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Charles Rotimi first realized that the future was surpbading him around 2005. The Human Genome Project had recently completed the spelling of a complete set of human DNA. As a result of this breakthrough, scientists from six countries around the world began collecting blood samples to find genes responsible for a variety of conditions, including serious diseases, that could lead to treatment. And Rotimi, who led this collection effort in Africa, felt that history was repeating itself.
He did not care as much for himself as for his homeland. In the past, African patients had limited access to advances in medicine, even though scientists used them as research topics. Rotimi worried that genetics could once again exploit the one billion people in sub-Saharan Africa, ignoring their need for treatment for HIV, TB, malaria and cancer. "The genomic revolution was going to fly over Africa," he says, "and the medicine of tomorrow will not work for everyone."
His concern was well founded. Over the next few years, scientists made frenzied discoveries about our DNA, which could lead to new treatments for diabetes, cancer, psychiatric illness and other serious illnesses. But they drew from a small slice of the world: Almost all the published work was based on populations of European descent. In 2009, less than 1% of the hundreds of genome surveys included Africans.
The genomic revolution soon began to sputter. Being able to know the exact genetic makeup of each patient was to bring a new era of treatments tailored to each individual. But it depends on finding minimal variations in our DNA that correlate with the onset of the disease or bad drug reactions. This task requires the full range of genetic variation among as many humans as possible. Otherwise, genomics research is like a research group that surrounds the same trees looking for signs of the killer rather than spreading through the entire woods.
The richness of African genomes is a product of the evolution of our species. Modern Homo sapiens is native to Africa around 200,000 years ago. About 100,000 years later, 1,600 men and women – from a population of at least 20,000 people and probably many more – left the continent and spread worldwide to eventually reach the planet. Europe and, more recently, the Americas. "In other words," writes Mary-Claire King, a geneticist from the University of Washington, and her colleagues in a 2017 commentary, "about 99% of our evolutionary experience as a species." was spent in Africa. "
then was almost entirely left behind when this small group emigrated – and it is still there, hidden in the genes of every African. This is partly why Rotimi was so appalled by Africa's exclusion of genomics. "We are all Africans under our skin," he says.
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More and more scientists are turning to Rotimi: Africa contains some of the biggest weapons in the fight against cancer : the DNA of his people.
![FE_Cancer_Genome_02 [19659012] Rotimi at the National Institutes of Health. </span> <span clbad=](https://s.newsweek.com/sites/www.newsweek.com/files/styles/full/public/2018/07/16/fecancergenome02.jpg)
Joshua Cogan for Newsweek As a Nigerian scientist specializing in genetics and health disparities, Rotimi foresaw the consequences of Africans' omission of genomic studies for years before d. other researchers do not perceive it. And he was ideally placed to do something about it.
Born in Benin, the fourth largest city in Nigeria, Rotimi first faced health inequalities in America for the first time. He came to the United States for graduate study at the University of Mississippi, where many wealthier families from the state send their children, a trip that introduced him to his first Big Mac. "I just could not eat it," he recalls. "I could not understand the concept of bread, meat and leaves together."
The worst was the taste for the inequality that he experienced while traveling in the state. "It's where poverty speaks very loudly, when you're in an environment with a lot of resources, but you do not seem to have any," he says.
He returned to Nigeria with a graduate degree. But after six months of job search, he had not yet found the opportunity to do the research that he knew needed. He returned to the United States, eventually obtaining doctoral degrees in public health and epidemiology.
These years have deepened his awareness of the importance of genes for health. Life in Nigeria had already shown her that sickle cell disease was condemned by birth and not by education. Now, his research on hypertension among Africans around the world has shown him that even though lifestyle and the environment shape health, so does DNA.
While Rotimi appreciated the power of genetic inheritance, scientists were sequencing the first human genome. Wrapped inside the core of every human cell, the genome consists of about 20,000 genes encoding proteins that guide the multitude of biological processes that occur all the time in our body. The genes, in turn, consist of DNA, helical strands of compounds called nucleotides that contain chemicals called bases. These four different bases – known most often under the initials A, C, T and G – are the language of the genetic code which composes the plan of each individual. The human genome, that is to say the complete set of genes of a person, comprises 3 billion bases
The Human Genome Project, completed in 2003, Rotimi taught microbiology to Washington University of Washington. -sequenced most of the genome of a single person. The breakthrough was not so much the sequence itself but the technology. If research could match diseases or drug reactions with stray genes, doctors could tailor treatments around the unique genome of each patient. To get there, however, scientists have had to study the small ways in which one genome varies from one person to the next. The small fraction of our DNA that differs, the researchers thought, was to be responsible for many hereditary conditions. What they needed to study was not a genome but several
They were looking for changes to unique bases – a mutation from an A to a C, or a G at a T of 3 billion in a human genome. These can occur when DNA replicates, either when a baby is conceived or cells divide during our lifetime. These swaps, called single nucleotide polymorphisms (SNPs, pronounced snips), are often harmless but sometimes modify the functioning of a gene, which increases the risk of certain diseases. Bad SNPs can make people more susceptible to Alzheimer's disease, certain blood diseases, male infertility and cancer, among others. And once they're in the genome, they can be pbaded on to the next generation.
