Professor John Speakman

Biography

For Speakman's biography see the Wikipedia page entry.

External Memberships

Committees

I serve on the following external committees:

Royal Society

• Section 10 medical sciences election committee
• Newton Fund International Fellowships Chairman
• University Research Fellowships (Panel B)

Royal Society of Edinburgh

• Section A3 election committee

Journals

In the last decade I have also served on the editorial boards of the following journals:

• Mammal review 2002 - date
• Aging Cell  (section editor) 2004 - 2007
• Journal of Comparative Physiology 2004 - date
• Functional Ecology 2004 - 2009
• Biology letters 2008 - 2013
• Biology Open (deputy editor in chief) 2011 - 2018                 
• Molecular metabolism (founding board member) 2011 - date
• Science 2011 - date
• IUBMB Life 2012 - date
• Clinical Endocrinology Physiology and Pharmacology 2013 - 2015
• Journal of Genetics and Genomics 2013 - date
• Physiological and Biochemical zoology 2015 - date
• Annals of Human Genetics 2016 - 2019
• International Journal of Obesity 2017 - date
• China Science Life Science 2018 - date
• Philosophical transactions of the Royal Society 2018 - date

Research Overview

Over my career so far I have worked on a wide range of topics. Binding them all together is a singular focus on understanding the factors that influence and limit energy expenditure. Since energy is central to all biological processes it provides a common currency for gaining deeper knowledge of the evolutionary forces that have molded animal (including human) adaptations. Early in my career, in the late 1980s and early 1990s, I was instrumental in developing the theoretical and practical basis of an isotope-based methodology for the study of energy demands in free-living animals: called the doubly-labelled water (DLW) technique. In 1997 I published a 400 page book (Doubly-labelled water: theory and practice. Springer New York) which has become the standard reference for the method. This expertise has led my group to become the partner of choice for scientists around the world wishing to apply these techniques in their own studies. 

I have used these techniques and the energy balance approach to provide paradigm shifting insights into our understanding of the limits on animal energy expenditure (notably the heat dissipation limits theory), the biology of ageing, and the evolutionary context of the human obesity epidemic (particularly the ‘drifty gene’ hypothesis). These studies have broad implications across many areas of enquiry. A common theme of my work has been to challenge and overturn prevailing ideas with new knowledge gathered from the study of energetics.  

Limits to Sustained energy expenditure and intake: I have a long interest in the factors that limit animal expenditure over periods of days and weeks: called sustained energy expenditure (or sustained energy intake – since over such long periods the two must balance). This approach has been used to provide valuable insights in several different areas. In 1998 using the DLW method we showed that African wild dogs have extremely high levels of free-living energy expenditure due mostly to the high costs of hunting (Gorman et al 1998 Nature391: 479-481: front cover). This creates a problem for wild dogs because if their prey is stolen (e.g. by lions or hyenas) the cost of replacing the food becomes extremely expensive. A mathematical model showed that only a slight shift in the level of kleptoparasitism would push the dogs over an energetic precipice to physiologically unsustainable levels of expenditure. This explained why wild dogs are driven to extinction in reserves where large lion and hyena populations are fostered for tourism. It has been widely assumed that this problem would also pertain to cheetah that are similarly kleptoparasitised, and also presumed to have high hunting costs, but work in collaboration with ex-student Michael Scantlebury has suggested otherwise (Scantlebury et al 2014 Science). This is primarily because while cheetah hunts are costly per unit time, they are very short in duration. Hence cheetah have flexibility to sustain much greater levels of kleptoparasitism than wild dogs. At the other end of the metabolic spectrum it has been widely speculated that to survive on their bamboo diet Giant Pandas must have low metabolic rates. We have shown that Panda metabolic rates are among the lowest ever measured in the Eutheria, and can be traced to a panda unique single nucleotide polymorphism in the dual oxidase 2 (DUOX2) gene, which causes a premature stop codon and truncated protein. DUOX2 is critical for thyroid hormone synthesis (Nie et al 2015 Science 349: 171-4). 

For most animals breeding is the most energetically expensive period in their lives. They consequently time such effort to match maximal food availability. In some situations this timing may go awry as was observed in populations of blue tits nesting in different habitats in Corsica. Quantification of energy demands using DLW of synchronised and non-synchronised individuals (Thomas et al 2001 Science 291: 2598-2600) showed that desynchronised individuals must work close to their physiological capacity, significantly increasing their mortality rate. This finding has major implications because often the timing of breeding is hard wired into circannual daylight cycles. If the timing of the pulse of maximal food availability changes – for example, due to global climate change, populations may mis-time their breeding events with catastrophic consequences. Elevated ambient temperatures may also have more direct effects on energy expenditure, and this is likely to be particularly important in hibernating animals. Using a mathematical model of hibernal energy balance my group was able to show how climate change will impact the biogeography of bats in North America (Humphries et al 2002 Nature 418: 313-316).     

To study this phenomenon of limits in more detail we group have used lactating mice as a model system. Starting in 1996 (Speakman and McQueenie 1996 Physiol. Zool. 69: 746-769) this has led to a series of more than 30 papers mostly in the Journal of Experimental Biology. This work was expanded into a more comprehensive theory concerning the more general limits on animal metabolic rates (the heat dissipation limit theory). The fundamental feature of this revolutionary idea is that endothermic animals are not normally constrained by extrinsic energy supply, but rather are limited by their ability to dissipate body heat, combined with the risk of hyperthermia. This theory was summarised in a landmark paper in 2010 (Speakman and Krol 2010 J. Anim. Ecol. 79: 726-746).

