What is Life?:How chemistry becomes biology (15 page)

A number of distinctly different mechanistic scenarios for the origin of life can be categorized as ‘metabolism first’ and we will
not go into their details. The key point is that despite major differences in the essence of their chemistry, all contend that holistic autocatalysis (a catalytic cycle that achieves closure)—in what might be thought of as a primitive metabolism—preceded the subsequent incorporation of a genetic capability. Second, all presume that the organization required to generate metabolic function came about spontaneously, or through random drift. In other words the ‘metabolism first’ scenarios presume that the functional coherence inherent in metabolic processes can come about of its own accord, that
disorganized
systems underwent spontaneous
organization
. But, as has been pointed out by several leading origin of life researchers, in particular Shneior Lifson
⁴⁶
and Leslie Orgel,
⁴⁷
that idea is highly problematic. It’s the Second Law problem again. How would metabolic cycles form spontaneously from simple molecular entities, and, more importantly, how would they maintain themselves over time? We run yet again into that thermodynamic brick wall. The same problem that puzzled physicists with respect to the emergence of
cellular
complexity is applicable to the emergence of
metabolic
complexity. Highly organized far-from-equilibrium chemical systems are not expected to be generated by spontaneous ‘downhill’ processes. And for those who say such transformations can take place, despite the Second Law, some experimental demonstration of such an occurrence is necessary. Harry Truman famously said: ‘I’m from Missouri—show me.’ So far no one has.

So both the ‘metabolism first’ and ‘replication first’ scenarios for the origin of life are problematic, not due to some minor issue, but because both have fundamental difficulties with the Second Law. We need to come up with a mechanism for the process
of complexification toward a far-from-equilibrium system that does not contravene the Second Law. If, and when, that issue is resolved, the question of ‘metabolism first’ or ‘replication first’ may actually take on a different perspective. The answer to the question as to which came first may then become apparent, or, at the very least, may become less relevant. We will consider a possible resolution of this sticky problem in
chapter 7
.

The prevailing view that life emerged from non-life leads to an immediate and highly problematic dilemma: was life’s emergence on earth deterministic or was it contingent? In other words, was it a fantastically improbable accident—a freak occurrence that would almost certainly never be repeated—or was life’s emergence inevitable given the existing laws of physics and chemistry. Two Nobel prize-winning biologists have famously faced off on this question. Jacques Monod viewed it as a bizarre accident unlikely to be repeated.
¹⁰
In his words: ‘That would mean that its
a priori
probability was virtually zero… The universe was not pregnant with life nor the biosphere with man.’ Christian de Duve, however, takes the opposite view and considers the emergence of life on earth-like planets a ‘cosmic imperative’ governed by the laws of chemistry and physics.
⁴⁸
De Duve goes as far as to contradict Monod with the statement: ‘It is self-evident that the universe was pregnant with life and the biosphere with man. Otherwise, we would not be here.’ So who is right? Did life on earth emerge by chance or necessity (to paraphrase the title of Jacques Monod’s classic text)?

The first point to note is that the Monod and de Duve positions are actually extreme ends of a continuous spectrum of possibilities. To illustrate this point consider the probability of snowfall during winter. Is snowfall in winter deterministic or contingent? In the Swiss Alps snowfall during winter would be considered deterministic. Due to the low temperatures that prevail in the Alps in winter the probability of snowfall is extremely high. Pretty well guaranteed. But on a Queensland beach the probability of snow falling, even in winter, is very close to zero. Queensland temperatures don’t get low enough. What about snowfall in Rome? Here the probability is intermediate—it does snow in Rome on occasion. In the last thirty years it snowed in 2012, 2005, and in 1986. Snowfall in Rome is a contingent event. The conclusion? A particular event could in principle be highly contingent or effectively deterministic or anywhere in between.

Of course one doesn’t have to understand the physics of snowing to be able to state whether snowfall at a particular location is deterministic or contingent. Simply by checking the historical record regarding snowfall at that location, you will have the answer. That’s why we can be supremely confident it will snow in the Alps this winter and that it won’t snow on the beach in Queensland. Regarding Rome, we must remain uncertain. All one can say definitively is that it
may
snow next winter in Rome, the probability being something like 10 per cent.

So, what can we conclude regarding the emergence of life on our planet? The short answer: almost nothing, and there are several reasons for that frustrating state of ignorance. In contrast to the meteorological phenomenon of snowfall which is well understood, we don’t understand the process by which life emerged, and we are
relatively ignorant regarding the prevailing conditions at the time. How can one expect to be able to judge the likelihood of a process we don’t understand and which took place under unknown conditions? Alternatively, as in the case of snowfall, one might be able to make a prediction without understanding the process, simply by carrying out a historical survey of the phenomenon in question. But here we run into a different problem. Our survey is restricted to a sample of one. Even though we are aware that the number of earth-like planets in the universe is likely to be spectacularly large, we only know the life situation on one of these—our own. With a sample of just one to guide us, our ability to reach a reasoned assessment of its likelihood elsewhere in the universe is obviously limited.

