Biodesign researcher Michael Lynch wins coveted lifetime achievement award in genetics

January 27, 2022

Michael Lynch, director of the Biodesign Center for Mechanisms of Evolution at Arizona State University, is the winner of the 2022 Genetics Society of America Thomas Hunt Morgan Medal for his far-reaching and influential contributions to science.

The award, one of the most prestigious in the field of genetics, is granted in honor of an individual member’s exceptional lifetime accomplishments as well as history of dedicated mentorship to fellow geneticists. Graphic illustration of a double helix. Michael Lynch, director of the Biodesign Center for Mechanisms of Evolution at Arizona State University, is the winner of the 2022 Genetics Society of America Thomas Hunt Morgan Medal for his far-reaching and influential contributions to science. Download Full Image

The Genetics Society of America is an international community of more than 5,000 scientists devoted to advancing the field of genetics. The Thomas Hunt Morgan Medal was established in 1981 and named in honor of the prominent geneticist Thomas Hunt Morgan (1866–1945). Morgan’s genetic work on DrosophilaDrosophila is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies." Source: Wikipedia  earned him the Nobel Prize in 1933 for discoveries unlocking the secrets of heredity, marking the first experimental verification that chromosomes are the carriers of genetic information.

“Given the numerous luminaries who have received this award in the past, few in the areas of evolutionary genetics, this was an extraordinary surprise and honor, and also a testament to how population and quantitative genetics is viewed among the broader community," Lynch said.

Lynch has followed Morgan’s tradition of penetrating inquiry over a lengthy and diverse career. His current research focuses on exploration of the underlying mechanisms of evolution at the gene, genomic, cellular and phenotypic levels. In more than 250 research publications, he has deepened the field’s understanding of the role of mutation, random genetic drift and recombination.

Over 160 years after Darwin’s “On the Origin of Species,” the field of evolutionary study remains not only the cornerstone of biology but one of the most explosively active areas of research in the life sciences. One of Lynch’s primary objectives is to integrate evolutionary theory with cell biology, using principles from population genetics and biophysics.

As Lynch explains in a paper published in Proceedings of the National Academy of Sciences, “Natural selection is just one of several evolutionary mechanisms, and the failure to realize this is probably the most significant impediment to a fruitful integration of evolutionary theory with molecular, cellular and developmental biology.

Lynch has been a major force in the development of neutral theories in which varying population sizes of different lineages influence mutation rates and guide the way in which genome architectures are ultimately structured. Such research has helped expand the discipline beyond the purely adaptive explanations of genes and evolution that have dominated the field since Charles Darwin.

Portrait of ASU Professor Michael Lynch.

Michael Lynch is the director of the Biodesign Center for Mechanisms of Evolution and a professor in ASU's School of Life Sciences. He is the principal investigator for the new NSF-funded Biological Integration Institute for Mechanisms of Cellular Evolution.

To advance these investigations, he recently formed the Biological Integration Institute on Mechanisms of Cellular Evolution, focusing on the emergent field of evolutionary cell biology and supported by the National Science Foundation. 

His quantitative and theoretical insights on the mechanisms of evolution are illuminated by laboratory investigations of a range of organisms, including the microcrustacean Daphnia, the ciliate Paramecium and many diverse microbial species.

The integration of evolution and cell biology is one of the last uncharted research terrains in evolution. In addition to addressing foundational issues in evolutionary theory and exploring the intricacies of cell structure and function, the research has many practical applications. These include investigations of the emergence of antibiotic resistance, the explosive growth of destructive microbial populations such as blue-green algal blooms, organismal responses to climate change and the development of new methods of biomass production.

“I was thrilled, but not surprised, at the announcement of this prestigious award to Professor Lynch. He is a prolific scientist who has been a pioneer in the field for decades,” said Joshua LaBaer, executive director of the ASU Biodesign Institute. “Further, his leadership of the new Biological Integration Institute will place the ASU Biodesign Institute at the forefront of investigations into the new and largely unexplored domain of evolutionary cell biology.”

