CONTENTS: Evolvability  Richard Dawkins  Genomic Imprinting  David Haig  A Full-Force Storm with Gale Winds Blowing  Robert Trivers  What Evolution Is  Ernst Mayr  Genetics Plus Time  Steve Jones  A United Biology  E. O. Wilson  Is Life Analog or Digital?  Freeman Dyson  Life: What a Concept!  Freeman Dyson, J. Craig Venter, George Church, Dimitar Sasselov, Seth Lloyd, Robert Shapiro  The Gene-Centric View: A Conversation  Richard Dawkins, J. Craig Venter  The Nature of Normal Human Variety Armand Marie Leroi  Brains Plus Brawn  Daniel Lieberman  Mapping the Neanderthal Genome  Svante Pääbo  On Biocomputation  J. Craig Venter, Ray Kurzweil, Rodney Brooks  Engineering Biology  Drew Endy  Eat Me Before I Eat You: A New Foe for Bad Bugs  Kary Mullis  Duck Sex and Aesthetic Evolution  Richard Prum  Toxo Robert Sapolsky  The Adjacent Possible Stuart Kauffman (with an introduction by John Brockman)   

The big story of the 20th and the 21st century is that we’re learning to control the world better. With the development of quantum mechanics, we understand the fundamental principles of what matter is and how it behaves that’s adequate for all engineering purposes.                                 

The limitation is just our imagination and our ability to calculate the consequences of the laws. We’re getting better at both of those as we gain experience. We have more imagination. As computing develops, we learn how to calculate the consequences of the laws better and better. There’s also a feedback cycle: when you understand matter better, you can design better computers, which will enable you to calculate better. It's kind of an ascending helix.

FRANK WILCZEK, currently the Herman Feshbach Professor of Physics at MIT, has received many prizes for his work in physics, including the Nobel Prize (2004) for work he did as a graduate student at Princeton University. Frank Wilczek's Edge Bio Page

My experience collaborating with Svante since 2007, has been that the data we’ve looked at from the incredible samples they have has yielded surprise after surprise. Nobody had ever gotten to look at data like this before. First, there were the Neanderthals, and then there was this pinky bone from Southern Siberia. At the end of the Neanderthal project, Svante told me we have this amazing genome-wide data from another archaic human, from a little pinky bone of a little girl from a Southern Siberian cave, and asked if I'd like to get involved in analyzing it.

When we analyzed it, it was an incredible surprise: This individual was not a Neanderthal. They were in fact much more distantly related to a Neanderthal than any two humans are today from each other, and it was not a modern human. It was some very distant cousin of a Neanderthal that was living in Siberia in Central Asia at the time that this girl lived.

When we analyzed the genome of this little girl, we saw that she was related to people in New Guinea and Australia. A person related to her had contributed about 5 percent of the genomes to people in New Guinea and Australia and related people—an interbreeding event nobody had known about before. It was completely unexpected. It wasn’t in anybody’s philosophy or anybody’s prediction. It was a new event that was driven by the data and not by people’s presuppositions or previous ideas.

This is what ancient DNA does for us. When you look at the data, it doesn’t always just play into one person’s theory or the other; it doesn’t just play into the Indo-European steppe hypothesis or the Anatolian hypothesis. Sometimes it raises something completely new, like the Denisovan finger bone and the interbreeding of a gene flow from Denisovans into Australians and New Guineans. 

DAVID REICH is a geneticist and professor in the Department of Genetics at the Harvard Medical School. David Reich's Edge Bio Page

THE REALITY CLUB: Robert Trivers

There are now 2000 gene therapies where you’ll take a little piece of engineered DNA, put it inside of a viral coat so all the viral genes are gone, and you can put in, say, a human gene or you can have nonviral delivery, but the important thing is that you’re delivering it either inside of the human or you’re taking cells out of the human and putting the DNA in and then putting them back in. But you can do very powerful things like curing inherited diseases, curing infectious diseases.                                 

