Of Glowing Proteins and Killer Viruses

This year’s Nobel prizes in physics, chemistry and medicine have a strong Japanese flavour.

As is the case with most great scientific discoveries, it all started with a bit of curiosity. In the 1960s, Osamu Shimomura wondered why crystal jellyfish gave off green pinpricks of light. Now, half a century later, Shimomura has been awarded for his curiosity with the Nobel prize in chemistry.

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Shimomura was fascinated by the chemistry involved in bioluminescence and collected more than one million jellyfish from Friday Harbor in Washington State in the US in the 1960s and early 1970s. He spent the next 40 years meticulously examining the proteins that made them glow. In a crystal jellyfish’s approximately 300 photo-organs, Shimomura found a protein he named aequorin that produces blue light, which subsequently is converted to green light by green fluorescent protein, or GFP.

In the decades since Shimomura isolated it, GFP has revolutionised stem cell research, cloning, organ transplants, neuroscience — and everything in between. That’s because GFP can be attached biochemically to proteins within a cell, making a formerly invisible protein fluoresce beneath blue light. Proteins are extremely small and cannot be seen, even under an electron microscope. But attaching GFP makes a protein fluoresce: it’s like seeing headlights from the window of a plane even if you’re too high to make out the cars.

Proteins in human cancer cells have been tagged with GFP, and the resulting fluorescent tumours have been implanted in mice. As cancer cells break from the tumour and begin to metastasise, or move about the body, they continue to fluoresce, and scientists can watch the cancer spread.

Four other scientists are largely responsible for making this curious glowing protein into the most useful modern imaging technique available. Douglas Prasher cloned the GFP gene and was the first to think about using GFP as a fluorescent protein tag. Sergey Lukyanov won the race to find the first red fluorescent proteins, which he found in corals in a Moscow aquarium, and his research led to the discovery of fluorescent proteins in many other marine organisms.

Unfortunately, the Nobel can be shared among only three people, and these two worthy scientists were denied a slice of the $1.4 million prize.

Two others, however, join Shimomura as the new chemistry laureates: Marty Chalfie, who was the first to use GFP to light up bacteria and worms, and Roger Tsien, who has been in the forefront of fluorescent protein research since 1994 and has created a series of fluorescent proteins whose colours span the spectrum.

Many more continue to contribute to GFP research. GFP has been used to show how HIV travels from infected to non-infected cells. In another study, scientists created a mouse with fluorescent neurons that connect its whiskers with its cortex. By replacing part of its skull with a glass window, they have been able to observe how the mouse rewires its brain to cope when half of its whiskers are removed. This fluorescent window into the brain is being used to study the effects of ageing and neuro-degenerative diseases.

GFP is the microscope of the 21st century. It lets us see things we have never been able to see before. And, like the microscope, it has completely changed the way we think about science.

Green fluorescent protein has been floating in the ocean for more than 160 million years, but it took an inquisitive scientist, fascinated by bits of green light, to begin unlocking its potential.

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Two French researchers were awarded the Nobel prize for medicine last week for discovering the AIDS virus, bypassing an American researcher who played a key role in the discovery.

Luc Montagnier of the World Foundation for AIDS Research and Prevention and Francoise Barre-Sinoussi of the Pasteur Institute, both in Paris, were awarded the Nobel prize in physiology and medicine by the Karolinska Institute in Stockholm for their 1983 identification of what was later named the human immunodeficiency virus (HIV).

The pair split the $1.4 million prize with Harald zur Hausen of the University of Heidelberg in Germany, who discovered that another virus, the human papilloma virus (HPV), causes cervical cancer.

Excluded from the prize was Robert C. Gallo, who for years was locked in a bitter dispute with Montagnier over credit for the discovery of HIV from work he did while at the National Cancer Institute in the US. Gallo is now at the University of Maryland.

Although the prize’s rules limit the number of scientists who can win the award to three, Jans Jornvall, scientific secretary to the assembly, made it clear the committee felt that Montagnier and Barre-Sinoussi deserved sole credit because in 1983 they published the first papers identifying the virus in the journal Science.

“We think the two that we named are the discoverers of the virus,” Jornvall said in a telephone interview. “If you look at the initial papers on the publication of the discovery you will find those who discovered it.”