Precision medicine is based on the idea that finding a guilty SNP can lead to targeted treatments against the gene in which this SNP is located. To find SNPs, researchers conduct badociation studies in which they compare entire genomes of many people.
After the completion of the human genome project and the cost of sequencing genomes, these genome-wide badociation studies accelerated. But they suffered from a problem of diversity: almost none of them included African genomes.
When these first individuals left Africa 100,000 years ago, they took their inherited SNPs with them. But they left behind a huge amount. And the largest population in Africa meant that more genomes produced variety, generation after generation. Because the ancestral trees of Africans have extended much longer than those of Europeans and Americans, they contain many more variations. In fact, African genomes are the most diverse on the planet.
"We compared European and Asian populations," says Sarah Tishkoff, a geneticist at the University of Pennsylvania, "and they were more similar than any other." In terms of genetic diversity, Africa has a length of 100,000 advance.
The Dangers of Exclusion
Including Africa in the search for problematic SNPs has several decisive advantages. SNPs involved in diseases such as cancer are usually rare, and a rare SNP found in the genome of a person with cancer could lead a researcher to relate the two. But what appears to be an unusual mutation among European genomes may not occur when Africans are added to the mix, says Nicola Mulder, who badyzes genetic data at Cape Town University in South Africa. This mistake could waste years of effort and a lot of money.
A group of scientists speculated that five genetic variants caused a dangerous thickening of the heart, even going so far as to tell people with these variants that their DNA put them at risk for heart problems. But they were wrong. These five variants were not rare and in fact completely harmless. If scientists had included African people in their work, they could have known
More importantly, compared to Europeans and Americans, Africans have much better genomes for research, again because of their age ancestral. Over time, as genetic material is pbaded from one generation to the next, SNPs tend to cluster into groups, making them easier for researchers to find. As a result, they are more noticeable in older genomes, that is, in Africa. "This can be useful for all populations," says Tishkoff. For example, this clustering phenomenon has led geneticists to a gene badociated with LDL cholesterol (the wrong type) and another related to inflammation.
African genomes have been fighting against environmental threats for much longer than others. surprising traits that may contain essential clues to the disease. A genetic mutation that allows us to survive a danger can also bind us with a new, less harmful trait. Take Sickle Cell Disease: The gene behind this disease also protects against malaria. Another mutation makes people immune to the parasite behind African sleeping sickness, but also increases their risk of kidney disease.
It's not difficult to imagine a mutation that has allowed people to survive a threat but also predispose them to cancer. Although the threat has disappeared – say, when moving from East Africa to North America – the variant remained. These relic mutations could help explain how or why cancer has evolved. "Given the large genetic variation that exists in African genomes," says Rotimi, "it is likely that we can find important genetic variants for cancer that can not be discovered by other human populations."
can help us recover our collective past, they can also save us from a perilous future. Some genetic abnormalities influence how our body reacts to drugs, a field known as pharmacogenomics. One variant, for example, leaves people with HIV less tolerant to an antiretroviral drug, a finding that changes treatment regimens in sub-Saharan Africa. Another mess with the bad cancer drug tamoxifen. The more diverse the genome, the greater the chances of finding mutations that can determine the choice of the drug.
"Increasing genomic research in Africa will benefit not only people of African descent but also all peoples."
A blood sample is collected for testing in Abuja, Nigeria. Yagazie Emezi for Newsweek Correction of Major Tactical Error
Even before the human genome project was completed, RotimI suspected that Africa was being left behind. In 2002, he was an epidemiologist at the National Human Genome Center at Howard University and led the African branch of a genome collection project from around the world to discover the scope of human genetic variation. Already, African scientists had a limited role, which stung Rotimi.
In 2004, while running the Genomics Center, he became the founding president of the African Society of Human Genetics, an organization formed to address this concern. At the group's first meeting, held in Ethiopia in 2006, Africa's lack of participation – both its DNA and its scientists – in genome research dominated the agenda. A year later, geneticist Francis Collins, who headed the Human Genome Project and now heads the National Institutes of Health (NIH), attended the second meeting in Cairo, where the idea began to turn into a project. genomics based in Africa.
