Max Delbruck Research Articles

George A. Mashour, MD, PhD, Recipient of the 2021 Excellence in Research Award

Article| October 2021 George A. Mashour, MD, PhD, Recipient of the 2021 Excellence in Research Award Kevin K. Tremper, PhD, MD Kevin K. Tremper, PhD, MD Search for other works by this author on: This Site PubMed Google Scholar ASA Monitor October 2021, Vol. 85, 22. https://doi.org/10.1097/01.ASM.0000795084.56772.28 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Search Site Citation Kevin K. Tremper; George A. Mashour, MD, PhD, Recipient of the 2021 Excellence in Research Award. ASA Monitor 2021; 85:22 doi: https://doi.org/10.1097/01.ASM.0000795084.56772.28 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentAll PublicationsASA Monitor Search Advanced Search Topics: awards and prizes It is my great pleasure to congratulate Dr. George A. Mashour on receiving the 2021 Excellence in Research Award from the American Society of Anesthesiologists (Schaumburg, Illinois). Dr. Mashour is internationally renowned in the fields of anesthesiology, neuroscience, and translational science, and is highly deserving of this recognition. After his undergraduate study of philosophy and classics, Dr. Mashour received his MD and PhD in neuroscience from Georgetown University (Washington, D.C.) in 2001 and was a two-time Fulbright Scholar in the neurosciences (Max Delbruck Center for Molecular Medicine, Berlin, Germany, 1998-1999; University of Bonn, Bonn, Germany, 2002-2003). He completed his residency and chief residency in anesthesiology at the Massachusetts General Hospital/Harvard Medical School (Boston, Massachusetts) in 2006 and a fellowship in neurosurgical anesthesiology at the University of Michigan (Ann Arbor, Michigan) in 2007. He is currently the Robert B. Sweet Professor and Chair of the Department of Anesthesiology at the University... You do not currently have access to this content.

George A. Mashour, M.D., Ph.D., Recipient of the 2021 Excellence in Research Award

George A. Mashour, M.D., Ph.D., Recipient of the 2021 Excellence in Research Award

Researchers rewarded for null results

Publishing null results and replication studies will now get Max Delbruck Center for Molecular Medicine and Charite University Hospital researchers a small cash bonus of €1,000 ($1,080) in their research funding. The cash incentives are part of a “behavior change experiment” at the two institutions, which are both members of the Berlin Institute of Health (BIH), to promote research integrity. BIH researchers also have access to electronic tools to assist with the effort, including an app to help researchers work out where to publish their nonstandard results. The two institutes also consider research practices such as publishing null results and open data when they evaluate scientists for funding, hiring, and tenure, says Ulrich Dirnagl, director of the BIH’s QUEST (Quality, Ethics, Open Science, Translation) Center for Transforming Biomedical Research. The BIH founded QUEST in 2017 to improve the value and usefulness of its biomedical research, and the approaches taken over

When Physics Meets Biology

We discuss a less known aspect of Feynman’s multifaceted scientific work, centered about his interest in molecular biology, which came out around 1959 and lasted for several years. After a quick historical reconstruction about the birth of molecular biology, we focus on Feynman’s work on genetics with Robert S. Edgar in the laboratory of Max Delbruck, which was later quoted by Francis Crick and others in relevant papers, as well as in Feynman’s lectures given at the Hughes Aircraft Company on biology, organic chemistry and microbiology, whose notes taken by the attendee John Neer are available. An intriguing perspective comes out about one of the most interesting scientists of the XX century.

How naked mole rats survive oxygen deprivation

Naked mole rats are famous for their lovable ugliness, their extremely long lives, their ability to evade cancer, and now, too, their capacity to survive without oxygen for 18 minutes. This suffocating experience would kill a mouse—a mammal of similar size, albeit with significantly more hair. According to a new study, the naked mole rat manages the feat by altering its metabolism (Science 2017, DOI: 10.1126/science.aan1505). Naked mole rats are both social and subterranean: The population in one of their underground colonies can surge to nearly 300 members. As a result, the air in these confined, packed spaces is often low in oxygen and high in carbon dioxide. To survive these conditions, naked mole rats switch to fueling their energy-producing glycolysis pathways with fructose instead of glucose, explains Gary R. Lewin of the Max Delbruck Center for Molecular Medicine, who led the research with postdoc Jane Reznick and Thomas J.

Salvador Luria and Max Delbrück on Random Mutation and Fluctuation Tests.

