In Issue 2, Professor Nicholas Farrell of Virginia Commonwealth University published a review on zinc finger proteins. I was lucky enough to meet Nick at the GRC on Metals in Biology in Ventura, California earlier this year (yes, it’s a tough job!) and had the chance to ask him about his research and career.
Read on to find out more about Prof. Farrell’s work, his time working at the interface between science and diplomacy, what he learnt from his experiences with the pharmaceutical industry and why he likes the scenic route…
Critical Review: Zinc finger proteins as templates for metal ion exchange and ligand reactivity. Chemical and biological consequences
Susana M. Quintal, Queite Antonia dePaula and Nicholas P. Farrell
Metallomics, 2011, 3, 121-139
What motivated you to specialise in biological and medical aspects of inorganic chemistry?
As a graduate student in the period 1969-1973 the cisplatin story was emerging (Rosenberg’s Nature paper on the antitumour effects of platinum compounds was published in 1969) and it was just such an unexpected finding that it caught many people’s imagination.
What projects are you working on at the moment?
We have three main projects within the general area of medicinal inorganic chemistry:
- The trinuclear compound BBR3464 is the prototype of polynuclear platinum compounds developed in my laboratory. We are working on “second-generation” analogs for clinical development.
- We also continue our work on the biological activity of the trans geometry – the original structure-activity relationships of platinum antitumour drugs said the trans geometry was therapeutically inactive. My lab has been the leader in challenging this assumption and we are now studying compounds with good antitumour activity in vivo.
- Finally, related to the Metallomics article, we are very interested in new biological targets for inorganic compounds. We think zinc fingers are highly promising in this regard. We are asking the question – how do you systematically change the chemotype of a cytotoxic agent to a more specific protein family? This approach could produce much more selective drugs.
In your opinion, what’s hot at the moment and/or going to be next big thing in your field?
That is hard to say. There are interesting advances in imaging the fate of inorganic ions and drugs in cells, which could have benefits in understanding the relevance of inorganic ions in neurodegenerative disease. Specifically for platinum, there are few, if any, clinical trials of new platinum and metal-based agents at this time. There are many reasons for this, some scientific some commercial. It is possible that newer formulations can be successful and expand the range of cancers sensitive to platinum.
If you could solve any scientific problem in any field, what would it be?
For biological and medical research, I think the whole issue of antibacterial multidrug resistance is a worldwide problem, with significant impacts for public health. The daunting task is to recognize the complexity of the contributing factors to develop global or at least regional strategies to combat antimicrobial resistance.
What’s the secret to running a successful research group?
My opinion is to lead by example. Students do feel part of the “group” – but should also be encouraged to expand their own knowledge base and in an ideal world would regularly challenge even the “preconceptions” of the group.
If you weren’t a scientist, what would you be?
I was good at languages in school and I like writing. However, within the realm of science, my tenure as a Jefferson Science Fellow in the Department of State for the academic year 2010-2011 has given me also a greater insight into the role and importance of science and technology in development and diplomacy. The challenge of foreign policy informed by science diplomacy can create conditions that make the citizens of all countries shareholders in this enterprise, capable of making genuine contributions to world-wide problems and, in so doing, offer educational and economic opportunities most often associated with the developed world.
What advice would you give your younger self? Is there anything you’d have done differently in your career?
I have always taken a broad view – sometimes the road to discovery is not linear. The “scenic” route is full of surprises.
You’ve worked at the interface between academic research and pharmaceuticals – tell us about that experience and what you learned from it.
When the pharmaceutical company buys into the project it is exciting as they put their full expertise behind it and their people are genuinely interested in providing new medicines. An academic does need a champion in industry but if that relationship changes for whatever reason – people moving, change of ownership, simple ambition – then your project can be “lost” amongst the competing ones. It is difficult but very desirable to maintain some control over the project.
It’s the International Year of Chemistry – what one discovery or development would you like to highlight?
Picking one development is not easy but the engagement of chemists in climate change and green energy (two but related) engages chemists in societal and environmental issues – an engagement which is very positive.