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A generic drug that's used to treat transplant patients has been shown to extend the life span of some animals. Guido Mieth/Getty Images hide caption

Shots - Health News

Rapamycin may slow aging. here's one way the drug will be tested.

July 1, 2024 • Longevity researchers are taking a generic drug they think may help extend people's lives. Now a dentist is testing if rapamycin stops gum disease — a canary in the coal mine for age-related diseases.

Anti-aging drug Rapamycin to prevent gum disease 

Paleontologist Dany Azar holds up one of his treasures that he discovered in Lebanon in a piece of amber from the early Cretaceous: The oldest mosquito ever found. Ari Daniel/For NPR hide caption

In Lebanon, the 'Amber Man' digs up golden time capsules from the age of the dinosaurs

June 28, 2024 • When dinosaurs reigned some 130 million years ago, flowering plants were taking over the world. That change is sealed in ancient amber specimens on the slopes of Lebanon that Danny Azar knows so well.

Reconstruction of a Lokiceratops rangiformis being surprised by a crocodilian in the 78-million-year-old swamps that would have existed in what is now northern Montana. Andrey Atuchin/Museum of Evolution hide caption

Named after the Norse god Loki, meet Lokiceratops, a new horned dinosaur species

June 28, 2024 • A brand new species of ceratops, or horned dinosaur, was recently discovered in northern Montana. The dinosaur is called Lokiceratops rangiformis , after the Norse god Loki, and is believed to have lived roughly eighty million years ago. The bones of the plant-eating dinosaur were found on private land in an area well known for its large amount of fossils, and at first, researchers thought the bones belonged to another species of dinosaur!

Joro spider sits in the middle of a spider web. GummyBone/Getty Images hide caption

Why you shouldn't worry about invasive Joro spiders

June 14, 2024 • Joro spiders are spreading across the east coast. They are an invasive species that most likely arrived in shipping containers from eastern Asia. Today, we look into why some people find them scary, why to not panic about them and what their trajectory illustrates about the wider issue of invasive species.

Later this year, the FDA plans to decide whether MDMA can be used to treat PTSD Eva Almqvist/Getty Images hide caption

Misconduct claims may derail MDMA psychedelic treatment for PTSD

June 3, 2024 • People with post-traumatic stress disorder (PTSD) may soon have a new treatment option: MDMA, the chemical found in ecstasy. In August, the Food and Drug Administration plans to decide whether MDMA-assisted therapy for PTSD will be approved for market based on years of research. But serious allegations of research misconduct may derail the approval timeline.

Former President Donald Trump holds a press conference following the verdict in his hush-money trial at Trump Tower on May 31 in New York City. Spencer Platt/Getty Images hide caption

Trump repeats claims — without evidence — that his trial was rigged

May 31, 2024 • Former President Donald Trump reiterated many of claims — without evidence — that his criminal trial was rigged, a day after a New York jury found him guilty of 34 counts of falsifying business records.

Researchers have detected microplastics in human testicles. Volodymyr Zakharov/Getty Images hide caption

Plastic junk? Researchers find tiny particles in men's testicles

May 22, 2024 • The new study has scientists concerned that microplastics may be contributing to reproductive health issues.

Harlan Gough holds a recently collected tiger beetle on a tether. Lawrence Reeves hide caption

To escape hungry bats, these flying beetles create an ultrasound 'illusion'

May 22, 2024 • A study of tiger beetles has found a possible explanation for why they produce ultrasound noises right before an echolocating bat swoops in for the kill.

A sea otter in Monterey Bay with a rock anvil on its belly and a scallop in its forepaws. Jessica Fujii hide caption

When sea otters lose their favorite foods, they can use tools to go after new ones

May 20, 2024 • Some otters rely on tools to bust open hard-shelled prey items like snails, and a new study suggests this tool use is helping them to survive as their favorite, easier-to-eat foods disappear.

Lauren Hill, a graduate student at Cal State LA, holds a bird at the bird banding site at Bear Divide in the San Gabriel Mountains. Grace Widyatmadja/NPR hide caption

On this unassuming trail near LA, bird watchers see something spectacular

May 13, 2024 • At Bear Divide, just outside Los Angeles, you can see a rare spectacle of nature. This is one of the only places in the western United States where you can see bird migration during daylight hours.

The inside of a cell is a complicated orchestration of interactions between molecules. Keith Chambers/Science Photo Library hide caption

AI gets scientists one step closer to mapping the organized chaos in our cells

May 13, 2024 • As artificial intelligence seeps into some realms of society, it rushes into others. One area it's making a big difference is protein science — as in the "building blocks of life," proteins! Producer Berly McCoy talks to host Emily Kwong about the newest advance in protein science: AlphaFold3, an AI program from Google DeepMind. Plus, they talk about the wider field of AI protein science and why researchers hope it will solve a range of problems, from disease to the climate.

NASA's Solar Dynamics Observatory captured this image of a strong solar flare on May 8, 2024. The Wednesday solar flares kicked off the geomagnetic storm happening this weekend. NASA/SDO hide caption

NOAA Issues First Severe Geomagnetic Storm Watch Since 2005

May 10, 2024 • Scientists at the National Oceanic and Atmospheric Administration observed a cluster of sunspots on the surface of the sun this week. With them came solar flares that kicked off a severe geomagnetic storm. That storm is expected to last throughout the weekend as at least five coronal mass ejections — chunks of the sun — are flung out into space, towards Earth! NOAA uses a five point scale to rate these storms, and this weekend's storm is a G4. It's expected to produce auroras as far south as Alabama. To contextualize this storm, we are looking back at the largest solar storm on record: the Carrington Event.

Esther Nesbitt lost two of her children to drug overdoses, and her grandchildren are among more than 320,000 who lost parents in the overdose epidemic. Andrew Lichtenstein/Corbis via Getty Images hide caption

In a decade of drug overdoses, more than 320,000 American children lost a parent

May 8, 2024 • New research documents how many children lost a parent to an opioid or other overdose in the period from 2011 to 2021. Bereaved children face elevated risks to their physical and emotional health.

This illustration depicts a washed-up Ichthyotitan severnensis carcass on the beach. Sergey Krasovskiy hide caption

Largest-ever marine reptile found with help from an 11-year-old girl

May 6, 2024 • A father and daughter discovered fossil remnants of a giant ichthyosaur that scientists say may have been the largest-known marine reptile to ever swim the seas.

A survey shows that doctors have trouble taking full vacations from their high-stress jobs. Even when they do, they often still do work on their time off. Wolfgang Kaehler/LightRocket via Getty Images hide caption

Perspective

When pto stands for 'pretend time off': doctors struggle to take real breaks.

May 4, 2024 • What's a typical vacation activity for doctors? Work. A new study finds that most physicians do work on a typical day off. In this essay, a family doctor considers why that is and why it matters.

Weliton Menário Costa (center) holds a laptop while surrounded by dancers for his music video, "Kangaroo Time." From left: Faux Née Phish (Caitlin Winter), Holly Hazlewood, and Marina de Andrade. Nic Vevers/ANU hide caption

'Dance Your Ph.D.' winner on science, art, and embracing his identity

May 4, 2024 • Weliton Menário Costa's award-winning music video showcases his research on kangaroo personality and behavior — and offers a celebration of human diversity, too.

Researchers in a rainforest in Indonesia spotted an injury on the face of a male orangutan they named Rakus. They were stunned to watch him treat his wound with a medicinal plant. Armas/Suaq Project hide caption

Orangutan in the wild applied medicinal plant to heal its own injury, biologists say

May 3, 2024 • It is "the first known case of active wound treatment in a wild animal with a medical plant," biologist Isabelle Laumer told NPR. She says the orangutan, called Rakus, is now thriving.

The federal government says it has taken steps toward developing a vaccine to protect against bird flu should it become a threat to humans. skodonnell/Getty Images hide caption

Launching an effective bird flu vaccine quickly could be tough, scientists warn

May 3, 2024 • Federal health officials say the U.S. has the building blocks to make a vaccine to protect humans from bird flu, if needed. But experts warn we're nowhere near prepared for another pandemic.

A Nazca booby in the Galápagos Islands incubates eggs with its webbed feet. Wolfgang Kaehler/LightRocket via Getty Images hide caption

The Science of Siblings

For birds, siblinghood can be a matter of life or death.

May 1, 2024 • Some birds kill their siblings soon after hatching. Other birds spend their whole lives with their siblings and will even risk their lives to help each other.

Planet Money

How do you counter misinformation critical thinking is step one.

April 30, 2024 • An economic perspective on misinformation

This image shows a brain "assembloid" consisting of two connected brain "organoids." Scientists studying these structures have restored impaired brain cells in Timothy syndrome patients. Pasca lab, Stanford University hide caption

Scientists restore brain cells impaired by a rare genetic disorder

April 30, 2024 • A therapy that restores brain cells impaired by a rare genetic disorder may offer a strategy for treating conditions like autism, epilepsy, and schizophrenia.

Katie Krimitsos is among the majority of American women who have trouble getting healthy sleep, according to a new Gallup survey. Krimitsos launched a podcast called Sleep Meditation for Women to offer some help. Natalie Champa Jennings/Natalie Jennings, courtesy of Katie Krimitsos hide caption

Helping women get better sleep by calming the relentless 'to-do lists' in their heads

April 26, 2024 • A recent survey found that Americans' sleep patterns have been getting worse. Adult women under 50 are among the most sleep-deprived demographics.

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Research is indispensable for resolving public health challenges – whether it be tackling diseases of poverty, responding to rise of chronic diseases,  or ensuring that mothers have access to safe delivery practices.

Likewise, shared vulnerability to global threats, such as severe acute respiratory syndrome, Ebola virus disease, Zika virus and avian influenza has mobilized global research efforts in support of enhancing capacity for preparedness and response. Research is strengthening surveillance, rapid diagnostics and development of vaccines and medicines.

Public-private partnerships and other innovative mechanisms for research are concentrating on neglected diseases in order to stimulate the development of vaccines, drugs and diagnostics where market forces alone are insufficient.

Research for health spans 5 generic areas of activity:

• measuring the magnitude and distribution of the health problem;
• understanding the diverse causes or the determinants of the problem, whether they are due to biological, behavioural, social or environmental factors;
• developing solutions or interventions that will help to prevent or mitigate the problem;
• implementing or delivering solutions through policies and programmes; and
• evaluating the impact of these solutions on the level and distribution of the problem.

High-quality research is essential to fulfilling WHO’s mandate for the attainment by all peoples of the highest possible level of health. One of the Organization’s core functions is to set international norms, standards and guidelines, including setting international standards for research.

Under the “WHO strategy on research for health”, the Organization works to identify research priorities, and promote and conduct research with the following 4 goals:

• Capacity - build capacity to strengthen health research systems within Member States.
• Priorities - support the setting of research priorities that meet health needs particularly in low- and middle-income countries.
• Standards - develop an enabling environment for research through the creation of norms and standards for good research practice.
• Translation - ensure quality evidence is turned into affordable health technologies and evidence-informed policy.
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Report of the sixth meeting of the WHO Diagnostic Technical Advisory Group for Neglected Tropical Diseases:...

The World Health Organization’s Global Neglected Tropical Diseases Programme (WHO/NTD) manages a diverse portfolio of 21 diseases and disease groups,1 ...

Target product profile for a diagnostic test to confirm cure of visceral leishmaniasis

Leishmaniasis is caused by protozoan parasites which are transmitted by the bite of infected female phlebotomine sandflies. The disease is poverty-related...

WHO Science Council meeting, Geneva, Switzerland, 30-31 January 2024: report

This is a visual summary of the meeting of the WHO Science Council which took place on 30 and 31 January 2024.

WHO Technical Advisory Group on the Responsible Use of the Life Sciences and Dual-Use Research (‎TAG-RULS...

The Technical Advisory Group on the Responsible Use of the Life Sciences and Dual-Use Research (TAG-RULS DUR) was established in November 2023 to provide...

