Rigurosidad del estudio que vincula mortalidad y maíz transgénico en ratas (19 septiembre 2012)

¡Compártelo!
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  

«Un estudio indica que ratas alimentadas con transgénicos tienen más tumores«. La noticia ha corrido como la pólvora a raíz de un estudio [1] publicado por un equipo de científicos franceses.

Aunque se ha atacado al estudio por el obvio sesgo del autor principal, Gilles-Eric Séralini, a raíz de su activismo anti transgénicos, parecen existir razones objetivas (no ad-hominem) para desconfiar de los resultados.

El artículo deja que desear tanto en metodología, exposición sesgada de únicamente las partes de los hechos que interesan y análisis estadístico más bien flojo. Adjunto abajo una recopilación de opiniones de científicos que clasifican los resultados desde inconcluyentes hasta absurdos.

El estudio

Se trata del artículo [1], publicado el 19 de septiembre de 2012 en la revista Food and Chemical Toxicology, impactada y con revisión por pares. Esto asegura un mínimo de «calidad científica» y objetividad, aunque cualquiera que sepa cómo funcionan estas cosas coincidirá en que revisión por pares no es sinónimo de fiabilidad absoluta. Además, el nivel de rigurosidad exigido varía ampliamente dependiendo de la revista en concreto. Esto solamente lo menciono para aclararlo al que crea que el 100% de lo que se publica debe necesariamente ser rigurosamente cierto, un ideal que todos perseguimos pero difícil de alcanzar en la práctica. Más aún en las complejas ciencias de la vida.

El experimento empleó a 200 ratas de laboratorio (Sprague-Dawley) durante 24 meses, la edad típica de  dichos animales, divididos en 10 grupos de 10 machos y 10 hembras cada uno. Al grupo de control (10+10 animales) se les dejó comer maíz no transgénico; a otros seis grupos se les dió maíz GM NK603 modificado transgénicamente (GMO) en distintas concentraciones y que había sido tratado o no con el pesticida round up (R) ; a otros tres grupos se les alimentó con maíz no GMO pero al agua se le añadió distintas concentraciones de pesticida R.

Como resultado principal, a muchas hembras de las alimentadas con maíz GMO o pesticida R les crecieron tumores mamarios, que son reportados en unas fotos con mucho impacto mediático:

Sobre un ~30% de las ratas del grupo de control también murieron y muchas desarrollaron tumores, pero son las únicas de las que no se muestran imágenes.

Rigor estadístico

Lo siguiente es mi opinión. 

La siguiente figura del estudio muestra la mortalidad de machos y hembras a lo largo del tiempo para distintas dosis de maíz GMO, pesticida (R) y ambos (GMO+R). Las gráficas escalonadas que van subiendo al ir avanzando el tiempo hacia la derecha indican la cantidad de individuos que mueren antes de esa fecha:


La zona gris a partir del día ~600, que indica la edad media de muerte del grupo de control, que por cierto, es de únicamente 10 ratas, valor muy corto biológica y estadísticamente.

En los machos (columna izquierda), se puede ver que realmente no sobreviven menos que esa media. De hecho, al grupo al que más concentración de GMO se le da parecen vivir más que la media del grupo de control.

En las hembras (columna derecha), sí que da la «sensación» de que mueren antes que en el grupo de control. A falta de una medida estadística (p.ej. mediante un valor chi2 de significancia), esta sensación viene de la impresión visual de que las muertes (los escalones de la gráfica) ocurren bastante antes en los alimentados con maíz GMO y/o pesticida R que los del grupo de control  (gráfica escalonada punteada).

Representado con dos líneas verticales discontinuas se muestra la la desviación estándar de la media (SEM, por standard error of mean). Se da el dato de la edad de muerte de hembras del grupo de control: 701±20 días. Interpreto del estudio que ese «20» es la SEM, cuya fórmula sería:

SEM = σ (desviación estándar de las muestras) / raíz_cuadrada(número de muestras)

De donde se puede despejar la desviación estándar σ=63,2 días de vida. Un intervalo de confianza del 95%, nos da un intervalo de confianza para la muerte de hembras de [575, 827] días.

