Within two months of my assuming the charge of the Director, Nehru Science Centre, Mumbai (13th February,2013) I had the honour and privilege to host two high profile lectures by two extraordinary people - Sunita Williams, Indian American, NASA Astronaut (4th April 2013) and Dr Richard Ernst (24th April, 2013) the 1991 Nobel Prize winning scientist in Chemistry, who singularly was awarded the coveted Prize “for his contributions to the development of the methodology of high resolution nuclear magnetic resonance (NMR) spectroscopy." Dr Ernst’s contribution laid the foundation for the evolution of magnetic resonance imaging (MRI), a noble medical diagnostic tool, which precisely and non invasively depicts and produces the images of tissue and organs in the body. The news of the death of Prof Richard Ernst has refreshed my memory of the lecture that Dr Ernst delivered at the Nehru Science Centre, Mumbai on 24th April, 2013. Dr Richard Ernst died at the age of 87, in the very city - Winterthur, outside Zurich, Switzerland, where he was born.
Three weeks before the lecture by Dr Ernst, we had hosted the lecture of Ms Sunita Williams on 4th April, 2013, which was followed by a mega press conference and interaction. These two events, particularly the press interaction of Sunita, Williams, helped our Centre get great publicity and good will. Dr. Ernst’s lecture and his unending patience to oblige almost every student with his autograph, post his outstanding and highly motivational and inspirational lecture, is something which everyone who attended the lecture will always remember. Dr Ernst’s talk, titled ‘Science and Society’, was interspersed with wit, humour and a personal touch. We were able to host the lecture of Dr Richard Ernst courtesy, Prof RV Hosur, TIFR, who had the honour to work with Prof Ernst and know him very closely in person. Just before his arrival in India, Prof Ernst had sent an email to Prof Hosur, indicating what he had in mind to speak and his email makes an interesting read which reveals his wittier part. He wrote ; “ Because I am not too certain to whom I will have to lecture in Mumbai and on which level, I prepared one lengthy show with about 500 slides with the title: Academic Opportunities in Preparation of a Prosperous Future to be cut on the spot to an acceptable length. It contains some historical information on NMR and on my personal history, some more recent scientific stuff, some slides on MRI, some slides on Tibetan art, some slides on our responsibility as scientists, some slides to illustrate my view of India with its attraction and its problems regarding its future science place”. Here comes the wittier part of his email. He wrote “ Of course, the entire lecture would take about 2-3 hours and would put everybody to sleep, including myself”. It is a different matter that although he spoke for more than 90 minutes, at our Centre, to a packed audience, forget about putting the audience to sleep, contrarily every minute of his lecture was applauded by not just the 300 plus students, teachers, parents and dignitaries who were seated in the main auditorium but also by another 200 plus students who witnessed the event through the CCTV in the neighbouring hall on a large screen - since they could not be accommodated in our main auditorium.
Although it has been 8 years since the lecture, I vividly remember one of the answers that he gave to a student. In response to a query as to what motivated him to be a scientist, Dr Ernst had an interesting story, which he shared with the students to a thunderous applause and laughter all around. He said “like most kids he too was curious and one such experience of a curious surprise was the beginning of his interest in science”. He added “ In our attic, I discovered a box full of chemicals, which belonged to an uncle. I took the chemicals in the basement and started to play with them and I was excited by what happened - a huge explosion. Fortunately I survived and so did our house and thus began my love for chemistry”. He continued “experimenting is one best way to get attracted to Science, which is what made him take to Science”. He urged the teachers and some parents - who were in attendance, to let the students perform experiments. He said, sometimes people say chemistry is too dangerous – you can’t do this and that with children – but that’s not really true. There are a few rules, which one has to obey, but otherwise you can do a lot of experiments and experience the joy of discovery very often in chemistry.”
Dr Ernst also spoke about his love for Asian arts, particularly, Tibetan scroll paintings - called thangkas, a unique and most exciting form of religious art, which exhibit outstanding creative talents of the artists. He showed images of quite a few of his collections of the Thangka paintings.
