The 2008 Nobel Prize in Chemistry

 
I'm not a big fan of giving out Nobel Prizes for technological achievements although I do recognize that some of them are noteworthy. This one goes too far in the direction of technology, in my opinion. The technique is useful and has led to many advances in the field but I don't think it's Nobel Prize work.

There were many other worthwhile candidates who made significant advances in the study of basic science, leading to a direct contribution to our understanding of how nature works. None of the names commonly discussed on the science blogs got the prize.

The Chemistry prize was announced today: The Nobel Prize in Chemistry 2008. Here's the press release from the Nobel Prize website.

8 October 2008

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2008 jointly to

Osamu Shimomura, Marine Biological Laboratory (MBL), Woods Hole, MA, USA and Boston University Medical School, MA, USA,

Martin Chalfie, Columbia University, New York, NY, USA

and

Roger Y. Tsien, University of California, San Diego, La Jolla, CA, USA

"for the discovery and development of the green fluorescent protein, GFP".

Glowing proteins – a guiding star for biochemistry

The remarkable brightly glowing green fluorescent protein, GFP, was first observed in the beautiful jellyfish, Aequorea victoria in 1962. Since then, this protein has become one of the most important tools used in contemporary bioscience. With the aid of GFP, researchers have developed ways to watch processes that were previously invisible, such as the development of nerve cells in the brain or how cancer cells spread.

Tens of thousands of different proteins reside in a living organism, controlling important chemical processes in minute detail. If this protein machinery malfunctions, illness and disease often follow. That is why it has been imperative for bioscience to map the role of different proteins in the body.

This year's Nobel Prize in Chemistry rewards the initial discovery of GFP and a series of important developments which have led to its use as a tagging tool in bioscience. By using DNA technology, researchers can now connect GFP to other interesting, but otherwise invisible, proteins. This glowing marker allows them to watch the movements, positions and interactions of the tagged proteins.

Researchers can also follow the fate of various cells with the help of GFP: nerve cell damage during Alzheimer's disease or how insulin-producing beta cells are created in the pancreas of a growing embryo. In one spectacular experiment, researchers succeeded in tagging different nerve cells in the brain of a mouse with a kaleidoscope of colours.

The story behind the discovery of GFP is one with the three Nobel Prize Laureates in the leading roles:

Osamu Shimomura first isolated GFP from the jellyfish Aequorea victoria, which drifts with the currents off the west coast of North America. He discovered that this protein glowed bright green under ultraviolet light.

Martin Chalfie demonstrated the value of GFP as a luminous genetic tag for various biological phenomena. In one of his first experiments, he coloured six individual cells in the transparent roundworm Caenorhabditis elegans with the aid of GFP.

Roger Y. Tsien contributed to our general understanding of how GFP fluoresces. He also extended the colour palette beyond green allowing researchers to give various proteins and cells different colours. This enables scientists to follow several different biological processes at the same time.

---

[Photo Credit: GFP Glowing Genes]

Steve Jones Says Human Evolution Is Over

There's so much wrong with this article by Steve Jones that I don't know where to begin. So I'll leave it up to Sandwalk readers to comment. Steve Jones is a Professor of genetics at University College, London (UK) and the author of Darwin's Ghost.

From Times Online via RichardDawkins.net.

Leading geneticist Steve Jones says human evolution is over
By Julia Belluz

Human evolution is grinding to a halt because of a shortage of older fathers in the West, according to a leading genetics expert.

Fathers over the age of 35 are more likely to pass on mutations, according to Professor Steve Jones, of University College London.

Speaking today at a UCL lecture entitled "Human evolution is over" Professor Jones will argue that there were three components to evolution – natural selection, mutation and random change. "Quite unexpectedly, we have dropped the human mutation rate because of a change in reproductive patterns," Professor Jones told The Times.

"Human social change often changes our genetic future," he said, citing marriage patterns and contraception as examples. Although chemicals and radioactive pollution could alter genetics, one of the most important mutation triggers is advanced age in men.

