Science
Martin Karplus, Chemist Who Made Early Computers a Tool, Dies at 94
Martin Karplus, a Nobel Prize-winning theoretical chemist who used computers to model how complex systems change during chemical reactions, a process that has led to advances in the understanding of biological processes, died on Dec. 28 at his home in Cambridge, Mass. He was 94.
His wife, Marci Karplus, said he died while recovering from a fall in which he broke a femur.
Over his long career, Dr. Karplus had crossed paths with some of the most important scientists of the 20th century, including Linus Pauling and J. Robert Oppenheimer.
Scientists can control the chemicals in a reaction, and they can measure and evaluate the results, but what happens in between is a mystery.
As Sven Lidin, chairman of the Nobel selection committee explained when announcing the 2013 winners in chemistry: “It’s like seeing all the actors before Hamlet and all the dead bodies after, and then you wonder what happened in the middle. And actually, there is some interesting action there, and this is what theoretical chemistry provides us with — the whole drama.”
Beginning in the 1960s, when computers were only a fraction as powerful as today’s smartphones, Dr. Karplus and his fellow Nobel laureates — Michael Levitt, originally from South Africa, and Arieh Warshel, who was born in Israel — began to build virtual models of molecules to understand what happens to them during complex reactions like photosynthesis and combustion.
The models used classical Newtonian physics to predict how multitudes of atoms and molecules move during reactions, and they used quantum physics to describe how chemical bonds are broken and formed during those reactions. This type of analysis proved particularly useful in understanding biological reactions involving enzymes, the proteins that govern chemical responses in living organisms.
There was initial resistance to the scientists’ work because it was difficult for others to accept that computer models could be accurate enough or could sufficiently account for the many variables in some reactions. But by the time the Nobel Prize was awarded in 2013, that skepticism was gone.
“Today, the computer is just as important a tool for chemists as the test tube,” the academy wrote in its announcement. “Simulations are so realistic that they predict the outcome of traditional experiments.”
At Harvard University, where Dr. Karplus spent most of his career, he and his research team in 1983 created a program for simulating molecular interaction, calling it Chemistry at Harvard Macromolecular Mechanics (CHARMM). The program is available to researchers worldwide.
In the late 1950s, Dr. Karplus made another important contribution to chemistry: He developed what is known as the Karplus equation. It makes it possible to calculate the magnitude and orientation of protons in organic compounds involved in nuclear magnetic resonance spectroscopy, allowing chemists to study the arrangements of atoms in molecules. It is now a basic part of chemistry education.
Martin Karplus was born on March 15, 1930, in Vienna into a well-off and intellectually accomplished Jewish family. He was the second son of Johann Karplus, a banker, and Isabella (Goldstern) Karplus, a hospital dietitian.
His paternal grandfather, Johann Paul Karplus, was a neurologist who discovered the functions of the hypothalamus, the crucial brain region that controls body temperature, hunger, heart rate and other vital activities. An uncle, Eduard Karplus, was an engineer and inventor. And Martin’s older brother, Robert, became a theoretical physicist at the University of California at Berkeley.
In the face of rising antisemitism in the 1930s and a few days after Nazi Germany annexed Austria in the Anschluss of March 1938, Martin, his brother, and his mother fled to Zurich and then to France, eventually arriving in Le Havre.
Martin’s father was initially imprisoned in Vienna, but he was able to join the family before they set sail for New York. They arrived on Oct. 8, 1938, and soon after moved to Newton, Mass.
At Newton High School, Martin discovered that his older brother had made such a mark there that many teachers doubted Martin’s ability to do as well, he recalled in a Nobel biography. One teacher, who was in charge of the Westinghouse Science competition, the nation’s top talent search in the sciences, told Martin that it would be a waste of his time to enter.
But he found another teacher who was willing to proctor his test for the competition. He went on to qualify as one of the country’s 40 finalists. Martin’s project on alcids, an aquatic bird, was chosen as the co-winner of the competition, after which he met President Harry S. Truman in Washington.
