tag:theconversation.com,2011:/institutions/wellcome-trust-sanger-institute-1203/articles
Wellcome Trust Sanger Institute
2020-02-17T18:14:09Z
tag:theconversation.com,2011:article/131257
2020-02-17T18:14:09Z
2020-02-17T18:14:09Z
Cancer du poumon : arrêter de fumer régénère les cellules pulmonaires protectrices
<figure><img src="https://images.theconversation.com/files/315774/original/file-20200217-11040-18yay1o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">file kwzup</span> </figcaption></figure><p><a href="https://www.who.int/tobacco/quitting/benefits/en/">Arrêter de fumer</a> est un <a href="https://www.bmj.com/content/321/7257/323">excellent moyen de réduire le risque</a> de développer un cancer du poumon. Cependant jusqu’à présent, les experts en ignoraient la raison précise. Nos <a href="https://www.nature.com/articles/s41586-020-1961-1">dernières recherches</a> révèlent que les voies respiratoires des personnes qui arrêtent de fumer se repeuplent de cellules normales, non cancéreuses, qui participent à la protection des poumons. De ce fait, le risque de cancer diminue.</p>
<p>Le cancer débute par une accumulation de modifications génétiques au sein d’une unique cellule. Ces mutations font sauter les verrous qui imposent, en temps normal, des contraintes à sa croissance ; <a href="https://www.nature.com/articles/nature07943">cette cellule devenue « rénégate » commence à se reproduire rapidement, de manière incontrôlée</a>.</p>
<p>Tout au long de notre vie, nos cellules acquièrent des mutations au rythme régulier <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536223/">d’environ 20 à 50 mutations par cellule et par an</a>. Heureusement, la grande majorité de ces mutations sont tout à fait inoffensives. Elles n’affectent pas nos cellules de manière mesurable, et passent inaperçues.</p>
<p>Mais il arrive parfois qu’une mutation touche le mauvais gène, dans la mauvaise cellule, et pousse celle-ci sur le chemin du cancer. Nous appelons ces modifications génétiques des « mutations pilotes » (de l’anglais <a href="https://www.nature.com/articles/nature07943">« driver mutations »</a>. Pour que la cellule concernée devienne une cellule cancéreuse à part entière, il faut probablement que surviennent <a href="https://www.cell.com/cell/fulltext/S0092-8674(17)31136-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867417311364%3Fshall%3Dtrue">cinq à dix mutations supplémentaires de ce type</a>.</p>
<p>Grâce aux progrès du séquençage, nous sommes désormais en mesure d’étudier les 3 milliards de <a href="https://www.rts.ch/decouverte/sante-et-medecine/corps-humain/8331780-comment-les-bases-azotees-de-l-adn-s-associent-elles-.html">bases de l’ADN</a> qui constituent l’empreinte génétique d’une cellule (ou génome). C’est le séquençage de l’ADN de cellules cancéreuses provenant de poumons de fumeurs, et sa comparaison avec celui de cellules provenant de non-fumeurs, qui nous a appris que le tabagisme augmente le nombre de mutations dans les cellules pulmonaires.</p>
<p>La liaison à l’ADN des agents cancérigènes contenus dans le tabac est influencée par leurs propriétés chimiques. Cela signifie que certains types de mutations sont plus susceptibles de se produire que d’autres. On peut donc reconnaître la <a href="https://www.nature.com/articles/nature08629">« signature » de mutations</a> qu’inscrit l’usage du tabac dans le génome. Ce n’est pas le cas des autres causes de dommages à l’ADN.</p>
<p>Notre équipe s’intéresse aux premiers stades du développement du cancer du poumon. Nous tentons plus particulièrement de comprendre ce qui arrive aux cellules normales qui se retrouvent exposées à la fumée de tabac.</p>
<p>Nous avons pour cela mis au point diverses méthodes permettant d’isoler, à partir de petites biopsies des voies respiratoires d’un patient, des cellules normales uniques. Chacune d’entre elle est ensuite cultivée dans incubateur afin d’obtenir suffisamment d’ADN pour le séquençage. Nous avons de cette façon <a href="https://www.nature.com/articles/s41586-020-1961-1">analysé les génomes de 632 cellules</a> provenant de 16 participants à l’étude, parmi lesquels 13 adultes (d’âge moyen ou plus âgés) répartis comme suit : quatre n’avaient jamais fumé, six étaient d’ex-fumeurs, et trois continuaient à fumer fumeurs actuels. Les cellules de trois enfants ont aussi été analysées.</p>
<p>Les résultats ont révélé que, chez les non-fumeurs, le nombre de mutations augmente régulièrement avec l’âge. Ainsi, à l’âge de 60 ans, chaque cellule pulmonaire normale contient environ 1 000 à 1 500 mutations. Ces mutations résultent de « l’usure normale » de l’organisme. Il s’agit du même type de mutations que celui qui survient dans d’autres organes du corps. En outre, seuls 5 % environ des cellules étudiées de non-fumeurs contenaient des mutations pilotes.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Les mutations pilotes sont à l’origine du développement de cancers.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/digital-illustration-lung-cancer-cells-color-233501644">Raj Creationzs/Shutterstock</a></span>
</figcaption>
</figure>
<p>Le tableau est très différent chez les fumeurs. Nous avons ainsi découvert que chaque cellule pulmonaire contenait en moyenne 5 000 mutations de plus que le nombre attendu dans des cellules provenant d’un non-fumeur du même âge. Ce qui est encore plus frappant, c’est que la variation du nombre de mutations d’une cellule à l’autre était également bien plus importante chez les fumeurs.</p>
<p>Certaines cellules présentaient 10 000 à 15 000 mutations, soit dix fois plus de mutations que ce à quoi on s’attendrait si la personne n’avait pas fumé. Ces mutations supplémentaires portaient bien la signature des substances chimiques contenues dans la fumée de tabac, confirmant donc qu’elles étaient bien directement attribuables à la consommation de cigarettes.</p>
<p>Parallèlement à l’augmentation du nombre total de mutations, nous avons également constaté une augmentation substantielle du nombre de mutations pilotes. Plus d’un quart des cellules pulmonaires de tous les fumeurs que nous avons étudiées en contenaient au moins une. Certaines en avaient même deux ou trois. Étant donné que cinq à dix de ces mutations peuvent provoquer un cancer, il est clair que de nombreuses cellules pulmonaires normales chez ces fumeurs d’âge moyen ou plus âgés deviendront probablement cancéreuses.</p>