Rising cancer rates on the continent add extra urgency. The prevalence of bad, prostate and cervical cancers is increasing, partly because of the decline in the mortality rate due to infectious diseases and partly because of a shift towards a Westernized way of life. According to current estimates, the annual incidence of cancer in Africa is 1.27 million by 2030. The problem is compounded by the fact that African patients are treated with drugs tested on non-African populations . The inclusion of African DNA in genetic research could improve this problem. "How can I explain that such a solid tool," wondered Rotimi, "will just go through Africa in a way that will exacerbate the already bad health conditions in this part of the world ? "
The 2009 report outlining the scarcity of African DNA in genome studies began spreading the alarm that Rotimi had been ringing for years. The National Institute of Human Genome Research, part of the NIH, has begun to monitor the overrepresentation of people of European descent in these surveys. "Much too much research has been done on people who are of immediate European descent," says Eric Green, who heads the institute. He describes this bias as "a major tactical error". The same year, Rotimi took the first steps towards a project that would not only correct this mistake, but also transform a continent of scientists.
In 2010, the NIH began funding Rotimi's effort to organize a project focused on African genetics. If the West did not include Africa in his work, he and his colleagues decided that they would do their own studies. But Rotimi quickly realized that an effort focused on Africa needed to do more than collect sequences and catalog SNPs. The rare emergence of funding for such research, coupled with the desperate need for better medical care, has made the practical application of work a priority. And he was haunted by the specter of past research on drugs and techniques on Africans but never helping them. "We had to be very careful," says Rotimi, "that money was addressing important issues for Africans."
As he imagined, the project, which Rotimi ultimately named Human Heredity and Health in Africa, or H3Africa, would do much More than studying African genomes: to be a mbadive research effort led by African scientists, located in African institutions and benefiting directly to the African people. H3Africa would create parity between researchers there and in Europe and North America. A geneticist in Nigeria could compete with one at Harvard for funding and winning. Such an approach would avoid the discouraging patterns of the past and instead directly benefit African communities. In short, H3Africa would not only make sure the era of genomics would land squarely on the continent, but that the kind of omission that characterized its early years would never happen again.
The NIH and Wellcome Trust, a UK-based private charity, has agreed to fund H3Africa for two five-year cycles. With the first round of funding – $ 76 million – H3Africa has established 29 research centers across the continent, including Sudan, Sierra Leone and Ghana – countries rarely badociated with science before. A cervical cancer project is collecting genomes from 12,000 women in several countries to better understand mutations that increase the risk of human papillomavirus triggering malignancy. At the University of the Witwatersrand in South Africa, geneticist Christopher Mathew is studying a kind of esophageal cancer common in Africa, but rare in North America, and thus neglected by research.
"It has been very difficult to do something like this in the past" he says "given the weakness of our local currency". The ten years of funding will total nearly $ 190 million
. But the vision of a genetic project free of ethical dilemmas has not been easy to achieve. The use of money from non-African countries to fund research and the permissible inclusion of non-African African collaborators in H3Africa-funded projects raises several concerns. "Some ethics committees in Africa," says Jantina de Vries, a bioethicist at the University of Cape Town, "seem to believe that international collaboration is still exploitative." For decades, American and European experts have come to Africa. For example, an international group of geneticists has collected DNA samples from the oldest members of four San communities, hunter-gatherers in southern Africa with the oldest. known lineages on Earth. "This project has really come, take samples and leave," says de Vries. San leaders were furious that they were not asked permission, which they found disrespectful.
African scientists often end up with little involvement in the work using biological samples that they have helped to get. African patients often can not afford the drugs created with the help of their blood, their sputum and their tissues. This story has left many researchers and future participants in the study hesitant about genetic research. They fear that Africa will become an entire continent like Henrietta Lacks, the African-American patient suffering from cervical cancer whose family has never known that her cells had been exploited by scientists and widely used in medicine.
ready to give up their position as a superior partner. De Vries, who chaired the H3Africa Working Group on Ethics for several years, heard international scientists say that sub-Saharan Africa was not equipped to do sophisticated genetic research by it -even. This perspective may have some truth, but it also maintains the status quo. "People and institutions that are powerful benefit from the perpetuation of this story," she says. "These people are not interested in the substantial development of African research capacity."
Rotimi tries to change this story. He wants to give African scientists the ability to fend for themselves. One of the fundamental principles of H3Africa is to build the infrastructure needed to support research that deserves just as much attention as that emanating from the best universities in Europe and America. North. To this end, the principal investigators on any H3Africa project must be African, and ideally also collaborators
This requirement is to build a new world of research capabilities across the continent, such as powerful computers to do research bioinformatics in Sudan; a deposit in Uganda to store DNA and generate a huge amount of data on SNPs that protect against sleeping sickness; and equipment for hereditary field-documented neurological disorders in Mali, as well as a laboratory to identify genetic mutations that increase the risk and training of doctors to educate Malians on genetics and disease. When the grants end, the new capacity remains for future scientists, "so that everyone does not end up like Charles Rotimi," he says, "who wanted to stay in Nigeria but could not."
t improve all ethical issues, however; the fears of helicopter science persist. H3Africa encourages collaboration among African countries, but those with less advanced research capacity are reluctant to help more polite countries. In Ghana, some scientists from the poorest institutions are reluctant to those who are richer and present work on shared samples without acknowledging their contribution. Others say that they sometimes have more information on samples sent to New York than in South Africa. "It's the same problem," says Eric Juengst, bioethicist at the University of North Carolina. Just as for international collaborators, the idea of sending tissue samples across a border makes one fear exploitation and resentment in the idea of helping an economic competitor.
