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10/04/06

Andrew Fire shares Nobel Prize for discovering how double-stranded RNA can switch off genes

 
Video length: 27 minutes
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By KRISTA CONGER

Andrew Fire took his first look around at Stanford and started screaming. His response wasn't unusual—for a newborn, that is. The molecular biologist was born at Stanford Hospital, attended public schools in Sunnyvale and graduated from the University of California-Berkeley, after being turned down by his only other college choice: Stanford.

All pretty normal, he hastens to point out—not mentioning that he completed high school at age 15 and college at age 19. But as of 2:30 a.m. Monday, the quiet Stanford medical school professor with the self-deprecating air will have to work a little harder to convince the world that he's nothing special. He won this year's Nobel Prize in Physiology or Medicine, and it will be a long time before he sees "normal" again.

Linda Cicero
Andrew Fire, PhD
Andrew Fire

Fire shares the prize with Craig Mello of the University of Massachusetts Medical School. The announcement from the Nobel Assembly at Karolinska Institutet came a mere eight years after they published their breakthrough discovery of RNA interference. The relatively rapid recognition is unusual in the rarified Nobel world, which often rewards researchers decades after their initial findings.

"I was very surprised," said Fire, professor of pathology and of genetics, of the early morning phone call from the committee. "At first I thought that maybe they had a wrong number, or that I was dreaming. But I guess it's real." Such prompt accolades are one indication of how their finding has turned the field of molecular biology on its head—and how it hasn't yet stopped spinning.

"This is an extraordinary achievement for Andy Fire and Craig Mello, for science and for Stanford," said Philip Pizzo, MD, dean of the School of Medicine. "It affirms the importance of basic fundamental research, which often yields new insights into human biology. Their discovery is already unfolding in new directions that may translate into discoveries of new diagnostic and therapeutic approaches for a variety of human disorders."

Fire, PhD, 47, and Mello, PhD, 45, are part of a team of researchers credited with recognizing that certain RNA molecules can be used to turn off specific genes in animal cells. The discovery, made while Fire was at the Carnegie Institution's Department of Embryology in Baltimore, marked the first time that biologists were able to selectively "silence" the voice of one gene in the cacophony of the tens of thousands that give a cell its marching orders from development to death. Their description of the process, called RNA interference or RNAi, in Nature in 1998, jumpstarted a new biological field by opening up previously inaccessible areas of research.

"It was clear from the first week that I met Andy that he was destined to do something great," said a longtime friend and Carnegie Institution colleague David Schwartz, PhD, professor of genetics and of chemistry at the University of Wisconsin-Madison. "He was just such a natural about it. There are people who are excellent at sports, you just put a baseball bat in their hands and the ball flies. Andy is like that with science; without a fuss, it just happens."

Before the discovery, the only method of removing a gene's influence from a population of cells involved a laborious and time-consuming series of experiments with no guarantee of success. It was virtually impossible to "knock-out" even a small fraction of genetic suspects in a particular pathway. Now researchers around the world are using RNAi techniques to quickly and randomly silence one gene at a time in swaths of cells. By plucking out those that act abnormally with regard to the pathway in question, they are able to identify even previously unknown genes involved in the pathway.

Linda Cicero
Andrew Fire, PhD
Andrew Fire (right), with Stanford President John Hennessy, became the third member of the medical school faculty to win a Nobel Prize.

The technique has also shown remarkable clinical promise. RNAi-based treatments are being tested in many animal models of disease—high cholesterol, HIV, cancer and hepatitis, among others—and clinical trials have been launched in humans with specific types of macular degeneration and pneumonia. The potential applications of the research are vast.

Despite some intriguing hints that RNA was more than just an assembly manual for proteins, much of this process remained a mystery until Fire and Mello published their findings in the nematode C. elegans, a tiny worm about the width of a No. 2 pencil lead. But Fire emphasizes that much of the preliminary legwork had already been done by other plant and animal researchers.

"We came into a field where a lot was already known," said Fire. "It was a complex jigsaw puzzle, and we were able to contribute one piece. Fortunately for us it was a very nice piece, but it would be really disingenuous to say we did the whole puzzle."

