The Internet age has yet to provide Barb Shantz with the answer she wants most.
There is no Wikipedia entry for why her son, Noah, was born with a small cerebellum. She can’t Google why her 7-year-old needs a walker, while his baby brother took his first steps at just 10 months.
“That was upsetting to Noah. We actually accessed psychology services,” says Shantz, who lives in Ottawa. “He got angry and cried and said, ‘Not fair.’ It makes your heart break in half.”
Noah suffers from a disease so rare it has no name. The best hope for solving his medical mystery is to identify the gene mutation responsible — by finding another patient just like him.
This other Noah could be anywhere. To find him, his doctors are searching on a new kind of Internet, the “Internet of DNA.”
While still embryonic, an Internet of DNA would see networks of databases connecting from around the world — allowing scientists to study massive datasets that could yield medical breakthroughs, novel drugs and new ways of diagnosing and treating patients.
“If we’re looking to 2025, I see a kind of World Wide Web for health, a true Internet for health, which just doesn’t exist today,” said Dr. Tom Hudson, a leading genomics researcher and president of the Ontario Institute for Cancer Research.
“What used to be looking under a microscope and someone saying ‘yes’ or ‘no’ is not the way of the future. We are transforming a lot of information into digital bits and that information is huge.”
Just as the World Wide Web revolutionized global communications, researchers hope an Internet for sharing genetic information will transform medicine. For researchers mapping diseases, it could mean the difference between wandering through a forest to try understand its size and shape and flying over the treetops to gain a broad view.
An Internet of DNA is also the next logical step in realizing the dream of the Human Genome Project, which required billions of dollars and a decade to complete. Today, sequencing costs have dropped a million-fold and a typical lab can produce hundreds of genomes in a week.
So far, this deluge of global data has been pooling in silos, while legal, technical and cultural barriers prevent scientists from easily sharing their data troves. But the next big discovery in diseases like cancer or schizophrenia is going to stem from a study population of millions, not hundreds or thousands — far more patients than any one scientist or even country can recruit.
The stakes are high — so high that in 2013, Hudson and others formed the Toronto-based Global Alliance for Genomics and Health. The coalition, involving more than 300 institutions, is working to create standards and policies necessary for an Internet of DNA to flourish.
“If nothing is done, there is a risk that balkanized systems will soon become established (as happened for electronic medical records in the United States), a significant lost opportunity to make important advances in human health,” according to the Global Alliance’s website.
Successes from small-scale data sharing projects already hint at the thrilling potential of larger genomic networks.
In 2011, Noah’s doctor, Kym Boycott of the Children’s Hospital of Eastern Ontario, contacted doctors across Canada and asked them to submit information about patients with rare and unexplained diseases.
The project, dubbed FORGE, received submissions for 371 disorders — a database that enabled Boycott’s team to identify the single gene mutations responsible for 146 previously unexplained diseases.
To solve ultra-rare cases like Noah’s, however, even bigger datasets are needed — bigger than even Matchmaker Exchange, which will eventually connect a dozen databases and currently represents about 20,000 patients worldwide.
Noah’s genetic sequence was uploaded into Matchmaker Exchange nearly two years ago. Boycott estimated 50,000 to 200,000 sequences are needed before she finds another patient like Noah.
In infectious disease, researchers are also realizing the potential of genomic data sharing, particularly during fast-moving epidemics like Ebola or Zika.
“We’re on the cusp of a sea change, in terms of how quickly data can be generated during outbreaks,” said Nathan Yozwiak, an associate director of viral genomics with Harvard University and the Broad Institute. “Viruses mutate very quickly but we can use that against them … When you look at the sequences from multiple patients and you compare the mutations over time, you can derive a lot of information from that.”
During the Ebola outbreak, Yozwiak and his colleagues sequenced virus samples from 78 patients in Sierra Leone. This confirmed the virus was transmitting person-to-person and had spread there from Guinea. It also showed where and how quickly it was mutating.
They shared their genetic sequences in a public database, even before publishing any papers, a rare move in the competitive world of academic research. The response was a deluge of emails from scientists wanting to collaborate or use the data for treatments or diagnostics they were developing.
Ultimately, the West African outbreak was a missed opportunity to learn from what could have become a massive database of Ebola genomes; in the three months after Yozwiak’s group released their data, no other sequences were shared.
With Zika, however, there has been a lot more emphasis on sharing despite political barriers preventing some scientists from accessing virus samples, Yozwiak said. In Wisconsin, researchers experimenting on monkeys are sharing data in real time. And in February, a powerful group of research organizations, non-profits and academic journals announced they would share any data that could help stop the epidemic.
