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Overexpression of ob gene in obesity
kind that is normal between researchers and the industry. However, the chairman of the Swedish Institute against Bribes-a : non-governmental institution monitoring ethics in trade and industry-has, on the basis of the articles published last week, officially criticised Hokfelt for "immense : lack of judgment". Grillner said that there has been no evidence of undue influence on Hokfelt or the committee. Hokfelt, he said, is a leading scientist and was in the 1980s the . most cited author in neuroscience and fifth in the entire biomedical field. As for the Madrid conference, in 1985-86 Hokfelt accepted 24 out of 54 invitations to conferences, one of which was arranged by Fidia. His request to change his business-class air-ticket for two economy
drugs to counteract neuronal degeneration, supported Levi-Montalcini after she retired from her research position in the USA and returned to Italy, since her research
the interest of the company. Dagens Nyheter cites Duilio Poggiolini, who has claimed that Fidia spent an equivalent of US$8 million in a campaign to make Levi-Montalcini a Nobel laureate. Poggiolini was an official in the Italian Health Ministry’s pharmaceutical section when in 1994 he was arrested on charges of accepting bribes from several pharmaceutical firms. He was released from prison in April this year and has been giving testimony to an inquiry in Italy into corruption. The newspaper also cited other sources, on the value to all Italian companies doing neuroscience research, of a Nobel Prize for an Italian tickets was granted. researcher The Golgi Award ($2000) was just one The paper states that Fidia focused on of many awards he has received during his Hokfelt, the only member of the commitcareer, said Grillner; most of the others tee representing neurobiology. Dagens ; carried substantially larger monetary Nyheter claimed that, among other things, value. In the 1990s he was for 3 years a Fidia paid for the ticket for H6kfelt’s member of the advisory board of Fidia in wife’s fares when he lectured at a conferGeorgetown, USA. Hokfelt has also ence in Madrid and that it sponsored a served on several boards of international conference at Hokfelt’s request. The paper research institutes and of other pharmadid not give the source of some of its ceutical companies. : statements. While describing a campaign Grillner said that Levi-Montalcini’s outto secure an award, the paper also standing contribution made her a serious emphasised that it had no evidence that candidate early on, and her work was Fidia managed to influence the Nobel scrutinised by specialists in different areas. committee. : He added that the decision to award her a In 1986 Hokfelt did receive the Golgi prize was very well received by the Award given by Fidia Research Foundascientific community. tion, and he had been a member of one of Fidia’s advisory boards. Hokfelt has said that his relations with Fidia were of the Mats Nilsson was
central
to
,
Overexpression of ob gene in obesity
Lethal slimming cocktails in Germany investigated Several doctors and pharmacists in Germany have been taken into custody. They
being investigated for prescribing, producing, and distributing diet pills containing a dangerous mixture of thyroid hormones, diuretics, amphetamine, and metformin in high doses. Such pills are are
said to have caused the death of at least four women in Germany. The scandal over these "death pills" has raised questions over the efficacy of drug regulations and their implementation in Germany. The regulation allows doctors to prescribe individual mixtures of drugs as long as these prescriptions accord with current medical standards. Chemists are obliged to prepare the prescribed mixtures, provided they are not harmful. A chemist may not make up more than 100 mixtures a day, but these regulations have been broken in the case of the diet pills implicated in the four deaths. The pills contained drugs with severe side-effects such as arrhythmia and lactic acidosis. Patients were led to believe that the components were purely of natural herbal origin. Thousands of people are said to have taken these mixtures. The diet pills are not unknown to the German drug authorities. In 1986 the Federal Drug Agency classed them as dangerous and made their prescription and production illegal.
