Mello, Craig Cameron

views updated Jun 08 2018

Craig Cameron Mello

American molecular biologist Craig C. Mello (born 1961) shared the 2006 Nobel Prize in Medicine with Andrew Fire for their discovery of RNAi. As a result of their co-research, the two men shared numerous other awards that underscored the impact, both immediate and potential, of their discovery.

In 2006 Craig Cameron Mello and Andrew Fire opened up new doors for gene technology and treatment of human diseases at the cellular level with their discovery of RNAi, also known as RNA interference or gene silencing. Mello was born on October 19, 1961, in New Haven, Connecticut. He is the son of James and Sally Mello and was the third child in a family of four children. His father was a paleontologist and his mother was a homemaker and artist.

Mello became interested in science through his father, who completed his doctorate in paleontology at Yale University in 1962. Upon receiving his doctorate, James Mello moved his family to Falls Church, Virginia, to take a position with the U.S. Geological Survey in Washington, D.C. A short time later the family moved to Fairfax, Virginia, when James Mello accepted the position of assistant director at the Smithsonian Museum of Natural History, also located in the nation's capital. Craig Mello would later recall that his fondest childhood memories involved family camping trips to the Blue Ridge Mountains in Virginia and to Colorado and Wyoming. During these vacations, he hiked and searched for fossils. He also fondly remembered family discussions around the campfire. Mello recalled that his family had a strong tradition of discussions, especially around the dinner table. The experience was extremely important to him, both emotionally and intellectually. The Nobelprize.org Web site quoted from Mello's autobiography: “I learned to argue, to listen, and to admit (sometimes grudgingly) when I was wrong about something,” he remembered. “These were often lively discussions, and my parents did a great job of allowing each of us to be heard. At a time when I was not performing so well in school, these daily discussions helped to build my confidence and self esteem.”

A Late Bloomer

Despite his obvious inquisitiveness and evident intelligence, Mello struggled through grade school. By his own account, he did not start to blossom as a student until he reached his middle school years. However, during his early education he possessed a certainty that he would grow up to become a scientist. That idea began to take firm root when he entered the seventh grade and was first exposed to a formal science education. For the first time in his life, he began to truly apply himself to his studies. In his spare time he enjoyed reading science fiction and he became an amateur astronomer.

A precocious adolescent, he already possessed an intuitive grasp of humanity's position within the earth's natural history, and he was mystified—even disappointed—by his elders' short-sighted views on science and the human condition. “I was amazed that so few adults (including my teachers) understood basic concepts such as deep (geologic) time, the vastness of the universe, and the common evolutionary origins of life,” he recounted, according to Nobelprize.org.

Further, while he was raised as a Roman Catholic, Mello rejected ideological elements of religion. Even at an early age, he found it hard to accept concepts such as the inerrancy of the Bible and of intelligent design (especially as it was presented to him as a counterargument to evolution). Because he had been exposed to the world's rich pageant of natural history through his father's workplace (the Smithsonian Institution), he found it impossible to unconditionally embrace religious dogma. “The ‘absolute knowledge’ offered was, in my view, inadequate to explain the world around me,” he recalled in the autobiography he penned when he received the Nobel Prize, on Nobelprize.org.

At the same time, he had no problem reconciling science with spirituality. “I believe that there is no more spiritual and worthwhile undertaking than that of trying to understand the world around us, and our place in it,” he stated in his Nobel autobiography.

When he entered Fairfax High School, he took all of the science courses the school offered, except for advanced physics. In 1978, when he was 18 years old, he became particularly interested in molecular biology after reading an article in the Washington Post that described the cloning of the human insulin gene in bacteria. The article explained how the bacterial cells read the human genetic code and produced functional human insulin. Mello was intrigued that bacterial cells could speak the same genetic language as human cells to produce a human protein useful for diabetic patients. Mello began to grasp the potential for treating disease at the genetic level and for molecular treatments such as gene therapy. After Mello earned a bachelor of science degree in biochemistry at Brown University in 1982, he did post-graduate work at the University of Colorado from 1982 to 1984, studying molecular, cellular, and developmental biology.

Earned Doctorate at Harvard

While in Colorado, he worked in the laboratory of Dr. David Hirsh, where he was introduced to C. elegans. As Mello recalled, at that time no one had yet succeeded in introducing DNA (deoxyribonucleic acid), into C. elegans, a method called DNA transformation. Also, researchers working with yeast had identified functional DNA elements that direct the replication and partitioning of chromosomes. Collaborating with Dan Stinchcomb, Mello took on a project to identify such elements from the worm. Project goals included understanding these essential functional chromosomal elements and then using them to produce stable artificial chromosomes for worm molecular genetics.

When Hirsh later accepted a position in industry, Mello transferred to Harvard University, where he continued his work with Stinchcomb, who was establishing an independent laboratory. Mello earned his Ph.D. in cellular and developmental biology from Harvard University in 1990.

After earning his doctorate, Mello became a postdoctoral fellow at the Fred Hutchinson Cancer Research Center in Seattle, Washington. He joined the laboratory of Jim Priess, a scientist. Mello learned about genetics, which would later help advance his work on RNAi. While working with Priess, Mello identified genes that act as regulators of the early development of C. elegans.