The family of Dr Ernst - his wife Ms Magdalena announced that Dr Ernst had died on Friday, 4th June, 2021, to the Swiss Federal Institute of Technology in Zurich - ETH Zurich, with which he was closely associated as the Professor Emeritus. The ETH, Zurich announced the death of Dr Ernst on their website, on Tuesday, 8th June, 2021. Dr Ernst is survived by his wife and three daughters. In his Nobel Prize autobiography, Dr Ernst praised the support of his wife in binding together his family and in helping him in concentrate on his passion for science. He said “I am extremely grateful for the encouragement and for the occasional readjustment of my standards of value by my wife Magdalena who stayed with me so far for more than 28 years despite all the problems of being married to a selfish work-addict with an unpredictable temper”. He added, “Magdalena has, without much input from my side, educated our three children: Anna Magdalena (kindergarten teacher), Katharina Elisabeth (elementary school teacher), and Hans-Martin Walter (still in high school). I am not surprised that they show no intention to follow in my footsteps, although if I had a second chance myself, I would certainly try to repeat my present career.”
Beginning in the late 1950s, but accelerating at an ever-faster pace in the twenty first century, science and technology has dramatically transformed modern medicine. However, before the World War II, the typical physician had a modest toolkit which only consisted of a thermometer, stethoscope, sphygmomanometer, and an occasional access to x-ray machines and electrocardiograph. Along with these medical devices a limited cabinet of pharmaceuticals assisted the physician of the 1940s, including sulfa drugs and negligible quantity of penicillin. After the War, biological research was transformed with the efforts of great scientists like Dr Ernst and others that helped in creating a new armamentarium of biophysics instruments- Electron Microscopes, Ultracentrifuges, Mass Spectrometers and new agents such as radioactive isotopes. A revolution in microelectronics and semiconductors initiated during the War together with the development of computers led the way to new fields of biomedical imaging such as Ultrasound, Computerized Tomography (CT) and Positron Emission Tomography (PET) scanners and most importantly the Nuclear Magnetic Resonance Imaging which is now famously referred to and known as Magnetic Resonance Imaging (MRI).
NMR - nuclear magnetic resonance, is a phenomenon that exploits the fact that all atomic nuclei that contain odd numbers of protons or neutrons have intrinsic magnetic characteristics. The NMR and Magnetic Resonance Imaging (MRI) are perhaps the most important non-invasive diagnostic tools in today's medicine. The basic components of any MRI system are the magnet, RF transmitter, gradient coil, and the receiver coil, along with a computer to analyse the incoming signal and produce image. MRI is a diagnostic technique that provides profound insights by revealing the picture of the inside of the body - without using X-rays or other potentially harmful radiation, for aiding the medical professionals. Dr Richard Ernst rightfully can be considered as the father of MRI, since it was he who developed the technique to make sense of the images by filtering out the noise component, using the Fourier Transforms and computers.
The MRI has proven to be invaluable for the diagnosis of a broad range of medical conditions in all parts of the body, including neurological and behavioral disorders, musculoskeletal injuries, cancer, heart and vascular diseases. MRI is also used to create maps of biochemical compounds within any cross section of the human body. These maps give basic biomedical and anatomical information that provide new knowledge to allow early diagnosis of many diseases, including the dreaded cancer. Since MRI has the ability to provide information about the state of health of organs and tissues, in addition to giving details of their shape and appearance, this imaging technique has major advantages over other diagnostic methods. And in all these cases, MRI works with no harmful intervention.
The MRI is significant and applicable to the human body because we are all filled with small biological magnets, the most abundant and responsive of which is the nucleus of the hydrogen atom, the proton. Remember that the human body is made up of nearly 70% of water, which consists of hydrogen. The principles of MRI take advantage of the random distribution of hydrogen protons, which possess fundamental magnetic properties. This process involves three basic steps. First, MRI generates a steady-state condition within the body by placing the body in a very strong (30,000 times stronger than the Earth's magnetic field) and steady magnetic field. Secondly, it changes the steady-state orientation of protons by stimulating the body with radio frequency energy. Thirdly, it terminates the radio frequency stimulation and listens to the body transmitting information about itself at the special resonant frequency using an appropriately designed antenna coil. The transmitted signal is detected and serves as the basis of the construction of internal images of the body using the mathematical analysis of Fourier Transforms and using computers to process this information.
