Day: May 10, 2023

For two decades, scientists have been comparing every person’s full set of DNA they study to a template that relies mostly on genetic material from one man affectionately known as “the guy from Buffalo.”

But they’ve long known that this template for comparison, or “reference genome,” has serious limits because it doesn’t reflect the spectrum of human diversity.

“We need a really good understanding of the variations, the differences between human beings,” said genomics expert Benedict Paten of the University of California, Santa Cruz. “We’re missing out.”

Now, scientists are building a much more diverse reference that they call a “pangenome,” which so far includes the genetic material of 47 people from various places around the world. It’s the subject of four studies published Wednesday in the journals Nature and Nature Biotechnology. Scientists say it’s already teaching them new things about health and disease and should help patients down the road.

Paten said the new reference should help scientists understand more about what’s normal and what’s not. “It is only by understanding what common variation looks like that we’ll be able to say, ‘Oh, this big structural variation that affects this gene? Don’t worry about it,'” he said.

A human genome is the set of instructions to build and sustain a human being, and experts define a pangenome as a collection of whole genome sequences from many people that is designed to represent the genetic diversity of the human species. The pangenome is not a composite but a collection; scientists depict it as a rainbow of stacked genomes, compared with one line representing the older, single reference genome.

The Human Pangenome Project builds upon the first sequencing of a complete human genome, which was nearly completed more than two decades ago and finally finished last year. Paten, a pangenome study author and project leader, said 70% of that first reference genome came from an African American man with mixed African and European ancestry who answered an ad for volunteers in a Buffalo newspaper in 1997. About 30% came from a mix of around 20 people.

The pangenome contains material from 24 people of African ancestry, 16 from the Americas and the Caribbean, six from Asia and one from Europe.

Although any two people’s genomes are more than 99% identical, Paten said “it’s those differences that are the things that genetics and genomics is concerned with studying and understanding.”

It may take a while for patients to see concrete benefits from the research. But scientists said new insights should eventually make genetic testing more accurate, improve drug discovery and bolster personalized medicine, which uses someone’s unique genetic profile to guide decisions for preventing, diagnosing and treating disease.

“The Pangenome Project gives a more accurate representation of the genome of people from around the world,” and should help doctors better diagnose genetic conditions, said clinical genetics expert Dr. Wendy Chung at Columbia University, who was not involved in the research.

If someone has a variation in a certain gene, it could be compared to the rainbow of references.

Study author Evan Eichler of the University of Washington said researchers will also learn more about genes already linked to problems, such as one tied to cardiovascular disease in African Americans.

“Now that we can actually sequence that gene in its entirety and we can understand the variation in that gene, we can start to go back to unexplained cases of patients with coronary heart disease” and look at them in light of the new knowledge, he said.

University of Minnesota plant genetics expert Candice Hirsch, who wasn’t involved in the research but has closely followed the effort, said she expects many discoveries to flow from it. Until now, “we really have only been able to scratch the surface of understanding the genetics that underlies disease,” she said.

The consortium leading the research is part of the Human Genome Reference Program, which is funded by an arm of the U.S. National Institutes of Health.

The team is in the process of adding to the collection of reference genomes, with the goal of having sequences from 350 people by the middle of next year. Scientists are also hoping to work more with international partners, including those focusing on Indigenous populations.

“We’re in it for the long game,” Paten said.
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Health agencies warn that viral hepatitis could kill more people by 2040 than HIV, tuberculosis and malaria combined if it remains a neglected disease and efforts to fight it remain underfunded.  

The World Health Organization reports every year that viral hepatitis, a potentially life-threatening liver infection, affects more than 350 million people globally and kills more than a million. Ninety percent of these infections and deaths are in low- and middle-income countries. 

Despite a cure for hepatitis C and a vaccine for hepatitis B, campaigners for a world free of this dangerous and debilitating disease remain far off that mark. 

“Over the last 10 years, we have seen really remarkable progress in this journey to eliminate viral hepatitis,” said Oriel Fernandez, senior director of the Viral Hepatitis Global Program at the Clinton Health Access Initiative, or CHAI.

“We have the tools to prevent, diagnose and treat viral hepatitis,” she said. “Secondly, the price of hepatitis drugs and diagnostics has significantly fallen over the years.” 

For example, Fernandez noted that in 2018, CHAI supported the government of Rwanda to set the lowest price for WHO-approved hepatitis B treatment. 

“The total cost to cure a patient dropped by 96%, from over $2,500 per person to less than $80 per person cured. And this made the idea of elimination affordable for Rwanda and really established a benchmark price for all countries to aim for,” she said. 

Pledging conference

But funding to help poor countries pay for the treatments and vaccines to cure and eliminate this debilitating disease remains elusive. To address this issue, the Hepatitis Fund and CHAI will hold the first-ever pledging conference in Geneva next week.  

The conference hopes to raise $150 million to support countries that are committed to the elimination of viral hepatitis and have taken action to implement programs toward this end. Organizers cite Egypt, Rwanda, Georgia, India, Indonesia, Nigeria and Vietnam among other countries that have begun this process. 