<h2>Il n’est jamais trop tard pour arrêter</h2>
<p>Mais le résultat le plus excitant a concerné les personnes qui avaient arrêté de fumer. Nous avons découvert que les anciens fumeurs possédaient deux groupes de cellules différents. Les cellules de l’un de ces deux groupes présentaient effectivement les milliers de mutations supplémentaires observées chez les fumeurs. Cependant, celles de l’autre groupe étaient, pour l’essentiel, normales. Autrement dit, ce groupe de cellules presque normales présentait le même nombre de mutations que celui que l’on s’attendrait à trouver dans les cellules d’une personne n’ayant jamais fumé.</p>
<p>Les cellules de ce second groupe étaient quatre fois plus nombreuses chez les anciens fumeurs que chez les fumeurs. Ce résultat suggère que, une fois qu’une personne a cessé de fumer, le nombre de ces cellules quasi normales augmente pour reconstituer la paroi des voies respiratoires. Nous avons pu constater que la multiplication de ces cellules se produisait même chez d’anciens fumeurs qui avaient consommé un paquet de cigarettes par jour pendant plus de 40 ans.</p>
<p>La raison pour laquelle cette découverte est si intéressante est que ce groupe de cellules quasi normales protège contre le cancer. En effet, lorsqu’un ancien fumeur développe un cancer du poumon, la cellule en cause provient toujours du <a href="https://www.cell.com/cell/fulltext/S0092-8674(12)01061-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867412010616%3Fshall%3Dtrue">groupe de cellules fortement endommagées</a> – et non du groupe de cellules quasi normales.</p>
<p>Nous comprenons maintenant pourquoi notre risque de cancer diminue de façon si importante lorsque nous arrêtons de fumer. C’est parce que le corps réapprovisionne les voies respiratoires avec des cellules qui sont, pour l’essentiel, normales. La prochaine étape de nos recherches consistera à déterminer comment les cellules de ce groupe parviennent à éviter les dommages causés par l’exposition à la fumée de cigarette, et comment nous pourrions les stimuler pour qu’elles se rétablissent encore davantage.</p>
<p>Des travaux antérieurs menés sur des souris fournissent peut-être un début d’explication : il existerait un groupe de cellules souches <a href="https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30123-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590918301231%3Fshall%3Dtrue">enfouies profondément dans les glandes qui produisent le mucus sécrété par les voies respiratoires</a>. À cet endroit, elles seraient naturellement mieux protégées de la fumée de tabac que les cellules situées à la surface des voies respiratoires.</p>
<p>Nos résultats démontrent à nouveau que, quel que soit l’âge, l’arrêt du tabac freine non seulement l’accumulation de dommages cellulaires supplémentaires, mais que cesser de fumer peut aussi réveiller des cellules qui n’ont pas été endommagées par le tabagisme.</p><img src="https://counter.theconversation.com/content/131257/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sam Janes est financé par Wellcome Trust et CRUK, en lien avec ce travail</span></em></p><p class="fine-print"><em><span>Peter Campbell reçoit des fonds du projet Mutographs, financé par Cancer Research UK, et du Wellcome Trust, en lien avec ce travail.</span></em></p>
Les poumons des anciens fumeurs contiennent quatre fois plus de cellules « normales », protectrices, que ceux des fumeurs. Pourquoi ?
Sam Janes, Professor of Respiratory Medicine, UCL
Peter Campbell, Head of Cancer, Ageing and Somatic Mutation, Wellcome Trust Sanger Institute
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/131056
2020-02-03T21:47:45Z
2020-02-03T21:47:45Z
Las células que protegen contra el cáncer de pulmón crecen de nuevo al dejar de fumar
<figure><img src="https://images.theconversation.com/files/313376/original/file-20200203-41490-1v932di.jpg?ixlib=rb-1.1.0&rect=7%2C0%2C5192%2C3274&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/stop-smoking-382326067"> Nuttaphong Sriset / Shutterstock</a></span></figcaption></figure><p>Sabemos que <a href="https://www.who.int/tobacco/quitting/benefits/en/">dejar de fumar</a> es un <a href="https://www.bmj.com/content/321/7257/323">paso fundamental si se pretende reducir el riesgo</a> de padecer cáncer de pulmón, pero hasta ahora los expertos no estaban seguros del motivo. La <a href="https://www.nature.com/articles/s41586-020-1961-1">investigación</a> en la que venimos trabajando durante los últimos tiempos ha revelado que el organismo de las personas que abandonan el tabaco restaura las vías respiratorias con células no cancerosas que ayudan a proteger los pulmones, lo que posibilita la disminución del riesgo de sufrir cáncer.</p>
<p>El cáncer se desarrolla cuando una sola célula experimenta unos cambios genéticos, llamados mutaciones, que enseñan a las células a ignorar las limitaciones propias de su crecimiento y <a href="https://www.nature.com/articles/nature07943">propician su replicación descontrolada a toda velocidad</a>. A lo largo de nuestra vida, la totalidad de nuestras células adquieren mutaciones a un ritmo constante (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536223/">entre 20 y 50 al año</a>). Por suerte, la inmensa mayoría de estas mutaciones son completamente inofensivas y no afectan a nuestras células en modo alguno.</p>
<p>Sin embargo, en ocasiones se puede producir una mutación en el gen menos oportuno de la célula menos indicada, lo que puede derivar en la aparición de un cáncer. Estas modificaciones genéticas reciben el nombre de “<a href="https://www.nature.com/articles/nature07943">mutaciones conductoras</a>”. Para que la célula fuera cancerosa, tendría que experimentar estas mutaciones conductoras <a href="https://www.cell.com/cell/fulltext/S0092-8674(17)31136-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867417311364%3Fshowall%3Dtrue">en una cantidad entre cinco y 10 veces mayor</a> de lo normal.</p>
<p>Gracias a los avances producidos en la tecnología de secuenciación del ADN, disponemos de la capacidad para estudiar los 3 000 millones de bases genéticas que componen el genoma o, lo que es lo mismo, la huella genética de una célula. Al secuenciar el ADN de las células cancerosas de los pulmones, tanto de personas fumadoras como no fumadoras, constatamos que el consumo de tabaco multiplica la cifra de mutaciones.</p>