Earlier in the twentieth century, Scientists tried to improve and expand on the amazing images produced by X-rays through the discovery of nuclear magnetic resonance imaging. The first successful nuclear magnetic resonance (NMR) experiment was made in 1946, independently by two scientists in the United States. Felix Bloch, working at Stanford University, and Edward Mills Purcell, from Harvard University, found that when certain nuclei were placed in a magnetic field they absorbed energy in the radio frequency range of the electromagnetic spectrum, and re-emitted this energy when the nuclei was transferred to their original state. They studied the hydrogen atom, because of its favorable nuclear properties. They chose to study the proton - the nucleus of the hydrogen atom (H), because the hydrogen nucleus is composed of a single proton and it has a significant magnetic moment. Hydrogen would turn out to be the most important element for MRI because of its favourable nuclear properties, nearly universal presence and its abundance in the human body as part of water (H2O). Befittingly Bloch and Purcell were awarded the 1952 Nobel Prize for physics, and their discoveries led to the NMR in condensed matter. There have been three other Nobel prizes associated with the fundamental discoveries arising from NMR and the most important one is the 1991 Nobel Prize in Chemistry, which was awarded to Richard Ernst for his contributions to the development of high resolution NMR spectroscopy, an important analytical tool in chemistry. The significance of his works can be seen in the citation of the Nobel Prize which said “ NMR spectroscopy has, during the last 20 years, developed into perhaps the most important instrumental measuring technique within chemistry. This has occurred because of a dramatic increase in both the sensitivity and the resolution of the instruments, two areas in which Prof. Ernst has contributed more than anybody else." The findings of Dr Ernst helped NMR spectroscopy to be used in all branches of chemistry, at universities as well as in industrial laboratories.
In the initial period the NMR was more of an esoteric tool when Ernst had completed his PhD in 1962 and there was no sight of its use in solving complicated chemical structures. The main Achilles heel of NMR was that radio signals sent out from these magnetic nuclei were very feeble, and so it was extremely difficult for an experimental observer to discriminate these weak signals from noise. As the sensitivity of NMR was disappointingly low, small amounts of nuclei were almost impossible to detect. It is here that Dr Ernst made a profound contribution in vastly improving the sensitivity of the signal. A major breakthrough occurred in 1966 when Ernst and Anderson, USA, discovered that the sensitivity of NMR spectra could be increased dramatically if the slow radiofrequency sweep that the sample was exposed to was replaced by short and intense radiofrequency pulses. The signal was then measured as a function of time after the pulse. The next pulse and signal acquisition were started after a few seconds, and the signals after each pulse were summed in a computer. The NMR signal measured as a function of time is not amenable to a simple interpretation. It is however possible to analyze what resonance frequencies are present in such a signal – and to convert it to an NMR spectrum – by a mathematical operation using the Fourier transformation, FT, which was performed rapidly in computer. This discovery by Ernst and his associates forms the basis of modern NMR spectroscopy. The ten-fold, and sometimes hundred-fold, increase in sensitivity has made it possible to study small amounts of material. The enormous potential of the new technique – called FT NMR – quickly became obvious to NMR spectroscopists. The chemical research community got access to it in the early seventies through commercial FT NMR instruments.
By the end of the sixties, NMR spectroscopists had begun to use new magnet designs, based on superconducting materials, and the quality of spectra – expressed both in terms of sensitivity and resolution – improved quickly during the seventies. Consequently, more complex systems could be studied and more sophishcated questions answered. However, if this finding was to move to very large molecules, macromolecules, another breakthrough was necessary. This breakthrough again carried the signature of Ernst. Inspired by a lecture of Jean Jeener, Belgium, at a summer school at the beginning of the seventies, Ernst and co-workers showed in 1975-76 how “two-dimensional” (2D) NMR experiments could be performed. Their demonstration of the 2D FT NMR opened entirely new possibilities for chemical research and the rest what they say is history.