For example, you can edit out the receptor for the HIV virus and cure AIDS patients in a way that's not dependent upon vaccines and multidrug resistance, which has plagued the HIV AIDS story from the very beginning. You’re basically making a human being which is now augmented in a certain sense so that, unlike most humans, they are resistant to this major plague of mankind—HIV AIDS.              

There are now people walking around who are genetically modified: There are some that are resistant to AIDS because they have had their T cells, or more generally, their blood cells modified. There are children that have been cured of blindness by gene therapy. None of this is CRISPR, but it’s in the same vein. CRISPR is overtaking it very quickly and it’s drafting behind all the beautiful work that’s been done with delivery of DNA, delivery of genetic components to patients.

GEORGE CHURCH is a professor of genetics at Harvard Medical School and director of the Personal Genome Project. George Church's Edge Bio Page

My vision of life is that everything extends from replicators, which are in practice DNA molecules on this planet. The replicators reach out into the world to influence their own probability of being passed on. Mostly they don't reach further than the individual body in which they sit, but that's a matter of practice, not a matter of principle. The individual organism can be defined as that set of phenotypic products which have a single route of exit of the genes into the future. That's not true of the cuckoo/reed warbler case, but it is true of ordinary animal bodies. So the organism, the individual organism, is a deeply salient unit. It's a unit of selection in the sense that I call a "vehicle".  

There are two kinds of unit of selection. The difference is a semantic one. They're both units of selection, but one is the replicator, and what it does is get itself copied. So more and more copies of itself go into the world. The other kind of unit is the vehicle. It doesn't get itself copied. What it does is work to copy the replicators which have come down to it through the generations, and which it's going to pass on to future generations. So we have this individual replicator dichotomy. They're both units of selection, but in different senses. It's important to understand that they are different senses.   

RICHARD DAWKINS is an evolutionary biologist; Emeritus Charles Simonyi Professor of the Public Understanding of Science, Oxford; Author, The Selfish Gene; The Extended Phenotype; Climbing Mount Improbable; The God Delusion; An Appetite For Wonder; and (forthcoming) A Brief Candle In The Dark. Richard Dawkins's Edge Bio Page

People have to go around measuring things. There's no escape from that for most of that type of work. There's a deep relationship between the two. No one's going to come up with a model that works without going and comparing with experiment. But it is the intelligent use of experimental measurements that we're after there because that goes to this concept of Bayesian methods. I will perform the right number of experiments to make measurements of, say, the time series evolution of a given set of proteins. From those data, when things are varying in time, I can map that on to my deterministic Popperian model and infer what's the most likely value of all the parameters that would be Popperian ones that would fit into the model. It's an intelligent interaction between them that's necessary in many complicated situations.

INTRODUCTION
by John Brockman

There’s a massive clash of philosophies at the heart of modern science.  One philosophy, called  Baconianism after Sir Francis Bacon, neglects theoretical underpinning and says just make observations, collect data, and interrogate them. This approach is widespread in modern biology and medicine, where it’s often called informatics.  But there’s a quite different philosophy, traditionally used in physics, formulated by another British Knight, Sir Karl Popper. In this approach, we make predictions from models and we test them, then iterate our theories.

 In modern medicine you might find it strange that many people don’t think in theoretical terms. It's a shock to many physical scientists when they encounter this attitude, particularly when it is accompanied by a conflation of correlation with causation. Meanwhile, in physics, it is extremely hard to go from modeling simple situations consisting of a handful of particles to the complexity of the real world, and to combine theories that work at different levels, such as macroscopic theories (where there is an arrow of time) and microscopic ones (where theories are indifferent to the direction of time).

At University College London, physical chemist Peter Coveney, is using theory, modeling and supercomputing to predict material properties from basic chemical information, and to mash up biological knowledge at a range of levels, from biomolecules to organs, into timely and predictive clinical information to help doctors. In doing this, he is testing a novel way to blend the Baconian and Popperian approaches and have already had some success when it comes to personalized medicine and predicting the properties of next generation composites.

—JB

PETER COVENEY holds a chair in Physical Chemistry, and is director of the Centre for Computational Science at University College London and co-author, with Roger Highfield, of The Arrow of Time and Frontiers of Complexity. Peter Coveney's Edge Bio Page.