academic institutions if you don't meet the standards of productivity.

And there we go… The numbers of published papers, the impact factor, the productivity question. Yes, papers were published. Yes, several grants were submitted. However, there is nothing less creative and less scientific than writing a grant proposal. Applying for financial funding for the results you already have, providing the frame to advance your science one microscopic step. No imagination, no innovation. Only linear thinking allowed, in a dramatic perversion of the scientific method. And this is the second conclusion of my experience. Grant proposal writing? Is it all about science, about progress, about risk taking? Or is it more trying to show that you can be as conservative as possible so no money is wasted, nice papers are published and numbers of publications can keep piling up? Moreover, grant proposal writing effort is irrelevant if you don't have the connections, the tap on the back from the "old guys" that know the system.

I wrote bad grants from lack of experience, I wrote OK grants. I even wrote good grants in terms of ideas and hypothesis. It did not matter. I can keep practicing and get almost perfect grants. But I hate it. Last summer we started a new direction on our main research project. We wanted to understand the role of hnRNP A2/B1 in the resistance to targeted therapy against EGFR mutations in lung cancer. We started with a simple hypothesis. Last week we look back at this hypothesis and we saw how naïf it was. Experiments have been done. Results analyzed and now we are facing a more complex scenario. Hypothesis is still partially valid but it has to be redefined and adjusted to new data. We wrote a couple of grant proposals that did not require a lot of preliminary data. Rejected of course. If I had to write again this proposal it would be different and include a modified approach. You can write proposals. But you cannot be sure they are going to follow your direction once you start doing experiments. You need a good amount of data to write a proposal that can be considered "good enough". But, how do you get more data if you don't have money to start doing your experiments?

Thanks to the crowdfunding campaign I received some funding to do a few things. And I have enough data to develop a more solid hypothesis in a couple of months. But time is running out, funding is going down and I can not keep working full time and getting paid 50% by the academic institution. I don't have two or three months. Crowdfunding was good but I need more than that.

Fourteen years. I've had different mentors, different principal investigators of the labs. They gave me ideas and directions. Some good. Some horrible. Good ones allowed to know more about this fascinating protein. Horrible ideas resulted in a lot of time wasted. In this process I have learned a lot and now I have at least three different projects related to hnRNP A2/B1 and cancer that can be developed:

  • 1)Early response to targeted therapy against EGFR mutations in lung cancer. This can provide an understanding of how the cells start the process of resistance and give an opportunity to a new therapeutic window.
  • 2)Exosomes and cellular communication under stress in lung cancer. I have less data on this but it could be enough to start developing a good project. It's all about the exchange information between cells using exosomes and how that can affect tumor progression, drug response and metastasis.
  • 3)Interaction with K-Ras in lung cances. Another way to block K-Ras. This is only an idea based on the literature but I think it's provocative and interesting.

However, on 7/2/15, in less than four weeks, all this will be stored in a folder in the computer. How long? I don't know. Hopefully we will be able to send a short report regarding results on resistance to targeted therapy so maybe somebody else can try to work on it. Or maybe, ten years from now I will start my own biotech company and work on these projects again.

Thank you for your support and I will try to get enough results in these last four weeks to get it published this year.

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