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.

It kills more people each year than car crashes, war or drugs do. This invisible killer is the air pollution from sources like cars and trucks or factory smokestacks.

But as wildfires intensify and grow more frequent in a warming world, the smoke from these fires is emerging as a new and deadly pollution source, health experts say. By some estimates, wildfire smoke — which contains a mixture of hazardous air pollutants like particulate matter, nitrogen dioxide, ozone and lead — already causes as many as 675,000 premature deaths a year worldwide, as well as a range of respiratory, heart and other diseases.

Research shows that wildfire smoke is starting to erode the world’s progress in cleaning up pollution from tailpipes and smokestacks, as climate change supercharges fires.

“It’s heartbreaking, it really is,” said Dr. Afif El-Hasan, a pediatrician who specializes in asthma care at Kaiser Permanente in Southern California and a board director of the American Lung Association. Wildfires “are putting our homes in danger, but they’re also putting our health in danger,” Dr. El-Hasan said, “and it’s only going to get worse.”

Those health concerns were coming to the fore this week as wildfires ravaged the Los Angeles area. Residents began to return to their neighborhoods, many strewed with smoldering ash and rubble, to survey the damage. Air pollution levels remained high in many parts of the city, including in northwest coastal Los Angeles, where the air quality index climbed to “dangerous” levels.

Los Angeles, in particular, has seen air pollution at levels that could be raising daily mortality by between 5 to 15 percent, said Carlos F. Gold, an expert in the health effects of air pollution at the University of California, San Diego.

That means current death counts, “while tragic, are likely large underestimates,” he said. People with underlying health issues, as well as older people and children, are particularly vulnerable.

The rapid spread of this week’s fires into dense neighborhoods, where they burned homes, furniture, cars, electronics and materials like paint and plastic, made the smoke more dangerous, said Dr. Lisa Patel, a pediatrician in the San Francisco Bay Area and the executive director of the Medical Society Consortium on Climate and Health.

A recent study found that even for homes that are spared destruction, smoke and ash blown inside could adhere to rugs, sofas and drywall, creating health hazards that can linger for months. “We’re breathing in this toxic brew of volatile organic compounds and polycyclic aromatic hydrocarbons and hexavalent chromium,” Dr. Patel said. “All of it is noxious.”

Intensifying and more frequent fires, meanwhile, are upending experts’ understanding of smoke’s health effects. “Wildfire season is no longer a season,” said Colleen Reid, who researches the effects of air pollution from wildfires on heath at the University of Colorado Boulder. “We have fires all year round that affect the same population repeatedly.”

“The health impacts are not the same as if you were exposed once, and then not again for 10 years,” she said. “The effects of that is something that we still don’t really know.”

A United Nations report from 2022 concluded that the risk of devastating wildfires around the world would surge in coming decades. Heating and drying caused by climate change, along with development in places vulnerable to fire, was expected to intensify a “global wildfire crisis,” the report said. Both the frequency and intensity of extreme wildfires have more than doubled in the past two decades. In the United States, the average acreage burned a year has surged since the 1990s.

Now, pollution from wildfires is reversing what had been a decades-long improvement in air quality brought about by cleaner cars and power generation. Since at least 2016, in nearly three-quarters of states in the U.S. mainland, wildfire smoke has eroded about 25 percent of progress in reducing concentrations of a type of particulate matter called PM 2.5, a Nature study in 2023 found.

In California, wildfire smoke’s effect on air quality is offsetting public health gains brought about by a decline in air pollution from automobiles and factories, state health officials have found. (By releasing carbon dioxide and other planet-warming gases into the atmosphere, wildfires are themselves a big contributor to climate change: The wildfires that ravaged Canada’s boreal forests in 2023 produced more greenhouse gases than the burning of fossil fuels in all but three countries.)

”It’s not a pretty picture,” said Dr. Gold of U.C. San Diego, who took part in the Nature study. If planet-warming gas emissions continue at current levels, “we’ve got some work that suggests that mortality from wildfire smoke in the U.S. could go up by 50 percent,” he said.

One silver lining is that the Santa Ana winds that so ferociously fueled the flames in recent days have been blowing some of the smoke toward the ocean. That stands in contrast to the smoke from the 2023 Canadian wildfires that drifted to New York and other American states hundreds of miles away, causing spikes in emergency room visits for asthma.

At one point that year, more than a third of Americans, from the East Coast to the Midwest, were under air quality alerts from Canadian wildfire smoke. “We’re seeing new and worsening threats in places that are not used to them,” Dr. Patel, the pediatrician, said.

The new normal is bringing about changes to health care, Dr. Patel said. More health systems are sending out air quality alerts to vulnerable patients. In the small community hospital where she works, “every child that comes in with wheezing or asthma, I talk to them about how air pollution is getting worse because of wildfires and climate change,” she said.

“I teach them how to look up air quality, and say they should ask for an air purifier,” Dr. Patel added. She also cautions that children should not participate in cleanup after a wildfire.

Scientists are still trying to understand the full range of wildfire smoke’s health effects. One big question is how much of what researchers know about vehicle exhaust and other forms of air pollution apply to wildfire smoke, said Mark R. Miller, a researcher at the Center for Cardiovascular Science at the University of Edinburgh who led a recent global survey of climate change, air pollution and wildfires.

For example, exhaust particles “are so small that when we breathe them in, they go deep down into our lungs and are actually small enough that they can pass from our lungs into our blood,” he said. “And once they’re in our blood, they can be carried around our body and start to build up.”

That means air pollution affects our entire body, he said. “It has effects on people who have diabetes, has effects on the liver and the kidney, it has effects on the brain, on pregnancy,” he said. What’s still not clear is whether pollution from wildfires has all of those same effects. “But it’s likely,” he said.

Experts have a range of advice for people living in areas with smoke. Keep an eye on air quality alerts, and follow evacuation orders. Stay indoors as much as possible, and use air purifiers. When venturing outside, wear N95 masks. Don’t do strenuous exercise in bad air. Keep children, older people and other vulnerable groups away from the worst smoke.

Ultimately, tackling climate change and cutting back on all kinds of air pollution is the way to reduce the overall burden on health, said Dr. El-Hasan of the American Lung Association. “Can you imagine how much worse things would be if we hadn’t started cleaning up emissions from our cars?” he said. “I’m trying to think, glass half full, but it does break my heart and it does worry me.”