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What Is Research and Why We Do It

• First Online: 23 June 2020

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• Carlo Ghezzi 2  

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The notions of science and scientific research are discussed and the motivations for doing research are analyzed. Research can span a broad range of approaches, from purely theoretical to practice-oriented; different approaches often coexist and fertilize each other. Research ignites human progress and societal change. In turn, society drives and supports research. The specific role of research in Informatics is discussed. Informatics is driving the current transition towards the new digital society in which we will live in the future.

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In [ 34 ], P.E. Medawar discusses what he calls the “snobismus” of pure versus applied science. In his words, this is one of the most damaging forms of snobbism, which draws a class distinction between pure and applied science.

Originality, rigor, and significance have been defined and used as the key criteria to evaluate research outputs by the UK Research Excellence Framework (REF) [ 46 ]. A research evaluation exercise has been performed periodically since 1986 on UK higher education institutions and their research outputs have been rated according to their originality, rigor, and significance.

The importance of realizing that “we don’t know” was apparently first stated by Socrates, according to Plato’s account of his thought. This is condensed in the famous paradox “I know that I don’t know.”

This view applies mainly to natural and physical sciences.

Roy Amara was President of the Institute for Future, a USA-based think tank, from 1971 until 1990.

The Turing Award is generally recognized as the Nobel prize of Informatics.

See http://uis.unesco.org/apps/visualisations/research-and-development-spending/ .

Israel is a very good example. Investments in research resulted in a proliferation of new, cutting-edge enterprises. The term start-up nation has been coined by Dan Senor and Saul Singer in their successful book [ 51 ] to characterize this phenomenon.

https://ec.europa.eu/programmes/horizon2020/en/h2020-section/societal-challenges .

https://ec.europa.eu/programmes/horizon2020/en/h2020-section/cross-cutting-activities-focus-areas .

This figure has been adapted from a presentation by A. Fuggetta, which describes the mission of Cefriel, an Italian institution with a similar role of Fraunhofer, on a smaller scale.

The ERC takes an ecumenical approach and calls the research sector “Computer Science and Informatics.”

I discuss here the effect of “big data” on research, although most sectors of society—industry, finance, health, …—are also deeply affected.

Carayannis, E., Campbell, D.: Mode 3 knowledge production in quadruple helix innovation systems. In: E. Carayannis, D. Campbell (eds.) Mode 3 Knowledge Production in Quadruple Helix Innovation Systems: 21st-Century Democracy, Innovation, and Entrepreneurship for Development. SpringerBriefs in Business, New York, NY (2012)

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Ghezzi, C. (2020). What Is Research and Why We Do It. In: Being a Researcher. Springer, Cham. https://doi.org/10.1007/978-3-030-45157-8_1

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Articles on Academic research

Displaying 1 - 20 of 37 articles.

Fake academic papers are on the rise: why they’re a danger and how to stop them

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Scientific breakthroughs: 2024 emerging trends to watch

December 28, 2023

Across disciplines and industries, scientific discoveries happen every day, so how can you stay ahead of emerging trends in a thriving landscape? At CAS, we have a unique view of recent scientific breakthroughs, the historical discoveries they were built upon, and the expertise to navigate the opportunities ahead. In 2023, we identified the top scientific breakthroughs , and 2024 has even more to offer. New trends to watch include the accelerated expansion of green chemistry, the clinical validation of CRISPR, the rise of biomaterials, and the renewed progress in treating the undruggable, from cancer to neurodegenerative diseases. To hear what the experts from Lawrence Liverpool National Lab and Oak Ridge National Lab are saying on this topic, join us for a free webinar on January 25 from 10:00 to 11:30 a.m. EDT for a panel discussion on the trends to watch in 2024.

The ascension of AI in R&D

While the future of AI has always been forward-looking, the AI revolution in chemistry and drug discovery has yet to be fully realized. While there have been some high-profile set-backs , several breakthroughs should be watched closely as the field continues to evolve. Generative AI is making an impact in drug discovery , machine learning is being used more in environmental research , and large language models like ChatGPT are being tested in healthcare applications and clinical settings.

Many scientists are keeping an eye on AlphaFold, DeepMind’s protein structure prediction software that revolutionized how proteins are understood. DeepMind and Isomorphic Labs have recently announced how their latest model shows improved accuracy, can generate predictions for almost all molecules in the Protein Data Bank, and expand coverage to ligands, nucleic acids, and posttranslational modifications . Therapeutic antibody discovery driven by AI is also gaining popularity , and platforms such as the RubrYc Therapeutics antibody discovery engine will help advance research in this area.

Though many look at AI development with excitement, concerns over accurate and accessible training data , fairness and bias , lack of regulatory oversight , impact on academia, scholarly research and publishing , hallucinations in large language models , and even concerns over infodemic threats to public health are being discussed. However, continuous improvement is inevitable with AI, so expect to see many new developments and innovations throughout 2024.

‘Greener’ green chemistry

Green chemistry is a rapidly evolving field that is constantly seeking innovative ways to minimize the environmental impact of chemical processes. Here are several emerging trends that are seeing significant breakthroughs:

• Improving green chemistry predictions/outcomes : One of the biggest challenges in green chemistry is predicting the environmental impact of new chemicals and processes. Researchers are developing new computational tools and models that can help predict these impacts with greater accuracy. This will allow chemists to design safer and more environmentally friendly chemicals.
• Reducing plastics: More than 350 million tons of plastic waste is generated every year. Across the landscape of manufacturers, suppliers, and retailers, reducing the use of single-use plastics and microplastics is critical. New value-driven approaches by innovators like MiTerro that reuse industrial by-products and biomass waste for eco-friendly and cheaper plastic replacements will soon be industry expectations. Lowering costs and plastic footprints will be important throughout the entire supply chain.    
• Alternative battery chemistry: In the battery and energy storage space, finding alternatives to scarce " endangered elements" like lithium and cobalt will be critical. While essential components of many batteries, they are becoming scarce and expensive. New investments in lithium iron phosphate (LFP) batteries that do not use nickel and cobalt have expanded , with 45% of the EV market share being projected for LFP in 2029. Continued research is projected for more development in alternative materials like sodium, iron, and magnesium, which are more abundant, less expensive, and more sustainable.
• More sustainable catalysts : Catalysts speed up a chemical reaction or decrease the energy required without getting consumed. Noble metals are excellent catalysts; however, they are expensive and their mining causes environmental damage. Even non-noble metal catalysts can also be toxic due to contamination and challenges with their disposal. Sustainable catalysts are made of earth-abundant elements that are also non-toxic in nature. In recent years, there has been a growing focus on developing sustainable catalysts that are more environmentally friendly and less reliant on precious metals. New developments with catalysts, their roles, and environmental impact will drive meaningful progress in reducing carbon footprints.  
• Recycling lithium-ion batteries: Lithium-ion recycling has seen increased investments with more than 800 patents already published in 2023. The use of solid electrolytes or liquid nonflammable electrolytes may improve the safety and durability of LIBs and reduce their material use. Finally, a method to manufacture electrodes without solvent s could reduce the use of deprecated solvents such as N-methylpyrrolidinone, which require recycling and careful handling to prevent emissions.

Rise of biomaterials

New materials for biomedical applications could revolutionize many healthcare segments in 2024. One example is bioelectronic materials, which form interfaces between electronic devices and the human body, such as the brain-computer interface system being developed by Neuralink. This system, which uses a network of biocompatible electrodes implanted directly in the brain, was given FDA approval to begin human trials in 2023.

• Bioelectronic materials: are often hybrids or composites, incorporating nanoscale materials, highly engineered conductive polymers, and bioresorbable substances. Recently developed devices can be implanted, used temporarily, and then safely reabsorbed by the body without the need for removal. This has been demonstrated by a fully bioresorbable, combined sensor-wireless power receiver made from zinc and the biodegradable polymer, poly(lactic acid).
• Natural biomaterials: that are biocompatible and naturally derived (such as chitosan, cellulose nanomaterials, and silk) are used to make advanced multifunctional biomaterials in 2023. For example, they designed an injectable hydrogel brain implant for treating Parkinson’s disease, which is based on reversible crosslinks formed between chitosan, tannic acid, and gold nanoparticles.
• Bioinks : are used for 3D printing of organs and transplant development which could revolutionize patient care. Currently, these models are used for studying organ architecture like 3D-printed heart models for cardiac disorders and 3D-printed lung models to test the efficacy of drugs. Specialized bioinks enhance the quality, efficacy, and versatility of 3D-printed organs, structures, and outcomes. Finally, new approaches like volumetric additive manufacturing (VAM) of pristine silk- based bioinks are unlocking new frontiers of innovation for 3D printing.

To the moon and beyond

The global Artemis program is a NASA-led international space exploration program that aims to land the first woman and the first person of color on the Moon by 2025 as part of the long-term goal of establishing a sustainable human presence on the Moon. Additionally, the NASA mission called Europa Clipper, scheduled for a 2024 launch, will orbit around Jupiter and fly by Europa , one of Jupiter’s moons, to study the presence of water and its habitability. China’s mission, Chang’e 6 , plans to bring samples from the moon back to Earth for further studies. The Martian Moons Exploration (MMX) mission by Japan’s JAXA plans to bring back samples from Phobos, one of the Mars moons. Boeing is also expected to do a test flight of its reusable space capsule Starliner , which can take people to low-earth orbit.

The R&D impact of Artemis extends to more fields than just aerospace engineering, though:

• Robotics: Robots will play a critical role in the Artemis program, performing many tasks, such as collecting samples, building infrastructure, and conducting scientific research. This will drive the development of new robotic technologies, including autonomous systems and dexterous manipulators.
• Space medicine: The Artemis program will require the development of new technologies to protect astronauts from the hazards of space travel, such as radiation exposure and microgravity. This will include scientific discoveries in medical diagnostics, therapeutics, and countermeasures.
• Earth science: The Artemis program will provide a unique opportunity to study the Moon and its environment. This will lead to new insights into the Earth's history, geology, and climate.
• Materials science: The extreme space environment will require new materials that are lightweight, durable, and radiation resistant. This will have applications in many industries, including aerospace, construction, and energy.
• Information technology: The Artemis program will generate a massive amount of data, which will need to be processed, analyzed, and shared in real time. This will drive the development of new IT technologies, such as cloud computing, artificial intelligence, and machine learning.

The CRISPR pay-off

After years of research, setbacks, and minimal progress, the first formal evidence of CRISPR as a therapeutic platform technology in the clinic was realized. Intellia Therapeutics received FDA clearance to initiate a pivotal phase 3 trial of a new drug for the treatment of hATTR, and using the same Cas9 mRNA, got a new medicine treating a different disease, angioedema. This was achieved by only changing 20 nucleotides of the guide RNA, suggesting that CRISPR can be used as a therapeutic platform technology in the clinic.

The second great moment for CRISPR drug development technology came when Vertex and CRISPR Therapeutics announced the authorization of the first CRISPR/Cas9 gene-edited therapy, CASGEVY™, by the United Kingdom MHRA, for the treatment of sickle cell disease and transfusion-dependent beta-thalassemia. This was the first approval of a CRISPR-based therapy for human use and is a landmark moment in realizing the potential of CRISPR to improve human health.

In addition to its remarkable genome editing capability, the CRISPR-Cas system has proven to be effective in many applications, including early cancer diagnosis . CRISPR-based genome and transcriptome engineering and CRISPR-Cas12a and CRISPR-Cas13a appear to have the necessary characteristics to be robust detection tools for cancer therapy and diagnostics. CRISPR-Cas-based biosensing system gives rise to a new era for precise diagnoses of early-stage cancers.

MIT engineers have also designed a new nanoparticle DNA-encoded nanosensor for urinary biomarkers that could enable early cancer diagnoses with a simple urine test. The sensors, which can detect cancerous proteins, could also distinguish the type of tumor or how it responds to treatment.

