Successes and misgivings of medicine's most ambitious era

BarcelonaThe arrival of immunotherapy in hospitals, the birth of gene editing and walking devices, the first drugs against Alzheimer's and injections for weight loss... It's difficult to look back and choose just a few milestones that demonstrate how, in the last fifteen years, medicine has funneled through countless advancements. Since 2010, tens of millions of medical articles have been published in high-impact journals, and as you read these lines, scientists and laboratories are not slowing down. Since its first issues, the ARA has reported on and delved into many of these achievements, and has not been oblivious to the ethical and economic challenges that health research has faced. Nor has it been unaware of the profound crisis of confidence that some disciplines have experienced in the last five years.

Teaching the body to defend itself

In the last fifteen years, science has brought hope to diseases that until recently were considered death sentences. Half a century of research worldwide led to the 2010 demonstration that stimulating the immune system to distinguish tumor cells from healthy cells and attack them can increase patient survival. James P. Allison and Tasuku Honjo had to wait until 2018 to receive the Nobel Prize for revealing that tumors are capable of suppressing the immune system and that, by blocking this natural mechanism, the body can release its defenses (T lymphocytes) and help control the tumor. This discovery has opened new avenues for patients without access to therapies.

The potential of immunotherapy was first demonstrated with melanoma, but its most measurable benefit has been in leukemias. Now, patients are surviving cancer for five, seven, or even ten years thanks to these advances, including those with metastatic disease. A revolution that would be incomprehensible without CAR-T (Chimeric Antigen Receptor T-cell) therapy, which is based on creating personalized drugs from the patient's own cells. To put it simply, the patient's T lymphocytes are extracted, genetically reprogrammed in the laboratory to neutralize cancer cells, and then reinfused. It wasn't until the 2010s that the first complete remissions of some cancers were demonstrated, meaning that all symptoms and signs of the tumor became undetectable.

Since then, and up until last year, the European Society for Blood and Marrow Transplantation (EBMT) registry lists nearly 14,000 patients who have received CAR-T therapy, and the confidence of the scientific community and the public in these treatments has steadily grown. However, it's not all good news: these treatments have not yet yielded solid results in the vast majority of cancers, such as breast, lung, or colorectal cancer. They can only be prescribed to certain groups of patients, as they can cause serious side effects, and their development and administration costs are extremely high (in Europe, around €300,000 per patient, depending on the healthcare center and the pharmaceutical company involved), making them inaccessible to all hospitals or covered by all healthcare systems.

In Catalonia, two publicly funded CAR-T therapies have been approved, financed through crowdfunding and produced strictly within an academic setting, without pharmaceutical company involvement. These are ARI-0001, for acute lymphoblastic leukemia, authorized in 2021, and ARI-0002h, for multiple myeloma, authorized in 2024, both from the Hospital Clínic. As of last April, more than 500 patients had been treated with them, and the cost difference compared to other commercial CAR-T therapies is enormous: the cost per patient is €90,000, nearly four times cheaper, according to calculations by the Spanish Consumers and Users Organization (OCU).

Modify the 'defective' material

Alongside the advancement of immunotherapy, another major revolution in modern medicine has been taking shape, one that still has a long way to go: gene therapy. This refers to how to eliminate, add, or modify a patient's genetic material. In 2012, CRISPR-Cas9 emerged, a technique that allows for the precise modification of the defective genes behind certain diseases. Although still in the experimental phase, it has opened the door to promising treatments, especially for rare genetic diseases. In 2023, the first CRISPR drug, Casgevy, was approved in the United States. It was authorized in Europe last year and is used to prevent debilitating pain in patients with sickle cell anemia, an inherited blood disorder that alters red blood cells, destroying them prematurely and preventing them from passing through blood vessels.

Now, science wants to take another step towards having CRISPR therapies for more common pathologies such as cholesterol and urinary tract infections caused by bacteria. Escherichia coli (E. coli) or lupus. The latter is a complex autoimmune disease that causes the body to attack itself due to a lack of coordination in its defenses: it not only activates antibodies when there is no danger, but also produces many, causing very aggressive symptoms. In 2022, one of its causes was discovered thanks to the genes of Gabriela, a 7-year-old girl. British researchers sequenced her genome—we'll talk about this revolution later—and identified a mutation. To verify the finding, they used CRISPR to introduce the alteration into mice and… Eureka!

