Release date: 2014-12-10
Timothy Ray Brown is the only AIDS person in the world that has been recognized as being cured. The story about Brown is overwhelming, and the story of his chief physician, Girout Hutt, is little known. Not long ago, in the eastern German city of Dresden, Dr. Hutt first described his story of healing Brown and the Nobel Prize. And the HIV finder, Nobel Prize winner Sinoosi in 2008, also exclusively accepted an exclusive interview with this newspaper.
This group of reports presents the epitome of the unremitting struggle of mankind for more than 30 years in the fight against AIDS.
Inspiration from an article
On the winter day of 1996, Hut, a third-year student at the Humboldt University School of Medicine in Berlin, received the latest issue of Science, which included the National Cancer Institute, Stephen O'Brien, and others on HIV infection and AIDS resistance. An article about genes.
Hutt learned from the article that although AIDS means nightmares for some people, it does not pose a threat to others - these people live in a genetic defect. Since 32 bases are deleted from the CCR5 gene, this gene is called CCR5-Δ32.
"Because of a natural genetic defect, HIV can't enter lymphocytes, and it no longer poses a threat to life." This has caused Hut's strong interest: Can you use genetic defects to find a cure for AIDS? Can you get AIDS? Is the patient's lymphocytes all replaced with cells with this genetic defect?
In fact, before this, Hutt was not "cold" about infectious diseases or HIV, and blood diseases and oncology were the focus of his attention. Charlotte Hospital Berlin is Hut’s long-cherished dream. This is the largest general hospital in Europe and one of the most traditional hospitals in Europe. Emir von Behring, the pioneer of diphtheria, Robert Koch, founder of pathogenic bacteriology, and Paul Elli, the pioneer of chemotherapy. Imagine that more than half of the Nobel Prize winners in physiology or medicine in Germany come from this medical center. Hut dreams of serving cancer patients and conducting experiments here. His ultimate goal is to cure cancer.
After graduating from medical school, Hut entered the Charlotte Hospital in Berlin. According to his own planning and efforts, Hut became a hematologist. He traveled between the clinic and the ward, and carried out a number of bone marrow transplants. Everything went on and on until the 2006, when Timothy Ray Brown appeared.
Opportunity favors prepared minds
Brown, an American translator living in Berlin, Germany, was tested in 1995 to carry HIV in his blood. This virus can lie in the human body for more than ten years, causing acquired immunodeficiency syndrome, which is often called AIDS.
"Gibt es keine heilung." The attending doctor told him in gentle, slow German.
AIDS kills millions of people every year. Before Brown, there had never been any cure. The result of this test is like a verdict - the death penalty is suspended for several years.
Brown did not panic. He continued his work and lived with the "boyfriend" Michelle from the former East Germany. Fortunately, in the first decade, his HIV virus appeared to be docile and indifferent, and did not bother his health.
However, new troubles have come, he was diagnosed with acute myeloid leukemia, a terminal illness with a five-year survival rate of only 25%.
At Charlotte Hospital, Hut conducted the first chemotherapy for Brown. But after 7 months, the leukemia relapsed.
Hutt is well aware that stem cell transplantation is the only hope for treating brown leukemia.
As a hematologist, Hut didn't know much about AIDS, but with the deepening of Brown's treatment, the article "Science" appeared in his mind more than a decade ago, he remembered the article mentioned in this article. A population with genetic mutations has immune function to HIV." This group of people can be found in Northern Europe, with a ratio of about 1% in Germany.
“Why don’t we do something better?†Hutt decided to gamble. What would happen if a stem cell of a CCR5-Δ32 mutant donor could be found? Not only can leukemia be cured, but AIDS can also be cured.
Today, Hutt is more willing to think of the idea of ​​"stem cell transplantation for AIDS" as a process that blood doctors can think through. But I have to admit that a solid knowledge reserve and a lot of reading in daily work play a very important role. Even in the medical world of strong hands, the opportunity always favors a "prepared mind" like Hutt.
I can’t believe it, no one has ever done this before.
Hutt is lucky. Germany has the world's largest and most complete bone marrow transplant library with nearly 20 million donor information. Through this bone marrow transplant library, 90% of patients will eventually be able to find a fitter; in the United States, this ratio is only 65%.
In the German bone marrow transplant library, Hutt discovered that 232 donors worldwide matched Brown, of which 80 lived in Germany. They tested one by one and found that the No. 61 donor was the target they wanted to find – the homozygous CCR5-Δ32 gene carrier.
Hut sat in front of the computer for several nights and looked at almost all the relevant literature he could find. "I can't believe it. No one has ever done this before." Hutt said, "My first feeling is that I missed it. I definitely miss something."
In a sense, this is indeed the case - Hutt does not know that most AIDS experts and clinicians have reached a consensus: the cure of AIDS is impossible.
In the history of Charlotte Hospital, bone marrow transplants have never been accepted by AIDS patients. Not to mention Hut’s expectations, the hospital expressed opposition.
Hut is not reconciled. He is looking for the director of the transplant center, Eckhart Tell. In the past few months, Hut did not report Brown's case to anyone, for fear that others would "steal" his patients and thoughts. Now, he must truthfully inform his own ideas and seek his support.