![Figure][1] Do mutations arise randomly over time? Or are they induced by unfavorable environments? By addressing these crucial evolutionary questions, Salvador Luria and Max Delbruck won a Nobel Prize and helped to start the field of bacterial genetics. In 1943, it had long been known

Quantum Explorers: Bohr, Jordan, and Delbrück Venturing into Biology

This paper disentangles selected intertwined aspects of two great scientific developments: quantum mechanics and molecular biology. We look at the contributions of three physicists who in the 1930s were protagonists of the quantum revolution and explorers of the field of biology: Niels Bohr, Pascual Jordan, and Max Delbruck. Their common platform was the defense of the Copenhagen interpretation in physics and the adoption of the principle of complementarity as a way of looking at biology. Bohr addressed the problem of how far the results reached in physics might influence our views about life. Jordan and Delbruck were followers of Bohr’s ideas in the context of quantum mechanics and also of his tendency to expand the implications of the Copenhagen interpretation to biology. We propose that Bohr’s perspective on biology was related to his epistemological views, as Jordan’s was to his political positions. Delbruck’s propensity to migrate was related to his transformation into a key figure in the history of twentieth-century molecular biology.

A slot machine, A broken test tube

Salvador Edward Luria (13 August 1912–6 February 1991) was an Italian microbiologist and a medical doctor, who won the Nobel Prize for Physiology or Medicine in 1969 jointly with Max Delbruck and Alfred Hershey, for their discoveries on the replication mechanism and genetic structure of viruses. However, less commonly known is how exactly he did so. In his autobiography, A Slot Machine, A Broken Test Tube, Luria has related his experiences in an intimate and enjoyable fashion.

Of slot machines and broken test tubes

The year 2012 was the birth centenary of the pioneer microbiologist/ molecular geneticist, Salvador Luria whose life exemplified the axiom that both brilliance and serendipity have a role in defining success. In 1943 Luria along with physicist Max Delbruck demonstrated that bacteria are ideal model organisms to address fundamental questions involving heredity, triggering the emergence of the new field of molecular genetics. Their famous Fluctuation Test carried out with the bacterium Escherichia coli provided statistical evidence for the spontaneous nature of mutations, supporting the Darwinian idea of natural selection. His observations on the role of host modification in determining bacteriophage host specificity and its epigenetic transmission ultimately led to the discovery of bacterial restriction-modification systems that opened the door to recombinant DNA technology. This article is an attempt to capture the myriad contributions to science and science education by one of the founding fathers of modern genetics.

Origin of the linearity no threshold (LNT) dose–response concept

This paper identifies the origin of the linearity at low-dose concept [i.e., linear no threshold (LNT)] for ionizing radiation-induced mutation. After the discovery of X-ray-induced mutations, Olson and Lewis (Nature 121(3052):673-674, 1928) proposed that cosmic/terrestrial radiation-induced mutations provide the principal mechanism for the induction of heritable traits, providing the driving force for evolution. For this concept to be general, a LNT dose relationship was assumed, with genetic damage proportional to the energy absorbed. Subsequent studies suggested a linear dose response for ionizing radiation-induced mutations (Hanson and Heys in Am Nat 63(686):201-213, 1929; Oliver in Science 71:44-46, 1930), supporting the evolutionary hypothesis. Based on an evaluation of spontaneous and ionizing radiation-induced mutation with Drosophila, Muller argued that background radiation had a negligible impact on spontaneous mutation, discrediting the ionizing radiation-based evolutionary hypothesis. Nonetheless, an expanded set of mutation dose-response observations provided a basis for collaboration between theoretical physicists (Max Delbruck and Gunter Zimmer) and the radiation geneticist Nicolai Timoféeff-Ressovsky. They developed interrelated physical science-based genetics perspectives including a biophysical model of the gene, a radiation-induced gene mutation target theory and the single-hit hypothesis of radiation-induced mutation, which, when integrated, provided the theoretical mechanism and mathematical basis for the LNT model. The LNT concept became accepted by radiation geneticists and recommended by national/international advisory committees for risk assessment of ionizing radiation-induced mutational damage/cancer from the mid-1950s to the present. The LNT concept was later generalized to chemical carcinogen risk assessment and used by public health and regulatory agencies worldwide.

