3 mindsets that led to scientific breakthroughs

Award-winning scientists offer advice based on a lifetime of discovery; their unusual research has saved millions of lives

After the Golden Goose Award ceremony at the Library of Congress, David Sachar, MD, talks with Rhema Bjorkland, PhD, a former AAAS fellow who is now Staff Scientist and Technical Advisor for Environmental, Health & Safety at the National Nanotechnology Coordination Office. (Photo by Alison Bert)

Their seminal research was done decades ago, but its impact prevails and their approach to science is as timely and relevant as ever.

This month, three distinguished scientists traveled to Washington, DC, to accept an unusual and prestigious honor. The Golden Goose Award recognizes "silly sounding" federally-funded research that has led to major breakthroughs in science and medicine. At the ceremony, the scientists — and family members of their deceased research partners — talked about their research for a standing-room-only audience at the Library of Congress.

Elsevier SVP Ann Gabriel speaks at the Golden Goose Awards ceremony at the Library of Congress. (Photo by Rachel Couch)"It is scientists like yourselves who are drawing attention to the immense benefits of blue-skies research or work that is driven not by commercial gain but by curiosity," said Ann Gabriel, SVP of Global Strategic Networks at Elsevier. Elsevier is the benefactor of the Golden Goose Awards, which are run by the American Association for the Advancement of Science (AAAS).

Earlier that day, we interviewed each of the living awardees in the Kennedy Caucus Room of the Russell Senate Office Building, where they were honored at a private luncheon. Here's a sample of the wisdom they shared and their advice to young researchers.

1. Question the "obvious."

It can be daunting to challenge your teacher, especially when questioning a scientific "truth" that has endured for decades.

But that didn't stop Noel Rose, Professor Emeritus in the departments of Pathology and of Molecular Microbiology and Immunology at Johns Hopkins University. He is now Senior Lecturer in Pathology at Brigham and Women’s Hospital/Harvard Medical School.

As a junior faculty member and medical student in 1951, Rose joined the lab of Ernest Witebsky — an immunologist he came to "revere" as his mentor. Their aim was to learn more about antigens specific to various organs. Rose conducted a series of experiments with thyroglobulin, hoping to figure out the biological mechanisms behind organ-specific antigens and possibly use them to screen for certain cancers. To induce an immune response, he injected thyroglobulins from various species into rabbits. As expected, the rabbits produced thyroglobulin-specific antibodies.

On the Golden Goose panel, Noel Rose, MD, speaks with moderator Frank Sesno, Director of the School of Media and Public Affairs at George Washington University, as David Sachar, MD, and Frank Witlebsky, MD (son of Ernest Witebsky) look on. (Photo by Alison Bert)

"Too often in medicine, we take things at face value because they seem so logical," Dr. Rose said at the Golden Goose ceremony. "We frequently don't have evidence for them, or even any understanding as to how they could happen. And that's really where my story resides. ...

Dr. Noel Rose with his mentor, Ernest Witebsky, ca 1966."We all were taught  that the immune system can recognize everything  in the universe, except yourself. I wondered what could be a rational mechanism for doing that? That was the question that grabbed me."

In the early 20th century, Nobel Laureate Paul Ehrlich, whose student Hans Sachs had mentored Witebsky, developed the theory of horror autotoxicus — Latin for "fear of self-poisoning."

"It came from this notion that the immune system ... cannot attack itself, which seemed very logical," Dr. Rose explained, with humor, at the award ceremony. "I mean, why would you? It would seem pretty stupid."

"All my teachers said, 'horror autotoxicus – you've got to believe it, it’s the law of nature, it's logical.’

Paul Ehrlich in his office in Frankfurt, Germany, ca 1900. (<a href="https://commons.wikimedia.org/wiki/Template:PD-US">PD-US</a>)

But at 26, he was not about to accept it as dogma. "Of course, being maybe a little rebellious at that point, a little skeptical, I began to work with this essential thyroid protein, thyroglobulin. And I found that thyroglobulins were very much the same in all animals we studied, including humans.

"I wondered, 'So how can, in this case, a rabbit but it might be you or me recognize all these other protein molecules but never the thyroglobulin of our own bodies. Horror toxicus told me that it won't.

"I thought, ‘Maybe I'll test it one of these days.' And by golly I did."

Rose injected thryroglobulin from rabbits back into the rabbits. The result shocked him — the rabbits produced antibodies that inflamed and even destroyed their own thyroid gland that houses the thyroglobulin. He then tested serum samples from patients with inflamed thyroids (termed Hashimoto thyroiditis) and showed that they had antibodies to thyroglobulin.

This was the first case of reproducing a well described human disease by immunization. “We call them autoimmune diseases — diseases  caused by a crazy, out-law immune system," Dr. Rose said.

Dr. Rose credits his mentor for responding with skepticism and demanding that he reproduce his results for what could be an important discovery.

"'Again, again!'" he said, "'Repeat it repeat it — you must have made a mistake.'"

But there was no mistake; this discovery would lead to an increased understanding of the more than 100 autoimmune diseases and while opening pathways to better diagnose and treat them.

Read about their research and watch a short film.

Read top-cited research by Drs. Rose and Witebsky published by Elsevier


2. "Take the science to where the problem is."

