It is often said that chemistry lacks “big questions” like physics and biology. But this is not entirely true. The origin of life is a quintessentially chemical problem, and it's as big as fundamental questions can get. More importantly, what chemistry may lack in terms of big questions it has in spades in terms of issues which directly impact the daily life of earth’s denizens. From waste disposal to food production, from new medicines to solar energy, chemistry is the driving force for scores of crucial problems that humans will face in the new millennium.

What do chemists spend their time thinking about? What questions would chemists want answered, preferably in the next few minutes? There are many, but here are a few of my favorites, starting with my top favorite.

1. Can we unravel the puzzle of life’s origins?

It’s the ultimate origins question. Darwin told us how life evolved but he did not tell us how it got started. Ever since Stanley Miller inaugurated the era of serious research in the origin of life, chemists have been at the forefront of answering the question at the crux of the matter: how did the simple, primordial molecules on an early Earth self-assemble to form self-replicating, robust chemical structures subject to Darwinian natural selection?

Forty years ago this question would have been seen as a product of the kind of lazy intellectual meandering that scientists indulge in after they have washed the last of their flasks and settled down with a beer. But in those forty years a series of remarkable discoveries have turned the origin of life into a hard scientific problem with well-defined potential answers. While Miller had already kick started the field by demonstrating how a collection of reducing gases catalyzed by lightning could form some of life’s key molecules, the discovery of deep sea black smokers has outlined an alternative pathway for life’s origins. Since the 80s a series of breakthroughs have firmed up the field’s basic hypotheses. Most notably, Thomas Cech’s groundbreaking studies on self-replicating RNA laid the foundations for an RNA world, the discipline's most widely accepted thesis.

More importantly, chemists have now found solid potential chemical pathways for the synthesis of life’s basic building blocks; nucleotides, ribose, amino acids and lipids. A few years ago John Sutherland caused a stir in the field when he discovered a potential joint synthesis of ribose bound to the bases comprising DNA and RNA. Steve Benner has recently documented how borate – a ubiquitous component of both earth and Martian rocks – can catalyze the formation of ribose using chemical reactions familiar to organic chemists. Similar synthetic routes have been discovered for lipids and amino acids.

The fact is that the molecular origin of life is no longer the realm of fanciful speculation. Reasonable pathways now exist for the formation of pretty much all of life’s building blocks. The next challenge is to find out how these building blocks comes together and form a self-contained, self-replicating system that can evolve by Darwinian natural selection and give rise to the kinds of biochemical pathways that drive the functioning of the cell. There is already some headway in this direction; for instance Jack Szostak’s group has found out that RNA can replicate inside primitive fatty acid vesicles. The fact is that even if we don’t know which single pathway operated on the early earth – and since evolution proceeds in multiple directions the question may even be pointless – we can get very close to narrowing down well-defined possibilities in the near future.

2. Can we ever beat photosynthesis?

It’s one of the holy grails of energy; coming up with a material for capturing the energy of the sun which can beat the efficiency of photosynthesis. This is an incredibly challenging problem, to say the least. And it’s one that could have an outsize impact on our very way of life, leading to energy from water splitting and biomass from energy conversion.

Evolution has had the luxury of tinkering around for billions of years before hitting on an exceptional solution that made multicellular life on earth possible. And yet this wonderful solution is still woefully inefficient; while the theoretical efficiency of photosynthesis is about 11%, in reality a variety of factors limit it to not more than 6%/. Clearly even nature has not managed to really utilize the energy of the sun, a fact that is perhaps not surprising considering the complex biochemical apparatus it has to marshal in its goal of synthesizing equally complex carbon-based organic compounds.

Humans can try to achieve the same goal as plants by doing two things; building chemical systems that mimic the photosynthetic apparatus and genetically engineering plants themselves to become better photosynthesizers. The second option, although tantalizing, faces some serious hurdles. Last year Nobel Laureate Hartmut Michel pointed out the kind of profound biological re-engineering we will have to do in order to overcome some very fundamental deficiencies in the photosynthetic machinery of plants. This is not impossible but we will be fighting 3.5 billion years of evolution in attempting it. Another fanciful option is to try to engineer silicon-containing leaves; we already know that photovoltaics can already achieve efficiencies of 45%, although they have the much simpler job of only converting solar energy to electricity. Nobody knows how a silicon-carbon hybrid plant will perform, but we have already started interfacing biology with electronics, so it’s certainly worth trying.