Complementarity in biological systems: A complexity view

Niels Bohr and Max Delbruck believed that complementarity—such as wave–particle duality—was not limited to the quantum realm, but had correlates in the study of living things. Biological complementarity would indicate that no single technique or perspective allows comprehensive viewing of all of a biological entity's complete qualities and behaviors; instead, complementary perspectives, necessarily and irrevocably excluding all others at the moment an experimental approach is selected, would be necessary to understand the whole. Systems biology and complexity theory reveal that, as in the quantum realm, experimental observations themselves limit our capacity to understand a biological system completely because of scale‐dependent “horizons of knowledge,” a form of biological complementarity as predicted by Bohr and Delbruck. Specifically, observational selection is inherently, irreducibly coupled to observed biological systems as in the quantum realm. These nested systems, beginning with biomolecules in aqueous solution all the way up to the global ecosystem itself, are understood as a seamless whole operating simultaneously and complementarily at various levels. This selection of an observational stance is inseparable from descriptions of biology indicates—in accordance with views of thinkers such as von Neumann, Wigner, and Stapp—that even at levels of scale governed by classical physics, at biological scales, observational choice remains inextricably woven into the establishment, in the observational moment, of the present conditions of existence. These conceptual shifts will not only have theoretical impact, but may point the way to new, successful therapeutic interventions, medically (at the scale of organisms) or environmentally/economically (at a global scale). © 2013 Wiley Periodicals, Inc. Complexity 18: 11‐20, 2013

Genesis of What Is Life?: A Paradigm Shift in Genetics History

Erwin Schrodinger's 1944 book What Is Life? has often been cited as a driving force in figuring out the structure of DNA and cracking the genetic code. Schrodinger's book drew upon a paper by Nikolai Timofeeff-Ressovsky, Karl Zimmer, and Max Delbruck— the “Three-Man Paper.” Creating a Physical Biology argues why and how this paper produced a paradigm shift in biology.

Looking for quantum in life

The 1935 paper ‘‘On the Nature of Gene Mutation and Gene Structure’’ by Drosophila geneticist Nikolai Timofeeff-Ressovsky, radiation physicist Karl Gunter Zimmer, and theoretical physicist Max Delbruck (a student of the physicist Niels Bohr) has held an important place in the historiography of molecular biology. Commonly known as the ‘‘Three-Man Paper,’’ it has been situated at the center of the ‘‘origins’’ narrative in the history of molecular biology. In Phage and the Origins of Molecular Biology, the 1966 festschrift for one of the authors of the Three-Man Paper, Delbruck, some of his colleagues and disciples trace the birth of molecular biology to his attempt to discover ‘‘other laws of physics’’ through his study the phenomena of life and heredity: first he used biophysical methods, such as irradiation and quantum mechanics, to understand the stability of the gene; then he studied the phage, the hydrogen atom of biology, to ask fundamental questions about the nature of heredity. According to Erwin Schrodinger, his theoretical musings in What is Life? were inspired by the ThreeMan Paper, and his somewhat mythologized version of the Three-Man Paper in turn encouraged some physicists to shift their research on the problem of genetics. Indeed, self-proclaimed molecular biologists cherished the Three-Man Paper, suggesting that it exhibits some of the salient features of their discipline: its interdisciplinary approach to the problem of heredity, especially the applications of concepts of physics and of physical instruments; and its pursuit of a reductionist understanding of life based on the action of material genes. At long last, with the publication of Creating a Physical Biology: The Three-Man Paper and Early Molecular Biology, some of the key historical and philosophical issues underlying the Three-Man Paper have been eloquently told with a scholarly attention to analytic precision. First of all, the book offers the first English translation of the Three-Man Paper. Lucidly translated by Brandon Fogel, the Three-Man Paper has been often invoked for its historical and philosophical

Ordinary geniuses: Max Delbruck, George Gamow, and the origins of genomics and big bang cosmology

Ordinary geniuses: Max Delbruck, George Gamow, and the origins of genomics and big bang cosmology

Yoshiki Hotta's influence

The first time I became aware of Yoshiki Hotta was in 1973 when I was a third year PhD student in Max Delbruck's lab in the Division of Biology at Caltech. I was then working on sensory transductio...

Giorgio Careri: A physicist in the life sciences

Physics provides the foundation and the fundamental understanding of biology. Schrodinger implied this belief in his beautiful book “What is life?”, a book that is loved by physicists and hated by some (many?) biologists. Few biologists move into physics, but many physicists move to biology as can be inferred for instance from the growth and size of the Biological Physics section of the American Physical Society. There are two routes from physics to the life sciences. Some establish their reputation in physics and at some point see the light and switch to the life sciences. Some study and absorb physics and then quickly move. Some examples of the first route are Max Delbruck and John Hopfield. Francis Crick belongs to the second class. Giorgio Careri was a member of the first class. His early work centered on statistical physics and liquid helium, but he became interested in the physics of proteins. Careri was one of the first to realize the importance of physics to biology and of biological systems to physics. Inspired by his liquid-state research, he explored the physics of the hydration shell of proteins, both experimentally and theoretically. His search for solitons in biological systems did not pan out, but his work on lysozyme has stood the test of time. The use of percolation theory provided physical insight into proton motion on the protein surface. While his imaginative original work has been largely overlooked, his reviews, written often in collaboration with John Rupley, have had considerable impact and are continuously used. His studies of the role of water in biological systems are classics and will remain signposts for future work. Hans Frauenfelder

