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Let's Know Things
Personalized CRISPR

Let's Know Things

Play Episode Listen Later Jun 3, 2025 15:45


This week we talk about gene-editing, CRISPR/Cas9, and ammonia.We also discuss the germ line, mad scientists, and science research funding.Recommended Book: The Siren's Call by Chris HayesTranscriptBack in November of 2018, a Chinese scientist named He Jiankui achieved global notoriety by announcing that he had used a relatively new gene-editing technique on human embryos, which led to the birth of the world's first gene-edited babies.His ambition was to help people with HIV-related fertility problems, one of which is that if a parent is HIV positive, there's a chance they could transmit HIV to their child.This genetic modification was meant to confer immunity to HIV to the children so that wouldn't be an issue. And in order to accomplish that immunity, He used a technology called CRISPR/Cas9 to modify the embryos' DNA to remove their CCR5 gene, which is related to immune system function, but relevant to this undertaking, also serves as a common pathway for the HIV-1 virus, allowing it to infect a new host.CRISPR is an acronym that stands for clustered regularly interspaced short palindromic repeats, and that refers to a type of DNA sequence found in all sorts of genomes, including about half of all sequenced bacterial genomes and just shy of 90% of all sequenced archaea genomes.Cas9 stands for CRISPR-associated protein 9, which is an enzyme that uses CRISPR sequences, those repeating, common sequences in DNA strands, to open up targeted DNA strands—and when paired with specific CRISPR sequences, this duo can search for selected patterns in DNA and then edit those patterns.This tool, then, allows researchers who know the DNA pattern representing a particular genetic trait—a trait that moderates an immune system protein that also happens to serve as a convenient pathway for HIV, for instance—to alter or eliminate that trait. A shorthand and incomplete way of thinking about this tool is as a sort of find and replace tool like you have in a text document on your computer, and in this instance, the gene sequence being replaced is a DNA strand that causes a trait that in turn leads to HIV susceptibility.So that's what He targeted in those embryos, and the children those embryos eventually became, who are usually referred to as Lulu and Nana, which are pseudonyms, for their privacy, they were the first gene-edited babies; though because of the gene-editing state of the art at the time, while He intended to render these babies' CCR5 gene entirely nonfunctional, which would replicate a natural mutation that's been noted in some non-gene-edited people, including the so-called Berlin Patient, who was a patient in Germany in the late-90s who was functionally cured of HIV—the first known person to be thus cured—while that's what He intended to do, instead these two babies actually carry both a functional and a mutant copy of CCR5, not just the mutant one, which in theory means they're not immune to HIV, as intended.Regardless of that outcome, which may be less impactful than He and other proponents of this technology may have hoped, He achieved superstardom, briefly, even being named one of the most influential people in the world by Time magazine in 2019. But he was also crushed by controversy, stripped of his license to conduct medical research by the Chinese government, sent to prison for three years and fined 3 million yuan, which is more than $400,000, and generally outcast from the global scientific community for ethical violations, mostly because the type of gene-editing he did wasn't a one-off sort of thing, it was what's called germ-line editing, which means those changes won't just impact Lulu and Nana, they'll be passed on to their children, as well, and their children's children, and so on.And the ethical implications of germ-line editing are so much more substantial because while a one-off error would be devastating to the person who suffers it, such an error that is passed on to potentially endless future generations could, conceivably, end humanity.The error doesn't even have to be a botched job, it could be an edit that makes the edited child taller or more intelligent by some measure, or more resistant to a disease, like HIV—but because this is fringy science and we don't fully understand how changing one thing might change other things, the implications for such edits are massive.Giving someone an immunity to HIV would theoretically be a good thing, then, but if that edit then went on the market and became common, we might see a generation of humans that are immune to HIV, but potentially more susceptible to something else, or maybe who live shorter lives, or maybe who create a subsequent generation who themselves are prone to all sorts of issues we couldn't possibly have foreseen, because we made these edits without first mapping all possible implications of making that genetic tweak, and we did so in such a way that those edits would persist throughout the generations.What I'd like to talk about today is another example of a similar technology, but one that's distinct enough, and which carries substantially less long-term risk, that it's being greeted primarily with celebration rather than concern.—In early August of 2024, a gene-editing researcher at the University of Pennsylvania, Dr. Kiran Musunuru, was asked if there was anything he could do to help a baby that was being treated at the Children's Hospital of Philadelphia for CPS1 deficiency, which manifests as an inability to get rid of the ammonia that builds up in one's body as a byproduct of protein metabolism.We all generate a small amount of ammonia just as a function of living, and this deficiency kept the baby from processing and discarding that ammonia in the usual fashion. As a result, ammonia was building up in its blood and crossing into its brain.The usual method of dealing with this deficiency is severely restricting the suffer's protein intake so that less ammonia is generated, but being a baby, that meant it wasn't able to grow; he was getting just enough protein to survive and was in the 7th percentile for body weight.So a doctor at the Children's Hospital wanted to see if there was anything this gene-editing researcher could do to help this baby, who was at risk of severe brain damage or death because of this condition he was born with.Gene-editing is still a very new technology, and CRISPR and associated technologies are even newer, still often resulting in inaccurate edits, many of which