January 22, 2011
Health Sciences Campus, Kochi
 

Dr. Martin Chalfie, the 2008 Nobel Laureate in Chemistry, recently addressed the Amrita fraternity at the Health Sciences Campus. Having received the Nobel Prize for his work with green fluorescent proteins (GFP), he has enabled a better understanding of how organs function, diseases spread and how infected cells respond to treatment.
 

The eminent scientist was warmly welcomed by a large group of students, faculty, doctors, scientists, researchers and invited guests.
 

“This is the first time we are hosting a Nobel Laureate in person,” stated Prof. Shantikumar Nair, Dean of Research at Amrita, as he welcomed the celebrated guest.
 

“As Chancellor Amma has desired, in all of our campuses, research and critical thinking is becoming more and more important,” he added. “It is indeed a privilege to have Dr. Chalfie here in person at this point.”
 

Dr. Nair also welcomed Prof. Sarah Heilshorn from Stanford University, who was an invited guest at Amrita to help promote research interactions between India and the US.
 

“It is not the science, it’s how you apply the science that is important,” Dr. Martin Chalfie remarked, as he began his historic address.
 

In his talk, Dr. Chalfie elaborated on his research and spoke about his interests, his inspirations and what he has learned over the years. Included below are excerpts from his talk.
 

Readers may remember that Dr. Chalfie previously addressed Amrita students and faculty , speaking through a satellite link during the 7th convocation of Amrita Vishwa Vidyapeetham, last year.
 

“We are very fortunate to hear from Dr. Martin Chalfie, who truly represents the highest pinnacle of excellence in research,” stated one student, after the talk.
 

Others who also addressed the gathering included Dr. Bipin Nair, Dean, Amrita School of Biotechnology and Dr. Prathapan Nair, Principal, Amrita School of Medicine.
 

Excerpts from Dr. Martin Chalfie’s address to the Amrita fraternity
 

I want to start by saying how really happy I am to be able to talk here today. I would like to talk about the discovery and some of the uses of a rather remarkable protein called the Green Fluorescent Protein (GFP).
 

There is a quotation from the American baseball player Yogi Berra. Yogi Berra is well known in the United States for saying various things that seem very obvious and silly but there are important points behind them. So, one of the things he has supposed to have said is that “You can observe a lot by watching.” GFP allows you to observe a lot and that is what I am going to talk about today.
 

Misconceptions of Being A Scientist
 

I want to start actually by saying a little bit about all the things I learned about scientists. I want to say these because I think this is some of the lessons that people learn. I think every single one of these things is not true.
 

The first of these is that scientists are geniuses. This means it slated at birth; if you do not have it at birth, you will never be a scientist. The scientists seem to have an innate skill in them. They never work for it.
 

The second thing is that scientists have great ideas, they do experiments and get great results and that is the end of it.
 

Third, the scientists use something called the scientific method. They think of a hypothesis and they immediately think of the right experiment to do, they test it out perfectly and publish and that is the end of it.
 

Fourth, scientists work alone. They do not take any assistance and that they are absolutely isolated from anyone else unless they are Watson or Crick.
 

Finally, except for Marie Curie, all scientists are men. The story of GFP shows that all this is complete nonsense.
 

My Interests
 

We have lots of mechanical senses. We have at least five different types of cells in our skin that allows for the sense of touch. These include cells that respond to hard touch, gentle touch, texture and high and low frequency vibrations. These are just the beginning of the mechanical senses that we have.
 

When we send the astronauts to space, they bounce because the bones can no longer sense the forces that are applied to them. Tennis players who only use one arm put lots of tension and force on the muscles on the arm that they use to play.
 

We know the molecules that allow us to see. We also know the molecules that allow us to detect chemicals whether they are odours or tastes. But all of these mechanical senses have one thing in common. We have absolutely no idea how they work.
 

I do not study touch in people, I study touch in very small 1-mm long worm C. elegans and these cells which are blue are the 6 of the 302 nerve cells in the animal that respond to gentle touch.
 

We were able to find quite a number of proteins. As we clone all of these genes, the first question we wanted to address was the question of what cells turned on these genes. We had three basic methods that allowed us to ask where is the gene turned on.
 

The animal is transparent. You can look right through it. One way is to use antibodies or you can use the gene’s regulatory apparatus like of E. coli lacZ gene, beta-galactosidase. The third is in situ hybridization to mRNA. All of these methods will answer the question, where is the gene active.
 

But all of these methods had problems. One of them was that the preparation took several days. So we had to prepare the specimen in a very particular way. First, we had to kill the organism. Secondly, we had to fix it. Then we had to permeabilize. All of these preparations did not give us a view about what was happening over time. We had to repeat these preparations when we wanted to do it a second time.
 

My Inspiration
 

My inspiration came from a seminar. The speaker, Paul Brehm, talked about the research of one of my co-Laureate Osamu Shimomura. At graduate school, Osamu Shimomura became interested in a fascinating biological problem. How is it that some organisms generate light? He was trying to understand the biochemistry behind it.
 

He was asked to come to the United States, where he started working on jellyfish, Aequorea victori, which produces green light. He started working on this one summer and every experiment he did, failed miserably. After doing numerous experiments, which failed, he took his preparations and threw them into the sink. This also included some seawater. He turned off the lights and as he was walking out of the door, he happened to glance back at the sink. He saw that it was glowing brightly!
 

He then realized that the sink had seawater; seawater had calcium in it and it was the calcium in the seawater that he had to have in his experiments. He used it to isolate the protein aequorin. Aequorin plus calcium produces light. It was a protein that fluoresced and allowed the jellyfish to produce green light instead of blue. We call it now the green fluorescent protein.
 

That was all I heard in the seminar. I do not remember anything else that was said. I began to fantasize and thought to myself that I have a transparent animal to work with and I want to know what cells turned on the genes. The next day I found out that Douglas Prasher was isolating the cDNA. We decided to collaborate. I had a new graduate student, Ghia Euskirchen, join my lab and Ghia started to work on this project. As the collaboration was set up, Ghia tried to put this into bacterium E.coli and it fluoresced green. We published our results in the magazine Science.
 

Advantages of GFP
 

GFP has been used in many different ways. It has been used to investigate problems relating to human health, to know how cancer cell metastasize and what tissues they go to. People have also used it to study the AIDS virus and quite a number of other inherited genetic diseases in people. It has been used to study the basic properties of cell biology, basic properties of nerve cell and the immune system.
 

In fact, I estimate that since we published our paper in 1994 there have been at least 60,000 papers published, using GFP-related experiments.
 

What Research on GFP Has Taught Me
 

The first thing is that scientific success comes via many routes. Most discoveries are accidental. You have to have the willingness to try, try and try. Scientific progress is cumulative. It is not the effort of one or a few individuals. It is the work of many individuals. All life should be studied, not just model organisms. Basic research is very essential; it is the engine that devices innovation, leading to insights into human disease and advances in agriculture and industry.