<p>La unión de los elementos carcinógenos del tabaco al ADN se ve influenciada por sus propiedades químicas. Así pues, determinados tipos de mutación tienen más probabilidad de ocurrir que otros distintos. En el caso del tabaco, este imprime una inconfundible <a href="https://www.nature.com/articles/nature08629">“rúbrica”</a> en el genoma al producir las mutaciones, al contrario de lo que ocurre con otros tipos de daño genético.</p>
<p>Nuestro equipo de trabajo se ha centrado en las etapas más tempranas del desarrollo del cáncer de pulmón. Tratamos de comprender, en particular, el proceso que atraviesan las células normales al ser expuestas al tabaco.</p>
<p>Con el fin de analizar de qué manera se ven afectadas, elaboramos procedimientos para conseguir aislar las células normales a partir de pequeñas biopsias de las vías respiratorias del paciente para, a continuación, cultivarlas en una incubadora y obtener así el ADN necesario para la secuenciación. Posteriormente, <a href="https://www.nature.com/articles/s41586-020-1961-1">analizamos los genomas de 632 células</a> de 16 participantes diferentes, entre los que se incluían cuatro personas que no habían probado nunca el tabaco, seis exfumadores y tres fumadores (todos de mediana edad o mayores), así como tres niños.</p>
<p>Entre aquellos que nunca habían fumado, descubrimos que el número de mutaciones celulares había aumentado a un ritmo constante a medida que habían pasado los años, por lo que en una persona de 60 años la cifra natural de mutaciones de cada célula del pulmón oscila entre las 1 000 y las 1 500. Estas variaciones, provocadas por el deterioro lógico de la salud con la edad, son el mismo tipo de mutaciones que se pueden observar en los demás órganos. De todas las células de personas no fumadoras estudiadas, tan solo el 5 % presentaban algún tipo de mutación conductora.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Las mutaciones conductoras son las causantes de que algunas células puedan llegar a ser cancerosas.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/digital-illustration-lung-cancer-cells-color-233501644">RAJ CREATIONZS/ Shutterstock</a></span>
</figcaption>
</figure>
<p>Sin embargo, los resultados que observamos en individuos fumadores fueron muy diferentes. Descubrimos que cada célula pulmonar presentaba una media de 5 000 mutaciones más que en cualquier persona no fumadora de la misma edad. Aún más sobrecogedor resultó comprobar que las variaciones entre las diferentes células de los fumadores también se veían incrementadas.</p>
<p>Algunas células habían sufrido entre 10 000 y 15 000 mutaciones, 10 veces más de lo que cabría esperar en una persona que no fuma. Estas mutaciones extraordinarias exhibían la firma de los químicos presentes en el humo del tabaco, lo cual confirmó que podían ser atribuidas a los cigarros.</p>
<p>Junto al aumento del número total de mutaciones, percibimos también un incremento sustancial de la cantidad de mutaciones conductoras. Más de la cuarta parte de las células de los pulmones de los individuos fumadores analizados tenían al menos una mutación conductora, e incluso algunos alcanzaban las dos o tres. Dado que basta con entre cinco y 10 mutaciones de este tipo para desarrollar cáncer, toda apunta a que muchas de las células normales de los pulmones de estos fumadores de mediana edad o mayores acabarán siendo células cancerosas. </p>
<h2>Nunca es tarde para dejarlo</h2>
<p>De todos los hallazgos que llevamos a cabo, el más emocionante se produjo en aquellas personas que habían abandonado el tabaco. Observamos que los exfumadores tenían dos tipos de células: el primer grupo presentaba las miles de mutaciones extra advertidas en personas que continuaban fumando; el segundo, sin embargo, estaba compuesto por células normales con la misma cantidad de mutaciones que se podría observar en las células de alguien que nunca había probado un cigarro.</p>
<p>Este grupo casi normal de células era cuatro veces más extenso en exfumadores que en fumadores, lo cual indica que las células se reproducen para recubrir el epitelio de las vías respiratorias de un individuo cuando deja de fumar. Esta proliferación de células prácticamente normales se puede apreciar incluso en personas que han fumado una cajetilla diaria durante más de 40 años.</p>
<p>La razón por la cual este descubrimiento es tan trascendental reside en que este tipo de células casi normales poseen la capacidad de proteger contra el cáncer. Si analizásemos una célula de un pulmón con cáncer de una persona exfumadora, procedería invariablemente del <a href="https://www.cell.com/cell/fulltext/S0092-8674(12)01061-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867412010616%3Fshowall%3Dtrue">grupo de células más perjudicadas</a>, nunca del grupo de células casi normales.</p>
<p>Por lo tanto, ahora sabemos que el motivo por el cual nuestro riesgo de padecer cáncer disminuye de manera tan significativa se debe a que las vías respiratorias se restituyen con células que son básicamente normales. El próximo paso será identificar cómo estas logran evitar deteriorarse al exponerse al humo de un cigarro y de qué forma podríamos estimularlas para que se recuperen de manera aún más eficaz.</p>
<p>Una posible explicación, extraída de las experimentaciones realizadas en el pasado con <a href="https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30123-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590918301231%3Fshowall%3Dtrue">ratones</a>, es que hay un grupo de células madre en un punto inaccesible de las glándulas encargadas de producir la mucosa secretada por las vías respiratorias. Dicha ubicación ofrecería, evidentemente, un grado de protección más elevado frente al humo del tabaco que la superficie de las vías respiratorias.</p>
<p>Por ahora, nuestra investigación permite reiterar que dejar de fumar a cualquier edad no solo frena la acumulación de un daño permanente, sino que puede despertar de su letargo a las células que no han sufrido los efectos nocivos de los estilos de vida adoptados en el pasado.</p>
<hr>
<p><em>Artículo traducido gracias a la colaboración de <a href="https://www.fundacionlilly.com/">Fundación Lilly</a></em>.</p>
<hr><img src="https://counter.theconversation.com/content/131056/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sam Janes recibe fondos relevantes para este trabajo de Wellcome y CRUK.