Richard Ernst was born on 13th August,1933 in Winterthur, northeastern Switzerland, near Zurich, and he was the oldest of the three children (two sisters and Richard)born to Robert Ernst and Irma Brunner. Richard Ernst’s father taught architecture at the technical high school of Winterthur. By the age of 13 years, Richard developed interest in music and chemistry. However his love for music was short lived and he decided to become a chemist rather than a musician and a composer. Richard completed his high school in Winterthur and subsequently he enrolled at the Swiss Federal Institute of Technology in Zurich (“the Federal Institute”), and in 1956, he was awarded a diploma in chemistry. He continued his education at the Federal Institute and, in 1962, was awarded a PhD degree. Between obtaining these 2 degrees, Ernst spent some time in military service as well. He completed his doctorate in physical chemistry in 1962 with a dissertation on nuclear magnetic resonance (NMR) in the discipline of physical chemistry. After completing his doctorate, Ernst spent the next year (1962-1963) as a researcher and teacher at the Federal Institute. However, in 1963, Ernst left Switzerland for the United States to become a research scientist and worked in the private sector at Varian Associates in Palo Alto, California, where he worked until 1968. In 1968, he returned to Switzerland to join the faculty of the Federal Institute to direct a research group on NMR at the Laboratory of Physical Chemistry. He went on to become a full professor at the Federal Institute (ETH, Zurich) in 1976.
As stated in the earlier paragraphs, Ernst's work on NMR spectroscopy began in the early 1960s at the Federal Institute. His contributions to the field—increasing the sensitivity and the resolution of the instruments—have made it possible to determine both the nature of a nucleus and the local structure of the molecule of which the nucleus is a part. In 1966, Ernst and a colleague found that NMR spectroscopy could be more effective if the slow sweeping radio waves traditionally used to bombard a sample were replaced by short, intense pulses. They used a computer to perform a complex series of mathematical operations (Fourier transformations) in the received signal. This improved the sensitivity by as much as 100-fold. Ernst's second major contribution to the field of NMR spectroscopy was made in the mid-1970s, when he developed 2-dimensional NMR techniques to study exceedingly large molecules. By the 1990s, various NMR techniques were in use to determine the 3-dimensional structure of organic and inorganic compounds and large complex molecules such as proteins; to study the interaction between biological molecules and metal ions, water molecules, drug molecules, and other substances; to identify chemical species; and to study the rates of chemical reactions.
Throughout his life, Ernst had an extremely broad range of interests and commitments. From his early youth, chemistry and art enthralled him in equal measure. During a trip to Asia, he developed a great interest in Tibetan art - Thangka Paintings, which he went on to collect, study and restore. Although not a Buddhist himself, Ernst was a great admirer of Tibetan Buddhism and thus his interest in India. His Holiness the Dalai Lama, the spiritual leader of Tibet, on the invitation of Prof Ernst, visited the ETH Zurich, as its guest in the year 2005. Ernst had a great interest for classical music. He was also concerned about the social issues and their context. He once said that he had never intended his research to be the exclusive reserve of the ivory tower of academia, but wanted it to be used in the development of meaningful and useful applications. He was considered a perfectionist. One of his recipes for success was that he put his all into everything he did, and did nothing by halves – anything else was a waste of time for him.
Ernst is credited with numerous inventions and holds several patents in the field. Besides the Nobel Prize, he has received many honors and awards, including honorary doctorates, the Marcel Benoist Prize (1986), the Wolf Prize in Chemistry (1991), and the Louise Gross Horwitz Prize (1991) of Columbia University (New York City). In 2002, Ghana issued a stamp to honor him as Nobel laureate. It was truly an honour and privilege for us to host his lecture at the the Nehru Science Centre, and I am certain that of the 400 plus students who attended his lecture, there will be more than a couple who may have made a choice to be a chemist, inspired his lecture and interaction. I join countless other scientific fraternity across the globe in praying for the noble soul of Prof Richard Ernst to rest in peace, while the humanity continues to be benefitted for perpetuity with his invention, that paved the way for MRI.
RIP