Such demurring is standard for Fire; colleagues often describe him as remarkably modest. Monday, Fire lived up to that reputation. After reluctantly agreeing to participate in numerous media interviews and press conferences, he made sure to credit "insightful and dedicated colleagues and students" with whom he has worked and "whose ideas and efforts are very much the subject of the prize." And he noted that scientists have a responsibility to society at large. "All of us in science look forward to sharing with the public both the responsibilities and opportunities that arise as we understand more about the human body," he said.

Fire added, "For me personally, the occasion of such an award is an opportunity to thank the many patient teachers and mentors who have opened doors to science and research, and especially my family, who have made everything possible.

"This day is a wonderful chance to acknowledge that science is a group effort," Fire continued. "The advances cited in the Nobel award grew from original scientific inquiry from numerous research groups throughout the world." He also thanked the National Institute of General Medical Sciences for providing the grants that made the research possible and continues to support both scientists.

Others were just a little more effervescent. "My wife and I have known him for 20 years, and we were jumping and hooting and hollering when we found out," said Schwartz, who is also the director of the Genomic Sciences Training Program at Madison's Laboratory for Molecular and Computational Genomics. "I spoke to him a couple of weeks ago and told him he was going to win the prize. With his typical understated personality, he said 'Let's talk about something else.'" In fact, Fire is so unassuming that he first suspected his early morning phone call was a prank by his old friend.

Fire will officially receive the award on Dec. 10 in Stockholm, and he and Mello will share the $1.4 million prize. He is the medical school's third Nobel laureate, joining emeritus professors Paul Berg, PhD, and Arthur Kornberg, MD.

"Professor Fire's contributions to his field have been of enormous importance and the recognition by the Nobel committee is a remarkable achievement at this early point in his career," said President John Hennessy. "The RNA research of professors Fire and Mello represents the very best of the collaborative nature of university scholarship. The fact that this basic discovery is already impacting the development of new therapies is a wonderful reminder of the importance of fundamental research."

As any graduate student can attest, fundamental research often means long hours of tedium. Although Fire is careful to credit others, he's no stranger to such drudgery. "I'd be working in the middle of the night," recalled Schwartz, "and Andy would be hunched over his microscope next door, feeding his worms. They had a mutation that made them so uncoordinated that he had to push food their way with a tiny brush." But the work paid off. "This is just gorgeous work that stands a chance to really change medicine, as well as being a remarkable tool for biology," said Schwartz. "Anyone who knows him will not be surprised that he won."

After Fire received his PhD from MIT, he was accepted as a Helen Hay Whitney Postdoctoral Fellow in Cambridge, England, in a laboratory headed by Nobel laureate Sydney Brenner, PhD. He conducted his initial work on gene silencing by double-stranded RNA between 1986 and 2003 while at the Carnegie Institution. He was an adjunct professor in the Department of Biology at Johns Hopkins University starting in 1989 and joined the Stanford faculty in 2003. Throughout his career, all of the major work in Fire's lab has been supported by research grants from the US National Institutes of Health.

Fire is a member of the National Academy of Sciences and of the American Academy of Arts & Sciences. He serves on the Board of Scientific Counselors and the NIH's National Center for Biotechnology. He has received and shared numerous awards, including the Maryland Distinguished Young Scientist Award, Meyenburg Prize, Genetics Society of America Medal, National Academy of Sciences Award in Molecular Biology, Passano Family Foundation Award, Wiley Prize, H.P. Heineken Prize in Biochemistry and Biophysics, Warren Triennial Prize, Rosenstiel Award, Gairdner Award, Massry Prize and Ehrlich/Darmstaedter Prize.

None of this has gone to Fire's head—and the Nobel Prize doesn't appear to be either. "I like what I do," he said when asked how the Nobel might affect his life. "I like teaching, I like research and I like talking to colleagues. This brings another dimension: an opportunity to have a voice beyond my own lab and field. That's a big responsibility, and I look forward to using that voice as needed. At the same time, I still want to do interesting and unusual experiments, while also making sure I don't get too much credit."

Now that's normal—at least for Fire.

Share your thoughts on Andy Fire and his discoveries related to RNA interference

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Reader Comments (64 comments accepted)

 the comments of Davy in Nottingham, UK, October 2, 2006 03:32 PM

Congratulations on the elegans work in RNA research

 the comments of pete/NYC, October 2, 2006 03:34 PM

Share credit where credit is due: Go Bears!

A fellow Cal Math graduate.

 the comments of Andy Spencer, San Francisco, October 2, 2006 05:03 PM

Reading the Fire/Mello RNAi paper in 1998 was one of the exciting reasons pushing me toward working in C. elegans as a postdoc.