Jornvall praised Gallo’s work but said the committee based its decision on the French researchers publishing their work first.

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“Dr Gallo is an excellent person and has meant very much for science, but there are many people who are excellent and do very much for science,” Jornvall said. “We named the three people we consider to be the discoverers of the viruses we named.”

Other researchers said Montagnier and Barre-Sinoussi clearly deserved the prize, but that it was disappointing that Gallo was excluded.

“Gallo deserves enormous credit,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. “It’s a shame you can’t give it to four people because Gallo’s contributions were enormous.”

In a written statement, Gallo congratulated the winners, adding that he was “gratified” by Montagnier’s “kind statement” that he was “equally deserving.”

“I am pleased that the Nobel Committee chose to recognise the importance of AIDS with these awards and I am proud that my colleagues and I continue to search for an AIDS vaccine,” he said.

Montagnier and Gallo were locked in a bitter dispute in the 1980s over the discovery of the virus. Beyond who should get the credit, millions of dollars were also at stake from fees for blood tests. President Ronald Reagan and French Prime Minister Jacques Chirac eventually signed an agreement in 1987 that divided the royalties equally, and Gallo and Montagnier published a paper together in The New England Journal of Medicine in 2003 acknowledging each other’s work.

In announcing the award, the Nobel Committee said Montagnier and Barre-Sinoussi’s initial discovery led to a series of crucial advances, including deciphering how the virus reproduces and infects cells and the development of the blood test and powerful antiviral drugs that have helped contain the spread of the virus and reduce the death toll.

The committee also praised zur Hausen’s work, saying he “went against current dogma” when he proposed that HPV caused cervical cancer, the second most common cancer among women and the most common sexually transmitted agent. Among other things, the work led to the development of vaccines against strains of the virus.

“The global public health burden attributable to human papilloma viruses is considerable,” the committee said.

“I’m of course totally surprised. It’s of course a great pleasure for me,” said zur Hausen, 72, said during an interview posted on the Nobel Committee’s website.

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An American and two Japanese physicists won the 2008 Nobel prize in physics for their discovery of tiny asymmetries in nature’s fundamental particles that help explain why our universe exists.

Yoichiro Nambu, of the Enrico Fermi Institute at the University of Chicago, will receive half of the $1.4 million prize. The other half will be split between Makoto Kobayashi, of the High Energy Accelerator Research Organization in Tsukuba, Japan, and Toshihide Maskawa, of the Yukawa Institute for Theoretical Physics at Kyoto University.

The three physicists were pioneers in understanding “broken symmetry,” which explains why the universe can contain life as we know it. When matter and antimatter collide, they annihilate one another, leaving only radiation. In a symmetric universe with an equal amount of matter and antimatter, life — if any could exist — would be nasty, brutish and short.

That doesn’t happen because there is a tiny imbalance of one extra particle of matter for every 10 billion antimatter particles, resulting in the matter-dominated universe we live in today.

How exactly this happened is still a mystery. But Nambu, 87, born in Tokyo, was among those who opened up the field to further questions with the discovery of “spontaneous symmetry breaking”.

Nambu’s work, done in the 1960s and 1970s, predicted the behaviour of the tiny particles known as quarks and underlies the Standard Model of the universe, which unites three of the four fundamental forces of nature: the strong nuclear force, weak nuclear force and electromagnetic force. The working of gravity, and how it relates to the other three forces, is still a mystery.

Kobayashi and Maskawa predicted there were three families of quarks, instead of the two then known. Their calculations were confirmed by experiments in high-energy physics, leading to the discovery of the six quarks known today. Quarks and leptons are considered to be the two basic components of all matter, which make up atomic particles like protons and neutrons.

“It is my great honour and I can’t believe this,” Kobayashi told Reuters news service.

Physicists are now searching for spontaneous broken symmetry in the Higgs mechanism, which threw the universe into imbalance at the time of the Big Bang 13.7 billion years ago.

Scientists at the Large Hadron Collider at the European Organization for Nuclear Research, or CERN, in Switzerland will be looking for the Higgs particle when they restart the collider in spring 2009.

Sources:
The Telegraph (Kolkata, India)

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