Ending cancer

The immuno-oncology field has seen tremendous growth in the last few years. Approved products such as cytokines, vaccines, tumor-directed monoclonal antibodies, and immune checkpoint blockers continue to grow in market size. Novel therapies like TAC01-HER2 are currently undergoing clinical trials. This unique therapy uses autologous T cells, which have been genetically engineered to incorporate T cell Antigen Coupler (TAC) receptors that recognize human epidermal growth factor receptor 2 (HER2) presence on tumor cells to remove them. This could be a promising therapy for metastatic, HER2-positive solid tumors.

Another promising strategy aims to use the CAR-T cells against solid tumors in conjunction with a vaccine that boosts immune response. Immune boosting helps the body create more host T cells that can target other tumor antigens that CAR-T cells cannot kill.

Another notable trend is the development of improved and effective personalized therapies. For instance, a recently developed personalized RNA neoantigen vaccine, based on uridine mRNA–lipoplex nanoparticles, was found effective against pancreatic ductal adenocarcinoma (PDAC). Major challenges in immuno-oncology are therapy resistance, lack of predictable biomarkers, and tumor heterogenicity. As a result, devising novel treatment strategies could be a future research focus.

Decarbonizing energy

Multiple well-funded efforts are underway to decarbonize energy production by replacing fossil fuel-based energy sources with sources that generate no (or much less) CO2 in 2024.

One of these efforts is to incorporate large-scale energy storage devices into the existing power grid. These are an important part of enabling the use of renewable sources since they provide additional supply and demand for electricity to complement renewable sources. Several types of grid-scale storage that vary in the amount of energy they can store and how quickly they can discharge it into the grid are under development. Some are physical (flywheels, pumped hydro, and compressed air) and some are chemical (traditional batteries, flow batteries , supercapacitors, and hydrogen ), but all are the subject of active chemistry and materials development research. The U.S. government is encouraging development in this area through tax credits as part of the Inflation Reduction Act and a $7 billion program to establish regional hydrogen hubs.

Meanwhile, nuclear power will continue to be an active R&D area in 2024. In nuclear fission, multiple companies are developing small modular reactors (SMRs) for use in electricity production and chemical manufacturing, including hydrogen. The development of nuclear fusion reactors involves fundamental research in physics and materials science. One major challenge is finding a material that can be used for the wall of the reactor facing the fusion plasma; so far, candidate materials have included high-entropy alloys and even molten metals .

Neurodegenerative diseases

Neurodegenerative diseases are a major public health concern, being a leading cause of death and disability worldwide. While there is currently no cure for any neurodegenerative disease, new scientific discoveries and understandings of these pathways may be the key to helping patient outcomes.

• Alzheimer’s disease: Two immunotherapeutics have received FDA approval to reduce both cognitive and functional decline in individuals living with early Alzheimer's disease. Aducannumab (Aduhelm®) received accelerated approval in 2021 and is the first new treatment approved for Alzheimer’s since 2003 and the first therapy targeting the disease pathophysiology, reducing beta-amyloid plaques in the brains of early Alzheimer’s disease patients. Lecanemab (Leqembi®) received traditional approval in 2023 and is the first drug targeting Alzheimer’s disease pathophysiology to show clinical benefits, reducing the rate of disease progression and slowing cognitive and functional decline in adults with early stages of the disease.
• Parkinson’s disease: New treatment modalities outside of pharmaceuticals and deep brain stimulation are being researched and approved by the FDA for the treatment of Parkinson’s disease symptoms. The non-invasive medical device, Exablate Neuro (approved by the FDA in 2021), uses focused ultrasound on one side of the brain to provide relief from severe symptoms such as tremors, limb rigidity, and dyskinesia. 2023 brought major news for Parkinson’s disease research with the validation of the biomarker alpha-synuclein. Researchers have developed a tool called the α-synuclein seeding amplification assay which detects the biomarker in the spinal fluid of people diagnosed with Parkinson’s disease and individuals who have not shown clinical symptoms.
• Amyotrophic lateral sclerosis (ALS): Two pharmaceuticals have seen FDA approval in the past two years to slow disease progression in individuals with ALS. Relyvrio ® was approved in 2022 and acts by preventing or slowing more neuron cell death in patients with ALS. Tofersen (Qalsody®), an antisense oligonucleotide, was approved in 2023 under the accelerated approval pathway. Tofersen targets RNA produced from mutated superoxide dismutase 1 (SOD1) genes to eliminate toxic SOD1 protein production. Recently published genetic research on how mutations contribute to ALS is ongoing with researchers recently discovering how NEK1 gene mutations lead to ALS. This discovery suggests a possible rational therapeutic approach to stabilizing microtubules in ALS patients.

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Race and LGBTQ Issues in K-12 Schools

What teachers, teens and the u.s. public say about current curriculum debates, table of contents.

• What do teachers think students should learn about slavery and gender identity?
• Should parents be able to opt their children out of learning about certain topics?
• How often do topics related to race and LGBTQ issues come up in the classroom?
• How do teachers’ views differ by party?
• What teachers think students should learn about slavery and gender identity
• Should parents be able to opt their children out of learning about race and LGBTQ issues?
• Influence over curriculum
• What teens want to learn about slavery
• What teens want to learn about gender identity
• 4. Public views on parents opting their children out of learning about race and LGBTQ issues
• Acknowledgments
• Teacher survey methodology
• Teen survey methodology
• General public survey methodology

Pew Research Center conducted this study to better understand how public K-12 teachers, teens and the American public see topics related to race, sexual orientation and gender identity playing out in the classroom.

The bulk of the analysis in this report is based on an online survey of 2,531 U.S. public K-12 teachers conducted from Oct. 17 to Nov. 14, 2023. The teachers surveyed are members of RAND’s American Teacher Panel, a nationally representative panel of public school K-12 teachers recruited through MDR Education. Survey data is weighted to state and national teacher characteristics to account for differences in sampling and response to ensure they are representative of the target population.

For the questions for the general public, we surveyed 5,029 U.S. adults from Nov. 9 to Nov. 16, 2023. The adults surveyed are members of the Ipsos KnowledgePanel, a nationally representative online survey panel. Panel members are randomly recruited through probability-based sampling, and households are provided with access to the Internet and hardware if needed. To ensure that the results of this survey reflect a balanced cross section of the nation, the data is weighted to match the U.S. adult population by gender, age, education, race and ethnicity and other categories.

For questions for teens, we conducted an online survey of 1,453 U.S. teens from Sept. 26 to Oct. 23, 2023, through Ipsos. Ipsos recruited the teens via their parents, who were part of its KnowledgePanel. The survey was weighted to be representative of U.S. teens ages 13 to 17 who live with their parents by age, gender, race and ethnicity, household income, and other categories. The survey on teens was reviewed and approved by an external institutional review board (IRB), Advarra, an independent committee of experts specializing in helping to protect the rights of research participants.

Here are the questions used for this report , along with responses, and the survey methodology .

Throughout the report, references to White, Black and Asian adults include those who are not Hispanic and identify as only one race. Hispanics are of any race. The views and experiences of teachers and teens who are Asian American or part of other racial and ethnic groups are not analyzed separately in this report due to sample limitations. Data for these groups is incorporated into the general population figures throughout the report.

All references to party affiliation include those who lean toward that party. Republicans include those who identify as Republicans and those who say they lean toward the Republican Party. Democrats include those who identify as Democrats and those who say they lean toward the Democratic Party.

Political leaning of school districts is based on whether the majority of those residing in the school district voted for Republican Donald Trump or Democrat Joe Biden in the 2020 presidential election.

Amid national debates about what schools are teaching , we asked public K-12 teachers, teens and the American public how they see topics related to race, sexual orientation and gender identity playing out in the classroom.

A sizeable share of teachers (41%) say these debates have had a negative impact on their ability to do their job. Just 4% say these debates have had a positive impact, while 53% say the impact has been neither positive nor negative or that these debates have had no impact.

And 71% of teachers say teachers themselves don’t have enough influence over what’s taught in public schools in their area.

In turn, a majority of teachers (58%) say their state government has too much influence over this. And more say the federal government, the local school board and parents have too much influence than say they don’t have enough.

Most of the findings in this report come from a survey of 2,531 U.S. public K-12 teachers conducted Oct. 17-Nov. 14, 2023, using the RAND American Teacher Panel. 1 The survey looks at teachers’ views on:

• Race and LGBTQ issues in the classroom ( Chapter 1 )
• Current debates over what schools should be teaching and the role of key groups ( Chapter 2 )

It follows a fall 2022 survey of K-12 parents that explored similar topics.

This report also includes some findings from a survey of U.S. teens ages 13 to 17 ( Chapter 3 ) and a survey of U.S. adults ( Chapter 4 ). For details about these surveys, refer to the Methodology section of this report. Among the key findings:

• 38% of teens say they feel comfortable when topics related to racism or racial inequality come up in class (among those who say these topics have come up). A smaller share (29%) say they feel comfortable when topics related to sexual orientation or gender identity come up.
• Among the American public , more say parents should be able to opt their children out of learning about LGBTQ issues than say the same about topics related to race (54% vs. 34%).

We asked public K-12 teachers what they think students should learn in school about two topics in particular:

• Whether the legacy of slavery still affects the position of Black people in American society today.
• Whether a person’s gender can be different from or is determined by their sex at birth.

For these questions, elementary, middle and high school teachers were asked about elementary, middle and high school students, respectively.

The legacy of slavery

Most teachers (64%) say students should learn that the legacy of slavery still affects the position of Black people in American society today.

About a quarter (23%) say students should learn that slavery is part of American history but no longer affects the position of Black people in American society. Just 8% say students shouldn’t learn about this topic in school at all.

Majorities of elementary, middle and high school teachers say students should learn that the legacy of slavery still has an impact on the lives of Black Americans.

Gender identity

When it comes to teaching about gender identity – specifically whether a person’s gender can be different from or is determined by their sex assigned at birth – half of public K-12 teachers say students shouldn’t learn about this in school.

A third of teachers think students should learn that someone can be a boy or a girl even if that is different from the sex they were assigned at birth.

A smaller share (14%) say students should learn that whether someone is a boy or a girl is determined by their sex at birth.

Views differ among elementary, middle and high school teachers. But teachers across the three levels are more likely to say students should learn that a person’s gender can be different from their sex at birth than to say students should learn gender is determined by sex at birth.

Most elementary school teachers (62%) say students shouldn’t learn about gender identity in school. This is much larger than the shares of middle and high school teachers who say the same (45% and 35%).

What parents and teens say

Parents of K-12 students are more divided on what their children should learn in school about these topics.

In the 2022 survey , 49% of parents said they’d rather their children learn that the legacy of slavery still affects the position of Black people in American society today, while 42% said they’d rather their children learn that slavery no longer affects Black Americans.

When it comes to gender identity, 31% of parents said they’d rather their children learn that gender can be different from sex at birth. An identical share said they would rather their children learn gender is determined by sex at birth. Another 37% of parents said their children shouldn’t learn about gender identity in school.

Teens, like parents, are more divided than teachers on these questions. About half of teens (48%) say they’d rather learn that the legacy of slavery still affects the position of Black Americans today. Four-in-ten would prefer to learn that slavery no longer affects Black Americans.

And teens are about evenly divided when it comes to what they prefer to learn about gender identity. A quarter say they’d rather learn that a person’s gender can be different from their sex at birth; 26% would prefer to learn that gender is determined by sex at birth. About half (48%) say they shouldn’t learn about gender identity in school.

For more on teens’ views about what they prefer to learn in school about each of these topics, read Chapter 3 of this report.

Most public K-12 teachers (60%) say parents should not be able to opt their children out of learning about racism or racial inequality in school, even if the way these topics are taught conflicts with the parents’ beliefs. A quarter say parents should be able to opt their children out of learning about these topics.