After graduating from Harvard Medical School in 1963, Dr. David Sachar had his pick of prestigious research positions. So his decision surprised many of his classmates.

David Sachar, MD, talks about his research at the Golden Goose Award ceremony. (Photo by Alison Bert)"Think about the spring of 1963," he said at the award ceremony. "John F Kennedy was president. The Peace Corps had just been established. The Ugly American, a critique of American foreign aid processes in the developing world, had been published a few years earlier. And the (graduation speaker at) Harvard Medical School was a Nobel Prize-winning parasitologist by the name of Dr. Thomas Weller."

One thing Dr. Weller said would change the course of Dr. Sachar's future.

"Dr. Weller told us, ‘If every one of the dollars spent in federally sponsored research ... worked, we might have the success of extending the average life expectancy in the United States, say, from 68.7 to 69.1.

"If 10 cents of each dollar — one 10th of that amount — were spent in the developing world, we might have the success of extending the potential life expectancy from age 40 to age 60.’

"And I was hooked."

He went to his chief of medicine at Beth Israel Hospital in Boston and told him of his decision to join the US Public Health Service — one of the seven uniformed services in the US.

"I said, 'Look, we all have to serve two years of government service as physicians. Many of my colleagues are going to the NIH in Bethesda or to the Naval Hospital or the Walter Reed Army Institute of Research in Washington, and that’s wonderful. But that’s not how I want to spend my two years in government service.

"I want to go to the developing world and save the world."

"My friends at Harvard said, 'Oh that’s great. When you come back from East Pakistan, you can treat all the cholera patients in Boston — as though if it didn’t exist in Boston, it didn’t exist, it didn’t matter. But it mattered."

In East Pakistan, now Bangladesh, Dr. Sachar devised an unusual method to better understand the intenstinal activity in cholera patients. After adapting standard methods for measuring electric potential across biological membranes – like frog skin – in the laboratory, he devised a novel technique for measuring electric charge across the intentinal wall in intact humans. Applying this technique to cholera patients in East Pakistan, Dr. Sachar showed that intestinal absorptive function was normal in cholera and was accelerated normally in the presence of sugar. That realization formed the basis for oral rehydration therapy (ORT) for diarrheal disease, widely credited with saving over 50 million lives worldwide.

Dr. Sachar went on to become a Clinical Professor of Gastroenterology at Mount Sinai School of Medicine in New York.

Read about his research and watch a short film.


Dr. Sachar's advice for young scientists

"In order to achieve success with the translation of basic scientific research to useful beneficial application," he said, "you have to take the science to where the problem is.

"I could have sat for years at the laboratory bench in Copenhagen studying the electric potential across the frog skin – forever.

"Until you are ready to seek out the place where the problem is occurring, the place where the disease is committing its ravages, you’re not going to achieve the ultimate goal of saving lives and enhancing social welfare."


3. Don't let your goals and expectations get in the way of good science.

Dr. Jack Levin, Professor of Laboratory Medicine at the University of California San Francisco School of Medicine, admits he's "prejudiced" when it comes to basic research. After all, it's what he'd done for more than six decades — with remarkable results.

But the reason he favors it over applied research may seen counterintuitive.

"I think basic research is likely to have a much greater impact over the long term than applied research," he said. "In addition, applied research traps you into a goal which may or may not be realistic and narrows your focus.”

"So I think research that is not overly focused in terms of a specific end has the ability to amplify its results not only in the field in which the person is working but in fields that do not seem to be relevant at that point."

That was indeed the case with the research he and the late pathobiologist Frederik "Fred" Bang were honored for with the Golden Goose Award.

Studying the blood of the horseshoe crab leads to a lifesaving medical discovery

Jack Levin, MD, speaks on the panel flanked by moderator Frank Sesno and Molly Bang, daughter of his research partner Fred Bang, who was awarded the Golden Goose posthumously. (Photo by Rachel Couch)

In the 1950s, Dr. Bang was studying the circulatory system of the horseshoe crab when he discovered that an unknown infection was causing their blood to clot. A decade later, he called on Dr. Levin for his hematology expertise.

Through his experiments, Dr. Levin identified the culprit: a bacterial endotoxin. Bacterial endotoxin is a component of the cell wall of Gram-negative bacteria such as E. coli and Salmonella and can cause serious illness.

Dr. Levin then used the blood of the horseshoe crab to develop a new way to screen for bacterial endotoxins. Today, the Limulus amebocyte lysate (LAL) test is the standard way to screen intravenous fluids, parenteral drugs, and implantable medical devices for endotoxins.

Underside of a horseshoe crab (© istock.com/Harold Naideau)

"I think that my work is an excellent example of the importance of conducting and supporting basic biological research, even when there's no obvious practical benefit at the time," Dr. Levin told the audience at the Golden Goose ceremony. "And certainly, the history of investigative science indicates that early failure was a common feature of many discoveries, which turned out to be very important."

Read about their research and watch a short film.

Read top-cited research by Drs. Levin and Bang published by Elsevier

Quick question for you

Which terms do you most associate with Elsevier? (check all that apply)

Data and analytics
Research platforms
Technology
Decision support tools
Publishing
Books and journals
Scientific articles
Healthcare content

Tags


Contributors


Comments


comments powered by Disqus