Every year, a committee of experts sits down with a tough job to do: from among all ICREA publications, they must find a handful that stand out from all the others. This is indeed a challenge. The debates are sometimes heated and always difficult but, in the end, a shortlist of  the most outstanding publications of the year is produced. No prize is awarded, and the only additional acknowledge is the honour of being chosen and highlighted by ICREA. Each piece has something unique about it, whether it be a particularly elegant solution, the huge impact it has in the media or the sheer fascination it generates as a truly new idea. For whatever the reason, these are the best of the best and, as such, we are proud to share them here.


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  • Life history evolution of insular dwarf elephants. (2021)

    Köhler, Meike (ICP)
    Moyà Solà, Salvador (ICP)

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    Life history evolution of insular dwarf elephants.

    Human activity is driving the ongoing 6th mass extinction of species in Earth’s history. Insular taxa are particularly vulnerable; though endemic species typically persisted for millions of years on their islands, they now disappear in only a few decades. Therefore, understanding how life history strategies evolve to keep species in the ecological game has become a major concern in ecology.

    Life history strategies evolve in response to ecological conditions; however, they also depend on the size of the animal: small animals live faster than large animals, mature earlier, and have a shorter lifespan, which is usually depicted as the “mouse-elephant curve”.

    Insular endemics undergo changes in body size, with taxa derived from small ancestors growing large and those derived from large ancestors evolving small (the “Island Rule), leading to giant mice and dwarf elephants. These size trends led to the widespread hypothesis that insular dwarfs live fast lives.

    Using bone, molar, and tusk histology of the smallest-ever elephant Palaeoloxodon falconeri from the Pleistocene of Sicily, we disprove this hypothesis. The spectacular size decrease in P. falconeri was instead associated with a shift towards the slow end of the slow-fast life history continuum: the dwarf insular elephant grew at a much slower rate than expected from body mass, extended the time to maturity (first reproduction), and increased the lifespan beyond that of its large continental cousins.

    We interpret this life history strategy as an adaptation to low resource levels (an ecological key-condition on islands). The slow growth, possible under absence of terrestrial predation (the other key condition on islands), allows increased investment in maintenance at the expense of early reproduction, thereby increasing the reproductive success of young mothers through improved calf survival.

    Associated with these advantages, however, is an extended generation time (the mean age of mothers at offspring birth). This implies that the time it takes for a "slow-living" species to recover from disturbance increases importantly, which explains the extreme vulnerability of island endemics.

  • Optical Schrodinger’s cat states in High Harmonic Generation (2021)

    Lewenstein, Maciej Andrzej (ICFO)

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    Optical Schrodinger’s cat states in High Harmonic Generation

    Over the past decades, astounding advances have been made in the laser technologies and the understanding of light-matter interactions. Thanks to this, scientists have been able to carry out complex experiments related, for example, to ultra-fast light-pulses in the visible and infrared range, and accomplish crucial milestones such as using a molecule’s own electrons to image its structure, to see how it rearranges and vibrates or breaks apart during a chemical reaction.

    The development of high-power lasers allowed scientists to study the physics of ultra-intense laser–matter interactions which almost always  treats ultra-strong ultra-short driving laser pulses only from a classical point of view. The famous theory coined as the “three-step model”, which had its 25th anniversary in 2019, dealt with the interaction of an electron with its parent nucleus  in a strong laser field, and elegantly described it according to classical and quantum processes. However, since the laser pulses are highly coherent and contain huge numbers of photons, this description so far has been incomplete, treating the atomic system in a quantum way but the EM field classically.

    So far, in the description of the most relevant processes of ultra-intense laser–matter physics, the quantum-fluctuation effects of the laser electric field, not even to mention the magnetic fields, were negligible. However, the quantum nature of the entire EM fields is always present in these processes, so a natural question arises: does this quantum nature exhibit itself?

    In the recent study published in Nature Physics, ICFO researchers, led by ICREA Prof. Maciej Lewenstein and Javier Rivera, with colleagues from Technion-China, Max Born Institute in Berlin, the experimental group of  Paraskevas Tzallas, from FORTH, have reported on the demonstration that intense laser–atom interactions may lead to the generation of highly non-classical states of light, the so called photonic Schrödinger cat states. This work opens the path toward fascinating applications in quantum information and quantum technologies.

  • Overweight-related fatty liver impacts immune response to therapies in liver cancer (2021)

    Llovet Bayer, Josep M (FRCB-IDIBAPS)

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    Overweight-related fatty liver impacts immune response to therapies in liver cancer

    Liver cancer is the fourth leading cause of cancer-related deaths and its incidence is on the rise, with one million new cases projected annually in 2025. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. For the treatment of patients with advanced HCC, sorafenib was approved in 2007, but recently immune checkpoint inhibitors (atezolizumab + bevacizumab), which promote the ability of the immune system to fight cancer, have become the standard systemic therapies.