Lynch is a member of the U.S. National Academy of Sciences and a fellow of the American Academy of Arts and Sciences. He has also served as president of the Genetics Society of America; the Society for Molecular Biology and Evolution; the Society for the Study of Evolution; and the American Genetics Association. Previously, he has held faculty positions at the University of Illinois, University of Oregon and Indiana University.

The Thomas Hunt Morgan Medal is only the most recent in a string of prestigious awards earned by Lynch, which includes the Lifetime Contribution Award from the Society for Molecular Biology and Evolution, bestowed in 2021.

Lynch is the author of several highly influential books, including two with Bruce Walsh focusing on quantitative genetics: “Genetics and Analysis of Quantitative Traits,” 1998, and “Selection and Evolution of Quantitative Traits,” 2018. In 2007, “The Origins of Genome Architecture” appeared, a book the journal Nature referred to as “… the best, most up-to-date and thorough summary of genome evolution published.

His most recent book, “The Origins of Cellular Architecture,” is available in its entirety online.

Richard Harth

Science writer, Biodesign Institute at ASU


New meta-analysis explores potential environmental causes of ALS

January 27, 2022

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, believed to affect as many as 30,000 Americans. A hundred and fifty years after its discovery, the disease remains mysterious and devastating, striking without warning.

Teasing out the constellation of factors that underlie this complex disorder has been a challenge for researchers. In addition to a hereditary component for some ALS and related neurodegenerative diseases such as Alzheimer’s disease, researchers have pointed to a broad range of environmental agents as possible risk factors. Graphic illustration of chemicals on a molecular level. A range of chemicals that can appear in the environment, including β-N-methylamino-L-alanine (BMAA), formaldehyde, selenium, manganese, mercury, zinc and copper, are examined for their possible links to ALS. Download Full Image

In a new meta-analysis of available ALS literature, Professor Rolf Halden and two doctoral students at Arizona State University Biodesign Institute explore environmental influences potentially linked to the disease, using rigorous quantitative methods. The study also examines the distribution of ALS over space and time, correlating geographic data with exposure risks and lifestyle or occupational hazards.

The new findings will help researchers begin to fill in the many remaining blank spaces in the full portrait of this disease, which the study projects will affect around 22,650 Americans by 2040.

Doctoral student and lead author of the study Melanie Newell points out that “narrowing possible risk factors to a likely subset will hasten the work needed to determine whether these factors are merely associated or actually causal to ALS. The realities for patients and caregivers of this horrific disease could be significantly improved by reducing the delay of diagnosis and avoidable (occupational and non-occupational) exposures early in life.”

Halden, director of the Biodesign Center for Environmental Health Engineering, adds that “the role of environmental factors in diseases, not just neurodegenerative diseases such as ALS, continues to be understudied and underappreciated. Many disease trends in industrialized nations are increasing to an extent and within a rather short time scale, which simply cannot be explained by inherently slow genetic changes. To improve U.S. and global health outcomes, studying environment factors is key.”

The review recently appeared in the journal Science of the Total Environment.

Rolf Halden is the director of the Biodesign Center for Environmental Health Engineering.

The brain under assault

ALS, also known as Lou Gehrig’s disease, named for the famous baseball player who suffered from the illness, causes degeneration of motor nerve cells in the brain (upper motor neurons) and spinal cord (lower motor neurons), resulting in increasingly severe paralysis. Other symptoms include twitching and cramping of muscles, loss of motor control in the hands and arms, weakness and fatigue, shortness of breath, and difficulty breathing and swallowing.

The disease is somewhat more common in men than in women, for reasons researchers are still trying to puzzle out. ALS usually strikes between the ages of 55 and 75. The disease is incurable, with most ALS patients undergoing rapid deterioration, dying three to five years after their initial diagnosis.

Around 5–10% of all cases are the result of so-called familial ALS, which occurs when two or more family members are stricken with the disease. Such patients tend to deteriorate more rapidly than ALS patients who are not related, typically succumbing to the ailment one to two years after diagnosis. Although gene mutations have been associated with the disease, these represent only 1–2% of all ALS cases. The overwhelming majority of ALS cases lack any clearly defined root cause. Diet, injury and exposure to a broad range of potentially harmful chemicals have all been implicated. The latter are the focus of the current overview.