Kenneth Kabagambe, who has been living in Uganda with hepatitis B since 2012, is the founding executive director of the National Organization for People Living with Hepatitis B. He said he started the organization to raise awareness of the disease and to shatter the myths that stigmatize people and discourage them from seeking help. 

“For example, there are issues to do with the myths and misconceptions, which actually are drawn from the lack of clear information about the transmission of hepatitis B and hepatitis C in the communities,” he said. “These actually have led to domestic violence in some families because people think that hepatitis B is just casually transmitted, which is not correct.”

Hepatitis B is spread through sexual transmission and through contact with the blood, open sores or body fluids from a person infected with the disease. The main mode of transmission, however, is from mother to child during birth and delivery.   

WHO reports that about 70% of hepatitis B infections worldwide occur in Africa, and 70% of those infected with the disease are children younger than 5.   

Birth doses

While vaccination is the best way to prevent hepatitis B, Fernandez noted that the first birth dose of this vaccine has very low coverage in Africa. 

“In 2021, only 17% of newborn babies in the WHO Africa region received a timely hepatitis B birth dose,” she said. “And only 14 of the countries in the region have policies for routine HB-dose vaccinations.”   

Fernandez said effective and affordable treatments are available for both hepatitis B and hepatitis C, which is largely spread through unsafe drug injections and is a particularly huge problem in countries in the Eastern Mediterranean and Central and Southeast Asian regions, as well as some countries in the Western Pacific. 

“I think the bottom line is we do have effective tools for prevention in the case of hepatitis C and B, and treatment in the case of a cure for hepatitis C,” she said. “They just have not been implemented effectively, and to do this, we need a surge in financing. It is not an insurmountable goal. Countries have shown that we can do this.” 

Conference organizers say that investing $6 billion annually to end hepatitis in 67 low- and middle-income countries would prevent the deaths of 4.5 million people by 2030.  

They add, “For every dollar spent on HBV [hepatitis B virus] elimination activities, there is a two to four times return on investment.”
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The growing abilities of artificial intelligence have left many observers wondering how AI will impact people’s jobs and livelihoods. One expert in the field predicts it won’t have much effect, at least in the short term.  

The topic was a point of discussion at the annual TED conference held recently in Vancouver.   

In a world where students’ term papers can now be written by artificial intelligence, paintings can be drawn by merely uttering words and an AI-generated version of your favorite celebrity can appear on screen, the impact of this new technology is starting to be felt in societies and sparking both wonderment and concern.  

While artificial intelligence has yet to become pervasive in everyday life, the rumblings of what could be a looming economic earthquake are growing stronger.  

Gary Marcus is a professor emeritus of psychology and neural science at New York University who helped ride sharing company Uber adopt the rapidly developing technology. 

An author and host of the podcast “Humans versus Machines,” Marcus says AI’s economic impact is limited for now, although some jobs have already been threatened by the technology, such as commercial animators for electronic gaming. 

Speaking with VOA after a recent conference for TED, the non-profit devoting to spreading ideas, Marcus said jobs that require manual labor will be safe, for now.   

“We’re not going to see blue collar jobs replaced I think as quickly as some people had talked about.,” Marcus predicted. “So we still don’t have driverless cars, even though people have talked about that for years. Anybody that does something with their hands is probably safe right now. Because we don’t really know how to make robots that sophisticated when it comes to dealing with the real world.”          

Another TED speaker, Sal Khan, is the founder of Khanmigo, an artificial intelligence powered software designed to help educate children. He is optimistic about AI’s potential economic impact as a driver of wealth creation. 

“Will it cause mass dislocations in the job market? I actually don’t know the answer to that,” Khan said, adding that “It will create more wealth, more productivity.” 

The legal profession could be boosted by AI if the technology prompts litigation. Copyright attorneys could especially benefit. 

Tom Graham and his company, Metaphysic.ai, artificially recreate famous actors and athletes so they do not need to physically be in front of a camera or microphone in order to appear in films, TV shows or commercials.    

His company is behind the popular fake videos of actor Tom Cruise that have gone viral on social media. 

He says the legal system will play a role in protecting people from being recreated without their permission.  

Graham, who has a law degree from Harvard University, has applied to the U.S. Copyright Office to register the real-life version of himself.            

“We did that because you’re looking for legal institutions that exist today, that could give you some kind of protection or remedy,” Graham explained, “It’s just, if there’s no way to enforce it, then it’s not really a thing.”                                

Gary Marcus is urging the formation of an international organization to oversee and monitor artificial intelligence.   

He emphasized the need to “get a lot of smart people together, from the companies, from the government, but also scientists, philosophers, ethicists…” 

“I think it’s really important that we as a globe, think all these things through,” Marcus concluded, “And don’t just leave it to like 190 governments doing whatever random thing they do without really understanding the science.”     

The popular AI website ChatGPT has gained widespread attention in recent months but is not yet a moneymaker. Its parent company, OpenAI, lost more than $540 million in 2022.     
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