The difficulties in relating living and non-living entities, first with respect to the very strange characteristics of living things (
chapter 1
) and then with regard to the seemingly intractable origin of life problem (
chapter 5
) have exposed the scientific quandary that modern biology has been contending with in recent years. In fact three core questions at the heart of the subject—what is life, how did it emerge, and how would one make it—remain troublingly unresolved. And though these questions may initially seem independent and quite unrelated, they are in fact intimately interconnected, as schematically illustrated in Fig. 5. If you think about it, being able to answer any one of the questions depends on knowing the answers to the other two. We don’t know how to go about making life because we don’t really know what life is, and we don’t know what life is, because we don’t understand the principles that led to its emergence. So, despite those spectacular advances in molecular biology over the past sixty years, the very essence of what biology claims to study remains troublingly obscure. That
gloomy view is not just the frivolous opinion of an over-zealous chemist on a subject that is not his own, but one that is beginning to be expressed more generally. Carl Woese, in an almost messianic article that we have already referred to, recently wrote:
¹

Fig. 5.
Three key questions governing holistic understanding in biology

Biology today is no more fully understood in principle than physics was a century or so ago. In both cases the guiding vision has (or had) reached its end, and in both, a new, deeper, more invigorating representation of reality is (or was) called for… Look back a hundred years. Didn’t a similar sense of a science coming to completion pervade physics at the 19th century’s end—the big problems were all solved; from here on out it was just a matter of working out the details? Déjà vu!

Woese, a leading contributor to the molecular approach to biology whose fruits have been so rewarding, seems to have lost all faith in the methodology that served him and molecular biology so well. Paradoxically it is the dramatic increase in knowledge brought about by molecular biology that has actually revealed how ignorant we are. So what went wrong?

The road from Darwin to modern biology was a convoluted one. Darwin’s monumental achievement was, of course, in providing
biology with a physical foundation, thereby successfully transplanting biology from the supernatural world into the natural world. In doing so, Darwin irrevocably changed our perception of ourselves and the world in which we live. But it was far from smooth sailing. First, natural selection, the very heart of Darwinism, was not fully accepted by biologists till well into the twentieth century. It was almost eighty years after the publication of
Origin of Species,
in the 1930s, that Darwinian theory was finally embraced, as part of what is termed the modern evolutionary synthesis. It was the winning integration of Darwinian evolutionary theory with Mendelian and population genetics that finally eliminated academic doubts as to the significance of the Darwinian legacy. That integration provided the mechanism by which natural selection could perform its magic, thereby eliminating the main sources of prevailing criticism.

But another revolution was beginning to build up momentum—the revolution in molecular biology. Indeed as already noted, a half-century of dramatic discoveries beginning with the structural elucidation of DNA in 1953 were revealed in quick succession—DNA replication, RNA transcription, protein translation, the ribosomal machine, with a long string of Nobel prizes illuminating the path to what Walter Gilbert termed the Holy Grail—elucidating the entire base sequence of the 3 billion bases in human DNA, the human genome project in which the entire human genome was sequenced. The reductionist dream appeared to have been realized, the essence of humankind had been reduced to a string of 3 billion letters. On its completion in 2000, Bill Clinton in a White House ceremony dramatically claimed ‘today we are learning the language in which God created life’ and added that the achievement would ‘revolutionize the diagnosis,
prevention and treatment of most, if not all human diseases’. Personalized medicine was promised by 2010. Abravenew world was with us, the mysteries of biology were finally solved. Any lingering details still to be resolved were just that—details, hardly worth mentioning in the big scheme of things. Just the way physics felt at the end of the nineteenth century…

Well, at the time of writing, the so-called Holy Grail and the language of life that it was supposed to have taught us have not delivered the promised rewards. Not only hasn’t early twenty-first-century biology reached its goal of solving the major biological problems, but there is a growing awareness that there is a largish elephant in the room. Life is more complicated than a representation provided by a string of 3 billion letters. The gap between the elucidation of the human genome sequence and understanding the significance of that sequence is cavernous. The uncovering of more and more structural and mechanistic information within the living cell hasn’t clarified what life actually is. Stuart Kauffman
⁴²
put it in succinctly in his thought-provoking text
Investigations:

despite the fine work… in the past three decades of molecular biology, the core of life itself remains shrouded from view. We know chunks of molecular machinery, metabolic pathways, means of membrane biosynthesis—we know many of the parts and many of the processes. But what makes a cell alive is still not clear to us. The center is still mysterious.

What both Kauffman and Woese were effectively saying, each in their own words, was: we see so many trees, yet we have no real view of the forest.

So where’s the problem? The answer in a nutshell is complexity, the organizational complexity that is life. The reductionist strategy
for dealing with complexity seems to have floundered. It works great for clocks, it has been a boon for our understanding of the natural world, but its performance in the life arena has been mixed. The spectacular advances in molecular biology, reductionist in its approach, have not opened the gates to the Promised Land. Our attempts to view biological systems as mechanical-materialistic machines have failed dismally. The reductionist methodology has not as yet brought us any closer to answering the basic life questions depicted in Fig. 5, nor the global ones that we discussed in detail in
chapter 1
. Tibor Ganti, a Hungarian chemical engineer, recognized the problem over thirty-five years ago when he stated that ‘living systems have special properties which arise primarily not from the substances of the system, but from their special organizational manner.’
⁴⁹
It is the
organization
of life rather than the
stuff
of life that makes life the unique phenomenon that it is.