While the promise of genomic data sharing is lofty, many researchers warn against overhyping. More data will likely lead to new drugs and insights eventually, but scientific progress is slow and meticulous. Simply identifying a disease gene doesn’t mean a cure is around the corner; the gene for Huntington’s disease, for example, was identified in 1993 but a cure remains elusive.
But Hudson believes data sharing will pave the path towards a future of precision medicine. And revelations gleaned from large data sets have already led to new cancer drugs for treating specific tumour types or mutations, he said.
“We’re not treating lung cancer anymore or melanoma anymore. We’re treating a melanoma patient with a BRAF mutation, or a lung cancer patient with an EGFR or ALK mutation.”
For patients like Noah, the databases of today won’t lead to a cure or treatment in their lifetime, Boycott admits. But finding that other Noah could finally give his disease a name.
A small step for science, yes. But hugely meaningful for patients and their families.
“It’ll give us a bit of closure,” Shantz says. “And it would help the next child diagnosed with the same thing Noah has.”
Creating an Internet of DNA is far trickier than inventing the World Wide Web ever was — the inventor of HTML, for one, never had to worry about protecting patient privacy or ensuring responsible use of the data being shared. Some of the potholes on the genomic information superhighway:
Privacy, privacy, privacy
The more people have access to data, the likelier that a breakthrough will result — and that privacy could be breached. This is a central paradox for genomic data sharing and so far, efforts to ensure privacy protections have been through trial and error. But the stakes are high; your genetic code contains information not just about your health, disease risk, ethnicity and heritage, but that of your relatives, too. And there is no telling how DNA might someday be used by everyone from insurance providers to law enforcement.
But perhaps the unavoidable reality is some privacy risk will always exist. “We will use our most modern technologies, we’ll monitor, we’ll encrypt,” said Bartha Knoppers, director of McGill’s Centre of Genomics and Policy, who heads the Global Alliance’s regulatory and ethics working group. “But we can never guarantee that you may not be re-identified one day. I think we just have to say that.”
Governing the Internet of DNA
If a patient in Canada shares genomic information and a researcher in Japan misuses it, what are the consequences? What oversight is needed, and who is responsible? What kind of consent forms should be signed by people who volunteer their DNA — and do their relatives also need to sign?
These are among the many complex problems being deliberated by groups like the Global Alliance for Genomics and Health.
“I do wake up sometimes, early or in the middle of the night, and wonder: ‘Am I being totally realistic?’” admits Knoppers. “This is so complex and every time you say, ‘Oh good, we’ve band-aided this part of the problem … something else comes up.”
Helping every country plug in
During the first month of Sierra Leone’s Ebola outbreak, lab workers in the city of Kenema collected blood samples from 78 patients — but it was not until those were shipped to Massachusetts that the viral genomes could finally be sequenced and analyzed.
In many countries, researchers lack the technology and expertise to sequence and analyze genetic data, let alone share it online. To ensure a truly global “Internet of DNA,” every nation will need the tools to contribute. “This requires a democratization of sequencing technology,” said Nathan Yozwiak with the Broad Institute. “Sequencing should occur as close to the sample collection point as possible; we really want to empower local capacity.”
In search of storage space
It’s hard to overstate the sheer size of genomic data already being generated around the world. “We’ve come to the point where it’s too big to store,” said Tom Hudson of the Ontario Institute for Cancer Research. He notes that a single project — the International Cancer Genome Consortium — has 89 types of cancer being sequenced in labs around the world, and that is already adding up to roughly a petabyte of data. “I forget how many zeroes that is, but it would take six months for someone to download that data on the fastest university network,” Hudson says.
“We need to come up with cheaper and cheaper ways of storing the data and exchanging the data. We’re facing huge bottlenecks,” he continued. The Internet of DNA “is not going to happen with today’s technology.”
Creating a cultural shift
Perhaps the biggest barrier to scientific sharing will prove toughest to change: research culture. In an academic reality where funding is scarce — and professional advancement depends on being the first to publish in prestigious journals — there are few incentives for scientists to share what’s in their notebooks. And those who do are often stymied by their own institutions. “Professors don’t want to share because they’ll get scooped,” said U of T’s Aled Edwards, founder of the Structural Genomics Consortium. “And the institution’s been told to protect their intellectual property — that means excluding people from using it.”
Such cultural barriers prevent not just data from being shared but everything from patient samples to molecular compounds used in experiments. The reward systems need to change, Hudson says, and the ones to change it are those who hold the power: universities, academic journals, and funders.