The Code Breaker by Walter Isaacson – a must-read on the biggest scientific story of our time

Walter Isaacson tells big discovery stories of science founded on personal friendships with all the people who drove them. He is a maestro. All his books involving contemporaries have a sharp, journalistic feel. The Code Breaker is no exception. Isaacson explores the biggest scientific story of our time; how humankind, after 3.7 billion years of creeping evolution, has in the twinkling of an eye first understood and then developed a mechanism to manipulate genetics. The book’s subtitle – Jennifer Doudna, Gene Editing, and the Future of the Human Race is no exaggerated puff. 

It is humbling to reflect that the post-Second World War generation’s comprehension of evolution has morphed from observing Darwin’s process of natural selection as random and haphazard to a comprehensive understanding of the three billion letter code of DNA (deoxyribonucleic acid). DNA defines who we are, what organs our offspring will build to supply life-giving energy to their 30 trillion cells, what limbs they shall sprout and what sensory organs they will develop to allow them to gaze on and better comprehend their world. 

The next generation has power through knowledge to shape that world for good or evil. The fact that Adolf Hitler and his ilk tried the same thing through the rough and ready cod-science of eugenics should sound a dire warning. The stakes in play are high. If we get this wrong, in the vindicated words of Dad’s Army’s Private Frazer, “we’re all doomed”.

This must-read book initially focused on Jennifer Doudna, the Nobel laureate American scientist credited with discovering the means of gene editing – the Crispr Cas9 technique – discovered in 2011. But it is much more than that. It starts with the backstory, aeons ago in the 1950s, when James Wilson and Francis Crick first revealed DNA’s elegant double helix structure and ends, timeously, with Covid-19. Today’s understanding of viral genetics and our consequential ability to rapidly construct drugs to combat dangerous variants are fully described.

The pace of events has been such since Isaacson first took up his pen that it must have been challenging to know when to stop writing. The Covid section towards the end of the book feels a bit like a bolt-on. But, an essential one, as the response to Covid-19 is the first mass practical demonstration of the tangible benefits the work of Crick, Watson, Doudna, and their swathe of global colleagues have brought to the genome party. 

The book starts literally at the beginning. Part One – Genesis; the origins of life, introducing readers to Doudna and giving a comprehensive but uncomplicated reprise of Crick and Watson’s research and generously acknowledging the contribution made by Rosalind Franklin, side-lined at the time. Franklin was who interpreted the grainy crystallographic Photograph 51, which revealed the symmetrical, twisting helix structure of DNA in atomic detail.

There follows an explanation of RNA (ribonucleic acid), DNA’s lesser-known cousin. This is important as the Covid (CoVs) viruses use RNA, not DNA, to replicate. The contribution of Professor Jack Szostak of Harvard and a 2009 Nobel laureate for his work in genetics, one of Doudna’s many mentors, is well covered. 

In Part Two – CRISPR, Jennifer Doudna moves west to Berkeley, California, to further her interest in gene editing. CRISPR is the catchy acronym for ‘clustered regularly interspaced short palindromic repeats.’ My Noddy’s Big Book of Science simplification is that it describes a pattern spotted in the double helix making understanding of function possible and opens the prospect of editing DNA to instruct different tasks. Mr Isaacson, unsurprisingly, goes into more detail. But his explanation is not condescendingly above the layman’s head, so often the case when scientists get carried away with their subject. We are always grateful that Mr Isaacson is a historian.

A great strength of the book is the slapping of colour when describing the broad scientific communities in which all these discoveries were made. The eggheads involved turn out to be mostly free spirits. At The Free Speech Movement Café – stone tables and a veggie menu – on the Berkeley campus, we find Jennifer Doudna meeting Jillian Banfield, involved in parallel work. They form an alliance, and things go on, helter-skelter, from there. 