Limits on heat dissipation may have important ramifications as our climate changes. This is because the risk of heatwaves is anticipated to rise in the future. In collaboration with Dr Zhi-Jun Zhao at the university of Wenzhou in China, we have shown in mice and desert hamsters that such changes may have devastating effects paticularly during lactation when there seems to be a critical window of vulnerability to high temperatures (Zhao et al 2020: PNAS). 

 Energetics and the biology of ageing and life histories. One of the important areas where the heat dissipation limit theory has significant implications is the study of ageing and life histories. In fact ageing, life histories and energetics have a long history of association via the ‘rate of living theory’ which was the first comprehensive theory of ageing, proposed early during the last century. This theory was based on the empirical observation that species with lower rates of metabolism live longer, and found a potential mechanism in the observations that free-radicals are an inevitable by product of oxidative metabolism. The rate of living and free-radical theory of ageing was the dominant theory of ageing until the late 1990s, and the suggested role of free-radicals and oxidative stress as mediators of life history trade-offs has been dominant since that time. My work, (along with many other researchers), has been instrumental in overturning both these ideas. By measuring the energy metabolism of individual mice he showed that it was actually mice with the higher rates of metabolism that lived longest (Speakman et al 2004 Aging cell3: 87-95). I also showed that the links between low metabolism and lifespan are statistical artefacts of not adequately accounting for co-variation due to body size and phylogeny (Speakman, 2005 J. Expt. Biol. 208: 1717-1730.

Energetics and obesity: I have made two distinct contributions to this field. The first is to revolutionise our perceptions of the evolutionary underpinning of the epidemic. Until the mid-2000’s the only evolutionary model for the development of obesity was the ‘thrifty’ gene hypothesis, proposed by Neel in 1962. This suggested that we become obese because in our ancient past deposition of fat provided a safeguard against periods of famine. However, in modern society the system promoting fat storage during periods of plenty results in deposition of excessive amounts of fat in preparation for a famine that never comes: and the result is an obesity epidemic. I have highlighted the many flaws in this superficially attractive idea, and suggested the alternative hypothesis that in our ancient past we were probably very good at regulating our body weight because of the twin threats of starvation and predation. However, 2 million years ago with the invention of fire, weapons and social behaviour we effectively removed the threat of predation: allowing the genes that define our upper body weight control point to drift in time. Because these genes are drifting, rather than being under selection, this explains why everyone does not get fat in modern society. This new idea was elaborated in a breakthrough paper in 2007 (Speakman, 2007 Cell metabolism 6: 5-11) and was subsequently coined the 'drifty' gene hypothesis (Speakman 2008 Int. J. Obesity 32: 1611-1617). This novel approach completely reconceptualises the reasons underpinning the obesity epidemic, and is gathering increasing support from, for example, the GWAS studies of obesity.

            My second main contribution to the obesity field is to enter the debate concerning the roles of physical activity and energy expenditure as factors driving the epidemic. In other words, do we eat too much or expend too little (or both). In the 1970 and 1980s it was widely thought that the problem was over-eating, but a highly influential paper by Prentice and Jebb in 1991 suggested the problem was really increasing levels of sedentary behaviour. By the early 2000’s, when I entered this field, it was almost universally believed that reductions in energy expenditure were the main issue. My group published the first data showing that the newly discovered FTO gene (the first GWAS gene linked to obesity) has its effects via modulation of energy intake rather than energy expenditure (Speakman et al 2008 Obesity 16: 1961-1965). This seminal contribution to our understanding of the biological effects of FTO has become the 22^nd most cited paper from over 7000 papers published in Obesity over the past 15 years. In collaboration with Klaas Westerterp, we have surveyed data on energy demands dating back to the 1980s. This work showed two things: first that energy expenditure has not declined over this period, and second that the energy demands of humans actually fit very closely to the expected levels of expenditure based on studies of wild animals (Westerterp and Speakman 2008. Int. J. Obesity 32: 1256-1263). This work was an integral part of a turning tide, and now, the idea that the problem with the obesity epidemic is elevated food intake, rather than reduced expenditure, is main stream again.

Current Research

The work of my group currently addresses several key issues with respect to energy balance

1) the role and mechanism by which restriction of calorie intake leads to improved health and lifespan. 

This work has been mainly performed in mice and utilised a method of exposing aniamls to graded levels of restriction to elucidate the patterns of change as restriction becomes more intense. Full details of this work can be found on the open science framework pages  https://osf.io/9yath. In 2020 I published a revolutionary new idea about why CR has the effects it does - called the 'clean cupboards' hypothesis published in the Naional Science Review 

2) The impact of macronutrients on wieght regulation.

There is a long standing debate about the roles played by different macronutrients in weight regulation. We have been working in this field mostly by exposing mice to different macronutrient diets and monitoring their responses in terms of food intake and body weight. A major paper on this work was published in Cell metabolism in 2018. (Hu et al 2018: Cell metabolism).

3) Measuring energy demands of free-living animals and humans using the doubly-labelled water method

4) Exploring the links between fast food consumption and obesity

5) The IAEA doubly-labelled water human database

https://doubly-labelled-water-database.iaea.org/home