By paying attention to what excited her, this clinician-scientist became a world-leading glaucoma genetics expert
Scientific research starts with a hypothesis, which scientists work to prove or disprove through testing or observation. There’s no place for gut instinct.
In academics, business, and poker, those hunches move us ahead.
A 1997 study in Science showed participants performed better in a gambling exercise when they backed reason with subconscious decisions. In other words, evaluate the data, but pay attention when your heart races.
Janey Wiggs ’76, Ph.D., ’81, let instinct and genuine excitement guide her to undergraduate and graduate degrees in biochemistry, followed by medical genetics research and ophthalmology studies at Harvard Medical School.
Had she not kept her mind open to new possibilities, Dr. Wiggs wouldn’t be a world-leading glaucoma and genetic eye disease expert. She wouldn’t be leading a team of researchers studying gene mutations that contribute to the leading cause of blindness. And she wouldn’t have devoted countless hours toward finding more targeted treatments—and ideally, a cure—for a disease predicted to affect 80 million people worldwide by 2020.
“Her work gives people hope that their kids or grandkids won’t have to experience a chronic lifetime disease,” says Tomas Brunner, president and CEO of Glaucoma Research Foundation. “Her research brings promise of new therapies for glaucoma—either gene therapies or another new development—and may even tie to other neurodegenerative diseases.”
It started with science
A moth and rock collector, the kind of kid that played with litmus paper and a microscope, science fascinated Dr. Wiggs from childhood. Because of an exceptional high school teacher, her interest in biology expanded to chemistry.
a group of genes involved in lactose
As an incoming freshman at Cal, she had her sights set on chemical engineering until the lac operon, introduced during a biology class, disrupted her plans.
Lac operon: a group of genes involved in lactose metabolism.
“It’s this ingenious feedback mechanism that allows bacteria to turn on genes when they’re needed and then turn them off when they’re not needed,” she says. “I walked out of that lecture completely transformed. It was the first time I’d ever heard anything about regulation of gene expression.” After learning about the lac operon, she became a biochemistry major.
It was an exciting time to study biomolecules. In 1975, while Dr. Wiggs pursued her B.A., about 150 molecular biologists, including scientists from UC Berkeley and Stanford, convened at Asilomar in Pacific Grove, California, to discuss recombinant DNA research. The historic conference led to regulations that governed the public and private use of recombinant DNA technology. The guidelines allowed scientists to resume research that had been halted six months before.
At Cal, Dr. Wiggs’s lab advisor, Mike Chamberlin, was a pioneer in understanding how nucleic acids function. Others from the university made breakthroughs or major discoveries in toxicology and enzymes.
The DNA of disease
Another transformative experience came during Dr. Wiggs’s doctoral studies at Cal, also in biochemistry. She “just happened” to come across a Scientific American article about the discovery of the genetic basis for sickle cell anemia.
The idea that gene mutations could cause disease stayed with Dr. Wiggs much like that lac operon. To learn more, she accepted an opportunity to teach an undergraduate course on “applications of recombinant DNA technology to problems at clinical medicine.”
“Through teaching that seminar I found myself excited about how we could manipulate DNA, and through our understanding of genetics, we could begin to develop like technologies that would lead to new possible therapies for humans,” she says. “It was from that understanding that I then went to medical school after getting my Ph.D.”
Like many aspiring MDs, Dr. Wiggs applied to one of the most prestigious: Harvard Medical School. Unlike many aspiring MDs, Harvard accepted her. They also awarded her the Pearl and Martin Silverstein academic scholarship in Health Sciences and Technology for two consecutive years, in 1983 and 1984.
A Washington native, Dr. Wiggs expected to return to the west coast after medical school. Due to the opportunities that naturally come from studying at Harvard, Dr. Wiggs stayed in the area a little longer. She’s still there, now a clinician-scientist at Massachusetts Eye and Ear in Boston, Massachusetts. In addition to being a practicing ophthalmologist, Dr. Wiggs serves as associate director of the Howe Laboratory and associate chief for Clinical Research at Mass. Eye and Ear, as well as the director of the CLIA-certified clinical diagnostic glaucoma lab.
“I saw a patient who was part of an enormous family that had glaucoma,” she says. “And I thought, ‘Wow, this is inherited.’”
While at Harvard, in the mid 1980s, Dr. Wiggs collaborated on research that aimed to identify the gene for retinoblastoma, a rare form of cancer that develops from immature retina cells. The research eventually led to a well-received publication in New England Journal of Medicine, 1988.1
With her mind already stayed on the link between genetics and eye disease, Dr. Wiggs did a clinical rotation in glaucoma. “I saw a patient who was part of an enormous family that had glaucoma,” she says. “And I thought, ‘Wow, this is inherited.’ I then learned a lot about the inherited types of glaucoma. Very little was known in those days about any genes that would cause the disease. It was a wide-open area. I realized I could be involved and hopefully make a contribution by identifying genes that contributed to glaucoma.”
The genetics of glaucoma
To date, Dr. Wiggs and the NEIGHBORHOOD Consortium, a national group of researchers dedicated to glaucoma research, have identified a number of genes that contribute to early-onset or adult-onset glaucoma. In a study published in June 2018, researchers—including Dr. Wiggs, NEIGHBORHOOD, and the UK Biobank Eye and Vision Consortium—identified 112 genomic loci associated with intraocular pressure (IOP), 68 of them novel.
Doctors use IOP to determine glaucoma risk. Elevated IOP causes the optic nerve damage that leads to vision loss in glaucoma patients. Medication designed to lower IOP helps glaucoma patients manage the disease.
With genetic information comes risk protection—with early diagnosis, doctors can properly monitor disease and prevent serious optic nerve damage. At present, doctors can’t restore whatever vision loss comes with glaucoma.
“With our current collection of genetic factors, we have pretty good specificity and sensitivity,” says Dr. Wiggs. “It’s not quite at 100 percent yet; it’s around 76 percent. I would expect in the next two to three years that there are going to be specific gene-based therapies for glaucoma related to some of the genes that are currently known.”
Let intrigue lead to passion
Back to the lac operon. Had it not been for that funny group of genes; and specifically, the Cal instructor that lectured on the topic, Dr. Wiggs may not have realized her passion for genetics, and glaucoma research would be without one of its key leaders.
“The passion I
felt that day walking out of that lecture … is still the driving force behind
the work I’m currently doing.”
“I could not have envisioned at that point exactly what I was going to be doing,” says Dr. Wiggs. “The passion I felt that day walking out of that lecture has carried through my whole career. It is still the driving force behind the work I’m currently doing.”
Incoming freshmen, recent grads, or anyone still searching for a career path, remember: Dr. Wiggs didn’t devote her career to the lac operon. She used an excitement about genes generally to guide her way.
“I don’t know that it’s really possible or absolutely necessary to always so clearly define a passion,” she says. “What actually might be an equally productive path is to find general areas where you’re intrigued, where there’s interest, and keep following those paths, and it might lead to passion.”
If intrigue and educated hunches lead you to a research career, develop a thick skin and incredible tenacity. “There are times you’ll be tempted to give up,” Dr. Wiggs says. “My first NIH grant got triaged. I had to rewrite it. During times like that, you think it’s too impossible. I would encourage people, young people in particular, to not let small setbacks hold you back. Learn from them, and just keep moving on.”
By Heather R. Johnson
Posted on May 6, 2019 - 8:00am