eventually go away, but that also means the intended edit sometimes goes away over time, too—the body's processes eventually replacing the edited code with the original.That said, these researchers, working with other researchers at institutions around the world, though mostly in the US, were able to rush a usually very cumbersome and time-consuming process that would typically take nearly a decade, and came up with and tested a gene-editing approach to target the specific mutation that was causing this baby's problems, and they did it in record time: the original email asking if Dr Musunuru might be able to help arrived in August of 2024, and in late-February of 2025, the baby received his first infusion of the substance that would make the proper edits to his genes; they divided the full, intended treatment into three doses, the first being very small, because they didn't know how the baby would respond to it, and they wanted to be very, very cautious.There were positive signs within the first few weeks, so 22 days later, they administered the second dose, and the third followed after that.Now the research and medical worlds are waiting to see if the treatment sticks; the baby is already up to the 40th percentile in terms of weight for his age, is able to eat a lot more protein and is taking far less medication to help him deal with ammonia buildup, but there's a chance that he may still need a liver transplant, that there might be unforeseen consequences due to that intended edit, or other, accidental edits made by the treatment, or, again, that the edits won't stick, as has been the case in some previous trials.Already this is being heralded as a big success, though, as the treatment seems to be at least partially successful, hasn't triggered any serious, negative consequences, and has stuck around for a while—so even if further treatments are needed to keep the gene edited, there's a chance this could lead to better and better gene-editing treatments in the future, or that such treatments could replace some medications, or be used for conditions that don't have reliable medications in the first place.This is also the first known case of a human of any age being given a custom gene-editing treatment (made especially for them, rather than being made to broadly serve any patient with a given ailment or condition), and in some circles that's considered to be the future of this field, as individually tailored gene-treatments could help folks deal with chronic illnesses and genetic conditions (like cystic fibrosis, Huntington's disease, muscular dystrophy, and sickle cell), but also possibly help fight cancers and similar issues.More immediately, if this treatment is shown to be long-term efficacious for this first, baby patient, it could be applied to other patients who suffer the same deficiency, which afflicts an estimated 1 in 1.3 million people, globally. It's not common then—both parents have to have a mutant copy of a specific gene for their child to have this condition—but that's another reason this type of treatment is considered to be promising: many conditions aren't widespread enough to justify investment in pharmaceuticals or other medical interventions that would help them, so custom-tailored gene-editing could be used, instead, on a case-by-case basis.This is especially true if the speed at which a customized treatment can be developed is sped-up even further, though there are concerns about the future of this field and researchers' ability to up its efficiency as, at least in the US, the current administration's gutting of federal research bodies and funding looks likely to hit this space hard, and previous, similar victories that involved dramatically truncating otherwise ponderous developmental processes—like the historically rapid development of early COVID-19 vaccines—are not looked at favorably by a larger portion of the US electorate, which could mean those in charge of allocating resources and clearing the way for such research might instead pull even more funding and put more roadblocks in place, hobbling those future efforts, rather than the opposite.There are plenty of other researchers and institutions working on similar things around the world, of course, but this particular wing of that larger field may have higher hurdles to leap to get anything done in the coming years, if current trends continue.Again, though, however that larger context evolves, we're still in the early days of this, and there's a chance that this approach will turn out to be non-ideal for all sorts of reasons.The concept of tailored gene-editing therapies is an appealing one, though, as it could replace many existing pharmaceutical, surgical, and similar approaches to dealing with chronic, inherited conditions in particular, and because it could in theory at least allow us to address such issues rapidly, and without needing to mess around with the germ-line, because mutations could be assessed and addressed on a person-by-person basis, those edits staying within their bodies and not being passed on to their offspring, rather than attempting to make genetic customizations for future generations based on the imperfect knowledge and know-how of today's science, and the biased standards and priorities of today's cultural context.Show Noteshttps://www.nejm.org/doi/full/10.1056/NEJMoa2504747https://www.nih.gov/news-events/news-releases/infant-rare-incurable-disease-first-successfully-receive-personalized-gene-therapy-treatmenthttps://www.wired.com/story/a-baby-received-a-custom-crispr-treatment-in-record-time/https://www.wsj.com/tech/biotech/crispr-gene-editing-therapy-philadelphia-infant-8fc3a2c5https://www.washingtonpost.com/science/2025/05/15/crispr-gene-editing-breakthrough/https://www.npr.org/sections/shots-health-news/2025/05/15/nx-s1-5389620/gene-editing-treatment-crispr-inheritedhttps://interestingengineering.com/health/first-personalized-crispr-gene-therapyhttps://www.nature.com/articles/d41586-025-01496-zhttps://www.nytimes.com/2025/05/15/health/gene-editing-personalized-rare-disorders.htmlhttps://www.nytimes.com/2025/05/31/world/asia/us-science-cuts.htmlhttps://www.livescience.com/health/genetics/us-baby-receives-first-ever-customized-crispr-treatment-for-genetic-diseasehttps://en.wikipedia.org/wiki/He_Jiankui_affairhttps://en.wikipedia.org/wiki/CCR5https://en.wikipedia.org/wiki/Berlin_Patienthttps://en.wikipedia.org/wiki/CRISPR_gene_editinghttps://en.wikipedia.org/wiki/CRISPRhttps://pmc.ncbi.nlm.nih.gov/articles/PMC6813942/ This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit letsknowthings.substack.com/subscribe

