Lifeboat Foundation

Ball is not alone in calling for a drastic rethink of how scientists discuss biology. There has been a flurry of publications in this vein in the past year, written by me and others^2–4. All outline reasons to redefine what genes do. All highlight the physiological processes by which organisms control their genomes. And all argue that agency and purpose are definitive characteristics of life that have been overlooked in conventional, gene-centric views of biology.

This burst of activity represents a frustrated thought that “it is time to become impatient with the old view”, as Ball says. Genetics alone cannot help us to understand and treat many of the diseases that cause the biggest health-care burdens, such as schizophrenia, cardiovascular diseases and cancer. These conditions are physiological at their core, the author points out — despite having genetic components, they are nonetheless caused by cellular processes going awry. Those holistic processes are what we must understand, if we are to find cures.

Ultimately, Ball concludes that “we are at the beginning of a profound rethinking of how life works”. In my view, beginning is the key word here. Scientists must take care not to substitute an old set of dogmas with a new one. It’s time to stop pretending that, give or take a few bits and pieces, we know how life works. Instead, we must let our ideas evolve as more discoveries are made in the coming decades. Sitting in uncertainty, while working to make those discoveries, will be biology’s great task for the twenty-first century.

Using a new technique, scientists created genetic blueprints for kangaroos, penguins, sharks and more.

Some hereditary genetic defects cause an exaggerated immune response that can be fatal. Using the CRISPR-Cas9 gene-editing tool, such defects can be corrected, thus normalizing the immune response, as researchers led by Klaus Rajewsky from the Max Delbrück Center now report in Science Immunology.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare disease of the immune system that usually occurs in infants and young children under the age of 18 months. The condition is severe and has a high mortality rate. It is caused by various gene mutations that prevent cytotoxic T cells from functioning normally. These are a group of immune cells that kill virus–infected cells or otherwise altered cells.

If a child with FHL contracts a virus—such as the Epstein-Barr virus (EBV), but also other viruses—the cytotoxic T cells cannot eliminate the infected cells. Instead, the immune response gets out of control. This leads to a cytokine storm and an excessive inflammatory reaction that affects the entire organism.

Plant cell-surface receptors that are known to participate in immunity, development, and reproductive processes include the LRR-, G-lectin-, Wall-associated kinase (WAK)-, Domain of Unknown Function 26 (Duf26)-, L-lectin-, Lysin motif (LysM)-, and Malectin-containing RLKs and RLPs (Fig. 1a–h). There are additional RLK families with different ectodomains, such as the proline-rich extensin-like receptor kinases (PERKs) and thaumatin-like protein kinases (TLPKs)^9,13. However, their function in immunity is not well-characterized. Cell-surface receptors with LRR-, G-lectin-, WAK-, and LysM-ectodomains have been reported to recognise PAMPs, while others perceive self-molecules or unidentified ligands (Fig. 1h; Supplementary Fig. 1). Recognition of the diverse array of ligands is likely to be accomplished by variable structures and combinations of different ectodomains (Fig. 1a–g). To trace the origins of different receptor classes within the plant lineage, we first identified RLKs and RLPs in 350 genomes from Glaucophyta, red algae, green algae, Bryophytes, and Tracheophytes. We define here RLKs as any proteins with both 1–2 TMs and KDs, and RLPs as any protein with 1–2 TMs, but lack KDs. In total, we identified 177,645 RLKs, almost up to 70% of which possess either LRR-, G-lectin-, WAK-, Duf26-, L-lectin-, LysM-and Malectin-ectodomains (Fig. 1i). Next, we searched for proteins with these ectodomains and TMs that lack KDs and found 41,144 RLPs (Fig. 1j). We further examined which of the identified RLKs and RLPs families are likely to be involved in immunity. A previous report suggested a positive correlation between the gene family sizes of cell-surface immune receptors and intracellular immune receptors (the NB-ARC family) across the angiosperms⁴. We examined the correlation between the relative size (%; number of identified genes in the family/numbers of searched genes × 100; see methods) of the RLK families, the RLPs families, and the NB-ARC family in each genome. Notably, most RLK families (except for the LysM-RLKs) exhibit positive correlations with the NB-ARC family, while most RLP families (except for the LRR-RLPs) do not exhibit positive correlation with the NB-ARC family (Main Fig. 1k). Furthermore, we checked the expression level of these receptor families in Arabidopsis thaliana during immunity. Notably, the RLKs, except for LRR-and Malectin-RLKs, generally exhibit higher expression levels compared to the RLPs during immunity (Main Fig. 1k; Supplementary Fig. 2). These data collectively suggest that the RLKs are more likely to be involved in immunity than the RLPs.