Congratulations to Dr. Fire, who has been a great contributor to the scientific community for a long time.

Cheers,

Andy Spencer

 the comments of Joan, October 2, 2006 05:09 PM

It is an amazing gift to humanity that Dr. Fire has found a way to interfere with viruses that attack and sicken people. I will eagerly follow the progress he and his team of researchers make. I would even volunteer to be in his human trial groups if there was a need. Thank you Dr. Fire and Stanford Medical Center. Congratulations on your well-deserved award.

 the comments of mosleh, October 2, 2006 05:57 PM

am really happy that this discovery was awarded because of its valuable importance and applications. RNAi is supposed to be as a short way to achieve many faraway dream on behalf of humanity. congratulations

 the comments of denise, October 2, 2006 06:12 PM

Terrific, congrats, could not have come to a more deserving person.

 the comments of Joao Guilherme M. Giraudo, October 2, 2006 06:19 PM

A huge thanks and an enormous congratulations for the Nobel Prize!

Regards

 the comments of Jikyu, Sacramento, October 2, 2006 08:52 PM

So this is the mechanism of controlling gene expression for eukaryotic cells much like how the inducible operons control gene expression for prokaryotic cells?

 the comments of Zaixin, China, October 2, 2006 09:36 PM

I am proud of Prof. Fire and Stanford as an alumni

 the comments of Rachel Iowa City, IA, October 2, 2006 09:43 PM

I think that this is a wonderful discovery and I hope that this is THE breakthrough for a myriad of diseases.

 the comments of Milenq Bulgaria, October 3, 2006 01:23 AM

You are the best!
Congratulations!!!

 the comments of zhang china, October 3, 2006 01:38 AM

very good!

 the comments of Ronald Antulov, October 3, 2006 02:14 AM

Congratulations! It is a discovery worth the Nobel prize.

 the comments of Robert Eibl, Bad Reichenhall, Germany, October 3, 2006 03:18 AM

As a former postdoc in Weissman lab, I expected a Nobel prize for medicine going to Stanford in the coming years. Of course, Andy Fire is a wonderful example that a real interest in life sciences and mathematics in younger years could be a good base for such a happy development. In addition, he demonstrates how valuable living in Stanford area can be. Congratulations!

 the comments of Youssef Farag, Mansoura, Egypt, October 3, 2006 07:29 AM

No one can imagine the great surprise that I was caught in when I knew that the authors of the Nature paper, which I was reading just two days ago, has been awarded the Nobel prize in physiology or medicine for 2006, specifically for that paper.

They have unmasked mechanisms that weren't scratched before & explained many ambiguous results. I now understand many vague concepts I faced during my biochemistry & immunology courses in my medical school. Their historical discovery will change the way of biomedical research leading to novel therapies that will change the lives of millions of patients with many diseases in the future.

I was about to email Dr. Fire & Dr. Mello some questions & inquiries regarding their work & the progress in the RNAi. Besides, I was planning to discuss with both of them to work in their labs after my graduation. But the image is now darker for me brighter not only for them but also for the humankind whom they spent their vacations working for. I don't think that they will have time til the Nobel Prize celebration ends to answer my questions or reply my request to work with them.

Dr. Fire and Dr. Mello, let me express my congratulations from the inmost of my heart for you, your research teams, & your families. I wish I could have a place in your lab soon after my graduation. I don't know why I consider myself a special person who knows those great scientists but I am happy that I believe I am.

Youssef
Final Year Medical Student
Mansoura Faculty of Medicine
Mansoura, Egypt.

 the comments of Ashwin, McMaster University, October 3, 2006 08:14 AM

Congratulations!!! You most certainly deserve this honour!

 the comments of Sudha ,India, October 3, 2006 09:37 AM

Hearty congratulations, Dr. Fire! As a former post-doc of Stanford med school, I am so proud and happy.

 the comments of Vivek Rai , Jawaharlal Nehru University, New Delhi, India, October 3, 2006 10:11 AM

Congratulations! Congratulations! It's great to see your exatraordinary work is being acknowledged with highest award i.e. for great international scientific research........Nobel Prize.

 the comments of Kartik Viswanathan, Stanford University, October 3, 2006 11:27 AM

