Research The Bayer Scientific Magazin, Edition 28

Photo:  private (1)

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This signal activates the 

macro-

phages

: they produce 

cytokines

, the 

central messenger substance of the 

immune system, which activate them-

selves and recruit further macrophages. 

The 

cytokines

 also stimulate further 

immune cells that combat infections.

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The 

DNA

 resembling the pathogen 

triggers the body into detecting an 

infection and places the entire immune 

system of the cattle into a state of 

alertness. The 

macrophages

 are also 

activated and ready to quickly attack 

any bacterial or viral intruders.

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The liposome protects the 

DNA

 until it 

reaches its target site: the immune cells. 

Immunostimulatory DNA

 triggers a par-

ticularly strong effect in 

macrophages

 

(“eater cells”). These are the road-sweepers 

of the immune system: if they encounter 

foreign matter, they render it harmless. They 

also absorb the liposome. The DNA is released 

inside the cell, where it stimulates specific 

receptors. 

Cytokines

Activation of other 

immune cells 

Activated 

macrophage

Macrophage

“Reduce the infection pressure”

Artur  

Summerfield

What’s the significance of this advancement in 

 Immunostimulatory DNA?

Immunostimulatory DNA enhances the immune system’s ability to 

react to microbial infection by putting the immune system into an 

alarm status. This can be beneficial for animals as it can potentially 

protect them at times when they are exposed to multiple pathogens 

or other stressors. Animals with stronger immune defenses are like-

ly to withstand infections better, which could reduce antimicrobial 

use, lessen animal suffering and minimize economic impact.

research

 spoke with Dr. Artur Summerfield, professor of Veterinary Immunology 

at the University of Bern, about opportunities for immunostimulation in veteri-

nary medicine.

How can immunostimulants benefit animal husbandry?

Vaccines, antimicrobial therapies and good animal husbandry prac-

tices will always be important. Immunostimulants will complement 

these approaches, offering veterinarians and producers an innova-

tive non-antibiotic option that can help enhance animals’ natural 

defenses and reduce the infection pressure. This would benefit ani-

mals as well as consumers.

Bayer research 28    July 2015

35

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Photos: Sabine Bungert/Bayer AG (3), Bayer HealthCar

e (1), Gettyimages (1), private (2)

COMPUTER MODELS SUPPORT THE SEARCH FOR NEW DRUGS

It’s like an obstacle race through the hu-

man body: an active ingredient admin-

istered in tablet form has to overcome 

numerous hurdles on its journey from 

the mouth to its target destination. The 

mucous membranes in the stomach and 

gut have to absorb the active ingredient 

 efficiently and deliver sufficient quantities 

into the bloodstream. The cardiovascular 

system has to distribute the drug through 

the body and ultimately transport it to its 

site of action. That’s why scientists spend 

years trying to turn their drug candidates 

into high-performers, capable of provid-

ing optimized action while at the same 

time causing a minimum of side effects 

and also being able to be broken down 

and excreted. To make drug products that 

are able to negotiate this obstacle course, 

scientists have to not only precisely un-

derstand what happens to an active in-

gredient as it makes its way through the 

body but also know as many details as 

possible about the processes it undergoes 

in different organs, right down to the in-

teractions in the individual cells. 

“The liver plays a special role,” explains 

Dr. Jörg Lippert, Head of Clinical Phar-

macometrics at Bayer HealthCare. This 

organ has an enormous influence on the 

action of drug products. The liver filters 

foreign chemical compounds out of the 

bloodstream – and that includes active 

pharmaceutical ingredients. It converts 

them into often inactive substances, or 

metabolites, which are then excreted via 

the kidneys in the urine. “If this process 

takes place too slowly, it can lead to a 

higher risk of side effects for these pa-

tients. But if drugs are metabolized too 

quickly, they cannot exert enough of an 

effect,” says Lippert. That’s why Bayer’s 

scientists determine how fast every new 

active substance is metabolized by the 

liver even before these drugs have been 

tested in humans. 

One of the approaches they use is com-

plex mathematical models. “For more than 

ten years now, we have been developing 

software that reflects human physiology 

in detail,” explains Dr. Lars Küpfer, Senior 

Scientist at Bayer Technology Services. The 

program simulates a human body with all 

the organs – including the liver – which in 

a real body are connected with one anoth-

er by the flow of blood. The scientists have 

developed mathematical formulae repre-

senting and interlinking the biochemical 

and physical processes in the cells and 

tissues. “We can now use the computer 

to predict how an active ingredient will be 

distributed in the body over time, metab-

olized in the liver and then excreted again 

– and we can do this for a number of dif-

ferent patient groups,” explains Küpfer. To 

do this, the scientists vary several param-

eters and factor different disease pictures 

or metabolic disorders into their models. 

“For example, we can quite precisely sim-

ulate patients suffering from cirrhosis of 

the liver or even a child’s body whose liver 

is not yet fully matured and may therefore 

function differently than an adult’s,” says 

Medical calculations: Dr. Jörg Lippert and Dr. Lars Küpfer 

(left to right) convert metabolic pathways in organs and 

cells into mathematical formulae and models.

Virtual tests for new  

therapies

When researchers design a new drug product, they have to know exactly what will happen to the active ingredient  

once it is inside the body. For this, they are increasingly turning to computer-based predictions and virtual patients.  

Scientists at Bayer are collaborating with external partners on innovative methods to better predict the safety and  

efficacy of new drug candidates and thus make drug development even more effective.

Mathematics makes drug 

 development more efficient

DOSSIER 

Computer models

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Bayer research 28    July 2015

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