In the course of the nearly 100 separate vignettes that make up this book, our work has been animated by several key ideas. First, the overarching theme of the book is that biological numeracy expands our view of the living world in a way that can reveal new insights into organisms and how they work that would otherwise be hidden. It can be thought of as a sixth sense complementing the already powerful arsenal of modern biology. In order to make biological numeracy useful the values reported for key biological parameters need to be characteristic and actually mean something. To that end, each of our vignettes has tried to report on carefully vetted, state-of-the-art data for a variety of key numbers that dictate the behavior of living matter. But it is not enough to merely quote the numerical values of these quantities. They must also be provided some context such that they are actually consonant with what we understand about biological systems. Hence, a second key thrust of our vignettes has been to adopt an attitude of order-of-magnitude thinking to try and use simple estimates to illuminate biological problems in a way that leaves us with an intuition for the meaning of these numbers.
Some challenges make the task of those seeking biological numeracy from reading the literature harder than one might have imagined. One challenge relates to the limited availability of numbers in textbooks and online resources and their often unclear connection to the primary literature. We hope that through efforts such as the BioNumbers database and this book we have helped remedy some of that challenge. Another challenge we have mentioned several times throughout the book are the misunderstandings that can exist when discussing absolute numbers of some cell component or other property of “the cell” without knowing the cell growth conditions. Differences in cell size can be as much as several fold and growth rate or different physiological conditions can create even further uncertainty by changing also the per volume concentrations of numbers of interest. As a result, we strongly believe that it is important that every paper that reports a quantitative characterization of cellular properties should at least mention the growth rate, and if referring to copy numbers in cells, aim to measure the cell size, which today can be done with a Coulter counter or FACS machine rather routinely. We hope that referees and editors will make this a “law”, though even better yet is that researchers will make it an intrinsic norm of our trade.
There were many more questions that intrigued us than we actually included in our long text. In some cases this was because we did not know how to answer them. In others we did not sense that the numbers told any compelling story just yet. In the hope that our readers might have insights into answering these questions or some inspiration about how to attack them, we decided to make available those questions here. We are anxious to hear ideas, concrete data or insights on any of them (just as on any of the vignettes that form the core of the book).
- How many different genes are in a gram of soil, ocean water and dung?
- How big are vacuoles?
- How long are axons (e.g. what happens in a whale)?
- What is the diversity of antibodies in a human?
- How large are the openings in cell membranes?
- What are the concentrations of non-coding RNAs?
- How many of each type of organelles are found in the cell?
- What is the energy cost associated with membrane rearrangements?
- How much sugar is needed to make and power a cell?
- What is the energy invested in carbon and nitrogen assimilation?
- How much force can be exerted by molecular motors?
- How big are osmotic and turgor pressures in cells?
- What is the rate of protein folding?
- What are the mass specific polymerization rates of the machines of the central dogma?
- What is the rate of posttranslational modifications of proteins (e.g. glycosylation)?
- How fast does a signal propagate from a receptor to the nucleus?
- What are the maximal growth rates of different organisms?
- How long does apoptosis take?
- How fast is signal transduction in the cell?
- How fast does the molecular clock tick?
- How many carbon fixation pathways exist in Nature?
- How many proteins are synthesized per burst of mRNA translation?
- How long are non-coding RNAs?
- What is the length of sequence required for homologous recombination?
- What are the rates of somatic recombination and transposition?
- What is the error rate in antibody recognition?
- What is the number of neurons in the brain?
- What proportion of the ribosome is rRNA?
- How many cell types are there in the human body?
We leave our readers with the hope that they will find these or other questions inspiring and will set off on their own path to biological numeracy.