De nuevo a falta de una medida numérica, personalmente no me parece que muchas de las muertes ocurran fuera de ese intervalo. Tratándose además de únicamente 10 animales por grupo, no se puede hablar de datos muy significativos estadísticamente.

Insisto en que resulta sospechoso que no den ningún valor de significancia estadística: ningún investigador sería tan torpe de dejar de apoyar sus resultados en dicho análisis estadístico… si apoyasen sus tesis.

En mi humilde opinión, el estudio no puede ser tenido por concluyente solamente con los datos aportados. Y más aún conociendo el sesgo ideológico de los autores. No digo que los estudios financiados por Monsanto carezcan de sesgo en sentido contrario, pero no hay que cegarse a la realidad de que en muchos de estos estudios se acaba torturando a los datos hasta que confiesen lo que a uno le interesa, tanto en un caso, como en otro.

La opinión de otros científicos

Os dejo a continuación una recopilación de otras críticas al estudio. Siento dejarlas en inglés, pero no tengo mucho tiempo para traducirlas. Las negritas y subrayados son míos.

Prof Maurice Moloney, Institute Director and Chief Executive , Rothamsted Research:

«Although this paper has been published in a peer–reviewed journal with an IF of about 3, there are anomalies throughout the paper that normally should have been corrected or resolved through the peer-review process. For a paper with such potentially important findings, it would have been more satisfying to have seen something with a more conventional statistical analysis. A comparison of each measured parameter, which took into account the variance throughout the experiment, which would have been revealed using a multiple range test, would have provided better evidence for the concluding remarks and the abstract. Figure 1 does not provide any data from the controls and their variance is unreported here. Table 2 reports different numbers of individuals used for the controls than the treatments. In all cases the controls have used less individuals than used in the treatments. The data in Table 2 do not show confidence intervals or provide evidence of significant differences between all the treatments and the controls. The lack of a dose response effect is argued by the authors to be indicative of a “threshold” effect. This is an extrapolation of their findings and could only be determined by intermediate dosing. The photographs are very graphic, but do not include a control. Sprague-Dawley rats frequently develop mammary tumours in well-fed controls. Are we to conclude from this that no controls developed tumours? Numerically, we cannot tell, because they are absent also from Figure 2. We are performing a more detailed analysis of the statistics in relation to the conclusions, but for the present it is fair to point out that normally a referee would insist on showing the control data and its variance in such a study.»

Prof David Spiegelhalter, Winton Professor of the Public Understanding Of Risk, University of Cambridge:

«In my opinion, the methods, stats and reporting of results are all well below the standard I would expect in a rigorous study – to be honest I am surprised it was accepted for publication.

“All the comparisons are made with the ‘untreated’ control group, which only comprised 10 rats of each sex, the majority of which also developed tumours. Superficially they appear to have performed better than most of the treated groups (although the highest dose GMO and Roundup male groups also fared well), but there is no proper statistical analysis, and the numbers are so low they do not amount to substantial evidence. I would be unwilling to accept these results unless they were replicated properly.»

Dr Wendy Harwood, senior scientist, John Innes Centre:

«The full data set has not been made available, but the findings do not contradict previous findings that genetic modification itself is a neutral technology, with no inherent health or environmental risks.

«We have to ask whether a diet with this level of maize is normal for rats. Another control with an alternative diet should have been included.

«Ten rats per group is a small number. For example, is the death of three out of ten controls compared to five out of ten males in the treated group statistically significant?

«The data from the control group fed non-GM maize is not included in the main figures making it very difficult to interpret the results.

«Without access to the full data, we can only say that these results cannot be interpreted as showing that GM technology itself is dangerous. However they do indicate possible concerns over long-term exposure to Roundup that require further study.»