Congratulations Dr. Fire. This institution is proud of you, and all of us graduate students hope to aspire to do great work as you have done. Congratulations from the cancer biology students.

 the comments of Barbara Elspas Palo Alto VA, October 3, 2006 12:30 PM

This is one giant leap for medicine and mankind. You put a smile on my face and hope in my heart.

 the comments of David, October 3, 2006 03:14 PM

Go Bears!

 the comments of Jennifer Sixt, October 3, 2006 03:36 PM

Congratulations Cal Math Alumnus!

 the comments of Cal Student, October 3, 2006 07:02 PM

Go Bears! this will no doubt benefit society, when will you come to teach at Berkeley?

 the comments of Ira Skolnik, October 3, 2006 07:12 PM

Andy - you and Rachel were our neighbors on Bright Leaf Way! We are so proud of you!!!
-Ira and Linda Skolnik

 the comments of Ram, India, October 3, 2006 08:51 PM

Great going Andy!

My heartiest congrats to you and Stanford. I am an alumnus of Stanford med school and was in L-308-A, Lane Building as a postdoc. Wonderful to know that my corridor-person received the Nobel!

Ram

 the comments of bushra pakistan, October 4, 2006 02:40 AM

Congratulations for the Nobel Prize!!!!!!

You really deserve that. I wish I could have a place in your lab as Ph.D as i'm going to apply for it this autumn.

Good luck
Regards

 the comments of Dongdong, October 4, 2006 04:04 AM

Congratulations!

 the comments of Saranyan Hyderabad, October 4, 2006 04:13 AM

Dear Dr.Fire,
For a lay person to the field of medicine, it is very nice to understand, and applaud, the depth of the research. Kudos to you sir and good luck with your future.

Regards,
Saranyan

 the comments of pritam, October 4, 2006 05:08 AM

Hearty congratulations!

 the comments of Yongyut, London, October 4, 2006 06:00 AM

Congratulations!!!
Your discoveries certainly benefit the society and will surely lead to saving many people's lives.

 the comments of azhagan, Mauritius, October 4, 2006 06:14 AM

Congratulations.

 the comments of Kim, Malmoe, Sweden, October 4, 2006 09:05 AM

Congratulations!
Welcome to Stockholm, Sweden!

 the comments of Dima Krylov Russia (Mosocw), October 4, 2006 09:26 AM

I'm so far from medicine and biology but I'm real proud of A. Fire and his colleague. Science is a winner! My congratulations to Stanford.

 the comments of Peng, Cornell, October 4, 2006 10:28 AM

Congratulations! Not only the prize but more importantly the great discovery

 the comments of Girija, October 4, 2006 10:39 AM

This discovery of RNA interference is a great service to the human race to fight against so many diseases. God bless Dr. Fire to make more and more outstanding contributions to this world! Congratulations to a remarkably modest man and his family!

 the comments of Piyush, India, October 4, 2006 11:18 AM

Dear Dr. Fire,

Heartiest congratulations.

 the comments of Vijay, Sunnyvale, October 4, 2006 11:31 AM

Fired up! Prof. Andy Fire deserves it. His discovery in his late 30s is recognized very early and credit goes to Stanford University. The Sunnyvale community is proud of Andrew Fire.

 the comments of Prof. Shlomo Elspas, M.D., USC/Keck School of Medicine, Los Angeles, October 4, 2006 11:48 AM

Mazal Tov, Andy!! We who have known you your whole life look forward to celebrating this well-deserved prize with you.

 the comments of Murad, October 4, 2006 12:18 PM

Congratulations on your well-deserved award. Now, clinical pharmacologists and pharmacodynamic modeling people can identify one step in the processes involved in viral attacks (especially HIV) to validate any assumptions of transduction compartments. This is made more amenable to modeling by Dr. Fire's efforts.

 the comments of Deborah at Nixon School, Palo Alto, October 4, 2006 01:24 PM

Congratulations Andy! I am so happy for you, your family and for the future support towards your ongoing research. A boon for all humanity in the research to follow, in the years to come.

 the comments of chaochen, October 4, 2006 06:58 PM

congratulations, Mr. Fire! you are a hero in life science

 the comments of حسین, October 4, 2006 08:08 PM

just want to congratulate you ....
I think all these are caused by stanford's unique integrity that we all should remember and adore everywhere in the world ...