Annette Tuffs
articles in Science, Amgen
University, Investigation of the role of the obese (ob) ;: gene in obesity is gathering pace. Barely a month after reports that injections of a hormone encoded by the murine ob gene make fat mice thin (Science 1995; 269:: 540-43, 543-46, 546-49) come two studies, from Sweden and Canada respectively, showing overexpression of ob in fat cells from massively obese men and women (Nature Med 1995; 1: 950-53, 953-56). ’, In obese subjects the density of ob mRNA averaged 80% higher than in the ’
non-obese. The human and
mouse findings are not directly comparable. The three groups reporting in Science last month worked
with a strain of mice homozygous for a mutation in the ob gene. These animals, which were grossly obese, weighing about twice as much as normal mice, produced no ob protein. As yet, however, there is no evidence of an ob mutation in obese human beings, and so far the pathogenesis of massive obesity has eluded explanation. In ’man the production of ob protein by adipose tissue alone (and not, for instance, by human liver, kidney, muscle,
764
cortex) suggests that the hotbe involved in a feedback loop, may from fat cells to hypothalamus, controlling energy intake and/or expenditure. In obese people a defect in the feedback mechanism could lead to insensitivity to the ob gene product, increased fat accumulation, and hence larger cells and enhanced expression of ob mRNA. The paradox between overexpression of ob protein in obese people and a total lack of the hormone (now known as leptin) in obese mice has yet to be resolved. : : Whether leptin-which reduces the: body weight of obese mice by 40% within a month and food intake by 60% within a few days-will turn out to be a miracle cure for human obesity remains to be seen. But several pharmaceutical companies are already backing what they see as a likely winner. Two of the mouse studies published last month emanated from industry research teams-one from Amgen, a biotechnology company based in California, the other from Hoffman- ’, La Roche. According to a newspiece (Science 269: 475-76) accompanying the or
cerebral
mone
New
paid Rockefeller
York, US$20 million for
exclusive access to the work of the third group, headed by Dr Jeffrey Friedman. Drug-company funding-from Sandoz and Parke-Davis in this instance-also supported the studies of human obesity carried out by the team at the Karolinska Institute in Stockholm. The obesity stakes are undoubtedly high: the accompanying newspiece says that, according to the National Institutes of Health, up to a third of all Americans are overweight, and they spend$30 million a year on trying to be slim. Even if leptin survives the lengthy toxicity and efficacy studies required for licensing of its use in man, a nagging concern will remain. In grossly obese mice given leptin the fat simply melted away, but normal mice injected with leptin also lost weight- with a reduction in body fat from 12% to 0-7% of body weight. In a society in which many already slim people aspire to a skeletal silhouette, the potential for abuse is obvious.
Dorothy Bonn
drugs to counteract neuronal degeneration, supported Levi-Montalcini after she retired from her research position in the USA and returned to Italy, since her research
the interest of the company. Dagens Nyheter cites Duilio Poggiolini, who has claimed that Fidia spent an equivalent of US$8 million in a campaign to make Levi-Montalcini a Nobel laureate. Poggiolini was an official in the Italian Health Ministry’s pharmaceutical section when in 1994 he was arrested on charges of accepting bribes from several pharmaceutical firms. He was released from prison in April this year and has been giving testimony to an inquiry in Italy into corruption. The newspaper also cited other sources, on the value to all Italian companies doing neuroscience research, of a Nobel Prize for an Italian tickets was granted. researcher The Golgi Award ($2000) was just one The paper states that Fidia focused on of many awards he has received during his Hokfelt, the only member of the commitcareer, said Grillner; most of the others tee representing neurobiology. Dagens ; carried substantially larger monetary Nyheter claimed that, among other things, value. In the 1990s he was for 3 years a Fidia paid for the ticket for H6kfelt’s member of the advisory board of Fidia in wife’s fares when he lectured at a conferGeorgetown, USA. Hokfelt has also ence in Madrid and that it sponsored a served on several boards of international conference at Hokfelt’s request. The paper research institutes and of other pharmadid not give the source of some of its ceutical companies. : statements. While describing a campaign Grillner said that Levi-Montalcini’s outto secure an award, the paper also standing contribution made her a serious emphasised that it had no evidence that candidate early on, and her work was Fidia managed to influence the Nobel scrutinised by specialists in different areas. committee. : He added that the decision to award her a In 1986 Hokfelt did receive the Golgi prize was very well received by the Award given by Fidia Research Foundascientific community. tion, and he had been a member of one of Fidia’s advisory boards. Hokfelt has said that his relations with Fidia were of the Mats Nilsson was
