Science Friday Podcast — AI Is Coming Up With Brand New Molecules, Fuelling Drug Discovery

Flora Lichtman talks with two biotechnology experts in the latest podcast about how AI is being used for drug discovery such as new antibiotics: Dr. César de la Fuente, bioengineer and presidential associate professor at the University of Pennsylvania in Philadelphia and Nobel laureate Dr. David Baker, director of the Institute for Protein Design and professor at the University of Washington in Seattle.

5 Live Science Podcast — Modified Insulin That Can Be Switched Off

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Dr Chris Smith talks with Dr David B. Sacks from the US National Institutes of Health about a new form of insulin that switches itself off before blood glucose levels drop too low. This required a "switch" to be engineered into the molecule. Hormones are chemical messengers, but unlike nerves they act over a longer period. Normally insulin, a hormone made in the pancreas, is released to tell the body's cells to use glucose. But when glucose levels fall back to normal, insulin production reduces to compensate. Self-injected insulin can result in excessive insulin in the blood after blood glucose has fallen sufficiently, potentially making levels too low.

5 Live Science Podcast — Artificial Pancreas

Image © Eugene Brennan

This week's program featured a segment about an "artificial pancreas" for Type 1 diabetes sufferers, which uses a closed loop control system to monitor blood glucose and administer a dose from an insulin pump.

What's a Closed Loop, Negative Feedback Control System?

Many systems use close loop control with negative feedback to control an output of interest. An example is the speed control on small engines, e.g. the one on your petrol lawn mower. If you run into longer grass, this slows down the blade and engine. To reduce the change in rotational speed (the output variable) and keep it at a setpoint (typically 3000 RPM for a mower), a governor is used. A vane, mounted adjacent to the engine's cooling fan that's integral to the flywheel, forms part of the governor mechanism. When the fan slows down, it blows less air onto the vane. The vane is connected via a linkage to a butterfly valve in the carburetor. This valve forms part of the throttle mechanism and as the valve opens up due to movement of the vane, more air/fuel mixture enters the engine. This generates more power which tends to compensate for the slowdown of the blade due to the long grass. Other systems use negative feedback and closed loop control, e.g. your phone charger which has electronics to keep the output at 5 V DC, irrespective of load. Without a voltage regulator, all power sources, including batteries, experience a voltage drop as they're loaded and more current drawn from them. Voltage stabilisation by a regulator is necessary so that the electronics in your phone for instance works in a predictable manner. Other examples of feedback control systems are servos on vehicles and aircraft and temperature and pressure control in industrial processes.

Why Negative Feedback and Not Positive Feedback?

The function of a feedback control system is to keep an output variable at a fixed or variable setpoint, irrespective of load. So in the lawn mower example the speed was the parameter that needed to be kept stable. In negative feedback, the actual speed is fed back and subtracted from the desired speed (the setpoint) to create an error signal. This error, via a controlled variable, drives the system in a direction to bring the output closer to the setpoint. In the lawnmower example, the controlled variable was the fuel. The term negative feedback comes from the subtraction that's involved. Positive feedback on the other hand causes the fed back signal to add to the set point, resulting in instability and the output diverging from a setpoint (e.g. positive feedback in a PA system, causing the squealing from loudspeakers). Many of the systems in our bodies are negative feedback control systems and like any control system if not tuned properly, there can be oscillations and instability. Hence the wobbling from side to side when we're learning to ride a bike!