The Top Line
What 'The Next Berlin Patient' and a PrEP's 100% efficacy mean for HIV drug development

The Top Line

Play Episode Listen Later Aug 2, 2024 26:38


This week on “The Top Line,” we discuss two studies in HIV research that were presented at the 25th International AIDS Conference in Germany. One of them is the report of a 7th person who has likely been cured of HIV. And there's something unique about this case that has sparked excitement among scientists. The other one is the report of a long-acting injection that showed 100% efficacy in preventing HIV infection in a phase 3 trial. Some experts have hailed the PrEP candidate as a game-changer. To dive deeper into these studies, Fierce Pharma's Angus Liu interviews Jared Baeten, M.D., Ph.D., senior vice president and head of clinical development of the virology therapeutic area at Gilead Sciences.  To learn more about the topics in this episode:  With seventh person seemingly cured of HIV, signs of hope for a broader cure  Watch out, GSK. Gilead's twice-yearly PrEP drug shows 100% efficacy for HIV prevention  See omnystudio.com/listener for privacy information.

HIV unmuted
The game-changing research from AIDS 2024

HIV unmuted

Play Episode Listen Later Jul 23, 2024 17:51


This episode of HIV unmuted introduces a new host and format for the award-winning IAS podcast. Our host, Juan Michael Porter II, the Senior Editor for TheBody/TheBodyPro, takes a deep dive with a single guest in an intimate conversation that gives the listener a glimpse of the guest – who they are and how they got into this work – and an understanding of their topic of expertise.   This new format opens with Sharon Lewin, the IAS President and AIDS 2024 International Co-Chair, walking us through the latest HIV science released at AIDS 2024, the 25th International AIDS Conference, and what it means for the HIV response. This episode delves into a broad range of exciting science, from long-acting injectables to new research on doxycycline prophylaxis to advances in cure research, including inspiration from the “next Berlin Patient”.  Through the lens of her personal story, Sharon walks us through the context and challenges of the HIV response, such as changing global health priorities and reduced funding for HIV. Astounding progress has been made in the HIV response. Yet, we are still missing critical targets. Sharon makes it clear that if we are to envision the end of the HIV pandemic, we must address persisting inequalities that remain in the HIV response: we must put people first. Meet our guest Sharon LewinThe IAS President and AIDS 2024 International Co-Chair, Sharon Lewin, is an infectious diseases physician and basic scientist and has worked in HIV-related clinical medicine and research for over 25 years. She is Director of the Peter Doherty Institute for Infection and Immunity, a joint venture of the University of Melbourne and Royal Melbourne Hospital in Melbourne, Australia. The Doherty Institute has over 850 staff working on infection and immunity through research, education and public health, and has a significant focus on virology, including HIV. She is an active clinician, working at the Alfred Hospital and Royal Melbourne Hospital, and a Melbourne Laureate Professor of Medicine at the University of Melbourne.    Meet our host Juan Michael Porter II Juan Michael Porter II is a health journalist, HIV advocate, culture critic, educator and the host of HIV unmuted, the IAS podcast. He is the Senior Editor of TheBody.com and TheBodyPro – and the first person openly living with HIV to hold the position. Juan Michael's reportage combines data dives, personal narratives and policy analyses to address the real-world consequences of ever-shifting legislation on people's health outcomes. He has written for the Public Broadcasting Service, SF Chronicle, Philadelphia Inquirer, Christian Science Monitor, NY Observer, TDF Stages, Playbill, American Theatre, Time Out NY, Queerty, Anti-Racism Daily, Positively Aware, Documentary Magazine, SYFY Wire, Scholastic and Dance Magazine.  

SUDDENLY: a Frank Sinatra podcast
44: In the Wee Small Hours

SUDDENLY: a Frank Sinatra podcast

Play Episode Listen Later Feb 17, 2024 97:32


In the Wee Small Hours is often considered Sinatra's best work and arguably the first concept album. The "concept" is something along the lines of “I am awake at 3am and I am feeling deeply sad about a lost love.” And that's really it. Just when you think there couldn't possibly be any more songs about the nuances of that kind of misery, there are seven more. It's relentless, it's brutal, it borders on self-harm and it changed the way we all listen to albums forever. So many emotions, such beautiful music, so much history, such an enormous legacy. And yet, what is there to say? Sometimes it's best just to listen - not just to Sinatra, but to the people out there in the world, all with their own problems, who heard this and felt something. Selected resources: * Woody Guthrie - Dustbowl Ballads (1940) (featured: "Dust Cain't Kill Me") * Gordon Jenkins - Seven Dreams (1953) (featured: "The Cocktail Party (The Fourth Dream)") * The Beach Boys - Pet Sounds (1967) (featured: "Wouldn't It Be Nice", "That's Not Me", "Caroline, No") * Paul Kelly - How to Make Gravy (autobiography, 2010) * Jane Russell & Hoagy Carmichael - "I Get Along Without You Very Well" (from Las Vegas Story, 1952) * Bob Crosby and His Orchestra (with Marion Mann, vocal) - "Deep in a Dream" (1938) * Laurie Anderson - "Smoke Rings" (from Home of the Brave, 1986) * The Berlin Patient (podcast hosted by Joel White, 2016-17) (Complete series available on YouTube and Internet Archive) * Sophie Calle - Take Care of Yourself (book and art project, 2007) * Nick Hornby - High Fidelity (novel, 1995) * Marian McPartland Trio - "This Love of Mine" (from self-titled album, 1956) Special thanks to W.M. Akers. contact: suddenlypod at gmail dot com website: suddenlypod.gay donate: ko-fi.com/suddenlypod