central
to
,
Overexpression of ob gene in obesity
Lethal slimming cocktails in Germany investigated Several doctors and pharmacists in Germany have been taken into custody. They
being investigated for prescribing, producing, and distributing diet pills containing a dangerous mixture of thyroid hormones, diuretics, amphetamine, and metformin in high doses. Such pills are are
said to have caused the death of at least four women in Germany. The scandal over these "death pills" has raised questions over the efficacy of drug regulations and their implementation in Germany. The regulation allows doctors to prescribe individual mixtures of drugs as long as these prescriptions accord with current medical standards. Chemists are obliged to prepare the prescribed mixtures, provided they are not harmful. A chemist may not make up more than 100 mixtures a day, but these regulations have been broken in the case of the diet pills implicated in the four deaths. The pills contained drugs with severe side-effects such as arrhythmia and lactic acidosis. Patients were led to believe that the components were purely of natural herbal origin. Thousands of people are said to have taken these mixtures. The diet pills are not unknown to the German drug authorities. In 1986 the Federal Drug Agency classed them as dangerous and made their prescription and production illegal.
Annette Tuffs
articles in Science, Amgen
University, Investigation of the role of the obese (ob) ;: gene in obesity is gathering pace. Barely a month after reports that injections of a hormone encoded by the murine ob gene make fat mice thin (Science 1995; 269:: 540-43, 543-46, 546-49) come two studies, from Sweden and Canada respectively, showing overexpression of ob in fat cells from massively obese men and women (Nature Med 1995; 1: 950-53, 953-56). ’, In obese subjects the density of ob mRNA averaged 80% higher than in the ’
non-obese. The human and
mouse findings are not directly comparable. The three groups reporting in Science last month worked
with a strain of mice homozygous for a mutation in the ob gene. These animals, which were grossly obese, weighing about twice as much as normal mice, produced no ob protein. As yet, however, there is no evidence of an ob mutation in obese human beings, and so far the pathogenesis of massive obesity has eluded explanation. In ’man the production of ob protein by adipose tissue alone (and not, for instance, by human liver, kidney, muscle,
764
cortex) suggests that the hotbe involved in a feedback loop, may from fat cells to hypothalamus, controlling energy intake and/or expenditure. In obese people a defect in the feedback mechanism could lead to insensitivity to the ob gene product, increased fat accumulation, and hence larger cells and enhanced expression of ob mRNA. The paradox between overexpression of ob protein in obese people and a total lack of the hormone (now known as leptin) in obese mice has yet to be resolved. : : Whether leptin-which reduces the: body weight of obese mice by 40% within a month and food intake by 60% within a few days-will turn out to be a miracle cure for human obesity remains to be seen. But several pharmaceutical companies are already backing what they see as a likely winner. Two of the mouse studies published last month emanated from industry research teams-one from Amgen, a biotechnology company based in California, the other from Hoffman- ’, La Roche. According to a newspiece (Science 269: 475-76) accompanying the or
cerebral
mone
New
paid Rockefeller
York, US$20 million for
exclusive access to the work of the third group, headed by Dr Jeffrey Friedman. Drug-company funding-from Sandoz and Parke-Davis in this instance-also supported the studies of human obesity carried out by the team at the Karolinska Institute in Stockholm. The obesity stakes are undoubtedly high: the accompanying newspiece says that, according to the National Institutes of Health, up to a third of all Americans are overweight, and they spend$30 million a year on trying to be slim. Even if leptin survives the lengthy toxicity and efficacy studies required for licensing of its use in man, a nagging concern will remain. In grossly obese mice given leptin the fat simply melted away, but normal mice injected with leptin also lost weight- with a reduction in body fat from 12% to 0-7% of body weight. In a society in which many already slim people aspire to a skeletal silhouette, the potential for abuse is obvious.
Dorothy Bonn