In 1992 Mello married Margaret Hunter. The couple had one child, Melissa. The couple separated and divorced, amicably, in 1994. When he remarried in August of 1998, to Edit Kiss, he became the stepfather of David and Sarah Apotheker. In 2000 the couple's daughter, Victoria, was born.

Began Research with Andrew Fire

In 1995 Mello joined the University of Massachusetts Medical School as a professor of molecular medicine and as a researcher. Throughout the late 1990s he worked on a project, through e-mail and the Internet, with Andrew Fire, who was employed at the Carnegie Institution of Technology in Baltimore, Maryland. In his autobiography, found on Nobelprize.org, he wrote, “We were both working on developing techniques for DNA transformation in worms,” recalled Mello. “Andy had some early success and developed a number of clever methods. I followed up with some improvements. And together we made DNA transformation a routine procedure for the worm. We developed the mutual trust and respect that ultimately led to our collaboration on RNAi.”

Working together, they discovered that RNA (ribonucleic acid) could do a great deal more than realized. Up until then, it had been thought that RNA only carried out the genetic instructions given by DNA. Working with small worms (nematodes), Mello and Fire discovered that doublestranded RNA (dsRNA) could be directed to turn off specific genes. This action was called RNA interference or RNAi. More specifically, in the technique, dsRNA triggers sequence-specific silencing of (or interfering with) gene expression, essentially tricking the cell into killing messenger RNA before it can produce a protein. In this way, the RNAi mechanism can destroy gene products that a virus needs in order to replicate itself. Essentially, it can stop the progression of invading viral infection.

Within a few years, it had been demonstrated that the RNAi process could work in mammalian cells and that the process could be reversible. Soon, scientists began deploying the process in laboratories throughout the world, trying to develop ways that it could be used in humans to combat genetic disease.

Shared Nobel Prize

Mello and Fire published a paper about their work with RNAi on February 19, 1998, in the scientific journal Nature. In 2006 they shared the Nobel Prize for Medicine for their discovery. Mello was only 47 years old when he received the prestigious international award.

The publication in Nature was followed by accolades. In 2002 Mello and Fire's work had been named the “Breakthrough of the Year” by Science magazine. In 2003 Mello and Fire won the Wiley Foundation Prize in the Biomedical Sciences from Rockefeller University, the National Academy of Sciences Award in Molecular Biology, and the fourth Annual Aventis Innovative Investigator Award at the Drug Discovery Technology World Conference. In 2004 the pair received the Warren Triennial Prize, the highest research honor bestowed by Massachusetts General Hospital. At the time, it was commented that the collaborators had opened up an entirely new area of biology. RNAi is now widely and routinely used in research and is expected to lead to medical breakthroughs in the fight against cancer and other diseases.

In awarding the Nobel Prize to the two men, the Nobel committee pointed out, according to Nobelprize.org, that RNAi had opened up exciting possibilities for use in gene technology, stating that the method “has already become an important research tool in biology and biomedicine. In the future, it is hoped that it will be used in many disciplines including clinical medicine and agriculture …. Plans are underway to develop silencing RNA as a treatment for virus infections, cardiovascular diseases, cancer, endocrine disorders and several other conditions.”

The year before the two men received the Nobel Prize, Mello and Fire were named to the National Academy of Sciences. In addition, they received several additional honors, including Brandeis University's Lewis S. Rosenstiel Award for Distinguished Work in Medical Research, the Canadian government's Gairdner International Award, and the Massry Prize.

In 2006 Mello and Fire traveled to Germany to accept the Paul Ehrlich and Ludwig Darmstaedter Prize, which is one of the highest and most internationally renowned awards conferred by the Federal Republic of Germany in the field of medicine. That same year, Mello became the first-ever recipient of the Dr. Paul Janssen Award for Biomedical Research, which was established by Johnson & Johnson in 2004.

Eventually, the University of Massachusetts Medical School and the Carnegie Institution of Technology were issued a patent, “Genetic Inhibition by Double-Stranded RNA,” (US Patent 6,506,559 B1). It is anticipated that the patent will have tremendous licensing potential both in the laboratory and for drug development. To their credit, both institutions were enthusiastic about making RNAi as widely available as possible, to help accelerate genetic research. As such, they developed a licensing policy that enables companies to easily obtain, for a basic fee, a broad and nonexclusive license for research scientists to use the technology. As a result, many companies have licensed the invention and many others continue to express interest.

In assessing recent research as well as his own accomplishments, Mello, who became the Blais University Chair in Molecular Medicine at the University of Massachusetts Medical School and was designated an Investigator of the Howard Hughes Medical Institute in 2000, said that with RNAi and the completion of the genome sequences for humans and numerous other organisms, “we now have unprecedented opportunities to develop new, life saving therapies and to advance the basic understanding of our biology,” according to Nobelprize.org.

He added that he feels mankind has a potentially bright future, but also faces significant challenges that need to be addressed and overcome. “The biological mechanisms at work inside our cells are truly ancient and remarkably stable, more stable even than the positions of continents and oceans on the face of the Earth. However, in my view, our thriving global economy has engendered serious problems. Climate change and other forces beyond our control could easily disrupt our economies causing widespread human suffering at unprecedented levels,” he said.