Let's Know Things
Antiretroviral Therapies

Let's Know Things

Play Episode Listen Later Sep 19, 2023 21:54


This week we talk about HIV, AIDS, and ART.We also discuss HAART, the Berlin Patient, and potential future cures.Recommended Book: Allergic by Theresa MacPhailShow Notes* https://www.unaids.org/en/resources/fact-sheet* https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-treatment-basics* https://clinicalinfo.hiv.gov/en/glossary/antiretroviral-therapy-art* https://www.paho.org/en/topics/antiretroviral-therapy* https://journals.lww.com/jaids/fulltext/2010/01010/declines_in_mortality_rates_and_changes_in_causes.13.aspx* https://link.springer.com/article/10.1007/s13181-013-0325-8* https://academic.oup.com/jac/article/73/11/3148/5055837?login=false* https://journals.lww.com/jaids/fulltext/2016/09010/narrowing_the_gap_in_life_expectancy_between.6.aspx* https://en.wikipedia.org/wiki/Tenofovir_disoproxil* https://en.wikipedia.org/wiki/Management_of_HIV/AIDS* https://www.verywellhealth.com/cart-hiv-combination-antiretroviral-therapy-48921* https://www.cdc.gov/hiv/risk/art/index.html* https://www.freethink.com/health/cured-of-hiv* https://www.jstor.org/stable/3397566?origin=crossref* https://www.nytimes.com/1982/05/11/science/new-homosexual-disorder-worries-health-officials.html* https://pubmed.ncbi.nlm.nih.gov/23444290/* https://my.clevelandclinic.org/health/diseases/4251-hiv-aids* https://web.archive.org/web/20080527201701/http://data.unaids.org/pub/EPISlides/2007/2007_epiupdate_en.pdf* https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(23)00028-0/fulltextTranscriptIn mid-May of 1981, the queer community-focused newspaper, the New York Native, published what would become the first-ever article on a strange disease that seemed to be afflicting community members in the city.What eventually became known as AIDS, but which was at the time discussed by medical professionals primarily in terms of its associated diseases, was clinically reported upon for the first time less than a month later, five official cases having been documented in an interconnected group of gay men and users of injectable drugs, who came to the attention of doctors for not being inherently immunocompromised, but still somehow contracting a rare type of pneumonia that only really impacted folks with severely impaired immune systems.In subsequent years, doctors started using a range of different terms for HIV and AIDS, calling them at different times and in different contexts the lymphotophic retrovirus, Kaposi's sarcoma and opportunistic infections, and the 4H disease, referring to heroine users, hemophiliacs, homosexuals, and Haitians, the four groups that seemed to make up almost all of the confirmed afflicted patients.The acronym GRID, for gay-related immune deficiency was also used for a time, but that one was fairly rapidly phased out when it became clear that this condition wasn't limited to the gay community—though those earlier assumptions and the terminology associated with them did manage to lock that bias into mainstream conversation and understanding of AIDS and HIV for a long time, and in some cases and in some locations, to this day.By the mid-80s, two research groups had identified different viruses that seemed to be associated with or responsible for cases of this mysterious condition, and it was eventually determined (in 1986) that they were actually the same virus, and that virus was designated HIV.HIV, short for Human Immunodeficiency Virus, is a retrovirus that, if left untreated, leads to Acquired Immunodeficiency Syndrome, or AIDS, in about 50% of patients within ten years of infection.So HIV is the virus, AIDS is a condition someone with HIV can develop after their immune system is severely damaged by the infection, and there are a bunch of diagnostic differentiations that determine when someone has transitioned from one category to the other, but in general folks with HIV will experience moderate flu- or mono-like symptoms, alongside swollen lymph nodes and rashes and throat problems and sores across their bodies in the early stages of infection, and as things progress, they develop opportunistic infections of the kind that can only really latch onto a human when their immune system is weakened or shut down. While AIDS, arriving after the immune system is well and truly damaged, brings with it a slew of opportunistic infections and associated issues, the afflicted person potentially developing all sorts of cancers, sarcomas, persistent infections, and extreme versions of the flu-like, mono-like symptoms they may have suffered earlier on.We don't know for certain how and where HIV originated—and that's true of both kinds, as there's an HIV-1 and HIV-2 virus, the former of which accounts for most infections, the latter of which is less common, and less overall infectious—but both HIV types seem to have been transmitted to humans from non-human primates somewhere in West-central Africa in the early 20th century, possibly from chimpanzees in southern Cameroon, but that's pretty speculative, and there's some evidence that these diseases may have made the leap several times; so while there's a pretty good chance, based on what we know now, that the disease made it into humans and mutated approximately somewhere in that vicinity, sometime in the early 20th century, possibly via chimps hunted and eaten by locals as bushmeat, we really don't know for certain.There are reports of what were probably HIV as far back as 1959 in the Belgian Congo, but that's a bit speculative, too, and based on imperfect notes from the time.Back then, though, and through the 1980s, folks who contracted HIV and who were not treated would typically die within 11 years of being infected, and more than half of those diagnosed with AIDS in the US from 1981 through 1992 died within 2 years of their diagnosis; such a diagnosis was a death sentence, basically; it was a really horrible and scary time.Today, the outlook for folks who contract HIV is substantially better: the life expectancy of someone who contracts the virus and who is able to get treatment is about the same as someone who is not infected; the disease isn't cured, but the level of HIV virus in the blood of a person receiving treatment is so small that it's no longer transmissible, or even detectable.What I'd like to talk about today is a new therapy that's making those sorts of outcomes possible, how some few people have now been cured of HIV entirely, and what's on the horizon in this space.—Antiretroviral therapy, or ART, typically consists of a combination of drugs based on those that were originally combined in this way in 1996 by researchers who announced their findings at the International AIDS Conference in Vancouver—they called their approach highly active antiretroviral therapy, or HAART, and this combo was based on findings from earlier drugs that addressed one of HIV's seven stages of development—but because they all hit that same, single stage, the virus was rapidly developing an immunity to them, and they were universally pretty toxic, with horrible side-effects.What's more, this drug cocktail increased patients' life expectancy by about 24 months, on average—which is a lot, about two years, but considering all those side effects, which included severe liver problems and anemia, the extra months of life generally weren't very pleasant extra months.In 1995, a class of drugs called protease inhibitors were introduced, which prevented HIV from making copies of itself using the body's structural proteins.That, combined with the effects of other, existing retrovirals, which hindered the virus's ability to hijack the body's cells to make more of itself, turned out to be a substantial improvement over just one or the other approach.The announcement in 1996 was notable because the researchers involved were able to knock the viral load in their patients down to an undetectable level, and then keep it there, by using three drugs from each of those two antiviral classes, those two different approaches.So HAART was a major improvement over what came before, but it was still imperfect; deaths tied to HIV plummeted by 50% in the US and Europe in just three years, but the life expectancy of folks using this therapy was still low compared to other people; someone who contracted HIV in their 20s and went on this therapy was still only expected to live till their early 50s; way better than a two-year increase, but still plenty of room for improvement.In addition to that lifespan duration limitation, the HAART bundle of therapies was just really difficult to maintain.Some people experienced a dramatic redistribution of body fat, some developed heart arrhythmias or insulin resistance or peripheral neuropathy or lactic acidosis—which is basically a toxic buildup of the acid that results from metabolism, which is usually cleared naturally, but when it doesn't, it's potentially deadly.Anything less than absolutely perfect adherence to the treatment schedule was also potentially deleterious to the desired outcomes; it wasn't a forgiving regimen, with some of the drugs requiring three capsules be taken every 8 hours, and there was a chance that if a portion of a dose of one drug was missed, or not administered on time, the virus could develop an immunity to it and the whole thing would fall apart.Consequently, the HAART regimen was generally reserved until things got really bad, and that meant it didn't have a very large effect on the infected