The wrong type of consensus — Response to Maley et al, Nature Reviews Cancer 2017

In a recent paper in Nature Reviews Cancer, Maley et al set out to define a consensus framework for classifying neoplasms. The paper’s premise is that such a theoretical framework is a necessary first step for developing new quantitative approaches. I disagree. I argue that the paper highlights the limited practical relevance of a purely intellectual exercise. Solid classification frameworks of clinical relevance need more detail and need to be grounded on applicability to real data in clinical practice.

TL;DR

For those of you in hurry, let me sum up what my claims are:

• This is a very good review of the field. Its particular strength is combining cancer evolution with the tissue microenvironment. You should definitely read it.
• However, the review poses as something it is not: a classification scheme of clinical relevance.
• The proposed classification scheme fails because (a) there is no practical way how to classify patients with it, and (b) evidence of clinical impact is circumstantial and anecdotal.
• The authors recognise all these problems, but dismiss them as areas of future research, rather than testing prototypes of their scheme on real data.
• Methodological and measurement innovations happen as we speak – no one needed this framework to kick start innovation.
• Consensus on specific approaches will be much harder, much more interesting and much more useful, than consensus on lofty ideas.

The Human Cell Atlas needs a pre-registered analysis plan

The Human Cell Atlas preprint came out some days ago on bioRxiv. It describes a project to collect all the cell types in the human body in one big reference map.

Our mission: To create comprehensive reference maps of all human cells—the fundamental units of life—as a basis for both understanding human health and diagnosing, monitoring, and treating disease. [from humancellatlas.org]

The contributors to the project are a Who-is-who of the leaders in single cell genomics and this will be a fantastic data set when it comes out. Because in-depth analysis of resources like this provides the foundation of all biology, as you know.

I enjoyed reading the preprint. It puts the project into a historical perspective and discusses promises as well as limitations. It even references Borges’ `On Rigor in Science’. (I love well-read scientists!) And even if all that means nothing to you, it is still worth reading as a comprehensive summary of the current state-of-the-single-cell-art.

But I kept wondering, with a project like this, how do you know whether it is a success or not? How do you know that your reference map is really comprehensive and covers all (most?) of what it is supposed to find?

Why science needs continuous leadership support

Hello, my fellow PIs, here is a question for you: Did you get trained well for your job?

Silly question, of course you did. Years of study and examinations culminating in a PhD have obviously trained you well in all things science.

But that’s not what I mean. Details of experiments and algorithms –what you learn in a PhD– are only a small part of a PI’s job. Once you start leading a group, the tough nuts to crack are people-problems.

Five selfish reasons for working reproducibly

And so, my fellow scientists: Ask not what you can do for reproducibility — ask what reproducibility can do for you!

The following is a summary of a talk I gave in my institute and at the Gurdon in Cambridge. My job was to motivate why working reproducibly is a good strategy for ambitious scientists. Right after my talk, Gordon Brown (CRUK CI) and Stephen Eglen (Cambridge DAMTP)  presented tools and case studies of reproducible work.

All materials are on github and below are my slides, thanks to slideshare:

The book of life and its history

Being so busy beating cancer one technical paper at a time, I often don’t get the opportunity to step back and see how our stuff  relates to what other people are doing in foreign territories … like the humanities. So I was thrilled to be invited to team up with Barbara Zipser, a researcher in the history of medicine at RHUL. In a chapter in her forthcoming book we contrast stemmatics and textual criticism in philology with phylogenetic methods in biology. The following fragment is part of my bit of the bargain. Enjoy!

Unlike physics, biology does not have a strong mathematical theory to explain and predict observed phenomena. This may be one of the reasons why biology is so rich in metaphors. The Tree of Life connects all forms of life on earth. Conrad Waddington famously compared the development of cell  types and tissues to marbles rolling down a grooved slope, the so called epigenetic landscape. And inside every single cell the nucleus contains an organism’s genome, the Book of Life written in the language of DNA. Similar to a text written in a human language, DNA transfers information, it can be transcribed into a different form (RNA instead of DNA) and it can be translated (into proteins).

The idea that the genome can be read and edited pervades all molecular biology and forms one of the most powerful and suggestive metaphors of modern science.

Feyerabend and the tyranny of science

In October 2011 PLoS Biology, a top biology journal, tried something new – it took a deeper look at the boundary between biology and philosophy:

“Does the cultural divide between science and the humanities, first articulated by C. P. Snow over 50 years ago, still exist between biology and philosophy? In a mini experiment to find out, we asked a philosopher and biologist to review the recent English translation of Tyranny of Science, by 20th century philosopher Paul Feyerabend, perhaps best known for rejecting the claim that science is a singular discipline unified by common methods and concepts.”

What a nice idea! The philosopher is Ian J Kidd from Durham in the UK, who does research on Feyerabend and other philosophers of science, while the biologist is Axel Meyer from Konstanz in Germany, who studies diversity in fish. And Feyerabend (1924-1994) is a very good choice, because he is notorious as a polemic writer and not known for holding back his opinions. If there is any divide of any kind anywhere, Feyerabend will be right in the thick of it.