NEWS

Seminal findings, highly cited papers, prizes and awards are an integral part of what defines a top-flight scientific career. Nature Medicine talked to one investigator whose work has been truly groundbreaking, but who, to the widespread surprise of the research community, was bypassed by both the Lasker and the Nobel committees for his discovery of nitric oxide’s cardiovascular effects. Salvador Moncada

Perhaps it was his deportation from El search in the UK and I managed to get a releasing factor (EDRF). “I wasn’t satisfied Salvador many years ago for political ac- fellowship to go to England in February, with the experimental model of mechani- tivism that taught Salvador Moncada the 1971.” cal removal of endothelium from strips of value of discretion. Certainly, as a man Moncada secured a place in Sir John tissue, so we decided to culture large who has married into a European royal Vane’s laboratory at the Royal College of quantities of vascular endothelial cells. family, it is a behavior that he must prac- Surgeons. “I was put in a project that was We measured EDRF coming from these tice on a daily basis. Now, three years part of the discovery that aspirin-like cells and quickly made the first break- after he was overlooked by the Nobel drugs inhibit prostaglandin biosynthe- through that later enabled EDRF to be committee for his role in the discovery of sis,” he says-work for which Vane was identified as NO-that EDRF was destroyed nitric oxide (NO) in the vascular en- later awarded the Nobel Prize. by superoxide radicals.” dothelium, Moncada retains a dignified However, a deep-seated belief that he On Furchgott’s speculation that EDRF public silence about the snub. “Insti- owed something to the country of his might be related to NO, Moncada tested tutions can give prizes to whomever they birth compelled him to return to the activity of NO in his bioassay and wish,” he says. “I am happy with the Honduras in 1974 “to see if it was possible found it to equate to EDRF. He then mea- work I’ve done.” to do research there.” He was quickly dis- sured NO levels directly following cell Moncada’s current directorship of the illusioned by the conditions. “There are stimulation using a chemiluminescence Wolfson Institute for Biomedical Research more developed countries in Latin machine adapted from the automobile in- at University College London is a long America such as Brazil, Argentina, dustry, which became the first demon- way, both in conceptual and geographical Mexico, Chile, where research is possible. stration that EDRF and NO are the same terms, from his scien- But Honduras is one of the substance. Indeed, Moncada’s Nature tific origins. Born in most underdeveloped coun- paper was the most cited work of 1987, the Central American tries, so there’s no infra- and he acknowledges Furchgott’s role in country of Honduras, structure, no money and no the abstract: “…it has recently been sug- Moncada moved across connections with the out- gested by Furchgott that EDRF may be © http://medicine.nature.com Group 2002 Nature Publishing the border to El Salva- side world to do scientific re- NO.” With the conclusion, “Thus NO re- dor at an early age and search.” leased from endothelial cells is indistin- went on to qualify as an He returned to the UK guishable from EDRF in terms of MD. His interest in car- and re-joined Vane who had biological activity, stability and suscepti- diovascular science was moved to the Wellcome bility to an inhibitor and to a potentiator. triggered by working research laboratories in We suggest that EDRF and NO are identi- with Peruvian pharma- Beckenham. It is the atmos- cal.” (Nature 327, 524; 1987). His team cologist Augusto Cam- phere and philosophy of also discovered that NO was made from pos, who was visiting those laboratories that the amino acid L-arginine by an enzyme the University of El Scientific adventurer Moncada is now trying to they named NO synthase. Salvador for a year. recreate at the Wolfson Again, I ask him how he feels, having The 1970s was a time Institute. “Wellcome was a very special made the first biological identification of of political unrest in El Salvador due to so- place, unlike any other industrial lab; it NO, discovered its synthetic pathway and cial inequalities, a poor economy and the was a very open and scientific environ- developed a widely used bioassay for its repressive measures of dictatorship. Civil ment with a lot of flexibility and a place measurement, to have been excluded war broke out between the government where lots of scientific discoveries were from being one of the three scientists and left-wing parties. Moncada joined the made and transformed into medicine.” awarded a Nobel Prize for the work. But throngs of protestors with the result that Moncada played a central role in the he is determined to let the story of his in- he was deported to Honduras, and forced discovery of thromboxane synthetase and volvement speak for itself. “I’ve explained to leave behind his first wife and child. its inhibitors, and the anti-aggregatory my work. The scientific community Like all young investigators who are se- agent, prostacyclin, for which he is protested, not me. Because there are no rious about building a career in research, named on the patent. The team also de- objective data to analyze [for prize-giving] he needed to gain experience working in veloped prostacyclin as a medicine for I have no comment to make. I know all an environment where the best intellects cardiopulmonary bypass operations and three winners and I’m good friends with and equipment were on-hand. For many pulmonary hypertension. them.” He then politely returns to dis- of his peers, that meant the US. But It was in 1985, following a visit by cussing current chronic degenerative dis- Moncada “...wanted to come to Europe Robert Furchgott to Beckenham, that ease projects running at the Wolfson for cultural reasons and for scientific rea- Moncada began investigations to deter- Institute. sons was particularly interested in re- mine the identity of endothelium-derived Karen Birmingham, London

98 NATURE MEDICINE • VOLUME 8 • NUMBER 2 • FEBRUARY 2002