</span></em></p><p class="fine-print"><em><span>Peter Campbell recibe financiación del proyecto Mutographs, un gran reto financiado por Cancer Research UK, y el Wellcome Trust en relación con este trabajo.
</span></em></p>
El estudio revela que los exfumadores tienen una cantidad de células protectoras “normales” cuatro veces superior a la de los fumadores.
Sam Janes, Professor of Respiratory Medicine, UCL
Peter Campbell, Head of Cancer, Ageing and Somatic Mutation, Wellcome Trust Sanger Institute
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/130830
2020-01-31T13:09:15Z
2020-01-31T13:09:15Z
Lung cancer: quitting smoking regrows protective lung cells – new research
<figure><img src="https://images.theconversation.com/files/313050/original/file-20200131-41532-16kwzup.jpg?ixlib=rb-1.1.0&rect=15%2C7%2C5184%2C3266&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The findings show it's never too late to quit.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/stop-smoking-382326067">Nuttaphong Sriset/ Shutterstock</a></span></figcaption></figure><p>We know that <a href="https://www.who.int/tobacco/quitting/benefits/en/">quitting smoking</a> is an <a href="https://www.bmj.com/content/321/7257/323">excellent way to reduce your risk</a> of developing lung cancer. But until now, experts weren’t quite sure why this was the case. Our <a href="https://www.nature.com/articles/s41586-020-1961-1">latest research</a> has uncovered that in people who quit smoking, the body actually replenishes the airways with normal, non-cancerous cells that help protect the lungs, in turn reducing their risk of getting cancer. </p>
<p>Cancer develops when a single rogue cell acquires genetic changes, called mutations, that instruct that cell to ignore all the normal constraints on its growth, <a href="https://www.nature.com/articles/nature07943">causing it to rapidly replicate out of control</a>. Throughout our lives, all of our cells acquire mutations at a steady rate – <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536223/">around 20-50 mutations per cell per year</a>. Thankfully, the vast majority of these mutations are entirely harmless and don’t affect our cells in any measurable way. </p>
<p>But occasionally, a mutation will land in the wrong gene in the wrong cell and push the cell along the path to cancer. We call these genetic changes <a href="https://www.nature.com/articles/nature07943">“driver mutations”</a>. For the cell to become a full-blown cancer cell, it would probably need <a href="https://www.cell.com/cell/fulltext/S0092-8674(17)31136-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867417311364%3Fshowall%3Dtrue">five to ten or more of these driver mutations</a>. </p>
<p>Thanks to advances in DNA sequencing technology, we’re now able to study all 3 billion bases of DNA that make up a cell’s genetic blueprint (called a genome). By sequencing the DNA of lung cancer cells in smokers and never-smokers, we know that smoking increases the number of mutations.</p>
<p>The binding of tobacco carcinogens to DNA is influenced by their chemical properties, meaning that certain types of mutation are more likely to occur than other types. For tobacco, this results in a distinctive <a href="https://www.nature.com/articles/nature08629">“signature” of mutations</a> appearing in the genome, which is unlike other causes of DNA damage.</p>
<p>Our team has been interested in the very earliest stages of lung cancer development. Specifically, we’re trying to understand what happens to normal cells when they’re exposed to tobacco smoke.</p>
<p>To study this, we developed methods of isolating single normal cells from small biopsies of a patient’s airways, then growing these cells in an incubator to obtain enough DNA for sequencing. We then <a href="https://www.nature.com/articles/s41586-020-1961-1">analysed the genomes of 632 cells</a> from 16 study participants including four never-smokers, six ex-smokers and three current smokers (all middle-aged or older) as well as three children. </p>
<p>Among the never-smokers, we found that the number of cell mutations increased steadily with age. So, by the time someone is 60 years old, each normal lung cell will contain about 1,000-1,500 mutations. These mutations are caused by the normal wear-and-tear of life, the same type of mutations we see in other organs in the body. Only about 5% of cells in never-smokers were found to have any driver mutations.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Driver mutations are what cause cells to become cancerous.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/digital-illustration-lung-cancer-cells-color-233501644">RAJ CREATIONZS/ Shutterstock</a></span>
</figcaption>
</figure>
<p>But the picture was very different in current smokers. We found that each lung cell on average carried an extra 5,000 mutations above what we would expect for a never-smoker of the same age. Even more striking was that the variation from cell to cell also dramatically increased in smokers.</p>
<p>Some individual cells had 10,000-15,000 mutations – ten times more mutations than we would expect if the person hadn’t smoked. These extra mutations had the signature we would expect from the chemicals in tobacco smoke, confirming that they can be directly attributed to cigarettes.</p>
<p>Alongside an increase in the total number of mutations, we also saw a substantial increase in the number of driver mutations. More than a quarter of lung cells in all the current smokers we studied had at least one drive mutation. Some even had two or three. Given that five to ten of these kind of mutations can caused cancer, it’s clear that many normal lung cells in these middle-aged or older smokers will likely become cancerous. </p>
<h2>Never too late to quit</h2>
<p>Our most exciting finding was in the people who had quit smoking. We found ex-smokers had two groups of cells. One group had the thousands of extra mutations seen in current smokers, but the other group were essentially normal. The group of normal cells had the same number of mutations as we would expect to see in the cells of someone who had never smoked.</p>
<p>This near normal group of cells was four times larger in ex-smokers than current smokers. This suggests that these cells increase to replenish the lining of airways after someone stops smoking. We could see this expansion of near-normal cells even in ex-smokers who had smoked a packet of cigarettes every day for more than 40 years.</p>