Tell agreed. He does not believe that this bold idea can eliminate the HIV virus in Brown. He just wanted to give Hut a chance to try it.
In February 2007, Brown accepted the stem cell transplant of No. 61 donor. Then, Brown stopped using AIDS drugs, and the HIV virus in the body seemed to disappear. After 60 days, Hutt and colleagues could no longer find the trailing cells in Brown.
In order to confirm that Brown has no HIV virus, Brown has become one of the most biopsied people in the world. Hutt and his team sampled Brown's blood, liver, rectum, and even the brain again and again. Hutt also sent Brown's samples to the laboratory of John S. Hopkins, professor of medicine at Johns Hopkins University, and other laboratories in the United States with high-precision equipment.
In general, nearly one million copies of HIV virus are still present in patients who are controlled by antiretroviral therapy, but in Brown, even the most sensitive tests can't detect the presence of HIV.
Nobel Prize? I didn't think so much.
Hutt was cautious and low-key. He did not immediately spread the news that Brown was suspected of being cured, nor did he submit any manuscripts to any professional journal. "If you encounter such a thing, unless you have full confidence, I don't want to immediately make the results public."
In February 2008, Hut participated in the "Retroviral and Opportunity Infections Annual Meeting" held in Boston, USA, which is one of the most professional academic conferences in the field of AIDS. Until then, Hutt delivered a manuscript to the organizers of the New England Journal of Medicine and the conference, requesting that the results of the detection of HIV residues not detected in the body after Brown's cessation of treatment were published.
However, the New England Journal of Medicine rejected his manuscript, and the "Retrovirus and Opportunity Infections Annual Meeting" only allowed him to post posters at the conference.
Like other circles, AIDS research institutions always like to question outsiders. This time I came to a young doctor who was not good enough in his own hospital. He didn't know much about AIDS and made some attempts that he had never had before. Most people are thinking, "Who is this kid?"
Hutt’s supporters include Jeffrey Lawrence, director of the HIV Research Institute at Cornell University School of Medicine and chief expert at the American Center for AIDS Research. In September 2008, Lawrence asked Hutt to share his findings at a small meeting attended by MIT's top AIDS experts, and handed Brown's samples to more laboratories in the United States for more sensitive testing. Similarly, the results of these samples were all negative.
The Wall Street Journal reporter Mark Scofors was invited to the meeting and wrote a report. The New England Journal of Medicine also revisited Hut’s submission and officially published it in February 2009.
Participate in academic conferences, interviews, and make statements... Hut’s life has changed since then. When the report of The Wall Street Journal was reprinted to Germany, a friend called him at six in the morning. "He exclaimed, 'I saw you in the largest circulation newspaper in Germany!'" Hut laughed. Prior to this, even Hut's parents did not know what his son's work was until they knew about it.
"Some people think that you are a strong contender for the Nobel Prize. What do you think?" When asked about this question, Hut made another hearty laugh. "I don't know how the Nobel Prize judging panel judges," Hutt said. "But if the whole process of treating Brown can evolve into a more viable and simpler treatment, it's not impossible. But, I I didn't think so much."
Today, Hutt is conducting research in an institution affiliated with Utrecht University in the Netherlands, and together with several other European centers, they try to replicate Brown's miracle. The team he leads continues to screen and accumulate donors for CCR5 gene defects, ready for the next opportunity.
Functional cure, enough
The cost of allogeneic stem cell transplantation is about $250,000, and the population containing the CCR5-Δ32 gene is extremely rare. Brown's path to seek medical care is clearly not what most AIDS patients can imitate.
After the Brown case, Hutt and his colleagues tried to replicate the Brown Miracle. On a global scale, a total of six AIDS patients have undergone stem cell transplantation, and unfortunately, they died several months after surgery.
Hutt is not pessimistic about this. "These are not ordinary transplants, but trials with experimental nature, the risk is quite high," Hutt said.
After Brown’s case, “Hey, AIDS can be curedâ€, “The road to cure AIDS has been found†and so on. Hutt believes that it depends on how people define "healing."
In the field of AIDS, there are two definitions of "cure" - functional cure. The virus in the infected person is completely inhibited. It is not important to have a virus. It is important that the patient can detect the virus even if he does not receive treatment. Exist; sterilized and cured, completely eliminating HIV from the body.
"I think the sterilization cure is good, but the functional cure, which is enough for AIDS patients," Hutt said.
What makes him very gratified is that it is possible to achieve a cure that has gradually become a consensus in the field of AIDS.
For Brown's treatment options to be more widely available, it is necessary to generate CCR5-Δ32 mutations in patients who have not been transplanted, preferably by simple injection.
At the Paula Canon Laboratory in Southern California, research into the dream has begun. According to Hut, the lab switched to a new method of gene editing, using zinc finger nuclease as a genetic scissors, which anchors and clips a fragment of a gene band. For example, they are able to cleave the coding sequence that produces the CCR5 receptor and obtain anti-HIV virus cells.
"Finding a safe way to inject zinc finger nuclease directly into the body still requires a 'Great Leap Forward' effort." Hutt said, "Although the revolution has not been successful, it has taken a very important step."
Source: Southern Weekend
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