Most of the scientists described here were from the US, the UK and France. Science is now a truly international activity; even if the main contributors to the pages of the leading journals are still based in the richest and most developed countries, those researchers are often from all around the planet, with an increasing number coming from China. The current route for training a scientist involves not only a PhD but also a period of several years working in different laboratories, preferably in other countries, gaining experience and techniques. Most leading laboratories are now mini-United Nations. However, it is a striking fact that, even in the US, men and women of Afro-Caribbean origin are still substantially under-represented. In each country, the recruitment into science is biased by the multiple effects of race and class on educational attainment and on what is seen as being possible. Increasing the number of scientists from ethnic minorities and from the working class is a complex issue that science cannot solve on its own, but it needs to be addressed – at the moment there is a substantial pool of talent that we are not accessing because of inherent inequalities in our education system.
The way in which these multinational teams work has also altered in comparison with the 1950s and 1960s. Although papers in genetics are still published by small groups and, very occasionally, by single individuals, there is a clear tendency for research to be produced by large multidisciplinary teams. This is especially the case in genomics, in which many groups from around the world may be involved in obtaining and analysing the data. In 2014, a paper appeared in
Nature Genetics
describing how hundreds of variants in the human genome contribute to differences in height between individuals; the article was signed by more than 440 authors.
3
Big Science, typical of particle physics and astronomy, had not been seen in biology until the major genome sequencing projects. It is now becoming commonplace, changing the relationship of individual scientists to the work they produce, rendering each person’s contribution relatively minor and highly specific. The increasingly tight budgets of funding organisations encourage large teams by promoting multidisciplinarity and often require the probable outcomes to be clear before the experiments have begun. It seems unlikely that the small, curiosity-driven teams that led to the cracking of the genetic code would survive in today’s climate.
How we think about genes and what they do has also been transformed. In the 1830s, when the word heredity was first applied to biological characteristics, they were said to be ‘passed down’, just like more worldly inheritances such as money, land or furniture. Once the electronic age began, characteristics were said to be transmitted; after the growth in interest in codes and computing during and following the Second World War, it seemed obvious to suggest that genes contain a code and transmit information. The most powerful metaphors in science are often those that flow from new technological developments. The summit of the current phase of technology is the computer – this is also the richest metaphor that science currently employs. Not all the metaphors we use to describe the genetic code and the way it functions are so complex – ‘transcription’ and ‘translation’ suggest that the code is a language that is written down, and is either copied from DNA into RNA (‘transcription’), or is turned into another language completely, that of proteins (‘translation’). These metaphors weigh heavily on how we think about the nature of the genetic code and what it does. The complex linguistic and computational metaphors wrapped up in the seemingly simple idea of a genetic code frame our ideas about heredity.
But a ‘frame’ means two things – it both enables and limits how we think. We understand the nature of heredity with a far greater richness than people a century ago because of the wealth of research that has been done and also, because of the way in which we think about this research, the context in which we interpret it. But we are unable to conceive of other ways of viewing these phenomena because we do not yet have the appropriate metaphors. The frame is also a cage.
Nirenberg and Matthaei, the first to crack the code, were outsiders, unaware of the debates of the previous decade that had led theoreticians to think that a repetitive sequence of bases would be meaningless. Their imaginations were free of the shutters that seem to have operated in thinking at other laboratories around the world. Ideas can help scientists understand data and can also prevent them from seeing what is under their nose: either way, they are essential to how science works.
Metaphors and analogies carry a risk. It is easy to forget that a particular term is a figure of speech, a way of viewing a given phenomenon, rather than being literally true. A gene is like a computer program, but it is not a program and does not function according to the same rules, even though it may be usefully understood in this way. Organisms are not machines, even if they work on physical principles and share some features with devices we have invented. The genetic code is not literally a code and it is not a language. It is a process that enables organisms to carry out particular functions by turning stored information into structures or actions, using evolved systems of control.
As became clear after the failed attempts to apply the strict mathematical view of information to genetic data, our way of describing information in genetics is primarily metaphorical. Although experimentation is generally the most powerful way of obtaining evidence that can test a hypothesis, to interpret this evidence we need theories and conceptual frameworks, which in turn are made up of words, metaphors and analogies. Understanding the power and limits of such metaphors will help us prepare for the breakthroughs of tomorrow, when we will reinterpret what we know and discover what we have yet to imagine.
New technological and scientific developments will provide us with new metaphors, new ways of understanding how life works, and new approaches to manipulating molecules. That future will inevitably contain opportunities and challenges. Synthetic life may enable us to resolve major economic and ecological problems, or it may inadvertently threaten the human race and the ecosystem. We may find ourselves able to manipulate aspects of our behaviour or anatomy by deliberately and precisely changing our genes and those of our offspring. This might open the road to health, fulfilment and pleasure, but it will also pose major ethical dilemmas. By revealing and cracking the genetic code, science has shown itself capable of revealing life’s greatest secret. But science cannot tell us what to do with that secret, nor ensure that the knowledge and technology that flow from it are used for the greatest good of the many and with the least damage to the planet. Such a positive outcome will require the active involvement of the populations of all countries, as well as a clear understanding of the scientific and political issues raised by the amazing discoveries we have made and by the yet more amazing discoveries that are to come.
UGA
GLOSSARY AND ACRONYMS
Amino acid.
A small molecule containing amine (-NH
2
) and carboxylic acid (-COOH) groups. There are hundreds of different amino acids, but only twenty of them generally occur in organisms. They are strung together to make proteins.
Anticodon.
A sequence of three bases of RNA found on the small tRNA molecule, which bind with a codon on the mRNA molecule.
AUG.