Next, we examined the presence or absence of ectodomains (LRR-, G-lectin-, WAK-, Duf26-, L-lectin-, LysM-and Malectin-ectodomains lacking TM or KD; ectodomain-only proteins), RLPs (TM-bound ectodomains) and RLKs (ectodomains encompassing both TM and KD) in the plant lineage (Fig. 2; Supplementary Fig. 3; Supplementary Data 1a–c). Ectodomains exhibit an ancient heritage, with LRR-, WAK-, LysM-, Malectin-, and L-lectin-domains dating back to the era of Glaucophyta. Similarly, relatively ancient counterparts such as LRR-RLPs, WAK-RLPs, LysM-RLPs, Malectin-RLPs, and L-lectin-RLPs are found in both Glaucophyta and Rhodophyta. In contrast, RLKs emerged more recently. Green algae harbour WAK-RLKs, Malectin-RLKs, and G-lectin-RLKs, and LysM-RLKs, L-lectin-RLKs, and Duf-26-RLKs are exclusive to Embryophytes (Fig. 2). Except for LRR-RLPs, all six families of RLP are basal to the RLK families.

Colorectal cancer (also called bowel cancer) typically develops in the large bowel (colon) or rectum. Recent studies have shown significant rises in the number of colorectal cancer cases, particularly those in young adults. As we discussed earlier, the recently released estimated cancer statistics for 2024 predict colorectal cancer as the leading cause of mortality in men under 50 and the second-leading cause of mortality in women. Additionally, experts predict over 150,000 new cases of colorectal cancers this year.

To combat these troubling figures, ongoing research focused on the prevention and treatment of colorectal cancers remains a high priority and urgent need. This includes data recently published in Science Advances which demonstrates pre-clinical efficacy for a new treatment approach.

The study involves genetic material known as microbial or mislocalized DNA. This type of DNA arrises from cells that become damaged, thus no longer providing the correct genetic instructions. Damaged DNA can elicit various reactions in the body, including activating the immune response. Damaged DNA can therefore influence how the body responds to diseases, including colorectal cancer.

Scientists from the German Cancer Research Center (DKFZ) and Heidelberg University have investigated in mice how spreading tumor cells behave at the site of metastasis. Some tumor cells immediately start to form metastases. Others leave the blood vessel and may then enter a long period of dormancy. What determines which path the cancer cells take is their epigenetic status. This was also confirmed in experiments with human tumor cells. The results of the study could pave the way for novel diagnostic and therapeutic applications.

The work appears in Nature Cancer.

What makes cancer so dangerous? Cancer cells that leave the primary tumor to reach distant sites of the body where they may grow into daughter tumors, called metastases. While most primary tumors can be effectively treated, metastases are the real danger. Oncologists estimate that more than 90% of all cancer deaths in solid tumors are due to metastases.

A gene editing tool using a system known as CRISPR-Cas9 has recently been approved by the U.S. Food and Drug Administration (FDA) for sickle cell disease. The drug is known as Casgevy and the media has hailed this treatment as a ‘cure’ for sickle cell anemia patients. While it is still unclear if the drug completely cures these patients, clinical trials show exciting efficacy.

Sickle cell disease is a genetic blood disorder affecting thousands of US citizens. Many of these patients are African American and Hispanic. In sickle cell disease, hemoglobin, a protein in red blood cells that helps carry oxygen throughout the body, is mutated. As a result, blood cells change shape in the form of a sickle, giving the disease its name. Unfortunately, the mutated cells cause disruption of blood flow and prevent other blood cells from delivering oxygen to the body. This disease is extremely rare and can lower the quality of life in patients. Previously, there were limited treatments options including transfusions and medications for pain management. However, Casgevy provides a new option to help treat the patient and relieve pain for over a year after a single treatment.

One-time treatment using Casgevy improved life quality for sickle cell patients. A single-arm trial was conducted at multiple health centers in adults and adolescents. These patients were screened for two vaso-occlusive crises (VOCs) which are described as severely painful events due to a lack of oxygen delivery from sickle cell blood cells blocking blood flow. The primary measure of success in the trial was the number of VOCs after treatment. In total, 44 patients received Casgevy and 33 were able to follow up and be evaluated. Of the 33 patients that made it through the trial, 29 of them did not experience any VOCs for 12 months. This is a 93.5% success rate based on the number of patients that were analyzed. All 44 patients were able to successfully undergo treatment without any graft rejection. In addition, researchers concluded that this treatment was not only effective, but safe with few side effects.

Some human neurons take years to reach maturity; an epigenetic ‘brake’ could be responsible.

Epigenomic analyses suggest promising new approaches for monitoring and treating cancer. What are the analyses uncovering, and how close are they to improving patient outcomes?