This is because cell divisions in males increase with age. "Every time there is a cell division, there is a chance of a mistake, a mutation, an error," he said. "For a 29-year old father [the mean age of reproduction in the West] there are around 300 divisions between the sperm that made him and the one he passes on – each one with an opportunity to make mistakes.

"For a 50-year-old father, the figure is well over a thousand. A drop in the number of older fathers will thus have a major effect on the rate of mutation."

Professor Jones added: "In the old days, you would find one powerful man having hundreds of children." He cites the fecund Moulay Ismail of Morocco, who died in the 18th century, and is reputed to have fathered 888 children. To achieve this feat, Ismail is thought to have copulated with an average of about 1.2 women a day over 60 years.

Another factor is the weakening of natural selection. "In ancient times half our children would have died by the age of 20. Now, in the Western world, 98 per cent of them are surviving to 21."

Decreasing randomness is another contributing factor. "Humans are 10,000 times more common than we should be, according to the rules of the animal kingdom, and we have agriculture to thank for that. Without farming, the world population would probably have reached half a million by now – about the size of the population of Glasgow.

"Small populations which are isolated can evolve at random as genes are accidentally lost. World-wide, all populations are becoming connected and the opportunity for random change is dwindling. History is made in bed, but nowadays the beds are getting closer together. We are mixing into a glo-bal mass, and the future is brown."

Be sure to keep in mind the definition of evolution [What Is Evolution?].

---

My Friend Publishes a Book

 
Many years ago I had a friend who lived just up the street. We didn't get to see each other very much because we went to different high schools. But we did go on one date—to a Simon and Garfunkel concert. It didn't make much of an impression on her because she doesn't even remember it!

Later on she became a well known radio and TV personality including a stint as the co-anchorwoman on the CBC National and a interviewer on "As It Happens" on CBC Radio and NPR.

Now she's written a book and I'm sure it's going to be an excellent read.

---

Framing Science

 
Matt Nisbet recently posted the following message under the title Framing Science Ranked Among Top 15 Science Blogs.

For the fourth straight month, Framing Science ranks among the top 15 science-related blogs, as tracked by Wikio. The position of a blog in the Wikio ranking depends on the number and weight of the incoming links from other blogs. (Blogrolls are not taken into account and Wikio only counts links from the last 120 days.)

I submitted a comment in which I noted that several famous science blogs such as Bad Astronomy, The Panda's Thumb, and RichardDawkins.net are not included in the Wikio rankings.

Since this has been discussed many times on the blogs, it's safe to assume that Matt knows about it. I think he understands that his ranking among the top 15 blogs is not quite what it seems. So I asked in the comment whether he was deliberately trying to deceive his readers or was this an example of framing?

Unfortunately, my comment must have gone astray in the ether since it didn't survive moderation. Isn't that strange?

---

Monday's Molecule #91

 
Identify this molecule. You need to describe what you see as accurately as possible and name the species from which this protein was purified. I don't think any of you can do it without a hint but I've received complaints that the hint makes it too easy. We'll see how you do without a hint.¹

There's a direct connection between today's molecule and a Nobel Prize. I'm looking for the person(s) who discovered the significance of the molecule—not necessarily the structure.

The first one to correctly identify the molecule and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are four ineligible candidates for this week's reward. You know who you are.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow. I reserve the right to select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

UPDATE: The molecule is a fragment of bovine prion protein and the Nobel Laureate is Stanley Prusiner. Four people got it right but the winner is Haruhiko Ishii.

---

1. OK, maybe one little hint ... this week's Nobel Laureate(s) on Sandwalk were inspired by this week's 2008 winners.

The 2008 Nobel Prize in Physiology or Medicine

 
This one is going to cause a stir in the scientific community. Nobody predicted this [The 2008 Nobel Prize in Physiology or Medicine].