A new read on ALS

The large-scale analysis of available literature on ALS encompassed some 1,710 papers, identifying 258 that met the stringent criteria for inclusion in the study. Two methodologies were used in the data analysis to reduce the probability of errors. A total of 83 environmental chemicals were assessed during the review. When combined, the two methods pointed to a group of seven chemicals, exposure to which correlates with increased risk of developing ALS.

Chemicals topping the list of environmental hazards in need of further research are β-N-methylamino-L-alanine (BMAA), formaldehyde, selenium and four heavy metals: manganese, mercury, zinc and copper (in order of decreasing significance). The new study also describes some of the challenges facing researchers in their efforts to home in on the range of culprits for this enigmatic disorder.

The study notes that ALS cases are not evenly distributed around the globe. Some geographic hot spots have been identified from historical data, particularly in the Western Pacific region.

Such data offer tantalizing suggestions that environmental factors specific to certain areas may be contributing to the ALS burden. Examples include the Chamorros people of the Mariana Islands, including Guam. The area reached a peak in 1956 of 100 ALS cases per 100,000 persons. Later, New Guinea reached the highest prevalence ever reported in 1963, with 147 cases per 100,000 persons. In the case of New Guinea, rates remain well above the global average today. Screening has ruled out genetic factors for most of these cases, strongly implicating environmental correlations.

Hidden threats

Toxic chemicals accumulating in the environment are good candidates for causative agents of ALS and other neurodegenerative diseases, as they emerge in associative studies and further are known, in some cases, to trigger genetic and epigenetic changes in the body. However, the picture becomes hazy as the effects of exposure to recognized neurotoxins such as metals, solvents, pharmacological agents or mixtures of these are colored by endogenous factors specific to each individual, including genetic predisposition and gene expression.

Use of a disease origin investigative tool, termed the Bradford Hill criteria, allowed the ASU researchers to tease apart confounding factors to more accurately measure, weigh and interpret disease risks by examining the interaction of multiple causal criteria. For a given chemical compound or group of chemicals to be deemed causative (not merely associated) with ALS, the Bradford Hill approach requires nine specific conditions to be met. To further validate the results, a literature search of geographic exposure events associated with ALS cases was also applied.

Of the top seven chemicals showing strong association with ALS, only BMAA met all the Bradford Hill criteria, though other chemicals remain strongly implicated and require further research to determine their role. Because exposure to toxic chemicals can lead to a heightened risk for ALS, particular occupations making liberal use of such chemicals are cited, including construction, paperwork, agriculture, electrical work, medical professions, military service and manufacturing.

In the case of BMAA, listed in the study as the greatest chemical threat, exposures are likely the result of dietary intake by consuming seafood from waters contaminated with cyanobacteria or from eating the cycad plant, which contains both BMAA and cycasin, another neurotoxin. In addition to farming and fishing, a variety of other occupations showed a positive association between known chemical exposure and ALS incidence, including mining, manufacture of electrical equipment, hobbies using heavy metals, welding (due to manganese exposure) and dentistry (due to mercury exposure).

Assembling the puzzle of ALS

The prevalence of ALS is on the upswing in the U.S. Although the National Amyotrophic Lateral Sclerosis Registry shows 5,000 people are diagnosed each year with ALS, the current study’s modelling predicts in excess of 6,400 potential annual diagnoses. ALS cases are predicted to increase to 22,654 in 2040 and to 209,830 in 2240 in the United States. Globally, increases in ALS caseloads are expected to be greatest in China, the U.S. and India.

Given the complex interplay of factors, including exposure to multiple chemicals, occupational risk, lifestyle choices, age, sex and genetic predisposition, developing a clear-cut pattern of causality will remain a challenge, particularly in the absence of early diagnostic signposts or biomarkers of ALS. Nevertheless, hypothesis-driven studies of known risk factors and their effects on disease incidence may be designed based on the results of this literature analysis. The research therefore offers hope and a productive path forward in battling this perplexing and devastating disorder.

Richard Harth

Science writer, Biodesign Institute at ASU