The other promising route is to create “artificial leaves” which are capable of achieving at least one important thing that photosynthesis does, splitting water to form hydrogen and oxygen. If realized this will be a godsend for solar energy and for the world’s energy problems in general. One of the leaders in the field is Dan Nocera, previously at MIT and now at Harvard. Nocera has created a cobalt-based catalyst which when combined with standard inexpensive silicon-based semiconductors generates hydrogen and oxygen when the assembly is placed in water at room temperature. But the efficiency of the setup is still about 5% at best, so much more work needs to be done.

Clearly there are promising efforts to mimic at least some aspects of photosynthesis and there’s no doubt that this ambitious goal should keep the midnight oil burning in chemistry labs. It is fascinating and deep pure science, with potentially revolutionary applications in energy and food production. Certainly a question that should keep chemists awake.

3. How do we make chemistry environmentally friendly?

With global warming, deforestation, fertilizer runoff and plastic waste piled up as high as skyscrapers, chemists face an unprecedented responsibility to be environmentally conscious. The chemical industry has had a mixed record of environmental stewardship. Episodes like Love Canal and Toms River have tarnished the reputation of the industry, even if the allegations are not all sensible. In 1991 Paul Anastas laid out a set of requirements for practicing what he called “green chemistry”. Since then the term has become embedded in chemists’ consciousness, but perhaps not quite enough.

Developments like the use of water and supercritical carbon dioxide to replace potentially toxic organic solvents, deployment of catalysts that function at room temperature and pressure, mindful consideration of product toxicities and amounts when performing chemical reactions and keeping track of energy requirements for chemical machinery and equipment are only some of the strategies adopted by chemists for responsible chemical analysis, synthesis and manufacturing. Yet there is a long way to go.

Chemists still have to develop perfectly biodegradable plastics – or materials which can replace plastics – to prevent the kind of plastic pileups that are destroying both land and the oceans. They have to work harder on using safe fertilizers and agricultural products that stay localized and do not persist in the environment. And they have to create even better technologies for preventing the release of harmful greenhouse gases. Responsible environmental stewardship will not only save the planet but it will go a long way in convincing the public of the value of chemistry. It should thus always be a major concern for chemists.

4. Can we design the perfect drug?

Most chemists in the field would probably say right away that the goal outlined by the question is a fool’s errand. And yet the quest for a drug that works perfectly on the disease it is supposed to treat or cure and causes zero side-effects is one that has driven drug discovery scientists in both academia and industry. One of the problems is that we still have a poor handle on the way drugs affect the entirety of a living system. We can study what happens in a limited sense in test tubes and model organisms, but put a drug in a human and we are still groping around in the dark. And yet nobody would dispute that reducing side effects is one of the most important goals in medicine, especially in areas like cancer where the side effects are often as awful as the disease.

Getting a grasp of side effects will need chemists to have a systems-level view of biology. It will require them to step out of their comfort zone and collaborate with biologists and computer scientists to understand how a particular drug affects the entire web of complex metabolic pathways on which cells depend. It will also involve being able to calculate the free energy of interaction between a drug and protein, a general goal whose solution may be decades into the future. Ultimately it may be impossible to have a drug with zero side effects, but the goal itself remains noble, part of a quest to cure suffering while causing no intentional harm. It’s a quest that chemists should cherish with doctors, and one that should certainly keep them thinking and experimenting.

5. How do we sell chemistry to the public?

Over the last two hundred years or so the chemical industry has really transformed human life. The products of chemistry –drugs, plastics, textiles, fertilizers, foods - underlie the very foundation of modern civilization. They have saved and improved billions of lives around the globe. And yet chemists are confronted with an increasingly wary public whose reactions to chemistry range from mildly skeptical to wildly hysterical.

Part of the problem is that almost any criticism of chemical or biological technology relies on emotions, and as decades of PR and propaganda have taught us, it is far easier to sell emotions than facts. Much of the effect is purely psychological; the mass media, zealous bloggers, journalists, filmmakers and some failings of the chemical industry itself have turned words like “chemicals”, “drugs” and “GMOs” into visceral triggers that elicit emotional rather than rational responses. Context and statistics are often ignored, and anecdotal evidence and generalizations often rule.

It’s not easy to counter misunderstandings about chemistry, especially when we are fighting emotions with facts. There is no simple answer to the problem, and I would point readers to a previous rumination on the topic. One potential solution is to create a non-profit, independent National Center for Chemistry Education that will instruct and educate the public and try to convey the fact that on balance, chemistry has done much more good than harm. But whatever the strategy, there is no doubt that battling chemical superstition will be an enduring concern for chemists in the future.

Note: I had forgotten about a wonderful 2011 piece by Philip Ball in the pages of this magazine which expounded on some other fundamental questions of concern to chemists. I thank SeeArrOh for the reminder.