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In cars, we first got cruise control, but now there’s brake assist, lane assist, even assisted parking — all of which build towards something driverless.

在汽车方面，我们首先有了巡航控制，但现在有了制动辅助，车道辅助，甚至辅助停车——所有这些都是为了实现无人驾驶。

Welcome to the new post-genomic biology

欢迎来到新的后基因组生物学

1

You could be forgiven for thinking that the turn of the millennium was a golden age for the life sciences. After the halcyon days of the 1950s and ’60s when the structure of DNA, the true nature of genes and the genetic code itself were discovered, the Human Genome Project, launched in 1990 and culminating with a preliminary announcement of the entire genome sequence in 2000, looked like – and was presented as – a comparably dramatic leap forward in our understanding of the basis of life itself. As Bill Clinton put it when the draft sequence was unveiled: ‘Today we are learning the language in which God created life.’ Portentous stuff.

The genome sequence reveals the order in which the chemical building blocks (of which there are four distinct types) that make up our DNA are arranged along the molecule’s double-helical strands. Our genomes each have around 3 billion of these ‘letters’; reading them all is a tremendous challenge, but the Human Genome Project (HGP) transformed genome sequencing within the space of a couple of decades from a very slow and expensive procedure into something you can get done by mail order for the price of a meal for two. Since that first sequence was unveiled in 2000, hundreds of thousands of human genomes have now been decoded, giving an indication of the person-to-person variation in sequence. This information has provided a vital resource for biomedicine, enabling us, for example, to identify which parts of the genome correlate with which diseases and traits. And all that investment in gene-sequencing technology was more than justified merely by its use for studying and tracking the SARS-CoV-2 virus during the COVID-19 pandemic.

That task hasn’t turned out as expected. The copious genome databases haven’t yet produced the flood of new treatments and drugs that some had predicted from gene-based medicine, nor delivered on the promise of therapies tuned to our own individual genomes. Despite the COVID-19 vaccines, drug development as a whole has stagnated or even slowed over recent decades, becoming ever more costly. And most drugs are still found by old-fashioned trial and error, not by leveraging genetic data. The outcomes have been particularly disappointing for understanding and treating cancer, long thought to arise from changes (mutations) in the sequences in our DNA that are either inherited or accumulated through age and environmental wear and tear. Despite the genetic data glut, biology seems to have settled back into a long, slow slog.

Fixing life remains difficult – but, in terms of understanding it, the course of cell and molecular biology over the past several decades isn’t a tale of unfulfilled promise. On the contrary, we’re in one of the most exciting periods since James Watson and Francis Crick discovered DNA’s double helix in 1953. The transformative advances of the post-genomic decades are revealing nothing less than a new biology: an extraordinary and fresh picture of how life works. And ironically, those advances turn out to undermine the skewed view of life on which the HGP itself was predicated, in which the genome sequence of DNA was  the ‘secret of life’.

Only around 1-2 percent of the entire human genome actually consists of protein-coding genes. The remainder was long thought to be mostly junk: meaningless sequences accumulated over the course of evolution. But at least some of that non-coding genome is now known to be involved in regulating genes: altering, activating or suppressing their transcription into RNA and translation into proteins. Many disease-linked regions are in these regulatory sequences, where mutations don’t change the proteins themselves but, rather, the rate or chance of them being made at all. So, to understand how life really works at the genomic level, we need to understand gene regulation. And that, as we’ll see, is not just eye-wateringly complicated but not at all what we have learnt to expect from the conventional molecular biology of the past 50 years.

The best metaphors for thinking about how life works come not from our technologies but from life itself.

思考生命如何运作的最佳隐喻不是来自我们的技术，而是来自生命本身。

The outcomes have been particularly disappointing for understanding and treating cancer, long thought to arise from changes (mutations) in the sequences in our DNA that are either inherited or accumulated through age and environmental wear and tear. 

这是一个复合句，主句是：The outcomes have been particularly disappointing.  for understanding and treating cancer 是介词短语作状语，ong thought to arise from changes (mutations) in the sequences in our DNA 是过去分词短语作定语，修饰前面的整个句子内容，that are either ... or ...是定语从句，修饰先行词changes (mutations)。

Thus, genes may still be ‘selfish’, and organisms may still be ‘machines’, brains ‘computers’, genomes ‘blueprints’, so long as we give those metaphorical words different interpretations to the everyday ones – thereby, of course, negating their value as metaphors.

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