Accepted to Harvard University, he concentrated on chemistry and physics. As he was finishing his undergraduate degree in 1950, both the University of California at Berkeley and the California Institute of Technology, known as Caltech, accepted him for graduate studies.
Unsure where to go, he visited his brother, Robert, who by then was working at the Institute for Advanced Study in Princeton, N.J. Robert showed him around, introducing him to Albert Einstein and J. Robert Oppenheimer, who had led the Manhattan Project that developed the atomic bomb and who had become the institute’s director. Dr. Oppenheimer recommended Caltech, where he had been a professor, calling it “a shining light in a sea of darkness,” according to Dr. Karplus’s biography. Decision made.
At Caltech he focused on biophysics, joining a graduate group led by Max Delbrück, who, along with Salvador E. Luria, had proved that Darwin’s theory of evolution also applied to bacteria. They, along with Alfred D. Hersey, would be awarded the Nobel Prize in Physiology or Medicine in 1969 for their work.
As Dr. Karplus wrote in his Nobel biography, a turning point in his life came two months after he started at Caltech. Dr. Delbrück suggested that Dr. Karplus present a seminar on his intended area of research: how vision works.
He began his presentation, but after 10 minutes Dr. Delbrück interrupted him to say that he did not understand what Dr. Karplus was saying. Dr. Karplus began anew, and Dr. Delbrück interrupted again, saying he still did not understand. Dr. Karplus began again, and Dr. Delbrück interrupted a third time.
At this point, Dr. Richard Feynman, who was awarded the Nobel Prize in Physics in 1965 and who was sitting in the audience, turned around and said to Dr. Delbrück: “I can understand, Max. It is perfectly clear to me.” Dr. Delbrück turned red and stormed out. Later that day, he called Dr. Karplus to his office and told him that he could no longer work with him.
Dr. Karplus switched to chemistry.
In the chemistry department, Dr. Karplus initially worked with Prof. John Kirkwood, but then Dr. Kirkwood left for Yale University. His graduate students were given the chance to switch to working with Linus Pauling. Only Dr. Karplus accepted.
Dr. Pauling was on the short list of the greatest scientists of the 20th century. He was one of only five people to receive two Nobel Prizes: the first in 1954 for chemistry, for determining how atoms are chemically bound in molecules; and the second, the Nobel Peace Prize, in 1962, for promoting nuclear disarmament. His scientific work led to the founding of quantum chemistry and molecular biology.
Dr. Karplus’s time with Dr. Pauling proved fruitful: He finished his doctoral dissertation just before Dr. Pauling departed on a trip in late 1953. Dr. Karplus, who had received a National Science Foundation postdoctoral fellowship, then left to spend two years at Oxford University.
In 1955, he was hired by the University of Illinois, which was doing advanced work on nuclear magnetic resonance (NMR) spectroscopy. It was during his five years in Illinois that he put together his Karplus equation.
In 1960, Dr. Karplus was hired to be a researcher at the IBM Watson Scientific Laboratory and to teach at Columbia University. With access to state-of-the-art computing power, he continued his research on NMR and also began to investigate creating models to explain chemical reactions.
Dr. Karplus changed jobs again in 1966, returning to Harvard. There he started to concentrate on biological reactions, which are the most complex. The work would lead to the creation of CHARMM and to his Nobel Prize.
In the 1990s, Dr. Karplus was appointed a professor at Louis Pasteur University, later renamed the University of Strasbourg, in France. He spent the next 20 years going back and forth between there and Harvard.
Dr. Karplus met Marci Hazard at Harvard, where she has worked for 51 years. They married in 1981. His first wife was Susan Karplus; their marriage ended in divorce.
In addition to his wife, he is survived by two children from the earlier marriage, Reba and Tammy; one child from his second marriage, Mischa; and one grandchild. (Susan Karplus died in 1982. His brother, Robert, died in 1990.)
In 2020, Dr. Karplus published his autobiography, “Spinach on the Ceiling: The Multifaceted Life of a Theoretical Chemist.” The title referred to the landing spot of a launched spoonful of spinach that he had been ordered to eat as a boy.
