Health

Honorable Lasker Award Development of Non-Invasive Prenatal DNA Test


It was a startling discovery: Tiny pieces of a fetus’ DNA were found floating in its mother’s bloodstream – not inside the mother’s cells, where genetic material is normally found, but rather outside of them.

But when Dr Yuk Ming Dennis Lo, a researcher in Hong Kong, described the discovery in 1997, it was greeted with something like a shrug. Industry experts were so indifferent that after Dr Lo’s team licensed fetal DNA detection technology to a British company, he said, the company turned around and returned the license.

Two decades later, the importance of this technique is beyond doubt. Dr Lo eventually helped turn her discovery into a non-invasive prenatal test for Down syndrome that has been performed tens of millions of times and is used in more than 60 countries.

His work was recognized on Wednesday with the Lasker Prize, one of the most prestigious awards in medicine, with a $250,000 win and pre-Nobel prize reputation. Dr. Lo won in the clinical medical research category.

The Lasker Foundation also presented awards in two other categories. Lauren Gardner, who created the Johns Hopkins University Covid-19 Dashboard, was awarded the public service award. A team of three researchers whose work concerns the way cells interact with their surroundings have received a fundamental medical research prize, leading to a fundamental discovery that opens up new scientific territory.

Dr Lo, of the Chinese University of Hong Kong, announced his signature discovery in 1997, shortly after he moved back from England to Hong Kong, his birthplace, where he carried out the following research University. It took several months before Hong Kong was returned to China, and the resulting exodus of experts from the city created opportunities to open plum universities for young scientists like him. .

For eight years, Dr. Lo has been trying to find the right concentration of fetal DNA in the mother’s blood. Such a finding, he hopes, could help eliminate the need for risky prenatal testing methods, which rely on taking samples of fetal tissue, and could instead open the door to other methods. Non-invasive screening.

Dr. Lo looked for fetal genetic material in the mother’s blood cells. But he has also seen reports describing how DNA from a tumor has been found to circulate not in blood cells, but in the aqueous part of cancer patients’ blood, plasma. If tumor DNA can be found in that part of the blood stream, why not fetal DNA?

He said: “I have a strange thought that the cancer that develops in the patient is like the placenta that has implanted in the uterus.

He started looking for traces of fetal DNA in the plasma. “That’s a good guess,” he said.

Penetration of fetal DNA in maternal plasma remains difficult. Dr. Lo needed a way to detect the extra copy of chromosome 21 that causes Down syndrome. The tests that separate the mother’s DNA from the child’s DNA don’t work well enough. Instead, in 2008, Dr. Lo embarked on a technique in which he looked at a large sample of randomly selected DNA fragments from the mother’s plasma and investigated whether fragments from chromosome 21 Is it a bit high?

Dr. Lo likens this task to trying to find out if someone has a coin or two in their wallet. Unable to look inside wallets, he can instead study their overall weight and, using an extremely finely tuned scale, can look for significantly smaller portions. of a pound.

“I started to really build that molecular balance,” he says.

Other Lasker awardees, too, have managed unexpected engineering feats, albeit in different fields.

Lauren Gardner, a civil and systems engineering professor at Johns Hopkins University, received a public service award for leading the creation of the Covid-19 dashboard, which she says still provides the full picture. the most detailed request about the pandemic.

On January 21, 2020, one of her doctoral students, Ensheng Dong, approached her about tracking new cases of pneumonia in her hometown, China. Mr. Dong has the tools: He can mine Chinese websites for early case data, and he knows how to build online maps. Dr. Gardner says she remembers the costs of not having timely access to data during outbreaks of Zika and Middle East respiratory syndrome, or MERS, and she wants to make sure that doesn’t happen again.

“I thought it would be of the most interest to the research community,” she said.

Within a few months, the dashboard received tens of millions of page views and more than 4.5 billion data requests per day. In the absence of similarly rapid or comprehensive case data from public health authorities such as the World Health Organization or the Centers for Disease Control and Prevention, the university dashboard has become become an accessible resource for policymakers, scientists and ordinary citizens.

It became so conspicuous, Dr. Gardner said, that she later received calls from the US State Department expressing concern about how certain geopolitically sensitive countries were represented on the map of the US. surname.

Dr. Gardner said that the panel drew some of its power from draining a university, not the government. That trait has stabilized over the 2020 period as the Trump administration downplays cases. But she says they ended up filling the gap in public data that the government should have filled.

“We are doing for the United States what the CDC should do, and for the world, what the WHO should do,” she said. “But they don’t have the resources to do that and that needs to change.”

With governments reducing investment in detecting and reporting Covid cases, the future of dashboards may be determined more by the loss of high-quality data than by the direction of the pandemic itself. Dr. Gardner said.

However, she said she hopes that public demand for accessible health data will outlast the dashboard, even if major challenges remain, such as economic deficits. costs and lack of national standards for how infectious disease cases should be reported.

“The best thing we’ve done is create an expectation of access to this type of data by those affected,” Dr. Gardner said. Similar maps and dashboards could be useful ahead of the next pandemic, she said: “Influenza data exists, but not in an easily digestible format, where I have it. can be considered a Marylander or a Texan if the flu comes to me.”

The Lasker Prize for Basic Medical Research goes to three scientists who have described how cells bind to networks of proteins and other molecules around them – findings that point to the treatment of a number of diseases.

Two of the winners – Richard O. Hynes, of the Massachusetts Institute of Technology and Dr. Erkki Ruoslahti, of the Sanford Burham Prebys Medical Discovery Institute in San Diego – independently identified a protein that helps bind cells with networks around them.

A third person, Timothy A. Springer, of Boston Children’s Hospital, has found proteins that guide immune cells in the body and help them recognize foreign antigens. That work, in the 1980s, attracted the skepticism of some scientists. Dr. Springer recalls one time a professor taking a napkin down to the bar at a scientific conference simply read, “It doesn’t work.”

But it did. Subsequent research has provided the basis for treatments for dry eye disease and multiple sclerosis, as well as ulcerative colitis and Crohn’s disease, two types of inflammatory bowel disease.

When the three scientists, each in their own laboratories, focused on the structures of the proteins they were studying, now called integrals, it became clear that they all belonged to the same family of molecules. . Dr. Springer recalled Dr. Hynes invited him to his lab, where they compared the sequences of the respective proteins. He eventually met Dr. Ruoslahti at a conference organized by Dr. Hynes.

“It’s like different types of apples – Gala apples to Fuji apples,” Dr. Springer said.

Despite their accomplishments, the Lasker Prize winners are still honing their findings. For Dr Lo in Hong Kong, that meant trying to use his insight from the 1990s – that tumors and fetuses both leave genetic signatures in the blood – to develop cancer screening tests. These tests are best for detecting larger tumors but can also find some early-stage cancers.

“If your method is sensitive enough,” he says, “it can really save lives.”



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