<p>The reason this finding is so exciting is that this near-normal group of cells protects against cancer. If we study a lung cancer cell from an ex-smoker, it always comes from the <a href="https://www.cell.com/cell/fulltext/S0092-8674(12)01061-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867412010616%3Fshowall%3Dtrue">heavily damaged group of cells</a> – not from the near-normal group.</p>
<p>Now, we know the reason our risk of cancer decreases so significantly is because the body replenishes the airways with cells that are essentially normal. The next step will be to identify how this group of cells manages to avoid damage from exposure to cigarette smoke – and how we might stimulate them to recover even more.</p>
<p>One potential explanation – suggested by past work in <a href="https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30123-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590918301231%3Fshowall%3Dtrue">mouse models</a> – is that there’s a group of stem cells buried deep in the glands that produce the mucus secreted by the airways. This location would naturally be better protected from tobacco smoke than the surface of airways. </p>
<p>For now, our research reiterates that stopping smoking – at any age – not only slows the accumulation of further damage, but it can reawaken cells that haven’t been damaged by past lifestyle choices.</p><img src="https://counter.theconversation.com/content/130830/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sam Janes receives funding from Wellcome and CRUK relevant to this work</span></em></p><p class="fine-print"><em><span>Peter Campbell receives funding from the Mutographs project, a Grand Challenge funded by Cancer Research UK, and the Wellcome Trust relevant to this work.</span></em></p>
The study found that ex-smokers had four times the amount of “normal” protective cells than smokers.
Sam Janes, Professor of Respiratory Medicine, UCL
Peter Campbell, Head of Cancer, Ageing and Somatic Mutation, Wellcome Trust Sanger Institute
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/116007
2019-04-30T09:05:52Z
2019-04-30T09:05:52Z
Malawi is testing a new malaria vaccine. But it’s still early days
<figure><img src="https://images.theconversation.com/files/270990/original/file-20190425-121228-1lfp0zl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=18761">CDC/ James Gathany</a></span></figcaption></figure><p><em>Malaria is a leading <a href="https://www.who.int/malaria/media/world-malaria-report-2018/en/">cause of death</a> and illness around the world. Over 200 million cases are reported every year, and more than 400 000 people <a href="https://www.who.int/malaria/media/world-malaria-report-2018/en/">die</a>. More than 90% of cases are reported in sub-Saharan Africa. Scientists have spent decades searching for an effective vaccine. Hence the recent excitement when Malawi’s government announced it had <a href="https://www.who.int/news-room/detail/23-04-2019-malaria-vaccine-pilot-launched-in-malawi">launched</a> a pilot programme for the world’s first malaria vaccine, RTS,S (also known as Mosquirix©), produced by the pharmaceutical company, GSK. It’s the first vaccine to demonstrate significant reduction in malaria in children. The Conversation Africa’s Ina Skosana asked immunologist Faith Osier about RTS,S.</em></p>
<p><strong>Why is this vaccine a big deal?</strong></p>
<p>This marks a major milestone in the history of malaria vaccine development. Although many strategies are under investigation, few have been successful enough to get tested in early clinical trials in humans. </p>
<p>RTS,S is the first malaria vaccine that has shown some protection in large scale clinical research studies. Almost all the previous vaccine candidates that have previously made it to clinical trials in humans failed to induce sufficient levels of protection. </p>
<p>Now that it’s jumped through the initial hoops, RTS,S will be tested in an implementation trial. This will involve making it available to 360 000 children: first in Malawi, and later in Kenya and Ghana. Malaria is endemic throughout <a href="https://dhsprogram.com/pubs/pdf/MIS18/MIS18.pdf">Malawi</a>, <a href="http://www.ghanahealthservice.org/ghs-subcategory.php?cid=4&scid=41">Ghana</a> and parts of <a href="https://www.who.int/news-room/feature-stories/detail/in-kenya-the-path-to-elimination-of-malaria-is-lined-with-good-preventions">Kenya</a>. </p>
<p>This next phase of the trial process will be used to further monitor the efficacy – as well as any potential adverse effects – of the vaccine in the context of routine use within national immunisation programmes.</p>
<p>Normally after the third phase of a clinical trial, one could consider licensing it if the results were good. In the case of this product, the results weren’t conclusively positive enough to proceed to licensing just yet. There was a lot of <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00807-7/fulltext">debate</a> in the scientific community about whether it should be licensed or not. </p>
<p>This next phase of the trial process (implementation) will be used to further monitor the efficacy – as well as any potential adverse effects – of the vaccine in the context of routine use within national immunisation programmes. </p>
<p>It’s important to point out that there’s been a long process before this. RTS,S has been put through clinical trials – which usually consist of three phases. </p>
<p>Those trials showed that the vaccine only had <a href="https://www.ncbi.nlm.nih.gov/pubmed/25913272">modest efficacy</a>: it protected on average four of every 10 children who had been vaccinated. The trial also showed that this level of efficacy <a href="https://www.ncbi.nlm.nih.gov/pubmed/25072396">waned rapidly</a> and was practically undetectable 18 months after the last immunisation. </p>
<p>There were also potentially concerning adverse outcomes that need to be monitored further. These included a higher rate of <a href="https://www.ncbi.nlm.nih.gov/pubmed/25913272">meningitis</a> and a<a href="https://mbio.asm.org/content/7/2/e00514-16"> higher mortality</a> rate in girls. It’s important to point out that these were not necessarily caused by the vaccine, so more investigation will be needed to understand this issue.</p>
<p>Nevertheless, given the high burden of malaria in sub-Saharan Africa, a partially effective vaccine is considered better than none, and it is better to save some lives, than none at all.</p>
<p><strong>What happens next?</strong></p>
<p>Scientists now keenly await the results of the trials in Malawi, Ghana and Kenya. This is expected to give results within three to five years.</p>