6 October 2008

The Nobel Assembly at Karolinska Institutet has today decided to award The Nobel Prize in Physiology or Medicine for 2008 with one half to

Harald zur Hausen

for his discovery of "human papilloma viruses causing cervical cancer"

and the other half jointly to

Françoise Barré-Sinoussi and Luc Montagnier

for their discovery of "human immunodeficiency virus"

Summary

This year's Nobel Prize awards discoveries of two viruses causing severe human diseases.

Harald zur Hausen went against current dogma and postulated that oncogenic human papilloma virus (HPV) caused cervical cancer, the second most common cancer among women. He realized that HPV-DNA could exist in a non-productive state in the tumours, and should be detectable by specific searches for viral DNA. He found HPV to be a heterogeneous family of viruses. Only some HPV types cause cancer. His discovery has led to characterization of the natural history of HPV infection, an understanding of mechanisms of HPV-induced carcinogenesis and the development of prophylactic vaccines against HPV acquisition.

Françoise Barré-Sinoussi and Luc Montagnier discovered human immunodeficiency virus (HIV). Virus production was identified in lymphocytes from patients with enlarged lymph nodes in early stages of acquired immunodeficiency, and in blood from patients with late stage disease. They characterized this retrovirus as the first known human lentivirus based on its morphological, biochemical and immunological properties. HIV impaired the immune system because of massive virus replication and cell damage to lymphocytes. The discovery was one prerequisite for the current understanding of the biology of the disease and its antiretroviral treatment.

Discovery of human papilloma virus causing cervical cancer

Against the prevailing view during the 1970s, Harald zur Hausen postulated a role for human papilloma virus (HPV) in cervical cancer. He assumed that the tumour cells, if they contained an oncogenic virus, should harbour viral DNA integrated into their genomes. The HPV genes promoting cell proliferation should therefore be detectable by specifically searching tumour cells for such viral DNA. Harald zur Hausen pursued this idea for over 10 years by searching for different HPV types, a search made difficult by the fact that only parts of the viral DNA were integrated into the host genome. He found novel HPV-DNA in cervix cancer biopsies, and thus discovered the new, tumourigenic HPV16 type in 1983. In 1984, he cloned HPV16 and 18 from patients with cervical cancer. The HPV types 16 and 18 were consistently found in about 70% of cervical cancer biopsies throughout the world.

Importance of the HPV discovery

The global public health burden attributable to human papilloma viruses is considerable. More than 5% of all cancers worldwide are caused by persistent infection with this virus. Infection by the human papilloma virus is the most common sexually transmitted agent, afflicting 50-80% of the population. Of the more than 100 HPV types known, about 40 infect the genital tract, and 15 of these put women at high risk for cervical cancer. In addition, HPV is found in some vulval, penile, oral and other cancers. Human papilloma virus can be detected in 99.7% of women with histologically confirmed cervical cancer, affecting some 500,000 women per year.

Harald zur Hausen demonstrated novel properties of HPV that have led to an understanding of mechanisms for papilloma virus-induced carcinogenesis and the predisposing factors for viral persistence and cellular transformation. He made HPV16 and 18 available to the scientific community. Vaccines were ultimately developed that provide ≥95 % protection from infection by the high risk HPV16 and 18 types. The vaccines may also reduce the need for surgery and the global burden of cervical cancer.

Discovery of HIV

Following medical reports of a novel immunodeficiency syndrome in 1981, the search for a causative agent was on. Françoise Barré-Sinoussi and Luc Montagnier isolated and cultured lymph node cells from patients that had swollen lymph nodes characteristic of the early stage of acquired immune deficiency. They detected activity of the retroviral enzyme reverse transcriptase, a direct sign of retrovirus replication. They also found retroviral particles budding from the infected cells. Isolated virus infected and killed lymphocytes from both diseased and healthy donors, and reacted with antibodies from infected patients. In contrast to previously characterized human oncogenic retroviruses, the novel retrovirus they had discovered, now known as human immunodeficiency virus (HIV), did not induce uncontrolled cell growth. Instead, the virus required cell activation for replication and mediated cell fusion of T lymphocytes. This partly explained how HIV impairs the immune system since the T cells are essential for immune defence. By 1984, Barré-Sinoussi and Montagnier had obtained several isolates of the novel human retrovirus, which they identified as a lentivirus, from sexually infected individuals, haemophiliacs, mother to infant transmissions and transfused patients. The significance of their achievements should be viewed in the context of a global ubiquitous epidemic affecting close to 1% of the population.