In contrast, more say parents should be able to opt their children out of learning about sexual orientation or gender identity (48%) than say parents should not be able to do this (33%).

On topics related to both race and LGBTQ issues, elementary and middle school teachers are more likely than high school teachers to say parents should be able to opt their children out.

How teachers’ views compare with the public’s views

Like teachers, Americans overall are more likely to say parents should be able to opt their children out of learning about sexual orientation or gender identity (54%) than to say they should be able to opt their children out of learning about racism or racial inequality (34%).

Across both issues, Americans overall are somewhat more likely than teachers to say parents should be able to opt their children out.

For more on the public’s views, read Chapter 4 of this report.

Most teachers who’ve been teaching for more than a year (68%) say the topics of sexual orientation and gender identity rarely or never came up in their classroom in the 2022-23 school year. About one-in-five (21%) say these topics came up sometimes, and 8% say they came up often or extremely often.

Topics related to racism or racial inequality come up more frequently. A majority of teachers (56%) say these topics came up at least sometimes in their classroom, with 21% saying they came up often or extremely often.

These topics are more likely to come up in secondary school than in elementary school classrooms.

As is the case among parents of K-12 students and the general public, teachers’ views on how topics related to race and LGBTQ issues should play out in the classroom differ by political affiliation.

• What students should learn about slavery: 85% of Democratic and Democratic-leaning teachers say students should learn that the legacy of slavery still affects the position of Black people in American society today. This compares with 35% of Republican and Republican-leaning teachers who say the same.

• What students should learn about gender identity: Democratic teachers are far more likely than Republican teachers to say students should learn that a person’s gender can be different from the sex they were assigned at birth (53% vs. 5%). Most Republican teachers (69%) say students shouldn’t learn about gender identity in school.
• Parents opting their children out of learning about these topics: 80% of Republican teachers say parents should be able to opt their children out of learning about LGBTQ issues, compared with 30% of Democratic teachers. And while 47% of Republican teachers say parents should be able to opt their children out of learning about racism and racial inequality, just 11% of Democratic teachers say this.

A majority of public K-12 teachers (58%) identify with or lean toward the Democratic Party. About a third (35%) identify with or lean toward the GOP. Americans overall are more evenly divided: 47% are Democrats or Democratic leaners, and 45% are Republicans or Republican leaners .

• For details, refer to the Methodology section of the report. ↩

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Summer 2024 - Quarterly Connections: News from the NRTC

Read our Summer 2024 newsletter to learn more about our research on the employment of people who are B/LV and other updates from the NRTC!

NRTC Presenting at AER Conference

Members of the National Research and Training Center on Blindness and Low Vision (NRTC) team will be presenting during the 2024 Association for Education and Rehabilitation of the Blind and Visually Impaired (AER) Biennial International Conference in Charlotte, NC, on July 24-28. The AER International Conference allows professionals who provide services to individuals who are blind or have low vision (B/LV) to connect and share the latest information, resources, data, and more. 

Up to 700 professionals are expected to attend this year's conference, themed One Community – Many Voices in Concert. This conference brings together a wide range of exhibitors and offers many sessions to share information about products and services related to B/LV. 

NRTC team members will present highlights from six research projects from our Rehabilitation Research and Training Center on Employment of People who are Blind or Have Low Vision grant, funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR). NRTC team members who work on the Older Individuals who are Blind Technical Assistance Center (OIB-TAC) grant, funded by the Rehabilitation Services Administration (RSA) under the US Department of Education, will present on topics related to services for older individuals who are B/LV . 

Scheduled presentations include: 

July 24 (9:00 AM EDT) – Hands On: Teaching Braille to Adults by Polly Abbott, Kendra Farrow, and Jennifer Ottowitz.

July 25 (4:45 PM EDT) – Labor Force Participation: Who’s Not Working and Why? by Anne Steverson and Michele McDonnall.

July 25 (4:45 PM EDT) – I’m Not Alone in This: Building Connections and Confidence Through Group Job Search Training by Karla Antonelli and Jennifer Cmar. 

July 26 (11:15 AM EDT) – A National Perspective on Employment and Visual Impairment: Positive Trends and Key Takeaways by Jennifer Cmar and Michele McDonnall.

July 26 (11:15 AM EDT) – How Using a Standardized Assessment will Strengthen the VRT Field by Kendra Farrow and Elyse Connors.

July 27 (10:00 AM EDT) – An Interactive Video to Educate and Improve Attitudes by Michele McDonnall and Karla Antonelli.

July 27 (11:15 AM EDT) – What Interests You Most About Working for Wondersmart? Outcomes and Reflections from Virtual Interview Training for Transition-Age Youth by Jennifer Cmar and Anne Steverson.

July 27 (1:45 PM EDT) – Braille Today: A Look at Current Usage Among Workers and Job Seekers by Michele McDonnall, Anne Steverson, and Jamie Boydstun.

July 27 (3:00 PM EDT) – Did I Really Do It?: The Importance of Documentation by Jennifer Ottowitz and Kendra Farrow.

For more information about the conference and agenda, visit the AER Conference Website .

Current Research Highlight: Exploration of National Datasets

While data on employment rates for B/LV individuals is readily available, there is limited research on the specifics of their employment status. This project aims to investigate employment outcomes beyond basic employment rates and explore the predictors of employment for B/LV individuals.

For this research project, we planned to utilize five large national datasets to uncover various aspects of employment for B/LV individuals, such as job quality, underemployment, earnings, self-employment, and employment continuity. These datasets are: (1) American Community Survey (ACS), (2) Survey of Income and Program Participation (SIPP), (3) Health and Retirement Study (HRS), (4) National Longitudinal Survey of Youth 1997, and (5) National Longitudinal Transition Study 2012 (NLTS 2012).

Since we last featured this project in our newsletter , we completed our analyses with the HRS dataset. Our research questions addressed the impact of developing vision loss in mid-life on employment, revealing that individuals with vision loss were more likely to leave the workforce due to retirement or disability compared to those without vision loss. Most of those who retired after experiencing vision loss were dissatisfied with retirement and felt forced into the decision. We identified several factors associated with continued employment for workers who experienced vision loss, including female gender, being married or partnered, being in better health, and having fewer chronic health conditions.

We also began working with NLSY97 data to address predictors of post-school employment outcomes for youth with B/LV. We selected variables, obtained the data, reviewed descriptive statistics, and began running statistical models.

Four new publications describing the results of this project’s findings are available:

McDonnall, M. C., & Cmar, J. L. (2024). Underemployment among college graduates with blindness and low vision . Journal of Visual Impairment & Blindness . Advance online publication.

Cmar, J. L., McDonnall, M. C., & Mitchell, G. L. (2024). Predictors of job retention after onset of visual impairment in late middle age . Journal of Aging and Health . Advance online publication.

McDonnall, M. C., Cmar, J. L., & McKnight, Z. (2023). How degree major and demographic factors influence employment and earnings for college graduates with visual impairments . Rehabilitation Counseling Bulletin . Advance Online Publication.

McDonnall, M. C., Cmar, J. L., & McKnight, Z. S. (2023). College degree majors and associated earnings: Are there differences between people with visual impairments and the general population? Journal of Vocational Rehabilitation , 59 (3), 263–272.

We were planning to analyze the NLTS 2012 data during year five of this project, but delays in the release of that data will prevent us from utilizing it. During year five, we will instead utilize RSA-911 data combined with Social Security Administration data to investigate employment outcomes for transition-age vocational rehabilitation consumers.

For more information and updates on our research project, please visit our research project webpage .

Training and Technical Assistance

New online course.

An Overview of Assistive Technology for People Who are Blind or Have Low Vision provides an overview of the types and uses of assistive technology devices and software for B/LV individuals. Course developers include Tim Richard, Evan MacDonald, Tommi Sue Celli, and Michelle Mason. (1.25 CRC, ACVREP, and NBPCB credit)

All NRTC courses are available through our learning management system . For more information about our courses, visit our Frequently Asked Questions page .

Featured Resource

Finding Services: A Beginner’s Guide to Visual Impairment is a new video that was created in response to comments from visually impaired participants in an NRTC research study. It explains and provides contact information for the major agencies or organizations that support people with vision loss. The video is hosted on our NTAC-BLV website on the Finding Services page . 

Putting Your Best Foot Forward

Putting Your Best Foot Forward (PYBFF) is a job search skills training program for transition-age youth who are B/LV. This program was designed to help youth learn the skills needed to find a job and succeed in the workplace. PYBFF includes five units with 40 hours of

content, covering topics such as preparing for an interview, disability disclosure, resume development, online job searches, and improving self-presentation. Our next PYBFF trainer workshop is scheduled for October 22-24, 2024. To learn more about PYBFF and sign up for our workshop waitlist, visit our Putting Your Best Foot Forward page .

Other NRTC News

Spotlight on successful employment.

The NRTC has a new person featured in our Spotlight on Successful Employment! As Kim Crothers began losing her vision, she relied heavily on assistive technology and screen magnification to perform her work as a graphic designer and illustrator. Kim’s greatest professional achievement is illustrating a children’s book for youth with visual impairments. Learn more about Kim and other B/LV employees on our Spotlight on Successful Employment page .

NRTC Welcomes New Employee

The NRTC welcomes Billy Hamilton as our new Research Associate. Billy will work under the center’s Rehabilitation Research and Training Center on Employment of People who are Blind or Have Low Vision grant. He will utilize his diverse skillset to support our ongoing research and dissemination activities.

NRTC Recruiting Applicants for the Vision Specialist Program

The NRTC is recruiting our next class of Vision Specialists in Vocational Rehabilitation. Our online graduate certificate program, funded by the Rehabilitation Services Administration, lasts one year (January to December). The courses are designed for professionals to help them become more effective in their work with individuals who are B/LV. Applications will be accepted until October 1, 2024. To learn more about this program and how to apply, visit our Vision Specialist page on our website.

Mentorship Survey

The NRTC is conducting a survey about career mentorship experiences. The study is open to people who are B/LV, between ages 30 and 70, who have received career mentorship. The survey will take about 10 to 15 minutes to complete and can be conveniently accessed on your computer or mobile device. Click this link to see if you qualify for this study .

The study (MSU IRB-24-005) has been reviewed by the Institutional Review Board for the Protection of Human Subjects at Mississippi State University and granted the Exemption Determination.

Implicit Association Test

The NRTC is excited to announce the availability of our implicit association test on blindness and visual impairment (IAT-BVI). This test is designed to measure implicit attitudes about the competence of individuals who are B/LV; it assesses how someone associates the concept of competence (competent vs. incompetent) with vision level (sighted vs. blind). Read our news item for more information . 

Stay up to date with the latest news from the NRTC by subscribing to our monthly NRTC Notes. Please feel free to forward our NRTC Notes to interested parties. To subscribe or change your contact information, contact the NRTC at [email protected] .

Publications, Presentations, and Miscellanies

Publications.

Crudden, A., Steverson, A., & Sergi, K. (2024). Why I’m not working: People with visual impairments explain . Journal of Vocational Rehabilitation . Advance online publication.

McDonnall, M. C., Sessler-Trinkowsky, R., & Steverson, A. (2024). Use of braille in the workplace by people who are blind . Journal on Technology and Persons with Disabilities , 12 , 58-75.

Cmar, J. L., & Antonelli, K. (2024). Systematic adaptation of the JOBS program for use with adults with visual impairments . The New RE:view . Advance online publication.

Presentations

Farrow, K. (2024, July). Building confidence, skills and inclusion through yarn and fiber arts [Conference session]. AER International Conference. Charlotte, NC.

Ottowitz, J., Farrow, K. (2024, July). Did I really do it? The importance of documentation [Conference session]. AER International Conference. Charlotte, NC.

Farrow, K. (2024, July). How using a standardized assessment will strengthen the VRT field [Conference session]. AER International Conference. Charlotte, NC.