By Chapter 13, commerce and patenting are rearing their ugly heads. Genentech was a company formed in 1972 to commercialise cutting edge discoveries, and Doudna joined up in 2008. By then, the company was worth $100bn. She couldn’t stand the culture and left after weeks. Isaacson now weaves the thread of commerce through the science tapestry, laying out the pitfalls of shielding life enhancing discoveries with patents. Scientists can be jealous. He never succumbs to the tempting error of lofty moralising. The case for balancing the profit motive with the public good is well presented.

Chapter 16 introduces a key player, Emmanuelle Charpentier, an itinerant French biologist who Doudna met at a meeting in Puerto Rico in 2011. The two decided to cooperate, drifted apart and eventually got together again. Their story was familiar amongst their peers, mutual interest initially forming a bond, competitive spirits splitting it and jealousy eventually making that split semi-permanent. Readers will at times marvel that so many cats in a global scientific sack managed to make progress in this complex field at all. 

Part Three takes us from the understanding of genetics to the development of gene editing. Taken in its simplest form, CRISPR Cas9, the gene-editing tool Doudna announced in a paper of 2012, had the potential to correct genetic defects causing hereditary disease, not only clipping out defective strands of DNA but replacing them with novel genetic material and resealing the helix. Think film editing, but with bits of genome scattered on the cutting room floor instead of 35mm celluloid.

Part Four moves on to therapy. It is 2019, and CRISPR Cas 9 has gone practical. Treatment of the sickle-cell scourge is possible. In a Nashville hospital, Dr. Fraygar Hangoul “plunged the needle of a large syringe into the arm of a thirty-four-year-old African American woman”. Isaacson does not often resort to romping-read prose, but the first-ever treatment in the USA of Victoria Gray, mother of four from Mississippi, with a CRISPR gene-editing tool, overwhelms his natural reticence. Cancer and blindness will be the next targets.

Part Five – Public Scientists take up the moral arguments neatly encapsulated in the phrase “utopians vs bioconservatives”. With a complete lack of regulatory direction, the scientific community has to make up the rules as they go along. Legislators are slow out of the blocks. 

The open road to creating designer babies looms and is fully explored in Part Six. Isaacson brings the story of global self-regulation up to date with the outcry following the birth of the first genetically modified twins in China in 2018. The Rubicon that Chinese scientist He Jiankui had crossed was to modify stem cells, making genetic changes hereditary. Part Seven starts with the famous quote of James Watson in 2000 to a House of Commons Science Select Committee, “if Scientists don’t play God, who will?” We have reached dystopian hubris land.

Isaacson plays fair in his dissection of the dilemma. He makes a case for managing the genetic genie that has escaped from the bottle to further the common good. As with all scientific discoveries, there is no prospect of backtracking, so we have to live with what we now know.

In Part Eight, there are some tableaux of the characters involved. Isaacson has taken the trouble to engage, often at length, with them all personally, so the book is grounded in first-class research. For example, James Watson became persona no grata when he said of genetic editing in 2003; “People say it would be terrible if we made all girls pretty. I think it would be great.” Modified from hero to zero at a stroke! 

Cue today’s equivalent – Boris Johnson being prepared to let Covid corpses “pile high”. Isaacson visits Watson in his Cold Harbour campus redoubt. He tries to persuade readers that Watson has not gone bonkers but without success.

Part Nine is the Coronavirus addendum. An 80-page summary of the global efforts which succeeded so brilliantly in decoding the RNA of the virus as it morphed and the forming pathway to tailored vaccines.

The Code Breaker is well written and a non-technical easy read, although style and compilation are occasionally clunky. The title reflects only half of the story. But writing technique is not the point. Walter Isaacson narrates in readable journalese the most fundamental change in our ability to control the future destiny of humanity since Mr Caveman invented fire to help Mrs Cavewoman with the cooking. 

If you are uninterested in how this came about, what your future holds, how the science needs to be regulated to mitigate risk and don’t care how future generations will handle this newfound power, do not trouble to read this book. You will have gathered by now, however, that I think you should. 

Seldom have the words “must-read” been so literally true as they are of Mr Isaacson’s latest tour de force.

The Code Breaker by Walter Isaacson (Simon & Schuster Ltd), RRP. £30, is out now.