Importance of the HIV discovery

Soon after the discovery of the virus, several groups contributed to the definitive demonstration of HIV as the cause of acquired human immunodeficiency syndrome (AIDS). Barré-Sinoussi and Montagnier's discovery made rapid cloning of the HIV-1 genome possible. This has allowed identification of important details in its replication cycle and how the virus interacts with its host. Furthermore, it led to development of methods to diagnose infected patients and to screen blood
products, which has limited the spread of the pandemic. The unprecedented development of several classes of new antiviral drugs is also a result of knowledge of the details of the viral replication cycle. The combination of prevention and treatment has substantially decreased spread of the disease and dramatically increased life expectancy among treated patients. The cloning of HIV enabled studies of its origin and evolution. The virus was probably passed to humans from chimpanzees in West Africa early in the 20th century, but it is still unclear why the epidemic spread so dramatically from 1970 and onwards.

Identification of virus−host interactions has provided information on how HIV evades the host’s immune system by impairing lymphocyte function, by constantly changing and by hiding its genome in the host lymphocyte DNA, making its eradication in the infected host difficult even after long-term antiviral treatment. Extensive knowledge about these unique viral host interactions has, however, generated results that can provide ideas for future vaccine development as well as for therapeutic approaches targeting viral latency.

HIV has generated a novel pandemic. Never before has science and medicine been so quick to discover, identify the origin and provide treatment for a new disease entity. Successful anti-retroviral therapy results in life expectancies for persons with HIV infection now reaching levels similar to those of uninfected people.

Harald zur Hausen, born 1936 in Germany, German citizen, MD at University of Düsseldorf, Germany. Professor emeritus and former Chairman and Scientific Director, German Cancer Research Centre, Heidelberg, Germany.

Françoise Barré-Sinoussi, born 1947 in France, French citizen, PhD in virology, Institut Pasteur, Garches, France. Professor and Director, Regulation of Retroviral Infections Unit, Virology Department, Institut Pasteur, Paris, France.

Luc Montagnier, born 1932 in France, French citizen, PhD in virology, University of Paris, Paris, France. Professor emeritus and Director, World Foundation for AIDS Research and Prevention, Paris, France.

---

Obama, Biden, McCain and Palin Agree on One Thing

 
Same-sex marriage is the law of the land in Canada and in many (most?) other Western industrialized nations. It's against the law in most states in the USA.

I was aware of the fact that John McCain and Sarah Palin were opposed to legalization of same-sex marriage. Last night I was shocked to learn that Barack Obama and Joe Biden also oppose legalization of same-sex marriage.

Unless the following is incorrect ...

IFILL: Let's try to avoid nuance, Senator. Do you support gay marriage?

BIDEN: No. Barack Obama nor I support redefining from a civil side what constitutes marriage. We do not support that. That is basically the decision to be able to be able to be left to faiths and people who practice their faiths the determination what you call it.

The bottom line though is, and I'm glad to hear the governor, I take her at her word, obviously, that she think there should be no civil rights distinction, none whatsoever, between a committed gay couple and a committed heterosexual couple. If that's the case, we really don't have a difference.

IFILL: Is that what your said?

PALIN: Your question to him was whether he supported gay marriage and my answer is the same as his and it is that I do not.

IFILL: Wonderful. You agree. On that note, let's move to foreign policy.

Isn't this the 21st century? Isn't Obama supposed to be a progressive?

---

Vote

 
There's an election coming up in Canada and the USA. Canada's is first.

No matter what you think about the candidates it's important to go out and vote. I plan on voting several times at least once for somebody. I don't know who, yet.