As with everything in the scientific field, the fact that it is still an experimental discipline also carries risks, such as the effects off-targetThis means that the intervention produces inherited alterations in genes that can be harmful in the long term, and raises doubts about the durability of the results, since not enough time has passed to observe their future effects. Furthermore, the use of gene-editing techniques has also been mired in controversy due to their ability to modify human embryos. The most publicized case was that of the Chinese scientist He Jiankui, who in 2018 created two genetically modified twins to make them resistant to HIV. Since the alterations were made in reproductive cells, these would be passed on to future generations. This action earned He social condemnation and imprisonment, but it also prompted the establishment of clear ethical standards and restrictions on experimental freedom in gene editing.

Success and questioning of vaccines

In terms of public health, the last fifteen years have been intense. It is impossible to talk about the coronavirus or COVID-19 pandemic without mentioning it—a tiny pathogen that caused the most devastating health emergency of modern times in just a few weeks. But there have been several emergencies over these three decades: the swine flu of 2010, the Ebola epidemics (2013-2020), and the emergence of mosquito-borne diseases like Zika (2016). The most remarkable aspect of many of these emergencies has been the development of vaccines. The historic smallpox vaccines are now helping to contain the epidemic of monkeypox —misnamed monkeypox— in Europe and Catalonia in record time, and the 2019 rVSV-ZEBOV vaccine has reduced the severity and aggressiveness of Ebola, an extremely deadly disease in Africa.

The urgency to develop a fast and safe vaccine against the Zika virus, which caused a major outbreak in Latin America between 2015 and 2016, led to the exploration of innovative technologies to protect pregnant women from infection, as they could transmit the virus to their unborn children. This is where the idea of messenger RNA (mRNA) began to spread: teaching the immune system to recognize a virus without exposing the body to the infectious agent, as was done with traditional vaccines.

The undeniable success of this technology came with COVID-19. The need to control the pandemic mobilized thousands of scientists and millions of euros and dollars. Laboratories had strong incentives to invest in mass production, and governments expedited the authorization and purchase processes even before clinical results were available. While a conventional vaccine takes between five and ten years to become available due to lack of funding, in this case, inoculations began in just over a year.

With adequate financial resources, science can respond quickly and rigorously to global threats, but the speed with which vaccines were developed and their widespread application generated distrust among a segment of the population, fueled by right-wing political groups and anti-vaccine movements. Several controversies have surrounded them, such as the alleged concealment of their potential to cause myocarditis and thrombosis in young people; a reality that the scientific community now attributes to the fact that so many millions of people had never been immunized simultaneously and that the pharmacological monitoring of very rare side effects was conducted in real-life situations. Beyond the ideological or sociological perspective—there were significant inequalities between the global north and south in access to vaccines—it was scientifically confirmed that they were safe and effective, and mathematical models estimate that they prevented approximately 2.5 million deaths worldwide and drastically reduced hospitalizations.

Gaining life and quality years

In recent decades, science has improved the quality of life for many stroke patients, probably more than in any previous period. We will discuss five examples. In a stroke, it is estimated that two million neurons die every minute. Every second counts, not only to save the patient's life but also to minimize neurological damage. One of the greatest advances in this field was the validation of mechanical thrombectomy, a technique based on removing the clot with a catheter, which increases the chances of full or near-full recovery. If we add to this therapy high-resolution brain imaging techniques and the consolidation of rapid emergency protocols (Stroke Code), which reduce the time between the stroke and treatment, it can be said that the care of these patients has significantly improved.

A second important example is the emergence of various assistive technology devices that should change the paradigm of mobility recovery in the future. Prostheses, exoskeletons, and interfaces Advanced brain-computer interfaces are examples of new creations with a clear aim to restore autonomy to patients when combined with rehabilitation. For example, in 2012 it was demonstrated that people with quadriplegia could control a 3D robotic arm with brain signals, and in 2022, that stimulating electrodes under the vertebrae—which mimic the signals of the nervous system—allows them to spinal cord injury patients walk againMost are experimental cases, but they break down barriers and demonstrate that restoring lost functions is possible.