<p>While we wait, the scientific effort to develop a more effective vaccine will continue as vigorously as ever. Researchers like myself are energised by the limited success of the current vaccine and are convinced that we can do better.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/novel-approach-brings-african-scientists-closer-to-a-malaria-vaccine-106276">Novel approach brings African scientists closer to a malaria vaccine</a>
</strong>
</em>
</p>
<hr>
<p><strong>So where are we in terms of finding a malaria vaccine?</strong></p>
<p>The development of vaccines against malaria is complex and challenging. The parasite responsible for the most severe disease complications in humans, <em>Plasmodium falciparum</em>, infects mosquitoes and humans and has distinct life-cycle stages in each of these hosts. It has evolved over millions of years to employ a myriad of strategies that enable it to evade destruction by the host immune system.</p>
<p>The parasite contains over 5000 proteins and displays variable proportions of these proteins to the immune system at different times. And the genes encoding these proteins can be cleverly switched on and off, or mutate in the course of an infection. It’s an ever-changing coat of many colours.</p>
<p>Scientists are tackling this problem from every possible angle.</p><img src="https://counter.theconversation.com/content/116007/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Faith Osier receives funding from the Wellcome Trust, the MRC/DFID African Research Leader Award, the European and Developing Countries Clinical Trials Partnership (EDCTP), the Sofja Kovalevskaja Award from the Alexander von Humboldt Foundation and TIBA - Tackling Infections to Benefit Africa. She is Vice-President/President-elect of the International Union of Immunological Societies.</span></em></p>
Given the high burden of malaria in sub-Saharan Africa, a partially effective vaccine is considered better than none.
Faith Osier, Immunologist , Wellcome Trust Sanger Institute
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/106276
2018-11-07T13:10:37Z
2018-11-07T13:10:37Z
Novel approach brings African scientists closer to a malaria vaccine
<figure><img src="https://images.theconversation.com/files/244103/original/file-20181106-74783-r02f38.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Scientists analysing data at the South-South Malaria Research Partnership project laboratory in Kenya. </span> <span class="attribution"><span class="source">Flora Mutere-Okuku</span></span></figcaption></figure><p>Malaria is still a major problem in Africa. There are over <a href="http://www.who.int/malaria/publications/world-malaria-report-2017/en/">200 million clinical cases</a> each year and approximately half a million deaths. </p>
<p>There are different ways in which malaria can be controlled. Preventive measures include use of insecticides in bed nets or indoor spraying programmes. Medicines can also be used to prevent or treat malaria, but resistance often develops and drugs lose their effectiveness. </p>
<p>The World Health Organisation <a href="http://www.who.int/en/news-room/detail/29-11-2017-global-response-to-malaria-at-crossroads">reported</a> that progress in controlling malaria has stalled. </p>
<p>As an immunologist, I dream that one day we will have an effective vaccine that will help eliminate malaria. I think this is possible because for over a century, we have known that humans do become immune to malaria. In places where there is lots of malaria adults don’t succumb to the disease, but their young children do. </p>
<p>In experiments conducted over 50 years ago, researchers showed that blood could be taken from <a href="https://www.nature.com/articles/192733a0">adults who had become immune</a> and used to treat children admitted to hospital with malaria. </p>
<p>Antibodies in the blood were responsible for this effect; in other words, antibodies could treat malaria. Researchers have been trying to isolate the exact antibodies that do this. The challenge is that our bodies make millions of antibodies, so pulling out those with the antimalarial activity has been difficult.</p>
<p>One way to identify these “good” antibodies is to compare the blood samples of people who get malaria with those who don’t with the aim of identifying the differences. This type of research has been going on for about 30 years, but the results have been <a href="https://www.ncbi.nlm.nih.gov/pubmed/20098724">inconclusive</a>. </p>
<p>Part of the reason is that in almost every study, the investigators do things differently. </p>
<p>It’s like cooking your favourite dish. You may have a particular recipe but if you check in with friends and ask how they prepare the very same dish, you will find that each of them does something slightly differently. In the same way, differences in the way scientists have conducted their experiments have contributed to a lack of clarity in the results. </p>
<p>We’ve embarked on a project that breaks this cycle. </p>
<h2>The project</h2>
<p>In experiments conducted over 50 years ago, researchers showed that blood could be taken from <a href="https://www.nature.com/articles/192733a0">adults who had become immune</a> and used to treat children admitted to hospital with malaria. </p>
<p>We used the latest technology to analyse our samples. We designed a small glass slide on which we stuck over 100 carefully selected proteins from the malaria parasite. With less than a drop of blood, we were able to simultaneously <a href="https://www.smartpartnership.net/science">measure antibodies</a> to all these proteins. </p>
<p>This was a major step-change. When I started this research 14 years ago, I used to measure antibodies to one parasite protein at a time, using a lot more blood, and in samples from one area in Kenya. </p>
<p>Developments in technology now mean that it’s possible to do this much more efficiently. And we’re really excited that we have been able to exploit these new innovations in Africa. </p>
<p>My team analysed antibodies in over 10,000 samples in three months. We are now working through the statistical analysis of this data to understand how people who are immune to malaria do it.</p>
<p>My team is also working on understanding how antibodies <a href="https://www.ncbi.nlm.nih.gov/pubmed/27546781">kill malaria</a> parasites. It’s still unclear if the antibodies attack the parasite from different angles or whether different antibodies are synergistic in their actions. </p>
<p>We also don’t know how much antibody is necessary. </p>
<h2>What we know</h2>
<p>So far, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2346713/">our studies</a> suggest that having a bit of one antibody is not good enough, and we may need high concentrations of antibodies against combinations of parasite proteins. </p>