ALZHEIMER’S Small molecule sheds light on toxic processes behind disease

The effect of a newly characterized small molecule on Alzheimer’s disease-related amyloid-β (Aβ) oligomers supports the hypothesis that the oligomers are more toxic than mature amyloid fibrils. The finding could help the search for effective Alzheimer’s treatments. Identified by Erich E. Wanker of the Max Delbruck Center for Molecular Medicine, in Berlin, and coworkers, the small molecule accelerates the conversion of Aβ oligomers into mature fibrils and reduces the oligomers' toxicity in cell-based assays ( Nat. Chem. Biol., DOI: 10.1038/nchembio.719). When they added the phenoxazone derivative, dubbed O4, to a solution of Aβ oligomers, the mixture quickly formed amyloid fibrils. In cell-based assays, brain cells cultured with both soluble Aβ oligomers and O4 were protected from damage. The researchers suggest that O4, which binds hydrophobic amino acids on Aβ peptides, stimulates the formation of fibrils by increasing the surface hydrophobicity of amyloid oligomers and easing aggregation. Ronald Wetzel,...

Quantifying green life: grand challenges in plant biophysics and modeling.

Biophysics is best defined as a mindset than as a specific subject matter (Nobel, 1974; Phillips et al., 2008). The biophysicist strives to quantify biological processes and to analyze them in terms of universal physico-chemical principles such as mass conservation, force balance, and thermodynamic equilibrium. Biophysics has played an important role in the growth of biology, especially in elucidating how the folded structure of proteins determines their function (Anfinsen, 1973; Dobson, 2003), but also in providing a solid foundation for electro-physiology, photosynthesis, respiration, and many other basic biological functions. The lasting contributions of physicists-turned-biologists such as Max Delbruck (Luria and Delbruck, 1943; Delbruck, 1970) and Francis Crick (Watson and Crick, 1953; Crick, 1970) illustrate the power of the physical perspective in biology.

PSPF - a protein sample production facility for structural biologists

INTRODUCTION The Protein Sample Production Facility (PSPF) is funded by the Helmholtz Association and offers state-of-the-art infrastructure and services for researchers at Helmholtz centers and other academic institutions and non-profit research centers to produce proteins for structural analysis by X-ray crystallography, NMR spectroscopy and electron microscopy. The PSPF dedicates 50 % of its capacity to cooperation and is currently located at two Helmholtz institutes: the Max Delbruck Center for Molecular Medicine (MDC) in Berlin-Buch and the Helmholtz Centre for Infection Research (HZI) in Braunschweig.

A systems biology tour de force for a near‐minimal bacterium

Ever since the 1930s, when a handful of physicists, chemists, and biologists banded together into the phage school led by Max Delbruck, there have been efforts to understand life at its simplest and most fundamental level. In the ensuing decades up to the present, we have achieved a complete understanding of the genetic and chemical structure of a number of viruses, and know in many cases the role of all of their genes. The same cannot be said for cells. The simplest cells are bacteria, but they generally contain thousands of genes. The desire to understand how cells work has long attracted biologists to work with simple, near-minimal cells because of the assumption that smaller organisms with fewer molecular parts will be less complex and easier to understand. Whole genome sequencing and decades of biochemical studies have shown that the simplest known cells that are capable of growth in laboratory media are the atypical bacteria called mycoplasmas. The interest in these tiny bacteria as model systems to study cellular function led to two of them, Mycoplasma genitalium and Mycoplasma pneumoniae, being among the first few bacteria of which the genomes were sequenced (Fraser et al, 1995; Himmelreich et al, 1996). As those genome sequences were published in the mid-1990s, molecular and systems biology techniques have advanced to the point that the DNA sequences can be leveraged to gain a much deeper understanding of the biology of these minimal cells. A trio of papers published in Science by seven research groups coordinated by Peer Bork, Anne-Claude Gavin, and Luis Serrano offer an unprecedentedly detailed analysis of the transcriptional regulation, proteome organization, and metabolic regulation of the minimal bacterium M. pneumoniae (Guell et al, 2009; Kuhner et al, 2009; Yus et al, 2009).