The opening ‘word’ of a gene, this mRNA codon instructs the cell’s protein synthesis machinery to ‘start here’, thereby also setting the reading frame for the gene. When AUG occurs in the middle of a gene, it codes for methionine.
Base.
A molecule – adensoine, cytosine, guanine, thymine or uracil – that forms part of a nucleotide in DNA or RNA.
Chromosome.
Cellular structures composed of DNA and proteins that contain genes.
Codon.
A sequence of three bases in a DNA or RNA molecule that codes for an amino acid.
CRISPR.
A new technique for editing genes in organisms, using a method derived from bacteria. The name comes from the kind of sequences where the phenomenon was first observed: Clustered Regularly Interspaced Short Palindromic Repeats. The technique has enormous scientific and medical potential.
Crystallography.
The study of the molecular structure of crystals.
Cybernetics.
The study of control and information flow in organic, mechanical or electronic systems, with an emphasis on the ability of negative feedback to produce apparently purposeful behaviour.
DNA.
Deoxyribonucleic acid, a double helical molecule composed of a sugar/phosphate backbone and four bases: adenine, cytosine, guanine and thymine (A, C, G and T). The genetic material in all organisms and some viruses.
Enzyme.
A large biological molecule – made of either protein or RNA – that catalyses (speeds up) a particular chemical reaction. Essential for life to exist.
mRNA.
Messenger RNA. These molecules are copied from the gene and move from the chromosome to the ribosome, where they bind with a series of transfer RNA molecules, each of which is attached to an amino acid.
Nucleic acid.
RNA or DNA.
Nucleoproteins.
The mixture of proteins and nucleic acids that make up chromosomes.
Nucleotide.
A molecule that combines a base with a five-carbon sugar (ribose or deoxyribose) plus phosphate; forms the basis of the nucleic acid sequence.
Operon.
A group of genes that act under the concerted control of a single genetic element.
PCR.
Polymerase chain reaction. Technique developed in the 1980s for amplifying small sequences of identified DNA. Now routinely used in science, in medicine and in the legal system.
Phage.
Short for bacteriophage. These are viruses that attack bacteria.
Protein.
A large molecule consisting of chains of amino acids. Proteins come in a vast variety of forms and carry out many biological functions.
Purines.
Ring-shaped molecules, rich in nitrogen, larger than pyrimidines. In DNA and RNA, adenine and guanine are purine bases; each pairs with a particular pyrimidine (A with C, G with T or U).
Pyrimidines.
Ring-shaped molecules, rich in nitrogen, smaller than purines. In DNA, cytosine and thymine are pyrimidine bases; in RNA, thymine is replaced by uracil. Each pairs with a particular purine (C with A, T or U with G).
Reading frame.
In a DNA or RNA sequence, the correct order in which the bases should be read.
Repression.
Inhibition of gene function.
Ribosome.
Complex RNA structure found in all cells that is the primary site of protein synthesis.
RNA.
Ribonucleic acid. A helical molecule composed of a sugar/phosphate backbone and four bases: adenine, cytosine, guanine and uracil (A, C, G and U). The genetic material in some viruses; carries out a wide range of regulatory functions in all cells.
Specificity.
A term widely used until the 1960s to describe the various qualities of molecules and in particular the ability of proteins to carry out many functions.
Transcription.
Copying of the genetic message from DNA to RNA.
Transcription factor.
RNA or protein molecule that binds to a particular DNA sequence and regulates the activity of a gene.
Translation.
The process whereby the genetic message in RNA is turned into an amino acid sequence; part of the protein synthesis process.
tRNA.
Transfer RNA. Small cloverleaf-shaped piece of RNA, predicted to exist by Crick and Brenner. Each tRNA attaches to a particular amino acid and also carries an anticodon that enables it to bind with the relevant codon on the mRNA molecule.
UGA.
The final word (or codon) in the genetic code to be deciphered, in 1967. Known as the opal codon, this mRNA sequence instructs the cell’s protein synthesis machinery to ‘stop here’.
FURTHER READING
Some of the research articles cited here are available as open access articles on the Internet; sadly, that is not true of all of them. You can generally find at least the abstract or summary of the article on line by putting its title into a search engine. Archival material covering the life and work of Avery, Crick, Nirenberg and others is available at http://profiles.nlm.nih.gov. The Wellcome Trust Codebreakers web site also holds many original documents: http://wellcomelibrary.org/using-the-library/subject-guides/genetics/makers-of-modern-genetics. Many informal photos of the key figures in this story can be found at http://www.estherlederberg.com.
Several academic works cover the material presented here and provide excellent additional sources: Lily E. Kay’s
Who Wrote the Book of Life?
, Evelyn Fox Keller’s
Refiguring Life: Metaphors of Twentieth-Century Biology, The Century of the Gene
and
Making Sense of Life,
and the articles and chapters by Sahotra Sarkar (see the reference list). Michel Morange’s
A History of Molecular Biology
provides the scientific context (declaration: I translated it; a second edition is apparently in the works), while H. Freeman Judson has written a huge and fascinating oral history of the subject
The Eighth Day of Creation: Makers of the Revolution in Biology.
If you want to explore the history of information without much mathematics, James Gleick’s
The Information
is for you, while for those interested in the scientific importance of metaphors, Theodore Brown’s readable
Making Truth: Metaphor in Science
is a great place to start. Above all, I recommend reading the memoirs of four of the central people involved in this work: the inevitable
The Double Helix
by James Watson, Francis Crick’s
What Mad Pursuit,
Maclyn McCarty’s account of work in the Avery lab,
The Transforming Principle,
and François Jacob’s marvellous but little-known
The Statue Within.