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In his study of the C. elegans roundworm, Nobel laureate Craig
Mello has shown how genetic information is remembered and used to inform
future generations. “There are a lot of additional secrets this
germline holds for us,” he said.
you’ve ever felt lower than a worm, stop that. And if you’ve ever felt
superior to a worm, you can stop that, too, on the authority of Nobel
Prize-winning biologist Craig Mello, who knows a lot more about worms
than most of us do.
“All living things are masters of information assimilation and
integration,” he said during a two-day visit to the University of
Delaware in April. “We think there is such a thing as ‘higher
organisms’ — and we’re them. But every organism is equally high. All
have sophisticated systems.”
Mello’s favorite worm is the C. elegans nematode, which
revealed the genetic tool now called “RNA interference” to him and his
collaborator Andrew Fire in 1998. They won the 2006 Nobel Prize in
Physiology or Medicine for that discovery, which Mello said C. elegans
deserves just as much. One of his slides is a thank-you note to C. elegans and includes a list of other prizes it has produced.
Now, 14 labs in the RNA Therapeutics Institute
that Mello directs are focused on this transparent worm, which is about
1 millimeter long, has no eyes and eats bacteria — one at a time. And
it is having an impact on medicine. The U.S. Food and Drug
Administration last year made its first approval of a new therapy based
on RNA interference for treatment of patients with a rare, hereditary
peripheral nerve disease. (More on RNA interference later.)
Move this whole section up, swapping places with the section above it.
After talking with biologist and Nobel laureate Craig Mello about
genetics and research, students pose
with him on the steps of Hullihen Hall.
After decades of scientific inquiry, the distinguished professor in
the University of Massachusetts Medical School’s Program in Molecular
Medicine and investigator with the Howard Hughes Medical Institute has
conserved something well worth passing along to others, no matter what
the focus of their study: A deep and joyous wonder at the marvels of
“When you study the world it makes the world more mysterious, not
less,” he said. “We’re marveling at the mystery of a world we can’t
understand…. Science does not reduce, rather it always deepens the
mystery of existence.”
Mello’s two-day visit became a celebration of the University’s
vibrant life-science enterprise, and his keynote speech at the inaugural
Delaware Life Science Forum helped to extend the connections between UD
researchers, clinicians and industry scientists.
He met with a dozen graduate students to discuss his research and
theirs. After he told them about the efficiency of research with this
worm and the effectiveness of the genetic injections made to study the
germline, one student had an idea. “Could you come and bless our injections?” he asked.
Mello laughed and invited several of them to visit his lab in
Worcester, Massachusetts, where they could see the work and perfect
techniques they sometimes struggle with. He even offered to stop by
their labs and see their injection setup.
During his visit to UD, Nobel laureate Craig Mello met with
students, sharing his joy of discovery and inviting some of them to his
lab in Massachusetts to observe the work there.
“Students seemed to be both surprised and excited that a scientist of
such high caliber would offer his time to help advance their science,”
said Ramona Neunuebel, assistant professor of biological sciences at UD.
“An important takeaway message from the students’ interaction with
Mello is that research is most successful when we collaborate and share
After speaking with those students, he delivered the Department of Biological Sciences’ annual Arnold M. Clark Memorial Lecture to more than 200 people at Wolf Hall.
And later, he was reunited with UD’s Pew Scholars in the Biomedical
Sciences, whom he knows from his work as chair of the national advisory
committee that selects the winners of those prestigious awards. UD’s Pew
Scholars include Salil Lachke (biological sciences, 2012), April Kloxin (chemical and biomolecular engineering, and material science and engineering, 2013) and Catherine Grimes (chemistry and biochemistry, 2014).
It is remarkable, Mello said, that UD has three Pew Scholars and it should be commended for recruiting such excellent faculty.
“I’ve been really impressed by what’s happening at the University of
Delaware … and it’s great to have an opportunity to come and see the
great things happening,” he said. “It’s an exciting time for biomedical
The 1998 discovery that led to the Nobel Prize for Mello and Fire showed that C. elegans
worms use a previously unknown process called RNA interference, which
draws on the organism’s genetic memory to exert powerful control over
cellular life by silencing certain genetic functions.
The C. elegans worms are rock stars in the world of genetic
biology, where their brief life cycle (two or three weeks) gives
researchers a turbo-charged way to see how specific genetic machinery
works and insight into what is called the “germline,” the genetic
information that is inherited by the next generation.
Mello said C. elegans and humans share ancestry that stretches billions of years, so what the worm teaches us gives us insight into our own species.
“It’s humbling and fascinating and complex to see what our ancestors are able to do,” he said.
Mello said his zeal for science started when he was in high
school and learned that bacteria could make human insulin. He saw that
as a powerful mechanism and his gratitude for that discovery knows no
bounds now that he has a daughter with Type 1 diabetes, whose life
depends on insulin.
His work has focused on these genetic mechanisms and he continues to
marvel over the constant flow of information between organisms and the
constant modifications they make along the way to survive.