McDonnall, M. & Antonielli, K. (2024, July). An interactive video to educate and improve attitudes [Conference session]. AER International Conference. Charlotte, NC.

McDonnall, M., Steverson, A., & Boydstun, J. (2024, July). Braille today: A look at current usage among workers and job seekers [Conference session]. AER International Conference, Charlotte, NC. 

Steverson, A., & McDonnall, M. (2024, July). Labor force participation: Who’s not working and why? [Conference session]. AER International Conference, Charlotte, NC.

Cmar, J., & Steverson, A. (2024, July). What interests you most about working for Wondersmart? Outcomes and reflections from virtual interview training for transition-age youth [Conference session]. AER International Conference, Charlotte, NC.

Antonelli, K., & Cmar, J. (2024, July). I’m not alone in this: Building connections and confidence through group job search training [Conference session]. AER International Conference, Charlotte, NC.

Cmar, J., & McDonnall, M. (2024, July). A national perspective on employment and visual impairment: Positive trends and key takeaways [Conference session]. AER International Conference, Charlotte, NC.

Ottowitz, J. (2024, August 15). Adapting to vision loss: Navigating the journey of adjustmen t [Conference session]. Chicago Social Work Conference, Naperville, IL.

July 19 (2:00 PM CDT) – Using AI: How, When and Why ? AI is the latest buzzword, but what exactly is it, and where does it fit in your teaching toolkit? Join us for a conversation with Ricky Enger as we explore real-world examples for using artificial intelligence in daily living, on the job, and for recreation. To learn more and register, visit our event page .

For Additional NRTC News and Activities

Visit our website at  www.blind.msstate.edu , like us on  Facebook  or follow us on X , Instagram ,  LinkedIn , or YouTube .

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Research & training, advances in hiv/aids research.

For an update on what medical science is doing to fight the global HIV/AIDS pandemic, read a Parade article by NIH Director Francis S. Collins and NIAID Director Anthony S. Fauci, AIDS in 2010: How We're Living with HIV .

Over the past several decades, researchers have learned a lot about the human immunodeficiency virus (HIV) and the disease it causes, acquired immunodeficiency syndrome (AIDS). But still more research is needed to help the millions of people whose health continues to be threatened by the global HIV/AIDS pandemic.

At the National Institutes of Health, the HIV/AIDS research effort is led by the National Institute of Allergy and Infectious Diseases (NIAID). A vast network of NIAID-supported scientists, located on the NIH campus in Bethesda, Maryland, and at research centers around the globe, are exploring new ways to prevent and treat HIV infection, as well as to better understand the virus with the goal of finding a cure. For example, in recent months, NIAID and its partners made progress toward finding a vaccine to prevent HIV infection. Check out other promising areas of NIAID-funded research on HIV/AIDS at http://www.niaid.nih.gov/topics/hivaids/Pages/Default.aspx .

Other NIH institutes, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute on Alcohol Abuse and Alcoholism, also support research to better control and ultimately end the HIV/AIDS pandemic. Some of these researchers have found a simple, cost-effective way to cut HIV transmission from infected mothers to their breastfed infants. Others have developed an index to help measure the role of alcohol consumption in illness and death of people with HIV/AIDS.

Find out more about these discoveries and what they mean for improving the health of people in the United States and all around the globe.

This page last reviewed on August 20, 2015

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Environmental Factor

Your online source for niehs news, advisory council considers military exposures, community-based research.

Exposure effects among U.S. service members, environmental justice, and expanding research in primary care settings also discussed.

By Ernie Hood

NIEHS-supported studies of exposures among active-duty personnel and veterans, along with developments in community-based research and environmental justice, were among the topics discussed at the June 4 meeting of the National Advisory Environmental Health Sciences Council . The Council is a congressionally mandated body that meets three times a year to provide guidance on the direction of research, training, and career development supported by NIEHS.

Veterans’ health

The NIEHS Division of Translational Toxicology (DTT) is working with federal partners in the Department of Defense (DOD) and Veterans Administration (VA) to advance a variety of environmental health research activities related to veterans and active-duty military personnel. DTT’s Warren Casey, Ph.D. , anchored a Council meeting mini-symposium on the subject.

“The goal of this research is to develop actionable tools to prevent exposure-related cancers,” Casey said.

In his presentation, Casey focused on the Project for Military Exposures and Toxicant History Evaluation in U.S. service members ( PROMETHEUS ), a collaborative effort between the government, academia, and private sector that is part of the DOD’s Murtha Cancer Center Research Program. PROMETHEUS is designed to study how exposures to toxic chemicals in the environment affect service members’ health by integrating exposure data, phenotypic data, and biospecimens unique to the DOD.

The mini-symposium also included scientific presentations by a VA official and NIEHS grantees, including two from the CounterACT program, which supports the development of medical countermeasures to treat chemical weapons exposures.

• Karen Block, Ph.D., who co-chairs the federal Toxic Exposure Research Working Group, described Veterans Health Administration research programs focused on understanding health outcomes from military toxic exposures, which differ from civilian exposures. She also discussed initiatives related to the Promise to Address Comprehensive Toxics (PACT) Act , the 2022 legislation that expands VA benefits for veterans exposed to burn pits, Agent Orange, and other toxins during their service.
• Mohammad Athar, Ph.D., from the University of Alabama at Birmingham, shared advances in the treatments of dermal exposures to the blistering agent lewisite.
• Livia Veress, M.D., from the University of Colorado, discussed the development of drugs to treat inhalation exposures to sulfur mustard, chlorine, and methyl isocyanate.

Director’s updates

In his report to Council, NIEHS Director Rick Woychik, Ph.D. , noted that National Institutes of Health (NIH) Director Monica Bertagnolli, M.D. , wants to improve health outcomes and research equity by integrating research with routine clinical care in real-world settings. The goal is to establish a primary care-focused clinical research network as part of a new $30 million NIH program called Communities Advancing Research Equity for Health (CARE for Health) .

“NIEHS is a long-standing pioneer in community-based research, so we are excited to support efforts to create a foundation for sustained engagement with communities underrepresented in clinical research,” Woychik said.

He also described the following NIEHS activities of note since the last Council meeting.

• NIEHS participated in the ACT for NIH congressional briefing, with attendees including House Minority Leader Hakeem Jeffries and Senator Ed Markey. “It was an incredible event, with many of the speakers, Republicans and Democrats, speaking in very positive and enthusiastic terms about supporting the work of the NIH,” Woychik said.
• NIEHS Deputy Director Trevor Archer, Ph.D. , has led the NIH-wide Environmental Justice Working Group, spearheading efforts to add an environmental justice component to the existing Centers of Excellence on Environmental Health Disparities . The funding announcement for the program is expected in July.
• Woychik toured California’s San Joaquin Valley and visited with community groups in one of the poorest and most polluted regions in the nation. “I strongly support an all-of-government approach to enhance environmental justice and health in areas with extremely limited resources,” Woychik explained.

The Council will reconvene virtually September 11-12 for its next meeting.

(Ernie Hood is a contract writer for the NIEHS Office of Communications and Public Liaison.)

Council members’ service celebrated

The Council meeting marked the end of three board members’ terms and several others who will soon be leaving.

Retiring council members are as follows.

• Trevor Penning, Ph.D., University of Pennsylvania.
• Irva Hertz-Picciotto, Ph.D., University of California, Davis.
• Karen Vasquez, Ph.D., University of Texas at Austin.

The following members whose terms will expire at the September virtual meeting also received certificates of appreciation for their service.

• Philip Bourne, Ph.D., University of Virginia.
• Jani Ingram, Ph.D., Northern Arizona University.
• Andrij Holian, Ph.D., University of Montana.
• Thomas LaVeist, Ph.D., Tulane University.
• Gary Miller, Ph.D., Columbia University.

Related Articles

Environmental justice advanced through new NIH-wide initiatives

NIEHS honors Juneteenth with health equity talk, wellness activities

Understanding gene-environment interactions can improve public health

Ask the Expert: How does NIEHS research on PFAS affect me?

NIEHS Women’s Health Awareness event celebrates 10th anniversary

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HIV/AIDS: Current Updates on the Disease, Treatment and Prevention

Praveen kumar gupta.

Department of Biotechnology, R.V College of Engineering, Bangalore, 560059 India

Apoorva Saxena

CCR5-delta 32 homozygous stem cell transplantation for HIV-infected individuals is being treated as a milestone in the global AIDS epidemic. Since 2008, when the second Berlin patient was cured from HIV after undergoing transplantation from a donor with delta-32 mutation, scientists are aiming for a long-term cure for the wider population. In 2019, a London patient became the second person to be free of HIV and came off the antiretroviral drugs completely. CCR5 gene is now being treated as a viable target for HIV treatment. It can be used in the treatment of HIV either through administration of drugs that bind to CCR5 and stop the receptor from working or through gene therapy to alter the CCR5 gene using CRISPR/Cas9 and prevent protein production. This review article aims to identify the obstacles and the need to overcome them in order to bridge the gap between current research and future potential cures for HIV.

Introduction

Human immunodeficiency virus or HIV is the cause of HIV infection that leads to the autoimmune disorder acquired immune deficiency syndrome (AIDS) [ 1 ] (Fig.  1 ). The major cause of spreading of HIV is through unprotected sex, during pregnancy from mother to foetus, through contaminated hypodermic needles and infected blood transfusions [ 1 ]. In the year 2016, an estimated 37 million people were living with HIV and 1 million deaths were reported. HIV/AIDS is a pandemic condition—an epidemic of diseases that spreads across large areas like multiple continents or even worldwide [ 1 ]. The first time AIDS was recognized was in the year 1981 by the United States Center for Disease Control and Prevention (CDC). Since the reported case of an individual who had successfully undergone a stem cell transplant from a person who showed a homozygous CCR5-delta 32 mutation, after receiving extensive high dose chemotherapy, there has been a greater interest in finding a potential cure.

Human Immunodeficiency Virus [ 5 ]

HIV is a type of retrovirus that adversely infects the immune system of a human, mainly targeting the CD4 + T-helper cells, accessory cells and the macrophages [ 2 ]. When it gains entry into the target cell, the viral genomic RNA undergoes a process of the reverse transcription with the help of reverse transcriptase enzyme and forms double stranded DNA (ds-DNA). This ds-DNA then gets integrated into the target cellular DNA with the help of enzyme integrase and other host co-factors [ 3 ]. The virus now can either become dormant or conceal itself and the target cell detection by the host immune system or it can get transcribed into new viral RNA and proteins that are released from the cell and begin the cycle again. HIV can be characterized into 2 major classes—HIV-1 and HIV-2. HIV-1, which is more virulent, infective and the major cause of HIV in humans, was discovered first and was initially referred to as HTLV-III or LAV [ 4 ] (Fig.  2 ). HIV-2 is less infective and far fewer people exposed to it are infected.

Structure of HIV-1 [ 8 ]

The crucial factor in gaining entry into target cell is through binding of HIV to the CD4 receptor present on the T-helper cells and to one of the chemokine receptors- either CCR5 or CXCR4 [ 6 , 7 ]. Binding to the co-receptor depends on the virus’s tropism which is the ability to bind to a specific receptor. Naturally, there are two types of tropic strains—R5 that bind to CCR5 and X4 which bind to CXCR4. Dual tropic strains are capable of binding to both. Of these two co-receptors, CCR5 is the prime receptor for virus’s entry into the target cell. R5-tropic strains prevail during early stages of infection, whereas the X4-tropic strains emerge later with disease progression. The envelope-like glycoprotein structure of HIV-1 is paramount in ensuring the viral entry into a target host cell [ 7 ]. This glycoprotein has 2 protein subunits: the gp41 (transmembrane) subunit and gp120 (external) subunit, which mimics a chemokine [ 6 , 7 ]. It does not manifest the unique structure of the chemokine but somehow manages to bind to both the co-receptors [ 6 ]. It forms a heterotrimeric complex wherein the gp120 subunit binds to the CD4 protein and specific co-receptor present on the target cell [ 6 ]. When this complex is formed, it triggers the release of a peptide which facilitates cell–cell fusion, that causes the viral membrane to fuse with the target cell membrane [ 6 ]. Binding to CD4 alone is not sufficient as it can result in gp120 shedding. So, it has to bind to the specific co-receptor for the fusion to proceed. The V1–V2 region of gp120 is recognized by the co-receptor, that influences which co-receptor will bind to the protein and is determined by degree of N-linked glycosylation and peptide composition. The highly variable V3 loop is the one that determines co-receptor specificity. The binding of gp120 glycoprotein to the CCR5 co-receptor is determined by two essential factors—the tyrosine-sulphated amino terminus of CCR5 receptor and following which there must be reciprocal action between the transmembrane domains of CCR5 and gp120 protein, i.e., inter-communication and synergy.