population, and those who did benefit from it suffered consequences, alongside those benefits.The change in terminology from HAART to ART arrived in 2001 when a drug called Viread, the brand name for tenofovir disoproxil, was released and added into the mix, replacing some of the most toxic and cumbersome of the previous therapies with a single pill per day, and one that came with far fewer, and far less extreme, side effects.In 2005 it was finally demonstrable, with a bunch of data, that beginning this type of therapy early rather than waiting until things get really bad was worth the trade-offs—researchers showed that if folks received access to ART upon diagnosis, severe HIV associated and non HIV associated illnesses  were reduced by 61%.As of 2016 there was still an average life expectancy gap between folks with HIV who received early care and people who were not infected of about 8 years, but that gap has been steadily closing with the introduction of new, easier to use, less side effect prone drugs—drugs that tend to attack the virus at different stages, and which take different approaches to hindering and blocking it—alongside innovations in how the drugs are delivered, like introducing substances that are converted by the body into the desired drug, which massively cuts the requisite dosage, in turn lessening the strain on the body's organs and the potential side effects associated with taking a higher dose of the drug, itself.We've also seen the advent of fixed-dose combination drugs, which are exactly what they sound like: a single pill containing the entire combination of drugs one must take each day, which makes a combination therapy much easier to administration and stick with, which in turn has substantially reduced the risk of severe side effects, and prevented mutations that might otherwise make a patient's virus more immune to some component of the drug cocktail.Some newer options just use two drugs, too, compared to the previous three-or-more, and most of these have been shown to be just as effective as the earlier, more bodily stressful combinations, and a recent, 2021 drug is injectable, rather than deliverable in pill-form, and can be administered just once a month—though a version of this drug, sold under the name Cabenuva, has been approved for administration every other month.So things in this corner of the medical world are looking pretty good, due new approaches and innovations to existing therapy models.These models remain imperfect, but they're getting better every year, and contracting HIV is no longer a death sentence, nor does it mean you'll always be infectious, or even detectably infected: the amount of HIV virus in one's blood can be kept undetectably low for essentially one's entire life, so long as one is able to get on the right therapy or combination of therapies and stick with it.That said, the global HIV pandemic is far from over, and access to these drugs–many of which are pricy, if you don't have insurance that will cover them—is not equally distributed.As of late-2022, the UN's official numbers indicate that about 39 million people, globally, have HIV, about 1.3 million were infected in 2022, and about 630,000 died from AIDS-related illnesses that year.That said, of those 39 million or so who are infected, nearly 30 million are receiving some kind of antiretroviral therapy, and about 86% of people who are estimated to be infected know their status, so they can seek such therapies, and/or take other precautious to protect themselves and others; though that also means about 5.5 million people, globally, have HIV and don't realize it.Here's a really remarkable figure, though: among people who are infected and know they are infected, about 93% of them were virally suppressed as of 2022.That's astonishing; 93% of people who have HIV and are aware of it are on some kind of therapy that has allowed them to suppress the virus so that it's nearly undetectable—the difference between the two, by the way, is that suppressed means 200 copies of the HIV virus per milliliter of blood, while undetectable is generally considered to be less than 50 copies per milliliter.So huge leaps in a relatively short period of time, and a massive improvement in both duration and quality of life for folks who might otherwise suffer mightily, and then die early, because of this virus and its associated symptoms.That said, there are some interesting, new approaches to dealing with HIV on the horizon, and some of them might prove to be even more impactful than this current batch of incredibly impactful ART options.As of September 2023, five people have been confirmed cured of HIV; not suppressed and not with viral loads at undetectable levels: cured.The first of these cured people, often referred to as the Berlin Patient, received a stem cell transplant from a bone marrow donation database that contained a genetic mutation called CCR5 Delta 32, which makes those who have it essentially immune to HIV infection.Three months after he received the transplant and stopped taking ART, doctors were unable to find any trace of the virus in his blood.He died from cancer in 2020, but there didn't seem to be any HIV in his blood from when he received the stem cell transplant, onward, and that happened in the early 2000s, and was formally announced to the medical community in 2008.At least two other people—two that we know about, anyway—have been cured of HIV using the same method; though at the moment at least, this option is severely limited as it requires that patients have a bone marrow match in donor databases, and that one of those donors have that specific, relatively rare mutation; so with existing science and techniques, at least, this is unlikely to be a widespread solution to this problem—though a 2017 experiment used stem cells derived from umbilical cord blood from a baby with that mutation to treat a woman' leukemia and cure her HIV, so there's a chance other approaches that make use of the same basic concept might be developed, opening this up to more people.Cancer drugs may also help some people with HIV: a drug that's been approved to treat several cancers called Venetoclax seems to also bind to a protein that helps HIV-infected T cells dodge the body's immune system and survive, and that realization has led to a series of experiments that showed HIV was suppressed in mice receiving this drug—though it bounced back a week later, and two weeks later in mice receiving both this drug and ART.This is unlikely to be a solution unto itself, then, but there's a chance either an adjusted version of this drug, or this drug in combination with other therapies, might be effective; and there's a clinical trial testing the efficacy of Venetoclax in human HIV patients at the end of this year, and another in 2024, so we may soon know if its safe and desirable to use this drug alongside ART, and that may, in turn, lead to a better understanding of how to amplify the drug's effects, or apply this method of hindering HIV from a different angle.CRISPR, the gene-editing technology borrowed from bacteria that allows for the cutting and removing and adding of genetic information, has enabled the development of several new potential HIV cures, one of which, called EBT-101, basically enters the body, finds helper T cells, and then cuts out chunks of the HIV virus's DNA, which prevents it from being able to replicate itself or hide away, reemerging later after another treatment has suppressed it.The benefit of this approach is that it could kill the viral reservoirs that otherwise allow HIV to persist in people who have undergone treatments, and a version of it that targets SIV, which is similar to HIV, but found in non-human primates—performed exactly as they hoped it would, finding and editing the targeted DNA, raising hopes than an HIV-targeting variation may manage similar wonders in human patients.This would be great if it ends up working, as one injection would theoretically clear all HIV from a person's system in relatively short-order, but the trials done so far have been small and on monkeys, and because of the nature of the research, it's not clear the monkeys were cured of HIV—just that the treatment got where it was supposed to go and made some DNA edits.A human trial of EBT-101 will finish up in March of 2025, though the researchers plan to follow up with their subjects for up to 15 years following the trial, to assess any long-term effects from their treatment, since CRISPR and this approach to messing with genes is still such a new thing.So while this may be a solution at some point, there's a good chance it won't be a real-deal, available option for another decade, minimum.So we've come a long way in a very short period of time with HIV and AIDS treatments, and the future is looking pretty good, with even more options and approaches on the horizon, including some actual cures, alongside high-quality, actually useable treatments.But there's still room to grow in terms of infection awareness, there are still distribution issues for some of these drugs, and there's still a fair bit of prejudice, the consequence of ignorance and historical misunderstandings and biases, keeping folks and institutions from doing as much as they otherwise could in many parts of the world; so a lot to be proud of, a lot to look forward to, but still plenty of room for improvement across the board. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit letsknowthings.substack.com/subscribe