<p>We are also <a href="https://www.ncbi.nlm.nih.gov/pubmed/26787721">learning</a> that antibodies kill parasites in many ways, and that studying any one of these in isolation may not adequately reflect reality. </p>
<p>I believe the key to making a better malaria vaccine is right here with us. With patience, perseverance and continued hard work, we will find the recipe required to make a really good malaria vaccine.</p><img src="https://counter.theconversation.com/content/106276/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Faith Osier receives funding from the Wellcome Trust, the MRC/DFID African Research Leader Award, the European and Developing Countries Clinical Trials Partnership (EDCTP), the Sofja Kovalevskaja Award from the Alexander von Humboldt Foundation and TIBA - Tackling Infections to Benefit Africa. She is Vice-President/President-elect of the International Union of Immunological Societies. </span></em></p>
Progress in malaria control has stalled. Research towards an effective vaccine is underway.
Faith Osier, Immunologist , Wellcome Trust Sanger Institute
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/25947
2014-04-25T10:26:22Z
2014-04-25T10:26:22Z
Why we sequenced genome of the sleeping sickness-spreading tsetse fly
<figure><img src="https://images.theconversation.com/files/47042/original/wwjr6m34-1398415203.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A pregnant female tsetse fly.</span> <span class="attribution"><span class="source">Geoffrey M. Attardo</span></span></figcaption></figure><p>After a decade of research, an international team <a href="http://www.sciencemag.org/content/344/6182/380">decoded the genes</a> of the tsetse fly – the transmitter of trypanosomiasis, or sleeping sickness. Human trypanosomiasis is a widespread tropical disease in Africa and can be fatal if not treated. Treatments are limited, but new knowledge of the tsetse fly, which carries the disease, now provides an important foundation for limiting its spread.</p>
<p>Thankfully, there has been a decline in sleeping sickness in recent years thanks to control measures by groups such as the World Health Organization. These have significantly reduced rates of infection – <a href="http://www.who.int/mediacentre/factsheets/fs259/en/">just over 7,000 cases were reported across Africa in 2012</a>. But the job is nowhere near finished.</p>
<p>Firstly, the disease has yet to be eradicated. This means that when control measures are relaxed – a state of affairs that’s all too often prompted by political unrest – cases increase rapidly. Also, more needs to be done about Nagana, an even more neglected form of sleeping sickness, that affects livestock and places a huge economic burden on developing economies.</p>
<h2>Biological foundations</h2>
<p>Working with a collective of 146 scientists from 78 research institutes across 18 countries, we have sequenced the genome of the tsetse fly, an insect that, despite its importance, is understudied. Our hope is that developing a greater understanding of this fly’s unique biology will help us to take advantage of its vulnerabilities and one day eradicate sleeping sickness in humans and livestock across Africa.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/47043/original/ybmdh3vz-1398415252.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/47043/original/ybmdh3vz-1398415252.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/47043/original/ybmdh3vz-1398415252.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=444&fit=crop&dpr=1 600w, https://images.theconversation.com/files/47043/original/ybmdh3vz-1398415252.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=444&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/47043/original/ybmdh3vz-1398415252.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=444&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/47043/original/ybmdh3vz-1398415252.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=558&fit=crop&dpr=1 754w, https://images.theconversation.com/files/47043/original/ybmdh3vz-1398415252.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=558&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/47043/original/ybmdh3vz-1398415252.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=558&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Tsetse fly larvae immediately after birth.</span>
<span class="attribution"><span class="source">Geoffrey M Attardo</span></span>
</figcaption>
</figure>
<p>This work is just the start, as we’ve only sequenced one subspecies of the fly – but it’s a promising one. Already we’ve identified aspects of the fly’s DNA that make it vulnerable. For instance, unlike most flies that lay eggs, tsetse flies gestate inside their mothers, feeding from specialised glands inside the uterus. If we can identify the genes that switch on milk production, we can stop flies producing young and reduce tsetse fly populations – one effective method for disease control.</p>
<p>Other insights into the tsetse fly genome include the discovery of DNA from a parasitic <a href="http://sangerinstitute.wordpress.com/2014/04/24/the-enemy-within/">wasp virus</a> within the tsetse genome. If the wasp itself can be found, it may be possible to use it for biological control of tsetse. Tsetse flies find their prey using by sight and smell. They have a strong colour preference for blue and black – a fact that is used in baiting tsetse traps. </p>
<p>We found evidence for this colour preference in the genome – tsetse flies have a limited range of light receptors but we found one similar to the blue colour receptor of fruit flies. We also found far fewer receptors of smell and taste than seen in mosquitoes or fruit flies. It may be possible to use this knowledge to improve tsetse traps by really working out their favourite tastes and odours.</p>
<h2>Economic impact</h2>
<p>The next stage of research needs to tackle Nagana. This disease devastates livestock and, in turn, the economies of small rural communities in parts of Africa where it is endemic. It’s thought that eradicating this disease could <a href="http://www.ncbi.nlm.nih.gov/pubmed/7501369">save rural African economies</a> billions of dollars.</p>
<p>Cattle affected by Nagana, like humans with sleeping sickness, become very weak. In cattle the disease is often fatal but where animals do survive, growth, milk yields and fertility are impaired. Across central African regions farmers use breeds of cattle that are less susceptible to Nagana, but these hardy animals produce very little meat compared with varieties used in more developed countries. Wiping out Nagana will enable farmers to keep efficient, productive livestock that will feed growing communities and create wealth.</p>
