Pathologist’s discovery of ‘gifted’ particles continues to increase understanding of the human body

June 04, 2012

By David Martin

A new society recognized a discovery H. Clarke Anderson, M.D., made in the the late 1960s.

H. Clarke Anderson, M.D., was teaching at the State University of New York in Brooklyn in the late 1960s when he made an important finding. Using an electron microscope, he discovered matrix vesicles, tiny spheres that help form cartilage, bone and teeth, a process known as biomineralization.

The discovery continues to resonate. A recent review of the role of matrix vesicles in biomineralization references 164 sources. The first footnote cites a paper that Anderson published in The Journal of Cell Biology in 1967.

Anderson became professor and chair of the department of pathology at the University of Kansas Medical Center in 1978. He continued to study matrix vesicles, eventually characterizing their biochemical and structural components.

Physiology was not the only specialty to benefit from his research. Evidence began to suggest that matrix vesicles are also key mediators of disease. Just as they help healthy skeletons mineralize, matrix vesicles initiate the abnormal calcification associated with osteoarthritis, coronary artery disease and other conditions.

"As time went along, the importance of the discovery became more and more obvious," says Anderson, now professor emeritus.

Once thought to be cellular debris, matrix vesicles are capable of transporting the biochemical cargo of their host cells. They have been compared to hormones in the way that they are able to pursue metabolic objectives away from their source. Rama Garimella, Ph.D., a research assistant professor of dietetics and nutrition who has worked with Anderson, says matrix vesicles are "gifted."

"Now we know they are much more than degenerative cellular debris," Garimella says. "They have the necessary enzymes for initiating physiological mineralization. They are biochemically very active."

Matrix vesicles' ability to carry out the objectives of cells from which they originate makes them relevant in the field of cancer biology. Garimella says vesicles are helping researchers understand tumor progression and metastasis; they also have the potential to identify biomarkers of disease and therapy. Garimella is currently investigating the role of vesicles in osteosarcoma, a malignant bone tumor that predominantly affects children and adolescents.

Garimella says Anderson made a vital contribution to the understanding of what makes us healthy and what makes us sick. "Now the entire world knows that these vesicles are nano-sized entities which have an important role in physiological as well as in pathological states," she says.

Anderson was studying ways to induce new bone formation when he made his initial discovery. One of the interesting aspects of his eureka moment is that he did not arrive at it alone.

Working independently, an Italian scientist named Ermanno Bonucci was also using an electron microscope to understand how bones formed. He too described what came to be known as matrix vesicles in an article published in 1967, the same year Anderson's paper appeared in The Journal of Cell Biology.

When Anderson and Bonucci later met at an electron microscopy conference, they felt like rivals. "It was a little chilly," Anderson remembers of their first meeting. "Each of us thought we were the discoverer. In truth, we came upon it at virtually the same time."

The scientists decided to share credit.

Matrix vesicles continue to intrigue investigators. They are the basis for an approved vaccine for viral meningitis and have been used in clinical trials against colorectal cancers. The presence of matrix vesicles in serum, urine and ascites suggests uses as a diagnostic tool.

"It's funny how you can discover something over 30 years ago and have it become very important," says the current chair of the department of pathology and laboratory medicine, Lowell Tilzer, M.D., Ph.D., a former student of Anderson's. "[It can] be unrecognized for years and then suddenly, as more people take up the work, it expands and has meaning for us for decades to come."

Anderson's influence can also be seen in the establishment of a new scientific association.

The International Society of Extracellular Vesicles held its first meeting in Sweden in April. Though matrix vesicles are one of many types of extracellular vesicles, conference organizers took time at their meeting in Gothenburg to recognize Anderson's contribution. A version of the video below was shown at the conference.

Last modified: Nov 03, 2013