This is a really, really cool video made by a bunch of people you may recognize. Even if you've already voted in the advance polls you should watch this video. It will make you laugh (unless you're offended by four letter words and women removing their bras).

---

[Hat Tip: Phil Plait of Bad Astronomy]

Tangled Bank #115

 
The latest issue of Tangled Bank has been published on Evolved and Rational [The Tangled Bank #115: The awesome level is over 9000!].

Welcome to the 115th edition of the Tangled Bank, a biweekly blog carnival featuring the best science and medicine posts in the blogosphere. The name of this carnival was taken from Charles Darwin's famous metaphor:

"It is interesting to contemplate a tangled bank, clothed with many plants of many kinds, with birds singing on the bushes, with various insects flitting about, and with worms crawling through the damp earth, and to reflect that these elaborately constructed forms, so different from each other, and dependent upon each other in so complex a manner, have all been produced by laws acting around us."

If you are new to Evolved and Rational, this blog deals with science, evolution, creationism, skepticism, atheism, and internet culture; albeit with a generous serving of lulz. If you like what you see, please subscribe to the RSS feed.

---

Send an email message to host@tangledbank.net if you want to submit an article to Tangled Bank. Be sure to include the words "Tangled Bank" in the subject line. Remember that this carnival only accepts one submission per week from each blogger.

Armor of God Pajamas

 

Hands up all of you who think that these armor pajamas are going to make the kids feel safe and secure at night?

I didn't think so.

The pajamas alone simply won't do. They'll also need semi-automatic handguns.

---

[Hat Tip: Friendly Atheist]

Any Questions?

 
David Scott Springer (DaveScot) is one of the IDiots who post on the Intelligent Design Creationism websites. One of his latest is an example of Google Trends, a nifty way of tracking Google search terms over a period of five years.

DaveScot posted a graph on Uncommon Descent showing the trend for "Intelligent Design" (blue), "Darwinian Evolution" (red), "Scientific Creationism" (orange), and "Theological Evolution" (green) [Fun With Google Trends - ID vs. Darwinism vs. Creationism]. Here it is ...


He ended the posting with the enigmatic "Any questions?"

Yes, as a matter of fact, I have many questions. For starters, why is there only a temporary blip in "Intelligent Design" in the Fall of 2005? That's when the Dover trial was in full swing so you might expect there to be an upswing in interest as the trial went on. After all, the daily reports were highlighting the destruction of Intelligent Design as a credible phenomenon and everyone likes a train wreck.

But why was there no significant interest before 2005 or after?

And why did he use "Darwinian evolution" as his query when he knows full well that this is mostly a creationist term.^(Update) The only people searching for articles on "Darwinian evolution" would be creationists. Wouldn't it be more informative to find out who was interested in just plain "evolution?" Wouldn't it be fun to see if that search term outranked "Intelligent Design?" You bet.

So here's the result: the top graph is for the USA and the bottom one is for the United Kingdom.




Any questions? I didn't think so.

Those of us who are involved in the creation/evolution debate tend to forget how little the general public knows about Intelligent Design Creationism. I'm teaching a class on scientific controversies and one section is about the evolution/creation debate. The 50 students in my class probably are there, in part, because they have an interest in this debate. When I asked them to explain "Intelligent Design" only a handful (~5) had any idea what it was and most of the students claimed they had never heard of it.

It looks like the wedge strategy isn't working very well.

Update: DaveScot was asked on Uncommon Descent why he used the term "Darwinian evolution" instead of just "evolution." His reply? .... "ID doesn’t dispute all “evolution”. It disputes Darwinian evolution." Is anyone still wondering why we call them IDiots?

---

Walking with Charles Darwin

 
Stavros Isaiadis posted this photograph of Darwin's walking stick on his blog Journey Through a Burning Mind [Damn those Immoral Darwinists!].



I'm sure Darwin used it while strolling on the Sandwalk. Undoubtedly the skull reminded him of his evil plan to destroy religion by publishing a book about evolution.

---

The New Model Organisms

 
A model organism is one that is amenable to a variety of studies. It often means that it has a well established genetics and that it is relatively easy to maintain in the laboratory.