Witness History
The Berlin Patient

Witness History

Play Episode Listen Later Feb 16, 2022 8:59


In the 1990s, doctors in Berlin began a cutting-edge treatment programme that led to a patient being cured of HIV/AIDS. The so-called "Berlin patient" was Timothy Ray Brown: he was suffering from leukemia as well as HIV/AIDS, and was given a bone marrow transplant from a donor with a rare genetic mutation which killed off the HIV virus. Timothy Ray Brown was a campaigner for AIDS research until his death, from leukemia, in 2020. Ashley Byrne speaks to his partner, Tim Hoeffgen. PHOTO: Timothy Ray Brown in 2012 (Getty Images)

HIV, Hope & Charity
HIV Heroes - The Berlin Patient

HIV, Hope & Charity

Play Episode Listen Later Dec 1, 2021 22:58


The second part of our special World AIDS Day trilogy is all about cures! Our HIV Hero is Timothy Ray Brown (The Berlin Patient), the first person to be cured of HIV. We also learn about Adam Castillejo (The London Patient), the second person to be cured of HIV.Sarah talks us through where we are in terms of finding an HIV cure and the different options that are currently being explored. SourcesI Am the Berlin Patient: A Personal Reflection (nih.gov)Timothy Ray Brown - WikipediaIs there a cure for HIV and AIDS? | AvertAdam Castillejo - WikipediaHIV vaccine trial starts at Oxford | University of OxfordFurther InformationAvert | Global information and education on HIV and AIDS

Medbuzz - Der medizinische Wissens-Podcast
Folge 14 | STDS: HIV – von einem der berühmt und berüchtigtsten Viren | Teil 2

Medbuzz - Der medizinische Wissens-Podcast

Play Episode Listen Later Nov 23, 2020 15:10


Im zweiten Teil unseres Podcasts über HIV sprechen wir nicht nur über Inkubationszeiten, Symptomatik, Diagnostik und Therapie sondern auch über einen der berühmtesten Patienten der Welt - "The Berlin Patient". Das HI-Virus, eine Abkürzung für Humanes Immundefizienz-Virus ist eines der berühmtesten, berüchtigtsten und gefürchtetsten Viren weltweit. Knapp 40 Mio Menschen sind durch das HI-Virus bereits ums Leben gekommen, fast genauso viele sind weltweit mit dem Virus infiziert.

2nd Page News
Episode 14 -Patients and Patience

2nd Page News

Play Episode Listen Later Oct 10, 2020 30:57


In this episode, Terry and Jerry discuss the passing of the Berlin Patient. He was the first person to be cured of HIV. In the second segment, they discuss the death of a patient in Quebec. She livestreamed her death. The hospital staff were less than professional. Jerry previews his predictions for the NFL season.

Basic World Radio
Duch of all trades OR Twice As Nice Feat. Down South Cadillac

Basic World Radio

Play Episode Listen Later Oct 7, 2020 103:58


Live from the new EverydayMedia studios we talked about Trump having the ‘Rona and his plan to cure himself and try and win the election. Review of the first presidential debate with the Biden clone. Aggressive robocalls for the elections. Muhfuggas not washing their hands during a pandemic, (WASH YO HANDS!! WASH YOUR ASS) , Berlin Patient passed away, and virtual learning part 2 Guest : Down South Cadillac Music Artist of The Week- Quisywita Y Songs: Magically & Nah, That’s Anxiety

Front Burner
A conversation with the 'Berlin patient,' the first person cured of HIV

Front Burner

Play Episode Listen Later Sep 5, 2019 18:16


In 2007, a man known as the "Berlin patient" was cured of HIV through a stem cell transplant. It was an incredible accomplishment that researchers all over the world scrutinized for years to come. He was the first and only documented case of a person who has been cured of HIV until March of this year, when a second patient was declared HIV-free from a similar treatment. Today on Front Burner, a conversation with Timothy Ray Brown, the "Berlin patient."

berlin hiv cured first person front burner berlin patient timothy ray brown
Science On Top
SoT 326: A Very Lovely Molecule

Science On Top

Play Episode Listen Later Mar 20, 2019 49:46


Hosts: Ed Brown, Penny Dumsday, Lucas Randall, Dr. Helen Maynard-Casely 00:01:16 NASA's InSight probe begins drilling into the Martian surface - and stops. 00:17:11 Twins are either identical (one egg splits into two copies) or fraternal (two eggs fertilised at the same time). But that's not always the case - as a mother in Queensland found out when she had sesquizygotic twins. 00:25:44 Timothy Ray Brown, who was known as The Berlin Patient, was the first person to be "cured" of HIV. Now a second man appears to have also been cured, using the same bone marrow transplant technique. 00:33:32 Saturn's largest moon, Titan, is also the only moon known to have a thick, dense atmosphere. But now, thanks to the Rosetta probe's studies of comet 67P/Churyumov-Gerasimenko, the origins of Titan's atmosphere may have been revealed. Dr. Helen Maynard-Casely is an instrument scientist for the WOMBAT high-intensity powder diffractometer at ANSTO, Australia's Nuclear Science and Technology Organisation. This episode contains traces of Loudwire's Toni Gonzalez reporting on an Australian study of people who listen to Death Metal.

