Thursday, September 25, 2008

In the Words of Sydney Brenner

Sydney Brenner says,

Actually, the orgy of fact extraction in which everybody is currently engaged has, like most consumer economies, accumulated a vast debt. This is a debt of theory, and some of us are soon going to have an exciting time paying it back - with interest, I hope.

I spent 20 years sharing an office with Francis Crick and many new and exciting ideas (both right and wrong) were generated from our conversations.

I was asked by a student what ethical standards should be adopted by life scientists. I could immediately think of two prescriptions. The first, common to all scientists, is to tell the truth. The second is to stand up for all humanity.

The attitude of my generation that all problems can be solved in the next decade, and should be solved in the next decade—these expectations are changed. Maybe science should be done better, but more slowly. I think a large number of mediocre people are in science today, and carried along by the system. General concepts are rare. Nobody publishes theory in biology—with few exceptions. Instead they get out the structure of still another protein. I'm not saying it's mindless. But the mind only acts on the day-to-day.

There will be no difficulty in computer's being adapted to biology. There will be Luddites. But they will be buried.

There is a strong and widely held belief that all organisms are perfect and that everything within them is there for a function. Believers ascribe to the Darwinian natural selection process a fastidious prescience that it cannot possible have and some go so far as to think that patently useless features of existing organisms are there as an investment for the future ...

Even today, long after the discovery of repetitive sequences and introns, pointing out that 25% of our genome consists of millions of copies of one boring sequence, fails to move audiences. They are all convinced by the argument that if this DNA were totally useless, natural selection would already have removed it. Consequently, it must have a function that still remains to be discovered. Some think that it could even be there for evolution of the future—that is, to allow the creation of new genes. As this was done in the past, they argue, why not in the future? ...

Some years ago I noticed that there are two kinds of rubbish in the world and that most languages have different words to distinguish them. There is the rubbish we keep, which is junk, and the rubbish we throw away, which is garbage. The excess DNA in our genomes is junk, and it is there because it is harmless, as well as being useless, and because the molecular processes generating extra DNA outpace those getting rid of it. Were the extra DNA to become disadvantageous, it would become subject to selection, just as junk that takes up too much space, or is beginning to smell, is instantly converted to garbage.

The Sydney Brenner quotations above are from Stephen Jay Gould's book The Structure of Evolutionary Theory

Most of what I have said over the years has probably been wrong or uninteresting and deserves to be ignored and forgotten. Consequently I was pleasantly surprised when I recently received a request for a reprint of one of my old columns, published elsewhere, with the exciting news - to me - that it had been quoted by the late Stephen J Gould in his massive book The Structure of Evolutionary Theory and that it had caused him to change his mind on one important issue. I had acquired the book on publication with the intention that as soon as I could find the time I would get down to read all 1,464 pages. Needless to say, all I have now read are the pages that refer to my column.

I learnt very quickly that the only reason that would be accepted for not attending a committee meeting was that one already had a previous commitment to attend a meeting of another organization on the same day. I therefore invented a society, the Orion Society, a highly secret and very exclusive society that spawned a multitude of committees, sub-committees, working parties, evaluation groups and so on that, regrettably, had a prior claim on my attention. Soon people wanted to know more about this club and some even decided that they would like to join it. However, it was always made clear to them that applications were never entertained and that if they were deemed to qualify for membership they would be discreetly approached at the appropriate time.

...we need to put everything into an evolutionary framework, simply because complexity arises in biological systems by accretion and modification and not by reinvention. Thus, the properties of many of the components in our cells, whether these are mRNAs or proteins, will be conditioned not only by processes of selection for specified activities and levels because these are positively required but may also take up any value because there are no negative consequences for the organism. This ‘don't care’ condition will almost certainly be present because it is a cheap solution to the regulation problem of complex systems. Thus a 20% or a twofold increase, or indeed the very presence, of a protein may be very significant or totally irrelevant depending on whether it is following a ‘don't care’ condition. Only experiment can decide that.

I once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of these should be allowed to come back. Of course, biochemistry never really went away but continued to flourish in the thousands of unread pages of biochemical journals. Protein interactions will not be solved by proteomics or protein chips but by protein biochemistry. The genome sequences tell us about the proteins we can expect to find in cells and give us the tools to make large amounts of the proteins for reconstitution studies and for detailed structural analysis. We do not have to resurrect biochemistry, and it will flourish because it provides the only experimental basis for causal understanding of biological mechanisms. That is why this article is not called ‘The return of biochemistry.’ [from "Biochemistry Strikes Back"]


  1. I've had the opportunity to attend two of Brenner's talks, both of which were scathingly frank and thought provoking (for example, in Vancouver he declared that Biology has no need for 'biologically interested computer scientists', but rather we need 'computationally savvy biologists', which miffed quite a few attendees). I got to speak with him personally when he last came to McMaster, and I can only hope that I'm as keen-of-mind when I'm in my 80s.

  2. It's a pleasure to read and listen to Brenner.
    Still, the old hard core biochemistry *is* dying, being replaced (outcompeted in funding) by people with kits and chips. More and more people grow up thinking protein purification is following Qiagen's one-size-fits-it-all protocol, solid phase assays can magically measure true solution Kd and using IP to fish out something that can barely be detected on Western actually means something.

    Hopefully all that will pass like a bad fad.

    And yes, Brenner is absolutely right that today "biologically interested computer scientists" are not a good substitute for "computationally savvy biologists". The latter, in general, somehow fail to learn and/or understand just how complex biological organization is.

  3. Worth adding to your list:

    The Human Genome Project, which Jim [Watson] led in its early years, has had one bad--one might say, boring--consequence in generating factory science that I have called "low input, high throughput, no output" biology.

    Science, Nov. 2007

  4. factory science that I have called "low input, high throughput, no output" biology

    Right on target! Witness numerous "omics". E.g., the incredible amount of money poured into "structural genomics" programs all over the world returned basically nothing (boring TIM barrels and random small proteins).

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  6. I absolutely agree with everything he says.

    Unfortunately few people whose name is not Sydney Brenner could ever dare to say these things in public.

    I am very curios how many people in biology actually have thought about these problems. Because my guess is that most are so heavily trapped in the factory approach to doing science that very few think about anything bigger than the small problem they work on and their immediate career goals.

    Also, I think that the problem with biologically interested computer scientists is actually much deeper than computer scientists not understanding the complexity of biology. Most people in computational biology come from an engineering or math background and as a rule they are not trained to think as a scientists (no offense to anybody, but these are my observations, there are many exceptions, but in general the rule holds). Which has very profound negative consequences for the way biology is done.

  7. Sydney Brenner is coming to the University of Waterloo on Wednesday October 22nd. Unfortunately for those from out of town, it's a day time lecture from 1:30 - 2:30 pm.