Antiretroviral Therapy

The usage of a combination of three or more antiretroviral drugs for suppression of the HIV infection is called antiretroviral therapy. Using multiple drugs in combination to increase the effectivity on various viral targets is called highly active antiretroviral therapy (HAART). It helps in maintaining the immune system to function, preventing HIV from developing resistance and other infections that potentially lead to death. The five classes of drugs used in combination to treat HIV infection are: entry inhibitors, nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors and protease inhibitors.

Zidovudine/ZVD (also called azidothymidine) is an extensively used antiretroviral medication [ 9 ]. It is a thymidine analogue and is dosed twice daily in combination with other antiretrovirals. Its function is to particularly inhibit the reverse transcriptase enzyme which is necessary for the production of ds-DNA.

Cellular enzymes are used in converting AZT into the 5′-triphosphate form. Research studies suggest that the termination of forming ds-DNA chains is a crucial factor that leads to an inhibitory effect.

Studies have also shown that at very high dosage of this drug, its triphosphate form may inhibit the DNA polymerase enzyme which is used for cell division by the uninfected cells and mitochondria for replication. It may lead to toxic but reversible effects on certain skeletal and the cardiac muscles, causing the condition of myositis [ 10 ]. However, zidovudine also shows greater affinity for the reverse transcriptase enzyme, which is around 100-fold. This selectivity has been proven by the cell's ability to quickly repair its DNA strands if broken by AZT during its formation, whereas the HIV virus will lack this ability (Fig.  3 ).

Structure of zidovudine [ 11 ]

Zidovudine is commonly used in combination with nucleotide reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, HIV integrase strand transfer inhibitor and protease inhibitor [ 9 ]. The combination of lamivudine and zidovudine is not recommended for non-pregnant HIV-infected adults and adolescents due to greater toxicity but is used as an alternative, though not a preferred one, in antiretroviral-naive pregnant women as an initial treatment [ 9 ]. However, for paediatric patients (neonates, infants and children of age 12 or less), zidovudine with lamivudine/emtricitabine is a preferred option. For adolescents greater than the age of 12, it is an alternative [ 9 ].

Zidovudine Administration and Pharmacokinetics

Administration and dosage.

It is usually administered orally or by continuous IV infusion, although not rapid infusion and IM injection [ 9 ] (Tables ​ (Tables1, 1 , ​ ,2). 2 ). The dosage for paediatric patients and adult patients depends on their body weight (Tables ​ (Tables3, 3 , ​ ,4 4 ).

Oral administration [ 9 ]

IV administration [ 9 ]

Dosage for paediatric patients [ 9 ]

Dosage for adult patients [ 9 ]

Administration

Zidovudine: 1 mg/kg every 4 h [ 9 ].

Pharmacokinetics

Pharmacokinetics gives a detailed view of the fate of drugs in the human system. It includes various components like absorption, distribution, excretion or elimination and metabolism (Tables ​ (Tables5, 5 , ​ ,6, 6 , ​ ,7). 7 ). The stability of such retroviral drugs should also be taken into account for both oral and parenteral dosage forms (Table ​ (Table8 8 ).

Absorption [ 9 ]

Distribution [ 9 ]

Elimination process [ 9 ]

Stability of antiretrovirals [ 9 ]

Contraindications [ 9 ]

• Zidovudine has a history of life-threatening hypersensitivity reactions like Stevens–Johnson syndrome and anaphylaxis to the drug or maybe due to some ingredient in the formulation.
• Lamivudine/zidovudine: hypersensitivity history.
• Abacavir/zidovudine/lamivudine: history of hypersensitivity to abacavir, zidovudine or lamivudine; hepatic impairments may be mild or severe.

CCR5 Gene Structure

C–C chemokine receptor type 5 (also called CCR5 or CD195) is a receptor for chemokines present on the white blood cells. The CCR5 gene in humans is located on the short arm (p) at position 21 on chromosome number 3 (Fig.  4 ). It is mainly expressed cells like T-cells, macrophages, microglia, dendritic cells and eosinophils and is found within a cluster of genes coding for some other receptors like XCR1, CCBP2, etc. [ 12 , 13 ]. The gene has two promoters, three exons and two introns. Pu or PR2, the upstream promoter, has a 1.9 kb region, 57 bp in length and precedes the exon 1 [ 12 ]. Exon 1, which is the start of the coding region, is followed by the first intron, 501 bp in length. The second exon 2 is intron-less. It is found as exon 2a, 235 bp in length, and exon 2b, 54 bp in length. Pd or PR1, the second promoter, accommodates the intron 1 and exon 2 regions [ 12 ]. A 1.9 kb length intron is located between exon 2 and exon 3. Exon 3 is also intron-less and consists of the full ORF of the CCR5 gene, 11 bp of the 5′ untranslated regions and the complete 3′ untranslated regions [ 12 ].

Location of CCR5 gene on chromosome 21 [ 14 ]

These two promoters are devoid of the consensus TATA and CCAAT sequences, although the Pd promoter has a non-consensus TATA sequence and have an unusually high content of pyrimidine in them [ 12 ]. The upstream Pu promoter was found to be weaker than the downstream Pd promoter which had exhibited up to fivefold greater activity. But these results were established as erroneous [ 13 ]. With the help of RT-PCR technique, it was later identified that the Pu promoter was used in stimulated T-cells and the Pd promoter was used in unstimulated primary T-cells [ 13 ]. The error resulted due to the use of transformed T-cells affecting the overall expression of CCR5 protein via the Pu promoter [ 13 ]. Results also showed that transcription of the CCR5 gene when controlled by the Pu promoter containing exon 1 resulted in CCR5A or B and when controlled by the Pd promoter resulted in truncated isoforms [ 13 ].

CCR5 Gene Expression Regulation

The expression of CCR5 gene is regulated at three levels: 1. genetic factors, 2. factors involved in activation, signalling and trafficking of the receptor which includes desensitization, internalization and recycling and 3. environmental triggers [ 13 ].

CCR5 receptor is part of the G-protein coupled receptor family, which binds to its ligand and releases αi and βγ G-protein subunits. This results in a mediated effector response. Such responses stimulate the release of phospholipase Cβ and adenylyl cyclase. This in turn facilitates the release of intracellular calcium and form inositol triphosphate [ 13 ]. This leads to activation of phosphorylation of the CCR5 receptor which occurs at the serine and C-terminal residues via protein kinase C and G-protein coupled receptor kinases [ 13 ]. The regulatory proteins, β-arrestin 1 and 2, bind to the activated serine and the conserved DRY motif in the intracellular loop [ 13 ]. The β-arrestin proteins have functions like desensitizing the receptor to further stimulation and participating in endocytosis. The CCR5 expression level is controlled by the rates of recycling and endocytosis [ 13 ]. In the endocytosis process, β-arrestin protein facilitates the binding process between clathrin-coated pits and the phosphorylated receptor. Infection and entry of HIV into cells do not require CCR5 signalling, but the chemokine-induced endocytosis decreases the available receptor for HIV entry. This is the process of chemokine-mediated anti-HIV activity [ 13 ].

Environmental factors affecting CCR5 expression are infectious pathogenic agents like Mycobacterium tuberculosis , which increases the CCR5 expression. Studies have shown that CCR5 expression is considerably increased in all leukocyte subset cells during tuberculosis and dual infection with HIV [ 13 ]. However, the level of CCR5 expression on CD4 + T-cells was not increased. Conversely, it was also shown that HIV affects the level of expression of CCR5, due to a correlation with HIV disease progression. Individuals with end stage HIV were shown to have the highest percentages of CCR5 expressing CD4 + T-cells [ 13 ].

The regulation of CCR5 is complex. The introns as well as sequences in the 5′ UTR and 3′ UTR affect CCR5 gene regulation [ 13 ]. Therefore, mutations in these regions should be considered critical in the regulation process.

CCR5-Delta 32 Mutation

The discovery of CCR5-delta 32 mutation in the CCR5 gene in 1996 which exhibited some protection against HIV was a ground breaking one. Studies showed that the CD4 + T-cells when expressing this mutation prevented HIV envelope fusion [ 12 ] (Fig.  5 ). The mutant allele has a length of 215 in comparison to the wild type which contains 352 amino acid residues [ 13 ]. This mutation basically results due to the deletion of 32 base pairs from the position of nucleotides starting from 794 till 825, a frameshift mutation, and seven new amino acids are incorporated between amino acid 174 and stop codon at amino acid 182 [ 13 ] (Fig.  6 ). This mutation affects the region of second extracellular loop where the resultant protein lacked the last three transmembrane domains and also some regions necessary for G-protein interaction and signal transduction.

Comparison of HIV infecting cell with CCR5 and without CCR5 [ 15 ]

Difference between wild type CCR5 and CCR5-delta 32 [ 16 ]

This mutation is majorly restricted to people of European descent. The gene frequencies are found to be around 10% and shows a decline from north to south latitude. A 2–5% gene frequency in Europe, the Middle East and parts of the Indian subcontinent was observed in more than 3000 individuals. The highest frequency, at 20.93%, was discovered in the Ashkenazi Jewish population. The mutant allele is absent in Black populations excluding the African American group who may have acquired the mutation through genetic admixture [ 13 ].

The origin of the delta-32 mutant allele has been dated back to the year 275–1875, which increased over a period of time as a result of selective pressure, mainly the Black plague. However, historical data have shown that Black plague may not in fact be the cause [ 13 ]. The distribution of the delta-32 mutant allele in a north to south gradient does not correlate to the casualties of the plague and instead follows a south to the north gradient. The Black plague has shown the greatest casualties in areas like the Mediterranean region and China, with lowest allele frequencies of the mutation [ 13 ].

Studies suggested that delta-32 arose without a selective event. Tandem repeats found in the coding region of the CCR5 gene could cause unequal homologous recombination, which results in the delta-32 allele. The origins of the delta-32 mutation, however, remain a mystery [ 13 ].

The hype about the delta-32 mutation comes from its ability to protect homozygous individuals from HIV. The protective effect of the delta-32 mutation is a result of eliminating the expression of CCR5 protein on the cell surface, which prevents HIV’s entry into the cell. In the year 1997, however, studies showed that some of them having the homozygous delta-32 mutation were HIV-infected [ 13 ]. Further studies revealed the HIV virus was of the X4 type, which led to very rapid CD4 + T cell decline. Hence, this mutation is limited in its function and does not protect against viral strains which utilize other receptors or show dual-tropism [ 13 ].

In contrast, however, the delta-32 protein product which is localized to the endoplasmic reticulum is an important factor. It is shown to exert a trans-dominant negative effect on the wild-type CCR5 protein, which inhibits its transport to the cell surface. Further analysis in vitro showed the reduction of surface expression of wild type CCR5 and CXCR4 through dimerization by this mutant protein product [ 13 ]. This confers an inhibition to R5, X4 and R5X4 HIV infections [ 13 ]. Homozygous delta-32 individuals with this mutant protein were shown to have suppressed CXCR4 surface protein expression and decreased susceptibility to X4 infection. Experimental proofs also suggested that delta-32 heterozygous individuals with HIV infection do not stably express the mutant protein, are devoid of the molecular mechanism of complete protection and only maybe partially protected [ 13 ].