Over his career, Dr. Karplus supervised close to 250 graduate and doctoral students, most of whom have gone on to successful academic careers. They are collectively known as Karplusians.
Science
Tuberculosis outbreak reported at Catholic high school in Bay Area. Cases statewide are climbing
Public health officials in Northern California are investigating a tuberculosis outbreak, identifying more than 50 cases at a private Catholic high school and ordering those who are infected to stay home. The outbreak comes as tuberculosis cases have been on the rise statewide since 2023.
The San Francisco Department of Public Health issued a health advisory last week after identifying three active cases and 50 latent cases of tuberculosis at Archbishop Riordan High School in San Francisco. The disease attacks the lungs and remains in the body for years before becoming potentially deadly.
A person with active TB can develop symptoms and is infectious; a person with a latent tuberculosis infection cannot spread the bacteria to others and doesn’t feel sick. However, a person with a latent TB infection is at risk of developing the disease anytime.
The three cases of active TB have been diagnosed at the school since November, according to public health officials. The additional cases of latent TB have been identified in people within the school community.
Archbishop Riordan High School, which recently transitioned from 70 years of exclusively admitting male students to becoming co-ed in 2020, did not immediately respond to the The Times’ request for comment.
School officials told NBC Bay Area news that in-person classes had been canceled and would resume Feb. 9, with hybrid learning in place until Feb. 20. Students who test negative for tuberculosis will be allowed to return to campus even after hybrid learning commences.
Officials with the San Francisco Department of Public Health said the risk to the general population was low. Health officials are currently focused on the high school community.
How serious is a TB diagnosis?
Active TB disease is treatable and curable with appropriate antibiotics if it is identified promptly; some cases require hospitalization. But the percentage of people who have died from the disease is increasing significantly, officials said.
In 2010, 8.4% of Californians with TB died, according to the California Department of Public Health. In 2022, 14% of people in the state with TB died, the highest rate since 1995. Of those who died, 22% died before receiving TB treatment.
The Centers for Disease Control and Prevention estimated that up to 13 million people nationwide live with latent TB.
How does California’s TB rate compare to the country?
Public health officials reported that California’s annual TB incidence rate was 5.4 cases per 100,000 people last year, nearly double the national incidence rate of 3.0 per 100,000 in 2023.
In 2024, 2,109 California residents were reported to have TB compared to 2,114 in 2023 — the latter was about the same as the total number of cases reported in 2019, according to the state Department of Public Health.
The number of TB cases in the state has remained consistent from 2,000 to 2,200 cases since 2012, except during the COVID-19 pandemic from 2020 to 2022.
California’s high TB rates could be caused by a large portion of the population traveling to areas where TB is endemic, said Dr. Shruti Gohil, associate medical director for UCI Health Epidemiology and Infection Prevention.
Nationally, the rates of TB cases have increased in the years following the COVID-19 pandemic, which “was in some ways anticipated,” said Gohil. The increasing number of TB cases nationwide could be due to a disruption in routine care during the pandemic and a boom in travel post-pandemic.
Routine screening is vital in catching latent TB, which can lie dormant in the body for decades. If the illness is identified, treatment could stop it from becoming active. This type of routine screening wasn’t accessible during the pandemic, when healthcare was limited to emergency or essential visits only, Gohil said.
When pandemic restrictions on travel were lifted, people started to travel again and visit areas where TB is endemic, including Asia, Europe and South America, she said.
To address the uptick in cases and suppress spread, Gov. Gavin Newsom signed Assembly Bill 2132 into law in 2024, which requires adult patients receiving primary care services to be offered tuberculosis screening if risk factors are identified. The law went into effect in 2025.
What is TB?
In the United States, tuberculosis is caused by a germ called Mycobacterium tuberculosis, which primarily affects the lungs and can impact other parts of the body such as the brain, kidneys and spine, according to the Centers for Disease Control and Prevention. If not treated properly, TB can be fatal.
TB is spread through the air when an infected person speaks, coughs or sings and a nearby person breathes in the germs.
