雅思阅读 83: The First CRISPR Cure（首个CRISPR疗法）

改编自 NHS England / Vertex Pharmaceuticals（2025年1月）。雅思阅读 Section 3 难度，约 1050 词。 素材来源：https://www.england.nhs.uk/2025/01/revolutionary-gene-editing-therapy-for-sickle-cell/

Reading Passage

A. For most of medical history, a diagnosis of sickle cell disease was a life sentence managed rather than cured. The inherited blood disorder, caused by a single mutation in the gene that makes haemoglobin, turns red blood cells into stiff, sickle-shaped discs that jam small blood vessels, triggering excruciating "crises" of pain, organ damage and, over decades, early death. Treatments existed — blood transfusions, drugs, bone-marrow transplants from a matched donor — but each carried heavy burdens, and matched donors were unavailable to most patients. That picture changed in January 2025, when England's National Institute for Health and Care Excellence recommended routine use of exagamglogene autotemcel, known as exa-cel or by its brand name Casgevy, for eligible patients with severe sickle cell disease. The treatment had already been authorised by regulators in the United States and Britain in late 2023, and by the European Commission in February 2024. What made it historic was not merely another approval. It was the first medicine ever brought to market whose mechanism of action is the precise gene-editing tool CRISPR-Cas9, the molecular scissors discovered in bacteria barely a decade earlier. The bacteria that evolved the system used it as a primitive immune defence, slicing up viral DNA; the molecular biologists Jennifer Doudna and Emmanuelle Charpentier showed, in 2012, that the scissors could be reprogrammed to cut any chosen gene, work for which they would later share a Nobel prize. Exa-cel is the long, uncertain bridge from that laboratory insight to a product on a hospital shelf.

B. The biological logic behind exa-cel is elegant in its inversion of the disease itself. Sickle cell disease arises because adult haemoglobin, carrying the mutated form, deforms red cells. Yet every human foetus makes a different, fetal form of haemoglobin that is perfectly functional and does not sickle. Around birth, a genetic switch called BCL11A shuts that fetal production down. Rather than correcting the mutated adult gene directly — a difficult proposition in every cell of the body — exa-cel takes a different route. Doctors first collect the patient's own haematopoietic stem cells, the precursors of all blood cells. In the laboratory, CRISPR-Cas9 cuts a single regulatory region, the erythroid enhancer, of the BCL11A gene inside those cells. The edit does not delete the whole gene; it merely disables the switch in red-cell lineages, allowing fetal haemoglobin to resume. The patient then receives conditioning chemotherapy to clear their diseased marrow, and the edited cells are returned by transfusion. Within months, the body builds a new blood supply rich in fetal haemoglobin, and the sickling stops.

C. Clinical trial data told a dramatic story. In the pivotal studies, patients who had endured dozens of pain crises a year reported, after treatment, periods free of any vaso-occlusive crisis — the hallmark complication of the disease. Long-term follow-up presented at the American Society of Hematology in 2024 showed durable benefit, with the longest observations now extending beyond five years for some recipients. The edited stem cells persisted, fetal haemoglobin levels stayed high, and patients who had once depended on repeated transfusions stopped needing them. Researchers were careful not to overstate. Exa-cel is not a trivial intervention. Conditioning chemotherapy brings side effects — infertility risk, infection risk during the vulnerable period before engraftment, and a hospital stay measured in weeks rather than hours. The patients who receive it are carefully selected, and the procedure is offered only at specialised centres. Yet for a patient facing a lifetime of crises, organ failure and a sharply shortened life expectancy, a one-time intervention that remakes the blood is qualitatively different from a medication taken for decades.

D. The arrival of Casgevy also exposed the deep fault lines of modern medicine. In the United States, the list price was announced at roughly two million dollars per patient before administration costs — a figure that drew immediate accusations that a cure for a disease disproportionately affecting people of African ancestry had been priced out of reach for the communities most in need. Manufacturing adds further strain. Every dose must be custom-made from that patient's own cells, edited in a GMP-grade facility, tested, frozen and shipped back; the supply chain does not scale like a pill. In Britain, the NHS negotiated a confidential discounted price and began treating patients through a small number of centres, but capacity constraints mean waitlists persist. Advocates argue that the very possibility of a cure creates a moral obligation to make it accessible, while manufacturers counter that the cost reflects a decade of research, a bespoke production process and a patient population that is, on any global scale, small. Neither side disputes that the science works; the dispute is about who benefits from it.

E. Looking ahead, Casgevy is widely seen not as an endpoint but as a proof of principle. The same CRISPR platform is being adapted for beta-thalassaemia, another blood disorder, and researchers are racing to extend ex-vivo editing to disorders of the liver, the eye and the immune system. Harder still is in-vivo editing, in which scissors are delivered directly into the body to edit cells where they live — an ambition that carries its own risks of off-target cuts and immune reactions. Some ethicists also worry that the ease with which a single gene can be altered may normalise requests for non-therapeutic edits. Yet within the narrow frame of sickle cell disease, the balance is unusually clear. For the first time, patients whose disease was described in ancient medical texts now have a route not merely to manage it, but to be free of it. Whether that freedom can be delivered fairly — at a cost patients and health systems can bear, at a scale that matches need — is now the question the scientists who invented CRISPR can no longer answer alone.

Questions 1-4

Choose the correct heading for paragraphs B, C, D and E from the list of headings below.

List of Headings i. Why the new treatment is priced so highly ii. The biological strategy behind the therapy iii. How the clinical results were measured and qualified iv. The early discovery of CRISPR in bacteria v. What comes next after the first approved edit vi. The financial cost of manufacturing pills at scale vii. Historical attempts to use gene therapy in the 1990s

1. Paragraph B: ____
2. Paragraph C: ____
3. Paragraph D: ____
4. Paragraph E: ____

Questions 5-8

Choose the correct letter, A, B, C or D.

5. How does exa-cel differ from earlier gene-editing approaches? A. It edits the mutated adult haemoglobin gene directly in every body cell. B. It reactivates fetal haemoglobin by disabling a regulatory switch in stem cells. C. It replaces the patient's bone marrow with that of a matched donor. D. It prevents the mutation from being inherited by the next generation.

6. What does the writer say about clinical outcomes? A. All side effects disappeared within months of treatment. B. The benefits have remained stable for some patients for several years. C. Most patients still require regular transfusions after editing. D. The trial was too short to draw reliable conclusions.

7. Why is manufacturing exa-cel difficult to scale? A. CRISPR enzymes are banned in most countries. B. Each dose is custom-made from the patient's own cells. C. The treatment must be produced as a generic pill. D. Patients refuse to travel to specialised centres.

8. What is the writer's view on in-vivo editing? A. It is already more effective than ex-vivo approaches. B. It raises distinct technical and safety concerns. C. It is ethically impossible to pursue. D. It will replace exa-cel within five years.

Questions 9-13

Do the following statements agree with the claims of the writer?

Write:

• TRUE if the statement agrees with the information
• FALSE if the statement contradicts the information
• NOT GIVEN if there is no information on this

9. Sickle cell disease is caused by a single mutation in the haemoglobin gene.
10. Casgevy was first approved by the European Commission before any other regulator.
11. The conditioning chemotherapy used before transfusion has no associated risks.
12. In the United States, the announced list price of exa-cel was around two million dollars per patient.
13. CRISPR-Cas9 was originally developed as a medical tool in the 1990s.

Questions 14-15

Complete the summary below using NO MORE THAN TWO WORDS from the passage.

Exa-cel edits the erythroid enhancer of the (14) __________ gene, allowing the body to resume production of (15) __________ haemoglobin.

答案与解析

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