Stem Cell Transplantation

Stem cells are undifferentiated cells that can differentiate into specialized cells and can also undergo mitosis to produce more stem cells. There are mainly two classes—embryonic stem cells (ECS) and adult stem cells. Stem cells are also taken from the umbilical cord blood just after birth. These act as a repair mechanism for the body, such as skin, blood or intestinal tissues. Adult stem cells are majorly used in medical therapies like bone marrow transplantation. Bone marrow is the spongy tissue present inside the bones which serves as a rich source of adult stem cells. Long-term control of HIV is possible with CCR5-delta 32 stem cell transplantation [ 13 ].

Allogeneic transplantation of stem cells with this mutation in patients with HIV infection and malignancy has been considered as an option since the late 1990s (Fig.  7 ). Human leukocyte antigen (HLA) is a critical factor to be considered during the process of transplantation. The HLA should be a proper match; otherwise, it would lead to rejection by the recipient’s immune system. The limited availability of HLA-matched unrelated donors has made it even more difficult. Only about 1% of Caucasians possess this CCR5 null allele [ 13 ].

Allogeneic hematopoietic stem cell transplant [ 17 ]

Gene Therapy

Zinc finger nuclease technology is a popular tool which can be used for targeting specific DNA sequences in the genome. It falls in the class of restriction enzymes and is artificially made by fusing a zinc finger DNA-binding domain and DNA-cleavage domain. This technique is also engineered to eliminate the CCR5 expression over CD4 + T-cells, and the modified cells have shown to have a half-life of 48 weeks [ 13 ]. But it has its own issues. It is difficult to ensure that the desired repair mechanism is one which is used to repair the double stranded break (DBS) [ 13 ]. It is also challenging to scale it upwards and is an expensive technique.

A breakthrough technique, the CRISPR/Cas9 gene-editing system, is also used to eliminate the CCR5 receptor on the blood stem cells which can give rise to differentiated blood cells that are devoid of this receptor [ 18 ] (Fig.  8 ). These gene-edited stem cells can be established into an HIV-infected patient through bone marrow transplantation and give rise to an HIV-resistant immune system [ 18 ]. This technique, however, can also go sideways which leads to unwanted results that can cause ethical issues to rise. As seen in the highly controversial case of the Chinese scientist, He Jiankui, who with the help of this technology deleted the CCR5 gene in the twins, Lulu and Nana, introduced some unintended mutations in their genetic codes. There is still a lot of research needed to make this technology bioethically a safe tool.

CRISPR/Cas9 gene editing [ 19 ]

Researchers have also engineered a molecule called the chimeric antigen receptor (CAR) and introduced a gene for that molecule into blood-forming stem cells [ 18 ]. This molecule has two receptors that will recognize the antigen (HIV) and direct the immune cells to locate and kill the HIV-infected cells [ 18 ]. When transplanted into mice, which would have the CAR-carrying blood stem cells, it would result in reduced levels of HIV by inducing the immune cells to fight effectively against the virus [ 18 ]. An 80% to 95% drop in viral load was observed in the mice [ 18 ]. It was concluded that gene therapy could be a feasible option for treatment in HIV-positive humans.

Immunological Approaches

Studies have shown that vaccine can contribute effectively in viral clearance such as the Rhesus CMV vaccine vector [ 18 ]. A vaccine vector is a kind of vaccine which consists of chemically weakened viruses that are transported in the body to generate an immune response. The genes used in these vaccines are antigen coding surface proteins from that particular pathogen.

SAV001-H is the first and only preventive HIV vaccine which uses killed HIV-1 virus [ 18 ]. It is unique from other vaccines, as it uses genetically engineered whole virus genome, eliminating its pathogenicity and inactivating its virulence through irradiation and chemical treatments, finally approaching to the first “whole-killed virus”-based HIV vaccine [ 18 ]. The results of Phase 1 clinical trial, which were completed in the year 2013, were found to have serious and adverse effects in the 33 participants [ 18 ]. There was also a surprising boost in the antibody production against p24 and gp120. The HIV viral core is mostly made up of the structural protein, p24, which is called the capsid. A crucial factor in the diagnosis of primary HIV-infected individuals is the p24 antigen assay. High levels of p24 are found in the blood serum during the period between infection and seroconversion. The antibody production is found to increase as much as 64-fold [ 18 ]. The antibody production against gp120, which is a glycoprotein, necessary for attachment to a cell receptor and allow HIV entry, is found to increase up to eight-fold [ 18 ].

Another promising vaccine called the Kang's vaccine also uses the “whole-killed HIV-1,” which is similar to vaccines developed for rabies, polio and influenza [ 18 ]. However, HIV-1 is genetically engineered in such vaccines and raises questions about safety and possibility of large quantity production.

Researchers have also tested an immunogen called eOD-GT8 60mer, a protein nanoparticle, which is designed to mimic a crucial part of the HIV envelope protein which will bind to and activate the B cells to produce plasma cells that secrete antibodies needed to fight HIV [ 18 ]. This nanoparticle was developed in the Schief laboratory and tested in mouse models engineered by the Nemazee laboratory [ 18 ]. The researchers showed that immunization with eOD-GT8 60mer produced antibody progenitors with some of the characters crucial to recognize and block the HIV infection, proposing that it could be a promising first step in a series of immunizations against HIV [ 18 ]. The vaccine appears to work well in mouse models. The researchers are now investigating other immunogens that could work in coexistence with eOD-GT8 60mer [ 18 ].

Case Studies

The berlin patient [ 20 ].

The strongest proof available in favour of a HIV cure stems from the case of Timothy Brown who is popularly known as the Berlin patient (Fig.  9 ). He is considered the first person ever to be cured of HIV. The victory was predicated on doctors taking advantage of nature’s own experiment—the genetic mutation of CCR5 gene that produces a protein co-receptor present on the surface of CD4 + T-cells that HIV uses to gain entry. He was attending university in Berlin when was diagnosed HIV positive. His initial treatment include ART, and he was taking low doses of zidovudine and protease inhibitors. He continued to live a normal life for the next 10 years. But one day, he was again feeling extremely exhausted and the doctor had diagnosed it to be anaemia. He had received red blood cell transfusion for nearly a week and was then sent to an oncologist, Dr Huetter, when the previous doctor was unable to resolve the situation. The oncologist performed a painful bone marrow biopsy and after further diagnosis he was informed that he had acute myeloid leukaemia (AML).

Timothy Ray Brown a.k.a. “The Berlin patient” [ 21 ]

He then started receiving treatment at one of the Berlin University hospitals and had to receive four rounds of chemotherapy treatment. During the third round of chemotherapy, he had gotten a fatally dangerous infection and was immediately put into an induced coma. His blood sample was collected and sent to a stem cell donor bank with the German Red Cross to find matches in case he needed transplantation. Luckily, he had 267 matches which sparked an idea to locate donors with a homozygous CCR5 delta-32 mutation on CD4 + T-cells who are almost immune to HIV infection. A donor was found at the 61st attempt and had agreed to donate when necessary (Fig.  10 ).

Adam Castillejo a.k.a “The London patient” [ 23 ]

However, Timothy Brown had been reluctant and had said no to transplantation as the success rate was only 50–50. But at the end of 2006, leukaemia had rebounded and he desperately needed transplantation to survive. He received the stem cell transplant on February 6, 2007 and stopped taking his antiretroviral medication. Nearly 3 months after he underwent transplantation, HIV was no longer found in his body and he had thrived until the end of the year.

Unfortunately, life had other plans for him. After coming back from a trip to the USA, he was diagnosed with pneumonia and the leukaemia was back. The doctors decided to treat him with a second transplantation from the same donor in February 2008. The recovery was a tough one. He was almost paralyzed and went nearly blind. He had, however, eventually learnt to walk again and fully recovered 6 years later. He was continuously tested for HIV with extensive and precise tests. It was finally good news for him! Since 2010, when he decided to go public, he had interviewed for various magazines: POZ Magazine , New York Magazine and Science Magazine among others and decided to devote his life in supporting research for cures against HIV. In July 2012, he started the Timothy Ray Brown Foundation under World AIDS Institute and has worked with many scientists, organizations, research laboratories and universities to work on cures such as vaccination against HIV.

The London Patient [ 22 ]

The London patient may be the second person with HIV to no longer have the virus. In March 2019, in a report published in journal Nature , a group of investigators had announced the cure of a second HIV-positive patient. His success story depicts that CCR5 is a viable target for HIV research and treatment.

The London patient, who had chosen to remain anonymous, came out in public on March 9 th 2020. Adam Castillejo grew up in Caracas, Venezuela, and later shifted to London with his mother, as his parents were divorced. He was first diagnosed with HIV in 2003 and had started taking drugs to control the HIV infection in 2012. He had taken antiretroviral therapy for years before being diagnosed with an advanced form of blood cancer called Hodgkin’s lymphoma. Again, as in the case of the Berlin patient, the cancer was resistant to standard chemotherapy, so his doctors had advised more intensive chemotherapy along with bone marrow stem cell transplant. In 2016, he had agreed to transplantation and received it from a healthy donor who carried the CCR5 mutation. So, when his immune system regrew, it lacked the protein and was impervious to HIV. His virologist, Dr Ravindra Gupta, from the University of Cambridge, thinks it is a cure because a year had passed and they had carried out a few more tests for the viral load. In Adam Castillejo’s own words, “I don’t want people to think, “Oh, you’ve been chosen.” No, it just happened. I was in the right place, probably at the time right time, when it happened.” Adam Castillejo wants to be the “ambassador of hope” for people with this illness.

Although the scientists describe this case as a long-term remission, experts are calling it a potential cure. Such transplants are, however, dangerous and can be fatal. They are also an impractical approach to cure the millions already infected. These are highly risky procedures and can lead to serious complications. There still has to be a lot of research done to extend this type of treatment to a wider population infected with HIV.

A comparative study of the two patients reveals that their cases were in fact quite similar (Table ​ (Table9 9 ).

Summary of the two cases—the Berlin patient and the London patient [ 24 ]

Lifestyle Practices to Prevent HIV Infection

Prevention is better than cure. And with HIV infections, one should practice prevention with utmost care and sincerity. An HIV diagnosis could turn one’s life upside down. So, it’s better to lead a healthy lifestyle by making the correct choices.

Measures for Protection Against HIV Infection

HIV is majorly spread through unprotected vaginal or anal sex. Choose less risky behaviour and be cautious. Not taking medicines to prevent or treat HIV is equally responsible for HIV infection. The number of sexual partners should be limited. One should get tested for sexually transmitted diseases and also know the sexual partner’s status. One can talk about pre-exposure prophylaxis to their respective healthcare provider. It is a preventive option for people who are not infected yet but are exposed to high risks of being HIV positive. HIV is also spread through intravenous injections and blood transfusions. Use of sterile equipment in such cases is a necessity.

Pre-exposure Prophylaxis

This is a preventive method of taking pills by people who are not HIV positive yet but who are at a high risk of getting infected and spreading it to others. A pill, named Truvada, contains two medicinal components, emtricitabine and tenofovir, that are used in combination with other drugs to treat HIV [ 25 ]. These medicines work on keeping the virus from creating a permanent infection.

Post-exposure Prophylaxis

Post-exposure prophylaxis (PEP) is a short course of HIV medicines taken soon after a possible exposure to HIV [ 25 ]. Every hour counts. For the treatment to be effective, the course should begin within 72 h after exposure to HIV; otherwise, it will not have any effect [ 25 ]. This treatment should be used only in cases of emergency. A person prescribed with PEP will need to take the medicines for 28 days at a stretch and then visit their respective healthcare provider for further tests [ 25 ]. Even if taken correctly, it may not be 100% effective. The sooner the medication is started, the better.