A few years ago, practically no one believed that science would find a way to cure HIV functionally. However, in October 2023, the ARA interviewed Adam Castillejos, "living proof" that it is possible. He is the London patient, the second person in the world to have been cured of both HIV and cancerThanks to a complex stem cell transplant from a donor with the CCR5 mutation, which makes cells resistant to the virus, he has recovered. Despite the exceptional nature of his case, medicine in recent years has shown its most spectacular side: there are now five people in the world who have been able to stop antiretroviral therapy with no trace of the disease in their bodies. It is not a standard treatment, but scientists are trying to learn from it to design less risky therapies, such as drugs that reproduce the protective mutation in the laboratory.

It's impossible to discuss without mentioning the scientific progress being made in treating this particularly tragic disease. In the next five years, the way it's addressed could change completely because, among other things, the interest of major pharmaceutical companies is on the rise. Although the prognosis for Alzheimer's patients has barely improved in the last three decades, significant progress has been made in the early detection of the disease through blood tests (so-called biomarkers), as well as in the use of improved imaging technologies. Another very important advance is the development of the first therapies that don't just alleviate symptoms, but alter the course of the disease. In Europe, after much back and forth, the two drugs that have been shown to slow the progression of Alzheimer's, Leqembi and Kisunla, have already been approved. The goal, therefore, is that the combination of early diagnosis and access to treatment will allow us to contain this serious neurodegenerative disease, whose prevalence is expected to increase in the context of an aging population: it is estimated that by 2030 alone there will be some 60 million people with Alzheimer's worldwide.

Now the world is experiencing the so-calledOzempic revolutionThe demand for weight-loss medications is historic, with treatments for acquired type 2 diabetes marking a turning point. Drugs based on semaglutide and GLP-1 (which mimic a hormone that regulates blood glucose levels), such as Ozempic, have gone from being known only to a select group of patients to becoming a global success in the fight against obesity. This is because they reduce appetite, delay gastric emptying, and promote weight loss when combined with physical activity. In fact, specific versions for obesity, such as Wegovy and Mounjaro, have already been approved. However, this medication is expensive, costing between €100 and €300 per month. Furthermore, discontinuing treatment leads to weight regain, which can make it a chronic therapy. On a positive note, research is underway to determine if these drugs could curb addictive behaviors such as alcoholism, smoking, or binge eating. This would be possible because they alter brain circuits related to reward and impulsivity.

Information is power

And just in case it wasn't clear enough, in the last decade a all-in In personalized medicine, researchers have joined forces to move beyond uniform treatments and take into account the patient's genetic, environmental, and lifestyle differences to fine-tune the approach. From diagnosis to prescribed therapy, they anticipate the patient's response to medications. A brief historical overview will provide context. In the 1990s, the Human Genome Project (HGP) was launched to sequence—determine the exact order of—the entire set of human genetic material. Between 2005 and 2010, a qualitative leap occurred: the rapid and cost-effective study of massive datasets—in days or weeks rather than years. Furthermore, the mass digitization of medical records and hospital registries began. Big Data was making its way into medicine.

In 2015, the Precision Medicine Initiative (PMI) was launched in the United States. Barack Obama created a program to obtain clinical records, biological samples, surveys, and mobile device data containing relevant health information from over a million participants. It was the seed of today's precision medicine, based on data analysis to detect previously invisible patterns. For example, genetic combinations that predispose individuals to a disease, explanations for why two patients react differently to the same treatment, or the identification of signals to predict the risk of developing an illness. And now, with the emergence of artificial intelligence (AI), the groundwork has been laid for even greater precision.

The last fifteen years are evidence that health science has shifted toward more preventive and personalized medicine: it no longer simply waits for disease to manifest before attacking it with an arsenal of therapies. This is undeniable. But it is also important to understand what its main challenge should be: to leave no one behind due to socioeconomic issues and to balance information and technology with its ever-ambitious spirit healing.