Prof Anthony Trewavas, Professor of Cell Biology, University of Edinburgh:

«The control group is inadequate to make any deduction. Only 10 rodents so far as I can see and some of these develop tumours. Until you know the degree of variation in 90 or 180 (divided into groups of ten) control rodents these results are of no value.

«These figures for normal appearance of tumours in these rodent lines are surely available and using a line which is very susceptible to tumours can easily bias any result. To be frank it looks like random variation to me in a rodent line likely to develop tumours anyway.»

Prof Ottoline Leyser, Associate Director of the Sainsbury Laboratory, University of Cambridge:

«Like most of the GM debate, this work has very little to do with GM. The authors of the paper do not suggest that the effects are caused by genetic modification. They describe effects of the roundup herbicide itself and effects that they attribute to the activity of the enzyme introduced into the roundup resistant maize. There is good evidence that introducing genes in to crops using GM techniques results in fewer changes to the crops than introducing them using conventional breeding.

«This is unfortunately rather a subtle point and is somewhat tangential to the immediate issue.»

Prof Tom Sanders, Head of the Nutritional Sciences Research Division, King’s College London:

«Most toxicology studies are terminated at normal lifespan i.e. 2 years. Immortality is not an alternative.

«No food intake data is provided or growth data. This strain of rat is very prone to mammary tumours particularly when food intake is not restricted.

«There is a lack of information on the composition of the diet. One concern is whether there were mycotoxins in the maize meal because of improper storage. Zearalanone is a well know phytoestrogen produced by filamentous fungi that grow on maize.

«The statistical methods are unconventional, there is no clearly defined data analysis plan and probabilities are not adjusted for multiple comparisons.»

Prof Mark Tester, Research Professor, Australian Centre for Plant Functional Genomics, University of Adelaide:

«The first thing that leaps to my mind is why has nothing emerged from epidemiological studies in the countries where so much GM has been in the food chain for so long? If the effects are as big as purported, and if the work really is relevant to humans, why aren’t the North Americans dropping like flies?! GM has been in the food chain for over a decade over there – and longevity continues to increase inexorably!

«And if the effects are as big as claimed, why have none of the previous 100+ plus studies by reputable scientists, in refereed journals, noticed anything at all?

«Finally, of course, this was a study of one event with one gene. To then extrapolate to all genetically modified crops is absurd. Even if it eventuates that there is an issue with this one event, or even this one gene, there is no reason at all for other genes introduced using GM to carry the same burden of risk. GM is an adaptation of a natural process that occurs all the time all over the planet – it is “only” a technology, a technique. It is how it is used that is more important. Generalisations about the risk of the technology per se are absurd.»


Prof Alan Boobis, Professor of Biochemical Pharmacology, Imperial College London:

«Some of the effects are presented in a way that makes it difficult to evaluate their significance. For example, there does not appear to be a statistical analysis of the mammary tumours. These occur quite often in untreated animals. One would usually also take into account the historical controls in the testing lab, in reaching a conclusion. The pesticide itself has been subject to long term studies in rodents by others.»

Referencias:
[1]  «Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize«,  Gilles-Eric Séralini, Emilie Clair, Robin Mesnage, Steeve Gress, Nicolas Defarge, Manuela Malatesta, Didier Hennequin, Joël Spiroux de Vendômois, Food and Chemical Toxicology, Sep. 2012 (artículo)
[2] Noticia en BBC
[3] http://esmateria.com/2012/09/19/los-expertos-rebaten-el-estudio-que-vincula-transgenicos-con-tumores-galopantes/
[4] http://www.sciencemediacentre.org/pages/press_releases/12-09-19_gm_maize_rats_tumours.htm
[5] http://www.sciencemediacentre.org/pages/press_releases/12-09-19_gm_maize_rats_tumours.htm


¡Compártelo!
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
Etiquetado con: , ,