Back in the late 1960s and early 1970s, scientists who were part of the 'phage group began to look around for new model organisms—especially eukaryotes. I decided to move from bacteriophage T4 to an already existing model organism, Drosophila melanogaster. Some workers set up entirely new systems, such as Caenorhabditis elegans [Nobel Laureates: Sydney Brenner, Robert Horvitz, John Sulston].

The research scientists who I knew at the time were having fierce debates over the proper choice of a new model organism and some of them choose systems that did not pan out. The ones that caught on were species like mouse, human, Arabidopsis, Tetrahymena, Dictyostelium, zebrafish, and some stange little fungus called Saccharomyces cerevisiae.

Now there's a whole new group of model organisms on the market and Cold Spring Harbor Laboratory has decided to publish protocols for each one of them [Emerging Model Organisms].

Here's the complete list. Some of them are new to me.

* Nematode (Pristionchus pacificus)
* Opossum (Monodelphus domestica)
* Planarians
* Snapdragon (Antirrhinum)
* Spider (Cupennius salei)
* Amphipod (Parhyale hawaiensis)
* Bichirs (Polypterus)
* Blind Cave Fish (Astyanax mexicanus)
* Butterfly (Bicyclus anynana)
* Choanoflagellates
* Comb Jellies (Ctenophora)
* Cricket (Gryllus bimaculatus)
* Demosponge (Amphimedon queenslandica)
* Dogfish (Scyliorhinus canicula)
* Finches
* Fruit Bat (Carollia perspicillata)
* Lamprey (Petromyzon marinus)
* Leech (Helobdella)
* Moss (Physcomitrella patens)
* Quail (Coturnix coturnix japonica)
* Snail (Ilyanassa obsoleta)
* Social Ameba (Dictyostelium discoideum)
* Tomato (Solanum lycopersicum)

---

Nobel Laureate: Severo Ochoa

 

The Nobel Prize in Physiology or Medicine 1959.

"for their discovery of the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid"

Severo Ochoa (1905 -1993 ) received the Nobel Prize in Physiology or Medicine for his discovery of an enzyme that synthesizes RNA from ribonucleotide triphosphates. The enzyme, polynucleotide phosphorylase [Monday's Molecule #90], was first isolated from the bacterium Azotobacter vinelandii. At the time it was thought to be the enzyme responsible for the synthesis of RNA in cells as described in the excerpt from the presentation speech below from the Nobel Prize website [1959 Presentation Speech].

Ochoa shared his prize with Arthur Kornberg who discovered a DNA polymerase [Nobel Laureate: Arthur Kornberg].

THEME:
Nobel Laureates

Ochoa's enzyme produces ribonucleic acids from ribonucleotides having twice the ratio of phosphoric acid residues as that contained in ribonucleic acid. The ribonucleic acid is formed by splitting out half of the phosphoric acid residues, and linking the nucleotides together to form large molecules, which, as far as we can prove today, do not differ in any way from natural nucleic acids. Kornberg's enzyme produces deoxyribonucleic acids in a similar, but not identical fashion. Both have arrived at the same, principally important result that in order to make the reaction start, it is necessary to add in the beginning a small amount of nucleic acid to act as a template. Otherwise the enzymes do not «know» which kind of nucleic acid they are to produce. As soon as they get a template to act as a guide, they start, just like a skilled type-setter, to copy the «manuscript» they have received. Here one recognizes life's own principle that like creates like. Even though several research workers had earlier suspected that such a mechanism was involved, the actual experimental proof is of greatest importance. Furthermore, Ochoa's enzyme has given us the possibility of enzymatically synthesizing simplified nucleic acids of great interest

Within a short time, scientists began to realize that polynucleotide phosphorylase did not require a DNA template. The enzyme synthesized random polymers of ribonucleotides in a reaction that is now recognized as a way of salvaging RNA in bacterial cells.