Meet the Microbiologist
102: HIV vaccines with Dan Barouch

Meet the Microbiologist

Play Episode Listen Later Feb 21, 2019 38:13


Why have scientists struggled to generate a protective HIV vaccine? Dan Barouch lays out the unique challenges and discusses the ongoing clinical trial with an adenovirus-based vaccine developed in his lab. Julie’s Biggest Takeaways HIV poses unique and unprecedented challenges for vaccine development including: Viral diversity: extremely wide range of viral diversity. No natural precedent: No human has cleared HIV based on their immune responses. Unknown correlates of protection: scientists are unsure what immune responses are important to induce. Barouch’s group uses a vaccine strategy comprised of computationally optimized mosaic HIV Env proteins, which represent pieces of the outermost glycoprotein, Env, that have been tied together in a way expected to generate protective immunity. Early data from animal and human trials suggests these mosaic antigens generate an immune response to a wider array of HIV types than previous vaccines. Clinical trials are ongoing to see if a strategy of mosaic antigen vaccination, followed by a boost with Env protein, is protective in people. Attenuated HIV hasn’t been used as a vaccine strategy because of fears it could revert to a disease-causing form; similar fears have prevented a whole-killed virus platform for vaccine development. A clinical trial testing safety in 3 locations around the world demonstrated that this vaccine strategy in people elicited immune responses shown to be protective in animals. An efficacy trial is ongoing in sub-Saharan Africa, with results expected in 2021. The trial is double blinded: neither the doctor nor the patient know who was administered the candidate vaccine or who was administered the placebo. HIV latent infection causes complications in vaccine development because HIV latency is seeded early, possibly in the first few days of infection. Once latency is established, the individual is infected for life. Any low level of HIV infection in vaccinated people could potentially seed this latent infection. Quickly-seeded latency means immune responses must react extremely quickly. Featured Quotes “The challenges in the development of a prophylactic HIV vaccine are among the toughest challenges in biomedical and scientific research.” “HIV poses unique challenges for vaccine development and truly unprecedented challenges that have never been posed before by vaccination. One such challenge is the viral diversity: HIV exists not as a single sequence, but as numerous different viral sequences — not only throughout the world, but also throughout regions, communities, and even within the same individual. So to create a vaccine against HIV, the immune responses have to be relevant for a vast diversity of viral sequences.” “At what efficacy level would an HIV vaccine be licenced by both the industry partners as well as the government regulators in a particular country, and at what level of efficacy would it actually have a major public health impact? It’s a moving target over time; it really depends on what the current state of the epidemic is at the time the vaccine is ready to be licensed.” “It’s critical to have high-quality research part of the clinical efficacy trials so that success or failure or something in between, that the HIV research field learns from it, and learns what worked well and what didn’t work well, and how to make better vaccines moving forward.” “I always encourage young scientists to pursue their dreams and to tackle hard problems. There’s a lot of easy problems to solve but some of the hardest problems are the most impactful in the end.” Links for This Episode MTM Listener Survey Barouch lab at the Center for Virology and Vaccine Research. MTM: Mark Connors. The Lancet: Evaluation of a Mosaic HIV-1 Vaccine in a Multicentre, Randomised, Double-Blide, Placebo-Controlled, Phase 1/2 a Clinical Trial (APPROACH) and in Rhesus Monkeys. The Lancet: A Step Forward for HIV Vaccines. Journal of Virology: Similar Epitope Specificities of IgG and IgA Antibodies Elicited by Ad26 Vector Prime, Env Protein Boost Immunizations in Rhesus Monkeys. PLoS One: First-in-Human Randomized, Controlled Trial of an oral, replicating adenovirus 26 vector vaccine for HIV-1. HOM Tidbit: I am the Berlin Patient: A Personal Reflection. HOM Tidbit: Doctor who cured Berlin Patient of HIV: ‘We knew we were doing something very special’.

Mamamia Out Loud
Prince Harry, Mrs Franklin and Your Unfashionable Breasts.

Mamamia Out Loud

Play Episode Listen Later Nov 9, 2016 45:23


Apparently there are other things going on other than the US election. Things like Prince Harry’s new girlfriend. Is she really ‘princess material’? And more to the point, should she want to be? And in case you missed it, boobs are now out of fashion. Vogue said so. Plus, Gable Tostee is looking at a six-figure deal to tell his story on 60 Minutes after being found not guilty of the murder of his Tinder date. But should we be watching? Show Notes Your host is Holly Wainwright with Mia Freedman & Jessie Stephens our producer is Elissa Ratliff  Jessie thinks you should listen to The Berlin Patient podcast. Mia wants you all to take the Bias quiz (google it) and Holly thinks you should watch anything Samantha Bee has ever made.  You can leave correspondence on the pod phone: 02 8999 9386 Questions, comments, and love: facebook.com/mamamiaoutloud  Twitter: @mamamiapodcasts Email outloud@mamamia.com.au Subscribe in iTunes go to apple.co/mamamia where you'll find all of our shows in one place and any books written by the many Mamamia guests.   

Nathan, Nat & Shaun
Nathan, Nat & Shaun Podcast - 3rd November 2016

Nathan, Nat & Shaun

Play Episode Listen Later Nov 3, 2016 28:42


Shannon Noll joined the guys to talk about his new music, what he's been up to and Australian Idol days! Nat flushed her money down the toilet… When has your money vanished? Kate's mum accidentally burnt hundreds of dollars and Natasha's mum gave away lots of boxes to charity after her grandad died, not knowing there were thousands of dollars inside. When has your money vanished? Britney hid $100 in a wooden box in the backyard when she was 8, thinking she would be able to find it with a metal detector… Didn't work. Lara's Nan hid thousands of dollars in her furniture, when she died her husband gave all the furniture away! Joel White has a podcast called The Berlin Patient, and it's hilarious! He spoke about how the podcast came about, the story behind some of his entries and how pathetic people get when they go through a break up! Were you pathetic after a break up? Danae found out her boyfriend had cheated on her for years so she sold her house and car and signed up to work... See acast.com/privacy for privacy and opt-out information.