    Our article published in Nature shows that checkpoint inhibitors are significantly less effective in patients with non-viral compared to viral-related HCC. We explored the most common non-viral etiology, non-alcoholic steatohepatitis (NASH), associated to overweight and diabetes. We identified a specific population of dysfunctional resident T cells (activated CD8+PD1+CxCR6 T cells) which drive NASH progression and are the primary mechanism of resistance to immunotherapies in murine models of NASH-HCC and in human NASH (Fig 1). In addition, through a meta-analysis of three randomized phase III clinical trials testing inhibitors immunotherapies in 1,600 patients with advanced HCC, we identified that these therapies are significantly more effective in viral-related HCC compared to non-viral etiologies.

  • Uncovering the drivers of cancer   (2021)

    López-Bigas, Núria (IRB Barcelona)

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    Uncovering the drivers of cancer  

    Most mutations detected in cancer genes in cancer patients are of uncertain significance. Knowing which mutations are responsible for the development of a tumor (drivers) is key to select the best way to target it. Although impressive strides have been made in the identification of the genes that when mutated contribute to tumor emergence and growth, recognizing the specific driver mutations in these genes is still far from resolved. 


    We reasoned that the mutations identified in thousands of patients in cancer genes may be used to solve this problem. We derived 185 machine learning models inspired in evolutionary biology to identify which mutations in each cancer gene are able to drive tumorigenesis in different cancer types. We showed that these models can effectively identify driver mutations. Applying them to all possible mutations in these cancer genes we have generated driver potential blueprints available at intogen.org/boostdm (see Figure). 


    These models, named collectively BoostDM, help to interpret variants of uncertain significance in a clinical setting. The incorporation of boostDM models to our Cancer Genome Interpreter (cancergenomeinterpreter.org) system improves the interpretation of the mutations detected in a patient’s tumor. For more on boostDM, see nature.com/articles/s41586-021-03771-1 and youtube.com/watch?v=1Nq_rm_yudk&t=29s.


  • Progress in the development of cutting-edge High Performance Computing tools for modelling of fusion multiphysics phenomena (2021)

    Mantsinen, Mervi Johanna (BSC-CNS)

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    Progress in the development of cutting-edge High Performance Computing tools for modelling of fusion multiphysics phenomena

    The final goal of fusion power plants is to produce electricity in the grid. This is planned to be done by heating up water as with fission power plants or thermal power stations. In the case of magnetically confined fusion, neutrons released from the hot fusion plasma escape the magnetic confinement and finish in the wall heating up water. In the case of DEMO (DEMOnstration power plant), the neutron production will be large and the reactor materials have to be neutron-resistant. Thereby, neutronics becomes an increasingly important field of study.

    To simulate the neutron transport in a fusion reactor, we have developed NEUTRO [1], a new module inside the Alya framework [2]. Alya is one of the largest and most advanced computational mechanics codes developed at Barcelona Supercomputing Center. Alya has been applied to many domains thanks to the multi-physics approach and has been developed to solve complex coupled problems such as combustion or cardiovascular system simulation. In our recent journal paper, we have validated NEUTRO and included nuclear data, which brings the code forward and improves it significantly. We are currently working to couple NEUTRO with the various other physics modules available in Alya to solve coupled high fidelity and high demanding computational problem of the first wall for the realization of DEMO.

  • The Vertebrates Genome Project introduces the era of the reconstruction of the genetic representation for all species (2021)

    Marquès Bonet, Tomàs (UPF)

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    The Vertebrates Genome Project introduces the era of the reconstruction of the genetic representation for all species

    The Vertebrate Genomes Project (VGP) Consortium published this year their flagship study focused on genome assembly quality and standardization for the field of genomics. This study includes 16 diploid high-quality, near error-free, and near complete vertebrate reference genome assemblies for species across all taxa with backbones (i.e., mammals, amphibians, birds, reptiles, and fishes) from five years of piloting the first phase of the VGP project. 

    Growing out of the decade-old mission of Genome 10K Community of Scientists (G10K) to sequence the genomes of 10,000 vertebrate species and other comparative genomics efforts, the VGP is taking advantage of dramatic improvements in sequencing technologies in the last few years to begin production of high-quality reference genome assemblies for all ~70,000 living vertebrates. Specific to conservation and in collaboration with the Māori in New Zealand and officials in Mexico, genomic analyses of the kākāpō, a flightless parrot, and the vaquita, a small porpoise and the most endangered marine mammal, respectively, suggest evolutionary and demographic histories of purging harmful mutations in the wild. The implication of these long-term small population sizes at genetic equilibrium gives hope for these species’ survival.

    The VGP involves hundreds of international scientists working together from more than 50 institutions in 12 different countries since the VGP was initiated in 2016 and is exemplary in its scientific cooperation, extensive infrastructure, and collaborative leadership. Additionally, as the first large-scale eukaryotic genomes project to produce reference genome assemblies meeting a specific minimum quality standard, the VGP has thus become a working model for other large consortia, including the Bat 1K, Pan Human Genome Project, Earth BioGenome Project, Darwin Tree of Life, and European Reference Genome Atlas, among others.