Thursday, May 28, 2020

various t-cell hypotheses to be tested, including .....

'There’s no day and no night, it’s a herculean effort'

Fauci protégé sending gallons of Israeli blood to US to probe virus mysteries

Finding himself on sabbatical in Israel for the pandemic, Daniel Douek has ended up carving out an important role for the Jewish state in America’s battle against COVID-19

Daniel Douek, a principal investigator at the National Institutes of Health (courtesy of Daniel Douek)
Daniel Douek, a principal investigator at the National Institutes of Health (courtesy of Daniel Douek)
Gallons of Israeli blood will be packed in liquid nitrogen on Monday and rushed to America’s national health agency, in the hope it will help to solve some of the biggest mysteries of the coronavirus.
Daniel Douek, the scientist who collected the thousands of samples, conducted an initial analysis and prepared them for shipment, said that he is “extremely excited” that they are leaving for the US.
Douek is a principal investigator at the National Institutes of Health, America’s primary agency for biomedical and public health research. His colleagues at the Maryland HQ will be taking delivery of the samples.
As he readied them for collection, he spoke to The Times of Israel about how his sabbatical in Israel turned in to a frantic race to conduct research on protecting people from coronavirus — and said he has “no doubt” that efforts will end with success.
Illustrative: Blood samples (AP Photo/Martin Mejia)
The NIH is determined to cast its net globally for coronavirus research. But few countries match Israel’s organized stock of blood samples from both healthy and sick citizens, and this has turned the country into an important center for NIH research, said Douek, a human immunologist.
He said that the project in progress aims to enable doctors, based on assessments of patients’ blood — cross-referenced with follow-up information on how they fare — to assess early on who is at risk of a sudden deterioration, and give them tools to intervene.
“Really understanding this would be a mark of success, and I’ve no doubt we will get there,” he said.
He called Israel a “golden source” for the samples he needs, saying: “Israel’s role is very central, because we’re getting big bleeds and there are lots of samples available and they are well stored.” This is due to the high level of blood testing and meticulous record-keeping, he added.
The NIH will analyze Israeli samples alongside samples from the US and other countries where they are available. The blood will help his organization find answers that could shape global health policy over the coming months, he said.
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, speaks about the coronavirus in the White House, April 17, 2020. (AP/Alex Brandon)
Douek’s boss, mentor and friend Anthony Fauci — he knows him as Tony — the director of the NIH’s infectious diseases section and currently America’s most talked-about physician, takes a keen interest in his work.
Aside from how to assess which patients are headed for deterioration, one of the most burning questions occupying Douek and his colleagues back in Maryland is how long a vaccine, once developed, will last. To answer this, “deep research” on the question of immunity is underway.
Douek, who grew up in a Jewish family in London and moved to America more than 20 years ago, knows Israel well and was excited to arrive in August for a yearlong sabbatical away from the pressures of the NIH campus, to concentrate on cancer research at the Weizmann Institute in Rehovot. Things didn’t quite work out as he planned.
“There’s no day and there’s no night; there’s no week and there’s no weekend,” he said. “We just need to get the coronavirus work done, it’s a Herculean effort.”
Douek was already being pulled into the NIH’s coronavirus efforts in February, and then in March he hit on the possibility of collecting blood at Sheba Medical Center in Ramat Gan, where he now spends several hours each day.
Daniel Douek, a principal investigator at the National Institutes of Health, delivering a presentation on viruses (courtesy of Daniel Douek)
“I was here at the Weizmann Institute for my cancer project, and got an email from somebody in the US who I had worked with on HIV, suggesting I get in touch with Sheba regarding coronavirus,” he recalled. “I asked Sheba if they would like to collaborate, and sent them a list of all the different experiments we can do on their samples, and we quickly started working together.”
Daniel Douek, a principal investigator at the National Institutes of Health, enjoying some down-time in Jerusalem before the pandemic began (courtesy of Daniel Douek)
Data from the Israeli samples he gathers is being analyzed alongside blood and information from the US and any other countries where the NIH secures samples. Ask Douek what, exactly, they are looking for, and you won’t get a simple answer.
“If you don’t know anything, measure everything — it’s a kind of guiding mantra for us,” he said, stressing that as a new disease, COVID-19 needs extensive investigation.
But he did share an outline of some of the big topics that are being probed.
While many scientists around the world are working on vaccines, questions remain about how long a vaccine would be effective.
“You may have heard people asking whether, if you become infected and recover, you are protected from contracting the disease again,” said Douek. “The answer is in the short term you are probably immune, but how immune are you? Will you get the disease mildly? And for how long are you immune? This is really important because we’re developing vaccines and need to know how long they will work for.”
Only the kind of large-scale blood sample analysis that he is involved in can shed light on these questions, he said.
Doctors at Ichilov Hospital treat a patient in the coronavirus unit. May 4, 2020. (Yossi Aloni/Flash90)
Despite extensive research, the question of which COVID-19 patients fare well and which fare badly is open, but Douek strongly suspects that the answer is waiting to be found in blood samples.
“To explore this, it all depends on getting samples of blood from two different cohorts of people — from people who are sick and people who’ve recovered,” Douek stated. “From people on the wards we want to ask: If you get an infection, what determines the course of the disease? Why do some people get a mild infection and some serious, and why do some die in the ICU and others survive the ICU?”
If there are differences in blood samples, his team will find them, he said, adding that this can pave the way for therapeutic treatments to strengthen patients whose blood analysis bodes badly.
This transmission electron microscope image shows SARS-CoV-2, the virus that causes COVID-19, isolated from a patient in the US, emerging from the surface of cells cultured in the lab. (NIAID-RML / Wikipedia)
One line of investigation which he says looks promising is t-cells, white blood cells that play an important part in the immune system. He said that many researchers around the world are focused on antibodies, but his team thinks t-cells are also worthy of significant attention, believing that their levels may help recovery.
Samples for this investigation are normally hard to come by, as scientists need “live” blood cells from blood that has been processed and frozen within six hours of being drawn. “This is a difficult thing to do and a lot to ask of a clinical center that is busy treating patients,” Douek said, noting that while such blood is hard to source in some countries, Sheba quickly obliged.
He said there are various t-cell hypotheses to be tested, including the possibility that people who fare badly have t-cells levels that are too low to fight the virus.
“If we understand what is happening with t-cells, we may be able to help patients,” he said. “If levels are too low, we can boost t-cells in some way, perhaps with a therapeutic vaccine, such as one of the prophylactic vaccines that are currently being developed.”
Daniel Douek’s Weizmann Institute ID card from his 1984 gap year (courtesy of Daniel Douek)
Douek, 55, studied at the University of Oxford, and went to America in 1997 for a postdoctoral fellowship. Soon afterwards he found himself working at the NIH, for Fauci, the physician who has become famous for advising — and locking horns with — US President Donald Trump during the pandemic.
“He’s my boss, he was the one who recruited me,” said Douek, referring to Fauci, and noting that, even today, “If I have big life decisions to make I call and ask his secretary if he has 10 or 15 minutes.”
Douek’s latest focus on t-cells brings him full circle. Speaking in his Weizmann Institute office, he reminisced about his 1984 gap year, spent in the very same building. Aged 18, fresh out of school, he spent a year working on t-cell research.
“I can draw a straight line from being a student two floors up, doing t-cells immunology, to who I am today, sitting here in this same building, talking to you about my collaboration with Sheba,” he said. “It all started when I was 18 years old.”

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