“It’s more convenient for viruses and all of life to have a common
code,” he said. “If you can’t read the other guy’s mail, you’ll be out
of luck. So the winners biologically are those that can read the other
He compares the underlying process of RNA interference to Google’s
search engine, which searches for data across the internet, tolerating
misspelled requests and delivering a trove of matches. So-called “Guide
RNA” allows for those searches at the genetic level, looking for coding
sequences that have been encountered before, recognizing some as
familiar, some as unfamiliar and — when necessary — silencing genetic
response for strategic reasons.
At one point in this research, Mello said, the lab was doing
transgene experiments — introducing pieces of genetic information into
the genome of the worm by microinjection — to understand what was
responsible for silencing genetic responses. A string of experiments
showed no cellular activity after certain injections. Over and over —
nothing. They discarded what they guessed were errors or duds. Then one
student looked at the results another way and realized that what seemed
to be negative results were really evidence of silenced genes.
“Some of the best stuff in your lab is probably in your trash can,”
Mello said with a grin. “There are a lot of additional secrets this
germline holds for us. We should all go back to our trash cans and hunt
That’s an important point for researchers, Neunuebel said.
“For graduate students it was worthwhile hearing that as researchers
we have to embrace many potential explanations for a scientific
phenomenon,” she said. “Otherwise, we may miss meaningful clues.”
While the potential for new genetic therapies is exciting for
medicine, Mello said he agrees with the scientific community around the
world that we are not ready to edit the human genome. Serious ethical
questions must be addressed, he said, as illustrated in the recent
scandalous work done by a Chinese scientist.
“There is still a lot of potential danger,” he said. “It is so easy
to do and we need tighter controls. The scientific community is well
aware of this issue. CRISPR [the gene editing technology] is a very good
thing, but like anything it could be misused.”
The inaugural Delaware Life Science Forum drew scores of research
scientists and entrepreneurs from UD, Delaware State University and
industry to the Audion at UD’s Science, Technology and Advanced Research
Campus to discuss their work and possible collaborations.
Presentations covered a wide range of study, including UD’s Velia
Fowler, chair of biological sciences; Terry Papoutsakis, professor of
chemical and biomolecular engineering; and Catherine Grimes, assistant
professor of chemistry and biochemistry. Presenting scientists from
industry included Nihmat Morjana, director of Siemens Healthineers; Adam
Marsh, chief science officer and co-founder of Genome Profiling; and
Tanja Gruber, senior staff scientist with the DuPont’s Industrial
Participants also got a lot of information about UD’s core
facilities and the top-tier instruments, equipment and skilled
technicians available to researchers.
“It’s great to see the opportunities you have here,” Mello said,
“maybe even to build out a medical school and increase the clinical
side. Genetics make medicine more of a hard science.”
It was exciting for the assembled scientists to hear of advances in every area.
“At the end of the day these are the people who are building our
longevity,” said Joy Goswami, who has a background in molecular biology
and is the assistant director of technology transfer at the Office of Economic Innovation and Partnerships, helping UD’s innovators get their ideas to market.
And it is important to develop opportunities for these experts to collide again.
“Delaware has so much talent,” said John Koh, director of the Delaware Biotechnology Institute,
which organized the Life Science Forum. “Science has driven so much of
Delaware’s economy for 200-plus years and we need to know how to engage
with each other in new ways to build an economy for the future.
“We have informatics invading every area and discipline and we need
to train scientists to be literate and recognize the power of these
technologies,” Koh said. “We need a much more nimble workforce and there
are a lot of common threads here — in public policy, regulatory issues,
biopharmaceutical manufacturing, diagnostics, biomolecular studies.
We’re recognizing that all those different areas can work together. It
requires more interdisciplinary teams and building the community. So we
want to facilitate these collisions between scientists of different
In addition to UD, other forum sponsors included: the Delaware
Prosperity Partnership, the Delaware Biotechnology Institute, Delle
Donne and Associates, Delaware Business Times and Delaware INBRE.
Mello is the Blais University Chair in Molecular Medicine and
co-founder of the RNA Therapeutics Institute at the University of
Massachusetts Medical School.
Before receiving the Nobel Prize, his work on RNAi was recognized
with the National Academy of Sciences Molecular Biology Award, the
Canadian Gairdner International Award, the Paul Ehrlich and Ludwig
Darmstaedter Prize and the Dr. Paul Janssen Award for Biomedical
He is a member of the National Academy of Sciences, the American
Academy of Arts and Sciences and the American Philosophical Society.
The Arnold M. Clark Memorial Lecture was established by Dr. Howard
Hudson, CAS’63, an anesthesiologist in Allentown, Pennsylvania, as a
tribute to his professor and undergraduate faculty adviser.
Clark was a professor of biology at UD from 1946 to 1981 and was instrumental in establishing the graduate program in biology.
His research areas included developmental genetics, aging, human
heredity and radiation biology. He studied Down syndrome and pushed for
the establishment of a genetic counseling program in Delaware.
Clark’s passion was teaching and mentoring, and he insisted that his
undergraduate students take as many non-science courses as possible in
order to become well rounded and better able to communicate with the
Article by Beth Miller; photos by Evan Krape and Suchat Pederson