Hossein Ghasemi
IRAN

 the comments of XU, October 4, 2006 08:47 PM

Congratulations!

 the comments of xjc, October 4, 2006 09:36 PM

great work, a deserved prize
congratulations

 the comments of SATENDRA K MANGRAUTHIA, I A R I, NEW DELHI, October 4, 2006 10:04 PM

Sir, it's really great news. My hearty congratulations to you. As I am a PhD scholar working on gene silencing and suppressors of gene silencing, this really gave me a lot of enthusiasm and happiness. Congratulations sir....

 the comments of yy76, October 5, 2006 12:10 AM

Congratulations!
Go Bears!!!

 the comments of Chao, Berkeley,CA, October 5, 2006 04:41 AM

Cheers, and congratulations! It is an exciting time for us! Proud of you!

 the comments of Emerick, UCSD, La Jolla, October 5, 2006 02:12 PM

He is on Fire! Congratulations professor and yes, Go Bears!

 the comments of Yinbao, October 5, 2006 09:58 PM

Congratulations!!!

 the comments of Ramani, US, October 5, 2006 10:47 PM

Congratulations Dr. Fire, on your well-deserved award. Very happy for you, your parents/family. Fundamental discoveries like these are boons for all humanity.

 the comments of Dr. Jayanta K Das, October 6, 2006 04:50 AM

Congratulations Professor Fire,
With regards.
Jayanta

 the comments of Chao, Berkeley, CA, October 6, 2006 06:17 AM

Congratulations, and cheers, today is Chinese traditional festival--Mid-autumn Day, Best wishes!

 the comments of Nikhil, Chicago, October 6, 2006 01:59 PM

Heartiest Congratulations Dr. Fire...! :-)

 the comments of Harshit Kumar, Pilani, India, October 7, 2006 12:24 AM

Congratulations on your great contribution to the scientific community.

 the comments of Yannick Comenge PARIS, October 7, 2006 08:16 AM

Congratulations on RNA research. My dream as post-doctoral fellow is to work on this kind of science. All the best,

Yannick Comenge
Secretary of French Pugwash Group
Phd in Microbiology

 the comments of vijay kumar university of Hyderabad, October 7, 2006 09:23 AM

congratulations Dr Fire, science proud of ur work, ur becoming a creater for discovery of new biological RNA tool, al da best for ur future work

 the comments of Robert, Sunnyvale, October 7, 2006 12:19 PM

Congrats to my childhood friend, Andy, who by all accounts has been the model of modesty in accepting this award. As Carnegie Institute's David Schwartz noted, "Anyone who knows him will not be surprised that he won." I can attest that all his Fremont High School and even Hollenbeck Elementary School friends are truly not the least bit surprised. Andy was not just the brain of the class/school, but was obviously set apart from even this, and always a really nice guy. I'm thrilled both for Andy and for this new door he's helped open wrt RNAi, and the potentially millions of future lives this will change for the better. Cheers, Andy!

 the comments of wangwei, October 7, 2006 07:37 PM

I hope China will win the prize.

 the comments of Rajendra bahadur Shahi,kathmandu,Nepal, October 8, 2006 12:36 AM

Congratulations !!
Andy Fire !!
And
The STANFORD!!

U have done great
We are there to follow you, Stanford/A.Fire!!
Best of Luck for your Future,
Why not Second time?

 the comments of ridhima in india, October 8, 2006 01:34 AM

congratulations! Dr. Fire.

 the comments of V. R. Swamy, Biogenes Inc., October 8, 2006 05:44 AM

Great! I was expecting the Nobel for RNAi. Andy Fire's papers have made me work on the siRNA design algorithm and the delivery strategies based on Nano carriers. No wonder, the passion of working with siRNA transfected us like a fire from Fire.

 the comments of Sumesh. India, October 8, 2006 06:49 AM

It is that time of the year when every researcher from variegated fields of human enquiry gets the special feeling of euphoria and elation by seeing the success achieved by the ingenius among them for doing dedicated basic research.
Congratulations!

 the comments of Prof. S. Mohan karuppayil, India, October 8, 2006 08:01 AM

congratulations Professor Fire
for making the silence of the genes
eloquent!
regards
mohan

 the comments of Kimberly,Birmingham,Alabama, October 9, 2006 03:10 PM

Great work! I am a student at a college in Alabama and my biology teacher has asked the class to write a report on you and Mr. Mello. I'm happy I had to do this assignment.

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