Brigid L.M. Hogan, PhD

An Unfinished Story

 

Brigid Hogan, PhD, was born into war, survived a blistering academic career at a time when young women were rarely seen and definitely not heard, and was given one of the timeliest breaks of her career over a chance lunch conversation at the Cold Spring Harbor Laboratory in 1982.

“I’ve been really lucky in many different areas of my life,” says Hogan, who grew up in the small village of Denham, 40 miles outside of London. “I can’t think of anything I would want to do more than to be a scientist studying how embryos develop, and how stem cells drive tissue regeneration. It has been an amazing life.”

Hogan’s distinguished career has been marked by equal measures of good fortune and fortitude, both of which have led to her recognition by the Federation of American Societies of Experimental Biology (FASEB) with its 2020 Excellence in Science Lifetime Achievement Award.

A global leader in developmental biology and stem cell research, Hogan recently closed her lab and stepped down as the Chair of the Department of Cell Biology at the Duke University Medical Center. She continues at Duke as professor of Cell Biology. Hogan served as president of both the Society for Developmental Biology (2000-2001) and the American Society for Cell Biology (2008-2009).

“You have to be tenacious to keep going when the times aren’t so good in science,” counsels Hogan, who received the 2015 Society for Developmental Biology (SDB) Lifetime Achievement Award. “There are many competitions and rivalries, which mean you have to be in the right place and be prepared for your moment when it comes.”

Pushing Forward—Always

With her childhood of carefree bicycle rides and Girl Guide adventures, Hogan might have been an unlikely candidate to study at the University of Cambridge and the Massachusetts Institute of Technology (MIT), or to later divide her long career between prestigious assignments in the United States and the United Kingdom. How did she manage the journey? Persistence and luck.

“I went to High Wycombe High School for Girls, and the two older women who usually taught science had retired. Instead, they hired a young man as a teacher, Mr. Jones,” she recalls. “He had just graduated from university, and was excited about DNA, genetics and cell biology. He swept aside the old curriculum, and introduced lively experimentation. We would get dog testes from the vet and look for chromosomes.”

Hogan says that as a girl she was infatuated with what she calls “monsters:” abnormal, atypical, or mutant things in the world. An uncle who was a pathologist took her to the hospital museum where they had large jars of formaldehyde preserving abnormal fetuses, human body parts, and other specimens.

“My nose was glued to the glass of the cabinet,” she says, adding that she preserved a rat at home. “I was seen as a bit strange for wanting to read science books and always asking questions. I know I was tolerated. Girls are supposed to hold back while the boys push ahead. I was always pushing ahead.”

She won a scholarship to Cambridge, where she received her BA (MA) and PhD in biochemistry. Hogan says even at this early stage of her career she wanted to work with embryos, observing that she was drawn to the “origami” of them, and later fascinated by how small buds are transformed into organs with branched shapes and complex tissue patterns.

But it was at Cambridge where Hogan first encountered science’s pervasive sexism. With few female professors, and an unfettered chauvinism, she and other female students faced everything from disparaging remarks to physical harassment. “There was a lot of misogyny,” she says. Today, she counsels female students to stay the course and fight back by reporting unethical or illegal behavior.

Excavating a Scientific Passion

After her postdoc work at MIT and time spent as a lecturer at Sussex University, Hogan shifted to London to work at a branch of the then Imperial Cancer Research Fund with John Cairns as director. He was a welcome mentor who encouraged her to take the time to find her passion. She explored everything from mouse embryonal carcinoma cells to isolating pre-implantation embryos.

Along the way, she met Anne McLaren at University College, London. A true pioneer, McLaren encouraged Hogan by offering support, advice, and technical know-how. During this period, Hogan was also introduced to a group of scientists who would prove to be lifelong friends. This dream team of mammalian developmental biologists included Janet Rossant, Elizabeth Robertson, Gail Martin, Ginny Papaioannou and the late Rosa Beddington.

“We were pushing the frontiers,” says Hogan, who was painstakingly learning how to manipulate mouse embryos at the time. “A lot of people were doing what we were doing, but somehow we were more powerful because we were working together, everybody sharing, and under Anne’s leadership seeing our work in the greater context of society.”

Hogan was also getting closer to her future. An important turn would come while attending a meeting at the Cold Spring Harbor Laboratory. The noted biologist and the institution’s then director, James Watson, sat down next to her at lunch one day, and he asked, “What’s new?” She told him about her idea to write a manual with detailed protocols for manipulating the mouse embryo and to teach a course about it.

Watson got up from the table and left without a word. As she was walking back to her room, he ran up to her. Watson, who had been trying to recruit mouse developmental biologists Frank Costantini and Elizabeth Lacy to his campus, announced that Hogan, Costantini, and Lacy would run the first Cold Spring Harbor Mouse Course the following summer.

“I was completely surprised and gratified,” says Hogan, adding that the course has been held every summer for the last 35 years. “That’s why I always tell my students to have their elevator speech ready. You don’t know what will happen next.”

The three researchers and Rosa Beddington also published Manipulating the Mouse Embryo: A Laboratory Manual in 1986. It has since become the Bible for the field.

Making Critical Contributions

Hogan’s love of “monsters” resurfaced during her 14 years at Vanderbilt University. Her lab was interested in different organs and their development, and scientists were creating knockout homozygous mutant mice, always uncertain of what phenotype would result from their work.

“We were there on the cusp of discovery,” recalls Hogan, who served as the Hortense B. Ingram Chair of Molecular Oncology and co- director of Vanderbilt’s Stem Cell and Organogenesis Program. “We would make a null mutant of a gene and sometimes we would get a defect. It was an extremely exciting time because we weren’t sure what the outcome would be.”

Her lab focused on the molecular, cellular, and genetic basis of organogenesis, the progression by which organs like the lung, eye, kidney, and axial skeleton develop from small embryonic rudiments of undifferentiated cells. Hogan, who was also an investigator with the Howard Hughes Medical Institute, conducted research on the role of Bone morphogenetic proteins (BMPs) in organ development, and how BMPs could promote the development and repair of various tissues and organs.

Her tenure at Vanderbilt also gave her a chance to enrich her personal life, which had pretty much been in service to her science up to that point. As prized as her freedom was, and the flexibility it afforded, Hogan says she found a life partner in her late husband Peter Cartwright, a respected Ob/Gyn physician at Vanderbilt Medical Center.

In 2002, Hogan transitioned from Vanderbilt to Duke University. At Duke, Hogan’s lab created mouse lines in which genes could be manipulated in specific cells to study lung development and repair from stem cells. The research holds promise for addressing asthma, pulmonary fibrosis, and Chronic Obstructive Pulmonary Disease, among other respiratory disorders.

Separate from her scientific achievements, Hogan considers her biggest contribution to her field to be her mentoring of more than 40 postdoctoral scholars and eight graduate students. She has been a persistent champion in advancing the careers of young researchers in developmental biology.

Today, facing another crossroads after closing her lab, Hogan is looking to continue her work as a mentor and to advancing her field. “I’ve been wondering what to do next,” she says. “I’m asking how can I be most useful? I know my story isn’t over yet.”