Within a few years Marshall Nirenberg, Gobind Khorana, and others began to exploit this enzyme to synthesize synthetic RNAs that were used to crack the genetic code [Nobel Laureates: Robert W. Holley, Har Gobind Khorana, and Marshall W. Nirenberg].

This is one example of a Nobel Prize that was awarded for the wrong reasons but few people begrudge Ochoa since he was widely recognized as an outstanding scientist. Arthur Kornberg worked with him for one year (1946) in New York where he (Kornberg) purified his first enzymes and fell in love with enzymes (Kornberg, 2001).

Ochoa was born in Spain and graduated from the University of Madrid with an M.D. degree in about 1925. He worked with Otto Meyerhof [Nobel Laureates: Otto Fritz Meyerhof] for a few years on metabolic enzymes before joining a series of labs in Europe. Eventually the civil war in Spain and the outbreak of World War II in Europe led him to join Carl and Gerty Cori in St. Louis, Missouri (USA) in 1942 [Nobel Laureates: Carl Ferdinand Cori and Gerty Theresa Cori]. From there he moved to New York University School of Medicine where he remained until his retirement in 1974.

Ochoa did not return to Spain until the year Franco died (1975). He celebrated his 70th birthday in spectacular manner according to Arthur Kornberg (Kornberg, 2001).

To celebrate his 70th birthday in 1975, Ochoa chose as guests the scientists he most respected worldwide. Symposia and celebratory dinners, starting in Barcelona, were followed by a visit with Salvador Dali in his museum in his hometown in Figueras and culminated in a gala of events in Madrid. It was a party, the likes of which has not been seen in scientific circles before or since.

---

[Photo Credits: Top: Kornberg (2001), Bottom: Severo Ochoa: La Conquista del Nobel]

Kornberg, A. (2001) Remembering Our Teachers. J. Biol. Chem. 276:3-11. [JBC Online]

Tamoxifen and Breast Cancer

 
When you get to my age, more and more of your female relatives, friends, and acquaintances will be diagnosed with breast cancer. They will be undergoing more or less radical surgery followed by chemotherapy and/or drug treatment. One of the most common drugs for the treatment of breast cancer is tamoxifen.

Tamoxifen is a chemical that binds to a protein called estrogen (or estradiol) receptor. The estrogen receptor is a protein that binds to DNA to increase (activate) or decrease (repress) gene expression. Its DNA binding properties are influenced by its interaction with the hormone estradiol (estrogen)—a discovery first reported by my friend Keith Yamamoto back in 1972 (Yamamoto and Alberts, 1972).

In normal cells, estrogen can stimulate the growth of tissues by turning on the genes that promote cell division. This is a good thing. However, it turns out that most of the breast cell cancers arise from cells that have estradiol receptors and in that case the presence of estrogen in your blood stream makes the cancer cells grow. These forms of cancer are called estrogen receptor positive (ER+) breast cancers.

That's the bad news. The good news is that such cancers respond well to tamoxifen. The effectiveness of tamoxifen is due to the fact that it binds to the estradiol receptor but doesn't convert it to the active regulator of gene expression.¹ When you take tamoxifen there's so much more of it in your bloodstream that it out-competes all of the estrogen. As a result the cancer cells can't grow, (but neither can any of the other tissues that need estrogen).

Hormone therapy (tamoxifen) is often combined with radiation or chemotherapy to reduce the risk of recurring cancer for women who have undergone surgery to remove tumors. However, if the cancer has not spread to the lymph nodes then hormone therapy by itself is effective against ER+ breast cancer. This is especially true for pre-menopausal women 40 years of age or older where chemotherapy does not add significantly to the effectiveness of tamoxifen [see tamoxifen].

---

1. This isn't quite true. Tamoxifen itself doesn't bind to the estradiol receptor protein, instead it is converted inside your body to other chemicals that do bind.

Yamamoto KR, Alberts BM. 1972 In vitro conversion of estradiol-receptor protein to its nuclear form: dependence on hormone and DNA. Proc. Natl. Acad. Sci. USA. 69:2105-2109. [PubMed]