Healthy Practices to Follow When Living with HIV

A healthy, well-balanced and nutritious diet can help a person lead a better life by preventing health related issues like malnutrition and stopping the progression from HIV to AIDS. A well-balance diet is rich in whole grains, fresh fruits and vegetables, protein, low fat dairy products and multivitamins like zinc and B12. It also constitutes what should be cut down—fried foods, processed foods and sugary drinks. Smoking should be stopped when diagnosed with HIV. According to CDC, in the USA, the rate of adults with HIV, smoking is two to three times higher in adults infected with HIV than the nearly 18% of uninfected adults who smoke. Researchers at the Syracuse University analysed the data from 212 adults infected with HIV and found that the ones who smoked reported having more symptoms like dizziness and coughing.

Putting a stop to illegal drug use is equally necessary. People should seek treatment for addiction to illegal drugs like heroin, cocaine and methamphetamines. Sharing of needles for drugs can leave one exposed to other infections like hepatitis which might lead to a faster progression from HIV to AIDS. A recent study from the University of Pennsylvania School of Medicine showed a dramatic increase in the ability of HIV to attack healthy cells when methamphetamine is present in the bloodstream. This indicates that illegal drugs are also aiding in the HIV infection.

Being physically fit through a good work-out three to six times a week can help improve a person’s mood, perspective and overall quality of life. A good amount of moderate exercise can help fight HIV symptoms of nerve pain, loss of appetite and reduce the risks of other chronic diseases like heart disease, diabetes and osteoporosis. Taking the prescribed medication on time is known as adherence. This is vital to help reduce the risk of HIV becoming drug resistant and helps the immune system function for a longer time.

Nowadays, with the help of Internet of Things or IoT, patient’s health can be monitored 24/7. The quality of care provided can be increased many-folds with the help of monitoring devices enabled with current technology [ 26 ]. Concept of E-Health and M-Health is currently trending. E-Health makes use of electronic and communication processes with improved cyber security [ 26 ]. Some of the E-Health devices include GPS tracking, pedometer and electronic health records [ 26 ]. M-Health systems provide doctors with the complete medical history of the patient, so the treatment becomes easier and does not delay in case of emergencies. It makes use of mobile phones and other communication systems to help the patients with information about preventive health care services and collects data in real time as well [ 26 ]. The other important applications include chronic disease management, monitoring of diseases and tracking of epidemic outbreaks [ 26 ].

Genomic Diversity and Clinical Implications

Despite billions of dollars being invested, there is currently no HIV vaccine available that can either prevent the disease or treat those who suffer from it. An AIDS patient harbours 100 million genetically distinct variants of HIV [ 27 ]. This high diversity of HIV-1 is due to high replication rates, errors in reverse transcriptase and recombination events that mainly occur during the viral replication process. Reverse transcriptase enzyme has approximately a rate of 10 –4 nucleotide substitutions per replication cycle. Deletions, insertions and duplications are major contributing factors to the genetic variation of the virus [ 27 ]. Genetic recombination also plays an important role in creating genetic diversity. Template switches between two copies of RNA strands occur regularly during reverse transcription [ 27 ]. This generates a lot of mutations with the help of inter- and intra-molecular jumps. These mutations can either be drug resistant or inhibit the viral replication capacity.

HIV-1 can be classified into four main groups: M, N, O and the recently identified P. The M group is further identified into 4 subtypes (A to J). Studies have shown that there is a worldwide spread of non-B subtype viruses, and with the introduction of antiretroviral drugs, more research has to be conducted regarding the responsiveness of the drug resistance in non-B subtypes [ 27 ]. Different types of HIV-1 resistance are observed in different subtypes at varied levels. For example, subtypes B and G have shown to develop resistance against nelfinavir [ 27 ]. Research is also being done in the role of polymorphisms for development of drug resistance, to assess the genotypes before and after the therapy to be able to establish any association between the two [ 27 ].

Variation of Disease Progression Rate

There are 3 phases of the progression of HIV-1 infection- primary infection, chronic asymptomatic phase of infection and finally, AIDS. In the asymptomatic phase, neither signs nor symptoms of the disease are present, and this phase lasts an average of about 10 years. They can be divided as typical progressors, rapid progressors, slow progressors and long-term progressors. Rapid ones (10–20%) develop AIDS within 5 years of infection [ 28 ]. Slow progressors (5–15%) remain free of AIDS 15 years after infection [ 28 ]. Long-term progressors that constitute 1% show no signs and symptoms [ 28 ]. Factors like host genetic make-up, immune responses, co-infection and viral genetics and adaptation are attribute to this huge variation in disease progression [ 28 ]. But there is no solid evidence as such.

Some individuals known as elite controllers are able to manage the viral replication for longer durations, others are shown to rapidly lose CD4 + T-cells after seroconversion in the absence of cART (combination antiretroviral therapy). Scientists have conducted research studies that has led to the conclusion that rapid progression before administration of cART stops the recovery of CD4 + T-cells once the suppressive response to HIV-1 through cART is achieved. These findings have implications in public health policy making, clinical outcomes and science research. Ideally, cART should be initiated as soon the patient is diagnosed with HIV-1 irrespective of the CD4 + T-cell count. However, in clinical settings where cART is not widely available, these results would support strategies that may help in promoting frequent testing to reduce the proportion of patients initiating cART at low CD4 + T-cell counts. For those testing early, frequent CD4 + T-cell count should be monitored close to the time of HIV diagnoses to establish the rapid progressors phenotype in order to avoid unnecessary CD4 + T-cell count decay among rapid progressors. Finally, interpretation of the immunopathological basis of rapid progression can help improve individual clinical outcomes and limit its impact in the global HIV-1 pandemic.

Development of Drug Resistance as a Major Barrier to Treat HIV

HIV-1 has a high mutation rate. An estimated 10 10 virions per day can be produced in untreated patients that may result in variants called quasispecies. The complexity is also increased due to high recombination rate whenever more than one variant infects the same cell. All these are contributing factors that help in invading the host’s immune system and fostering drug resistance. Salvage therapy is also useful in cases when more than one regimen failed or a single regimen failed for a patient. It can be used to suppress the virus levels below the detection level and should have high genetic barrier to resistance to prevent rebound [ 29 ]. Clinicians need to focus on patient’s adherence as well as access to antiretrovirals (ARVs), drug interactions, tolerability, genotypic and phenotypic resistance testing, cross-resistance, genetic barrier and potency of ARVs [ 29 ].

Overcoming Obstacles and Future Prospects

At present, the reason for not being able to achieve a complete cure with the help of ART, in spite of achievement of undetectable viral load, is due to the presence of dormant virus or HIV latency. In a method call shock and kill, immune stimulants shock the latent virus from hidden reservoirs and then attempt to kill reactivated HIV [ 18 ]. An enzyme has been identified which is called histone deacetylase (HDAC) which is responsible for the sustained latency. Some studies show promise but are yet to be confirmed by clinical trials. Flushing these latent CD4 HIV-infected cells from their reservoirs with these HDAC-inhibitors into the blood circulation makes them susceptible to ART. Vorinostat and panobinostat are two such promising drugs [ 18 ].

Histone deacetylase inhibitors seem to have a broad spectrum of epigenetic activities. Vorinostat (also called Zolinza) is a U.S. Food and Drug Administration approved medicine, which has been used for the treatment of cutaneous T-cell lymphoma (CTCL) [ 18 ]. They help in flushing the virus from the reservoirs into the circulation. The dose is 400 mg. Other drugs on the pipeline are Protein kinase C agonist bryostatin-1 and GS-9620—TLR7 agonist [ 18 ].

Romidepsin (also called Istodax) is another HDAC inhibitor drug, which induces HIV-1 transcription to form plasma HIV-1 RNA that can be easily detected with standard assays [ 18 ]. This gives a possibility of reversing the HIV-1 latency in vivo without hindering T cell mediated immune response [ 18 ]. These findings will help the researchers with future clinical trials aiming to eliminate the HIV-1 reservoirs.

Research for curing HIV is at an infant stage but a promising one. Scientists are working on two broad types of HIV cures—a functional cure and a sterilising one.

The approach of the functional cure is to reduce the virus levels in the body to an undetectable stage, where the patient no longer needs to be on HIV medication or has no risk of progression to AIDS nor transferring the virus to others. Unlike the functional cure, however, a sterilising cure aims to get rid of HIV from the body completely by eliminating cells from latent reservoirs. It has proved to be an extremely challenging task for scientists, who believe it may be unachievable in the majority of them living with HIV. However, some findings by researchers at the University of Pittsburgh could lead to a foundation for an HIV vaccine. Clinical trials are in the works.

Abivax, a French company, is developing a drug that binds to some specific sequence of the viral RNA and inhibits its replication. During clinical trials, it has shown that this may have the potential to become a functional cure. The key is that it can target the reservoir of HIV viruses that hide inactive within our cells. It can target the reservoirs where HIV viruses act as inactive, within the infected cells. The result of phase IIa trial was quite promising. Fifteen patients were given the drug in combination with ART, and it was observed after 28 days of treatment that eight patients showed a 25% to almost 50% reduction of their HIV reservoirs compared to those only taking ART. The company is planning a phase IIb clinical trial to confirm the effects of the drug in the long term.

Research and development in HIV and its cure have come a long way since the disease was discovered in the 1980s. ART was a major milestone that has changed the lives of millions for good, but the next ambitious goal is to find an HIV cure before the year 2020. There are several approaches to an HIV cure ranging from shock and kill therapy, immunotherapy, vaccine development to gene editing using zinc finger nucleases and the CRISPR/Cas9 system, but finding the best possible solution is a challenge. One of the biggest challenges around any HIV treatment is the ability of the virus to rapidly mutate and develop resistance. Many of the new approaches do not provide any valuable insights as to whether the virus has the potential to become resistant. As of now, none of these functional cures have reached late-stage clinical trials, and the aim of finding an HIV cure until 2020 seems far-fetched. However, 2020 will likely be marked as an important milestone as the first late-stage trials will be executed. If successful, it could bring the approval of the first functional HIV cure in ten years.

There are two gene therapies undergoing human trials—one is to destroy the CCR5 receptor of the immune cells of people infected with HIV and the other therapy includes the CRISPR technology which is still under early trials. This mutation does not necessarily protect the person against all types of HIV. It was found that in one of the patients who had received the bone marrow treatment, it was found to have the CXCR4-tropic form. It uses a different type of receptor to enter and infect the cells. It was, however, not known whether this virus was acquired after the treatment or if some patients do contract a small amount of CXCR4-tropic virus that starts to multiply when other types are not present.

HIV research continues on many fronts that could provide the same results and only some of which rely on the CCR5 delta 32 mutation, which should be explored extensively. There are many strategies which are in the early stages of development. Scientific process can be slow but if done correctly, advances can be made to find a scalable, cost-effective cure for everyone.

Acknowledgments

The authors listed in this paper wish to express their appreciation to the RSST trust Bangalore for their continuous support and encouragement.

Authors Contribution

All authors have contributed equally with their valuable comments which made the manuscript to this form.

There was no funding provided for the above research and preparation of the manuscript.

Compliance with Ethical Standards

The authors declare that they have no conflict of interest.

All the authors listed hereby confirmed that in the above research, there were no human participants and/or animals involved in any kind of determination, evaluation or research studies.

There is also final confirmation given by all the listed authors for the submission of manuscript in its actual state. The authors listed above also confirm that the above-mentioned manuscript is in its original state and the manuscript is neither submitted anywhere nor in the submission process in any other journals. In addition, all the authors have solely contributed their original work in the preparation of this manuscript. If the copying or similarity have been found, then in all situations the listed authors are solely responsible.

Significance Statement

This article aims to increase awareness among the society about the current scenario of HIV/AIDS. The scientists are working on 2 types of cures—functional and sterilizing. The path to finding a cure is a promising one as late-phase trials begin in 2020.

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