From glaciers to the genome: Franklin Institute honors 8 scientists

Douglas C. Wallace was the first to tie inherited mutations in mitochondrial DNA to disease.

The 36-year-old woman had given birth to two children who died of a rare genetic disease called Leigh syndrome, one at 6 years old, the other at 8 months. She also had suffered four miscarriages.

This year she gave birth once again, this time to a healthy child, with the help of a short snippet of DNA from a female donor - leading to international headlines about a "three-parent baby."

Science fiction? No, just the logical outgrowth of research that Douglas C. Wallace was doing 40 years ago.

Wallace, a pioneer in the field of mitochondrial DNA who is now at Children's Hospital of Philadelphia, is one of eight new winners of the annual awards given by the Franklin Institute, to be announced Monday.

The others include a climate scientist who has made 22 polar expeditions, a psychologist renowned for his study of how the human brain pays attention, and the developers of a widely used method for making coatings and adhesives.

They will come to the Franklin Institute in May for several days of activities, culminating in a black-tie ceremony.

The museum has bestowed awards in the sciences and business since the 1820s to such luminaries as Nikola Tesla, Stephen Hawking, Pierre and Marie Curie, and Albert Einstein. Among the laureates are 117 who also have won Nobel Prizes.

Wallace is not in the business of three-parent babies, as the procedure is not allowed in the United States. And he scoffs at the term, which sort of misrepresents what happened, in the lab of a fertility clinic in Mexico.

Briefly, physicians removed the "nuclear" DNA from a donor egg, so named because it is in the cell nucleus, and replaced it with DNA from the birth mother - about 20,000 genes' worth.

But they did not transfer a small stretch of the birth mother's DNA, just 37 genes contained in the bean-shaped cellular "organelles" called mitochondria.

That's because mutations in the mother's mitochondrial DNA had caused fatal neurologic disease in her other children, according to an abstract the physicians submitted to the American Society for Reproductive Medicine. The team left intact the donor's mitochondrial DNA, enabling the birth of a healthy child.

Wallace said it was an encouraging development, if confirmed. In 1988, while at Emory University, he was the first to show that inherited mutations in mitochondrial DNA could cause disease.

Hundreds of such mutations have been reported since, yet successful treatments remain scarce.

"If they effectively have corrected the genetic defect and the child is going to be normal, I think it would be a great thing," Wallace said.

Wallace, meanwhile, has long trained his sights on encouraging a more fundamental shift in the field of medicine.

There is no dispute that genetic mutations cause a host of rare mitochondrial diseases. But Wallace contends that mitochondrial dysfunction also plays a key role in a variety of more common diseases, such as Alzheimer's, cancer, autism, obesity, and diabetes.

Whereas nuclear DNA carry the recipes for the body's structure, mitochondria are responsible for producing energy in the cell, converting oxygen and nutrients into a chemical called ATP. If that process is disrupted, it stands to reason that it could spell trouble for the larger organism.

Indeed, Wallace and his colleagues have shown in mice that mitochondrial mutations lead to cardiomyopathy, diabetes, and certain neurodegenerative diseases.

Wallace's first major breakthrough came in the 1970s, when he and colleagues showed that DNA inside mitochondria was inherited through the mother. He also has studied how mitochondrial DNA can be used to track the migration of our ancestors out of Africa.

Others in the new class of Franklin award winners have played pivotal roles in their fields.

Michael I. Posner, of the University of Oregon, pioneered the use of two techniques for measuring brain activity that now are so ubiquitous it is hard to imagine the field of psychology without them.

One is simply measuring the amount of time it takes to perform a given task. The other is mapping the activity of various brain regions with the use of imaging devices, at first with PET scans, and more recently with MRI machines. In particular, Posner is known for using these tools to study attention.

Then there is Claude Lorius of the French National Center for Scientific Research, who has studied ice cores to create a record of climate change over the last 400,000 years. And Mildred Dresselhaus of the Massachusetts Institute of Technology, acclaimed for her work in "nanocarbon" materials such as graphene.

Will any of the eight become as well-known as Einstein, their predecessor in winning a Franklin award, in 1935? Perhaps not, but that has not stopped colleagues from mentioning them in the same breath as the famous physicist.

Wallace came to CHOP in 2010 after talking to Marc Yudkoff, a senior researcher in the field of metabolic disease. In a 2011 interview with the Scientist magazine, Yudkoff recalled his delight when Wallace asked about moving to the Philadelphia hospital.

He said: "It was a bit like Einstein asking if he's welcome in a physics department."

The complete list of winners:

Krzysztof Matyjaszewski, Carnegie Mellon University
Mitsuo Sawamoto, Kyoto University

Computer and Cognitive Science:
Michael I. Posner, University of Oregon

Life Science:
Douglas C. Wallace, Children's Hospital of Philadelphia

Marvin L. Cohen, University of California, Berkeley

Materials Science and Engineering:
Mildred Dresselhaus, Massachusetts Institute of Technology

Bower Award, Achievement in Science:
Claude Lorius, French National Center for Scientific Research

Electrical Engineering:
Nick Holonyak, University of Illinois at Urbana-Champaign