Hot & Delicious: Rocks The Planet
101 Comedian Greta Lee Jackson - Skit Box

Hot & Delicious: Rocks The Planet

Play Episode Listen Later Oct 29, 2016 70:14


101 Comedian Greta Lee Jackson - Skit Box   Love love LOVE that more and more influencers and creators are reaching out via LinkedIn, Twitter, Facebook and email to join me as guests on the Hot & Delicious: Rocks The Planet! podcast. I’ve been hearing from fans that I previously didn’t even know existed and it’s rather exciting to feel like I'm making a positive impact and see my world expanding.   3 weeks ago Sydney-based sketch and stand-up comedian, writer and director Greta Lee Jackson of Skit Box internet fame dropped me an email and Facebook message via Hot & Delicious: Rocks The Planet! about catching-up and the next thing you know I’m setting up to record the first ever Hot & Delicious: Rocks The Planet! podcast at national broadcaster ABC (Australian Broadcasting Corporation for you overseas peeps).   It's fantastic to be catching up with Greta Lee at a time when her career has reach that tipping point where things are really starting to hum with Skit Box’s ‘Activewear’ clip reaching 4.3M+ Views on YouTube via the Van Vuuren Bros, 775K+ views of the more recent ‘Activewear’ clip featuring Ellie Goulding, her brand new digital TV series ‘Wham Bam Thank You Ma’am’ launching on ABC’s iView in November, the Berlin Patient podcast (drops this week) and her return to Sydney Fringe Festival in early September with ‘Red Flag’.   A crazy busy 24 hours in Sydney, but recording with Greta Lee Jackson and another the next day with Hot Dub Time Machine really made my week!   Let’s get into it!   Connect with Greta Lee Jackson of Skit Box online: https://twitter.com/gretaleejackson https://twitter.com/SkitBox http://www.skitbox.tv/ https://www.instagram.com/gretaleejackson/ https://www.facebook.com/GretaLeeJacksonKillingIt https://www.youtube.com/user/skitboxtv The Berlin Patient shiz: http://berlinpatient.com/about/ Download the podcast: https://itunes.apple.com/au/podcast/the-berlin-patient/id1166366992?mt=2 https://www.facebook.com/theberlinpatient/ https://www.instagram.com/theberlinpatient/   Hit Hot & Delicious: Rocks The Planet up on social media here: Twitter https://twitter.com/hotndelicious Instagram https://www.instagram.com/hotndelicious/ Facebook https://www.facebook.com/HotnDelicious Hot & Delicious YouTube - Ballistyx Snowboard Show, interviews & more. https://www.youtube.com/user/HotnDeliciousRecords 'Hot & Delicious: Rocks The Planet’ entertainment, travel, photography & lifestyle blog: http://hotndelicious.com/   For social media, photography & influencer business enquiries contact: info@hotndelicious.com

Getting Curious with Jonathan Van Ness
What's Going On In HIV Research? with Kayla McLaughlin

Getting Curious with Jonathan Van Ness

Play Episode Listen Later Aug 10, 2016 37:29


Jonathan sits down with Physician Assistant and PrEP Research Clinician Kayla McLaughlin to talk about what PrEP is, how far HIV research has gotten since the 1980s, and why HIV is so hard to cure. Plus, Kayla discusses the curious cases of the Mississippi Baby and the Berlin Patient.  Find out what today's guest and former guests are up to by following us on Instagram and Twitter @CuriousWithJVN.  Transcripts for each episode are available at JonathanVanNess.com. Check out Getting Curious merch at PodSwag.com. Listen to more music from Quiñ by heading over to TheQuinCat.com. Jonathan is on Instagram and Twitter @JVN and @Jonathan.Vanness on Facebook.

POZ I AM Radio
Learn about the Timothy Ray Brown Foundation

POZ I AM Radio

Play Episode Listen Later Sep 23, 2012 61:00


Timothy Ray Brown is returning to POZ I AM Radio to talk about the Timothy Ray Brown Foundation the world’s first AIDS foundation devoted exclusively to finding a cure for the disease Timothy Ray Brown is “The Berlin patient”, the man who once had HIV. Although American, he was living in Berlin and receiving treatment for HIV when he was diagnosed in 2006 with leukemia. He was treated by Dr Gero Huetter who had a cutting-edge idea of treating his leukemia with a stem cell transplant from a person who was born immune to HIV infection. The rest is medical history. Timothy is recognized by international researchers as the first and only documented case of a person being cured of HIV. Now, almost 20 years after he was diagnosed, the 45-year-old is, essentially, cured. He now lives in San Francisco and since he decided to out himself as the person who had been known only as “The Berlin Patient”, he has become a bit of a celebrity at various AIDS functions. His most important goal is to assist in making his cure provide an impetus for creating a universal cure for HIV which will be accessible and available to everyone regardless of their economic means or background. He believes that this is one of the most important challenges to medical scientists of our time. He is counting on your support in assisting the achievement of this goal.

san francisco foundation berlin hiv aids although american berlin patient timothy ray brown robert breining jeromy dunn
POZ I AM Radio
Timothy Brown - The Berlin Patient talks

POZ I AM Radio

Play Episode Listen Later Jul 8, 2012 62:00


Timothy Ray Brown is “The Berlin patient”, the man who once had HIV. Although American, he was living in Berlin and receiving treatment for HIV when he was diagnosed in 2006 with leukemia. He was treated by Dr Gero Huetter who had a cutting-edge idea of treating his leukemia with a stem cell transplant from a person who was born immune to HIV infection. The rest is medical history. Timothy is recognized by international researchers as the first and only documented case of a person being cured of HIV. Now, almost 20 years after he was diagnosed, the 45-year-old is, essentially, cured. He now lives in San Francisco and since he decided to out himself as the person who had been known only as “The Berlin Patient”, he has become a bit of a celebrity at various AIDS functions. His most important goal is to assist in making his cure provide an impetus for creating a universal cure for HIV which will be accessible and available to everyone regardless of their economic means or background. He believes that this is one of the most important challenges to medical scientists of our time. He is counting on your support in assisting the achievement of this goal.

san francisco berlin hiv aids timothy brown although american berlin patient timothy ray brown robert breining jeromy dunn