<h2>Next steps</h2>
<p>Further research will also need to look in more detail at natural genetic variation among tsetse flies. Using this genome as a basis, we’ll want to sequence other flies that have been caught in the wild to find out how they are adapting to insecticides and other control measures. This will also help us to improve our control strategies and target different tsetse sub-species in different regions more effectively.</p>
<p>As is often the case, a genome sequence is a starting point. The genome can help to make vital decisions about targets for control mechanisms and treatments. However, the changes needed to make a real impact on communities require political will to coordinate activities across national boundaries and substantial investment in further research, monitoring and control measures.</p><img src="https://counter.theconversation.com/content/25947/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew Berriman receives funding from The Wellcome Trust, Medical Research Council and the BBSRC.</span></em></p>
After a decade of research, an international team decoded the genes of the tsetse fly – the transmitter of trypanosomiasis, or sleeping sickness. Human trypanosomiasis is a widespread tropical disease…
Matthew Berriman, Group Leader, Neglected Tropical Diseases, Wellcome Trust Sanger Institute
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/15216
2013-06-14T13:17:00Z
2013-06-14T13:17:00Z
Attention The Times: Prince William’s DNA is not a toy
<figure><img src="https://images.theconversation.com/files/25585/original/9ts5499w-1371212253.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The Times claimed today that Prince William has Indian ancestors.</span> <span class="attribution"><span class="source">Vincent Lyon-Dalberg-Acton</span></span></figcaption></figure><p>An ancestor of Prince William’s from the 19th century was half Indian, <a href="http://www.thetimes.co.uk/tto/news/uk/article3790940.ece">according to The Times</a>. This claim is based on <a href="https://theconversation.com/will-i-am-indian-but-does-it-matter-15215">analysis of his distant cousins’ DNA</a>. We have such technology today, but how comfortable would you be to find out what your DNA tells about you on the front page of a newspaper?</p>
<p>Your DNA contains information about your past, present and future: From medical health, such as predispositions to diabetes, to your ancestry, such as whether they were Indian or African.</p>
<p>Genetic testing, in whatever form, will reveal something personal about you and your relatives. But the trouble is that even though your DNA makes you unique, it is <a href="https://theconversation.com/are-you-a-viking-yes-but-so-is-everyone-else-14144">not so special</a>. There are more commonalities betweeen our DNA than there are differences. We are all related to each other in some way.</p>
<p>This is a tension that clinical geneticists and genetic counsellors routinely deal with when working with families affected by inherited disease. This is also why genetic testing in health services have developed with the family in mind, rather than the individual. </p>
<p>There are four moral and ethical principles most commonly applied to genomic research as well as clinical genetic practice. They can be summarised as: allow people to make their own minds up about whether to be tested or not (autonomy), do no harm (non-malificence), do good (beneficience), and create a just and equitable product or service (justice). </p>
<p>Let’s apply those principles to William’s case. </p>
<p>First, there was no autonomy. He was not personally tested and so he did not make a decision about this. Also, we are also not sure whether he was given a choice about the story running.</p>
<p>Second, is this information potentially harmful to William? Only he can comment, but personally I would be miffed if genetic information about my ancestry was shared with the world before I knew it. </p>
<p>Third, this story could do William some “good”. Again only William can say whether the Anglo-Indian relationship plays to his advantage. However, irrespective of this, I would doubt that the primary motives behind the testing were to do good for William.</p>
<p>Finally, the article in The Times ran with an advert for the company that did the testing. While this appears distinctly distasteful, the bottom line is that such testing is not available for all (unless you can pay) and there was no equity in decision-making, because William had no choice.</p>
<p>A team from Harvard University <a href="http://www.forbes.com/sites/adamtanner/2013/04/25/harvard-professor-re-identifies-anonymous-volunteers-in-dna-study/">recently revealed</a> that 40% of publicly available, supposedly anonymous, DNA sequences could be linked back to the individual who gave them. Thus anyone providing DNA for research must be counselled to the fact that there is always a chance of being identified and personal medical information being shared. Once identified then so too can his or her family.</p>
<p>Anyone in the public eye is particularly vulnerable - genetic exploitation is possible on scales never imagined before. While it might titillate the masses to discover that William has Indian ancestry, we should never forget that there is a real person with real feelings behind this story. </p>
<p>Genetics unites all of us. But revealing personal information about somebody, without their consent, irrespective of their position or status, is potentially harmful. While the discussion is about ancestry today it could be more serious if predispositions to life-threatening conditions are revealed? If it were me, I’d rather know this first and have a chance to talk to my family before anybody else knows about it.</p><img src="https://counter.theconversation.com/content/15216/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr Anna Middleton works for the Wellcome Trust Sanger Institute. She receives funding from the Wellcome Trust and Health Innovation Challenge Fund, UK.</span></em></p>
An ancestor of Prince William’s from the 19th century was half Indian, according to The Times. This claim is based on analysis of his distant cousins’ DNA. We have such technology today, but how comfortable…
Anna Middleton, Ethics Researcher and Registered Genetic Counsellor, Wellcome Trust Sanger Institute
Licensed as Creative Commons – attribution, no derivatives.