When a person breathes in the TB germs, they settle in the lungs and can spread through the blood to other parts of the body.
The symptoms of active TB include:
- A cough that lasts three weeks or longer
- Chest pain
- Coughing up blood or phlegm
- Weakness or fatigue
- Weight loss
- Loss of appetite
- Chills
- Fever
- Night sweats
Generally, who is at risk of contracting TB?
Those at higher risk of contracting TB are people who have traveled outside the United States to places where TB rates are high including Asia, the Middle East, Africa, Eastern Europe and Latin America.
A person has an increased risk of getting TB if they live or work in such locations as hospitals, homeless shelters, correctional facilities and nursing homes, according to the CDC.
People with weakened immune systems caused by health conditions that include HIV infection, diabetes, silicosis and severe kidney disease have a higher risk of getting TB.
Others at higher risk of contracting the disease include babies and young children.
Science
Contributor: Animal testing slows medical progress. It wastes money. It’s wrong
I am living with ALS, or amyotrophic lateral sclerosis, often called Lou Gehrig’s disease. The average survival time after diagnosis is two to five years. I’m in year two.
When you have a disease like ALS, you learn how slowly medical research moves, and how often it fails the people it is supposed to save. You also learn how precious time is.
For decades, the dominant pathway for developing new drugs has relied on animal testing. Most of us grew up believing this was unavoidable: that laboratories full of caged animals were simply the price of medical progress. But experts have known for a long time that data tell a very different story.
The Los Angeles Times reported in 2017: “Roughly 90% of drugs that succeed in animal tests ultimately fail in people, after hundreds of millions of dollars have already been spent.”
The Times editorial board summed it up in 2018: “Animal experiments are expensive, slow and frequently misleading — a major reason why so many drugs that appear promising in animals fail in human trials.”
Then there’s the ethical cost — confining, sickening and killing millions of animals each year for a system that fails 9 times out of 10. As Jane Goodall put it, “We have the choice to use alternatives to animal testing that are not cruel, not unethical, and often more effective.”
Despite overwhelming evidence and well-reasoned arguments against animal-based pipelines, they remain central to U.S. medical research. Funding agencies, academic medical centers, government labs, pharmaceutical companies and even professional societies have been painfully slow to move toward human- and technology-based approaches.
Yet medical journals are filled with successes involving organoids (mini-organs grown in a lab), induced pluripotent stem cells, organ-on-a-chip systems (tiny devices with human cells inside), AI-driven modeling and 3D-bioprinted human tissues. These tools are already transforming how we understand disease.
In ALS research, induced pluripotent stem cells have allowed scientists to grow motor neurons in a dish, using cells derived from actual patients. Researchers have learned how ALS-linked mutations damage those neurons, identified drug candidates that never appeared in animal models and even created personalized “test beds” for individual patients’ cells.
Human-centric pipelines can be dramatically faster. Some are reported to be up to 10 times quicker than animal-based approaches. AI-driven human biology simulations and digital “twins” can test thousands of drug candidates in silico, with a simulation. Some models achieve results hundreds, even thousands, of times faster than conventional animal testing.
For the 30 million Americans living with chronic or fatal diseases, these advances are tantalizing glimpses of a future in which we might not have to suffer and die while waiting for systems that don’t work.
So why aren’t these tools delivering drugs and therapies at scale right now?
The answer is institutional resistance, a force so powerful it can feel almost god-like. As Pulitzer Prize–winning columnist Kathleen Parker wrote in 2021, drug companies and the scientific community “likely will fight … just as they have in past years, if only because they don’t want to change how they do business.”
She reminds us that we’ve seen this before. During the AIDS crisis, activists pushed regulators to move promising drugs rapidly into human testing. Those efforts helped transform AIDS from a death sentence into a chronic condition. We also saw human-centered pipelines deliver COVID vaccines in a matter of months.
Which brings me, surprisingly, to Robert F. Kennedy Jr. In December, Kennedy told Fox News that leaders across the Department of Health and Human Services are “deeply committed to ending animal experimentation.” A department spokesperson later confirmed to CBS News that the agency is “prioritizing human-based research.”
