Nobel Physicists Are Impacting Drug Discovery Too

How the exploration of quantum entanglement—spooky action at a distance—could change drug development

Earlier this month, the Royal Swedish Academy of Sciences awarded the Nobel Prize in Physics to three scientists for their experiments with entangled photons, establishing the violation of Bell inequalities and pioneering quantum information science. The work of Alain Aspect (Université Paris-Saclay and École Polytechnique, Palaiseau, France), John F. Clauser (J.F. Clauser & Assoc., Walnut Creek, CA, USA) and Anton Zeilinger (University of Vienna, Austria) corroborates the development of new technological applications based on quantum physics that we have been witnessing in recent years.

So why are three CADD scientists and a chemist, who all specialize in small molecule drug discovery, writing about a Physics Prize?

At first sight, this Nobel might appear to have nothing to do with drug discovery. However, quantum entanglement is necessary for the exponential speed-up that quantum computing could offer over classical computation, [i] and quantum computers have the potential to have a game-changing impact on the development of new drugs.

Quantum Entanglement

In a few words, the work of the 2022 Nobel laureates in Physics is based upon fundamental concepts at the basis of the theory of quantum mechanics (QM). Specifically, it relies on the way quantum systems interact with each other. At the beginning of the 20th century, a vibrant scientific debate was going on between two different interpretations of QM. On one side, the Copenhagen interpretation, based on the Born rule, proposed QM as intrinsically indeterministic. On the other side, physicists led by Albert Einstein, Boris Podolsky, and Nathan Rosen (referred to together as “EPR”), insisted on proposing an interpretation able to preserve two fundamental principles, locality and realism, which would be shattered by the principles espoused by the Copenhagen school.

However, even at that time, the EPR school had to acknowledge that the theoretical predictions based on the Copenhagen interpretation agreed with several experimental results. EPR then started questioning whether QM, in its original formulation, was somehow incomplete. In 1935, [ii] the trio published a famous paper detailing a thought experiment based on a pair of particles prepared in an “entangled state” so that the measurement of a property on one particle (such as position, momentum or the spin, as in the Bohm’s variant of the EPR experiment) would reveal the property of the other one, regardless of the distance between them. Einstein described entanglement as “spooky action at a distance” to signify the paradoxical nature of this result. The non-locality revealed by the EPR thought experiment, according to the authors, should have revealed that QM was an incomplete theory and postulated the existence of local hidden variables which could preserve locality and realism.

In 1964 [iii] Bell published a paper that described what has become known as Bell’s theorem. In this work an upper bound to the average of the results of an EPR-like experiment was derived under the assumption of realism and locality. However, it is possible to show mathematically that a quantum system (built according to the traditional formulation of QM without resorting to hidden variables) can exceed this upper bound. The violation of Bell’s inequality has also been demonstrated experimentally and reveals that quantum objects can be indeed strongly correlated as in the EPR experiment. John Bell died in 1990 at the age of 62 and sadly did not live to receive a Nobel Prize for his work. However, this year’s Physics Prize was awarded for experiments using entangled photons that established the violation of Bell inequalities described in his theorem and proved that the correlations do not depend on the formulation of QM, but rather on its intrinsic non-local nature.

Quantum computers--a gamechanger for drug discovery

Quantum entanglement is a prerequisite for quantum computing—something that has the potential to have a game-changing impact on many aspects of science including the development of new drugs. Whilst today’s classical computers use bits in the form of electrical (or optical) pulses in one of two physical states to represent a 1 or 0, quantum computers use subatomic particles to encode information in what are known as “qubits”. Unlike classical bits, qubits can represent multiple different possible combinations of 1 and 0 at the same time, in a phenomenon known as superposition. In a system of entangled qubits, the change of state of one is immediately transmitted to the others. The result is an improvement in the processing speed of the quantum computer. Whereas doubling the number of bits in a conventional computer doubles its processing power, adding extra qubits to a quantum computer can result in an exponential increase in speed.

The opportunities offered by quantum computing are particularly appealing when tackling large optimization or combinatorial problems, two categories that are frequently found in drug discovery. Quantum computing has the potential to impact the whole pharmaceutical process, particularly within the R&D space. It is likely that computer-assisted drug discovery (CADD) will be one of the first areas to benefit significantly from quantum computing, and scientists at San Francisco-based Menton.AI already use D-Wave’s quantum annealer to help them with the design of new molecules. [iv] Many other CADD applications may also be impacted by this new technology, as we discussed here a couple of years ago.

The technology is still in its infancy, and there are still challenges to overcome. However, quantum computing is no longer a hypothetical concept, and a number of companies now provide basic quantum computing cloud services. Whilst quantum computing is not going to replace today’s classical computing, it can provide capabilities that its conventional computing cousin cannot, and we are likely to see it playing an increasing role in drug discovery over the coming years.

References

[i] R. Jozsa, N. Linden. “On the Role of Entanglement in Quantum-Computational Speed-Up.” Proceedings: Mathematical, Physical and Engineering Sciences, 2003, 459, (2036), 2011–32.

[ii] A. Einstein, B. Podolsky, and N. Rosen. “Can Quantum-Mechanical Description of Physical Reality Be Considered Complete?” Phys. Rev., 1935, 47 (10), 777–780.

[iii] J.S. Bell. “On the Einstein-Podolsky-Rosen paradox.”Physics Physique Fizika 1964, 1, 195-200

[iv] V.K. Mulligan, H. Melo, H.I. Merritt, S. Slocum, B.D. Weitzner, A.M. Watkins, P.D.Renfrew, C. Pelissier, P.S. Arora, R. Bonneau. “Designing Peptides on a Quantum Computer.” bioRxiv, 2019

About the authors: 

The writers of article are part of Charles River Laboratories. 

Charles Baker-Glenn, DPhil, is an Associate Director in the Small Molecule Drug Discovery Division and manages the Computer-aided Drug Design (CADD) team within Early Discovery. He is a medicinal chemist by training.

Riccardo Guareschi, PhD, is a Senior Scientist of the CADD team within the Small Molecule Drug Discovery division, and a theoretical and computational chemist with a background in quantum chemistry.

Pascal Savy, PhD, is Research Leader in the Early Discovery CADD group and a medicinal chemist by training

David Clark, PhD, is Senior Research Leader in CADD and a founding scientific member of Argenta, acquired by Charles River in 2014.