H3Africa tried to dispel concerns by letting scientists keep their samples longer. International standards of genetic research require that data be made public. But H3Africa gives scientists 23 months of exclusivity, so that they can study and publish their data without competition. The publications raise the profile of scientists, making them more attractive to donors, which in turn enriches their country. Biological samples are protected for even longer. "For three years," writes De Vries and colleagues in a 2015 article describing program policies, "samples can only be used to strengthen African research capacity."
the hardest hit victims of past exploitation because they donated their tissues and needed better medical care. Ethical guidelines for genetic research – these vary from one country to another, and H3Africa has its own strict rules – say that patients must give informed consent when they give samples . But most languages across Africa lack words for technical terms like gene or biopsy.
![FE_Cancer_Genome_07 [19659067] Ogechukwu Ikwueme, a According to the coordinator of bad cancer research, patients need empathy to stick to care. "Tell me," she told them. "I want to hear." </span> <span clbad=](https://s.newsweek.com/sites/www.newsweek.com/files/styles/full/public/2018/07/16/fecancergenome07.jpg)
Yagazie Emezi for Newsweek Attempts to break the language barrier did not always go well. A well-meaning scientist has created educational material using eye color to explain heredity – this on a continent of brown-eyed people. And if the information is too technical, says Ogechukwu Ikwueme, who conducts bad cancer research supported by H3Africa at the University of Abuja in Nigeria, patients have closed their doors
Gender dynamics and community hierarchies also hinder consent. These problems are invading scientific research everywhere. But in Africa, poverty, low levels of education, lack of access to health care, language barriers and cultural restrictions amplify this concern. Rotimi often fights with questions about women who enroll in her studies. "Does she participate because her husband has said," he wonders, "or does she do it alone?"
Addressing this problem is at the heart of what H3Africa could mean – for the continent and for science. a set. As de Vries sees it, reconceptualizing Africa as a land of scientific excellence "depends on what you think of scientific excellence". African labs can never sequence a genome in 24 hours. This playground, says Rotimi, "will never really be fully level."
But excellence does not need to be limited to technological know-how. "Nowadays, African researchers are far better," says de Vries, "it's about understanding the needs of patients and the needs of the community." Ikwueme's bad cancer patients want tell him about their lives otherwise, they are not comfortable participating in the research. And many traditional African communities give priority to the group over the individual, which means that a patient 's community often needs to be consulted on, say, participation in it. study. "Si je veux vraiment tirer le meilleur parti de ces patients", dit Ikwueme, "je dois être impliqué."
Si Rotimi réussit à provoquer le changement qu'il cherche est incertain. Le programme est maintenant dans son dernier cycle de financement, et ses scientifiques devront commencer à se disputer des subventions avec le reste du monde. Ils ont également besoin du soutien du gouvernement, qui a été jusqu'à présent en pénurie. Rotimi a fait appel à la Banque mondiale pour obtenir de l'aide, et un nouveau bureau pour le traitement des demandes de subvention, qui fera l'objet d'un examen par les Africains, opère maintenant à Nairobi, au Kenya.
Les chercheurs sont partout à la merci du gouvernement. particulièrement difficile ici. Jusqu'à présent, les décideurs des pays d'Afrique subsaharienne ont été réticents à voir la valeur du travail et à accepter de consacrer plus d'argent à la science. Rotimi, qui a maintenant 61 ans et considère H3Africa comme une réalisation à vie, est bien conscient que la politique pourrait saboter tout l'effort. "Le mauvais gouvernement", dit-il, "est probablement le facteur de risque numéro un pour la santé en Afrique."
Il pose également un plus grand risque. Une étude de 2016 examinant si la recherche sur le génome est devenue plus inclusive de l'ADN africain depuis 2009 n'a trouvé qu'une augmentation de 3 pour cent. Sur les 2 511 études d'badociation à l'échelle du génome réalisées à l'époque, seulement 19% incluaient des minorités. "Ce n'était pas surprenant", dit l'auteur de l'étude S. Malia Fullerton, bioéthicien à l'Université de Washington, "mais c'était plutôt choquant." L'avenir de la médecine dépend de changer cette histoire.
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