Kennedy is right.
His directive to wind down animal testing is not anti-science. It is pro-patient, pro-ethics and pro-progress. For people like me, living on borrowed time, it is not just good policy, it is hope — and a potential lifeline.
The pressure to end animal testing and let humans step up isn’t new. But it’s getting new traction. The actor Eric Dane, profiled about his personal fight with ALS, speaks for many of us when he expresses his wish to contribute as a test subject: “Not to be overly morbid, but you know, if I’m going out, I’m gonna go out helping somebody.”
If I’m going out, I’d like to go out helping somebody, too.
Kevin J. Morrison is a San Francisco-based writer and ALS activist.
Science
A push to end a fractured approach to post-fire contamination removal
The patchwork efforts to identify and safely remove contamination left by the 2025 Eaton and Palisades fires has been akin to the Wild West.
Experts have given conflicting guidance on best practices. Shortly after the fires, the federal government suddenly refused to adhere to California’s decades-old post-fire soil-testing policy; California later considered following suit.
Meanwhile, insurance companies have resisted remediation practices widely recommended by scientists for still-standing homes.
A new bill introduced this week by state Assemblymember John Harabedian (D-Pasadena) aims to change that by creating statewide science-based standards for the testing and removal of contamination deposited by wildfires — specifically within still-standing homes, workplaces and schools, and in the soil around those structures.
“In a state where we’ve had a number of different wildfires that have happened in urban and suburban areas, I was shocked that we didn’t have a black-and-white standard and protocol that would lay out a uniform post-fire safety standard for when a home is habitable again,” Harabedian said.
The bill, AB 1642, would task the state’s Department of Toxic Substances Control with creating standards by July 1, 2027. The standards would only serve as guidance — not requirements — but even that would be helpful, advocates say.
“Guidance, advisories — those are extremely helpful for families that are trying to return home safely,” said Nicole Maccalla, who leads data science efforts with Eaton Fire Residents United, a grassroots organization addressing contamination in still-standing homes. “Right now, there’s nothing … which means that insurance companies are the decision-makers. And they don’t necessarily prioritize human health. They’re running a business.”
Maccalla supports tasking DTSC with determining what levels of contamination pose an unacceptable health risk, though she does want the state to convene independent experts including physicians, exposure scientists and remediation professionals to address the best testing procedures and cleanup techniques.
Harabedian said the details are still being worked out.
“What’s clear from my standpoint, is, let’s let the public health experts and the science and the scientists actually dictate what the proper standards and protocol is,” Harabedian said. “Not bureaucrats and definitely not insurance companies.”
For many residents with still-standing homes that were blanketed in toxic soot and ash, clear guidance on how to restore their homes to safe conditions would be a much welcome relief.
Insurance companies, environmental health academics, and professionals focused on addressing indoor environmental hazards have all disagreed on the necessary steps to restore homes, creating confusion for survivors.
Insurance companies and survivors have routinely fought over who is responsible for the costs of contamination testing. Residents have also said their insurers have pushed back on paying for the replacement of assets like mattresses that can absorb contamination, and any restoration work beyond a deep clean, such as replacing contaminated wall insulation.
Scientists and remediation professionals have clashed over which contaminants homeowners ought to test for after a fire. Just last week, researchers hotly debated the thoroughness of the contamination testing at Palisades Charter High School’s campus. The school district decided it was safe for students to return; in-person classes began Tuesday.
Harabedian hopes the new guidelines could solidify the state’s long-standing policy to conduct comprehensive, post-fire soil testing.
Not long after the federal government refused to adhere to the state’s soil testing policy, Nancy Ward, the former director of the California Governor’s Office of Emergency Services, had privately contemplated ending state funding for post-fire soil testing as well, according to an internal memo obtained by The Times.
“That debate, internally, should have never happened,” Harabedian said. “Obviously, if we have statewide standards that say, ‘This is what you do in this situation,’ then there is no debate.”
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