Lee Kuan Yew Distinguished Visitors Programme: Public Lecture: Drug development in the 21st century: are we going to cure all diseases?

Description: Many important drugs such as penicillin, aspirin and digitalis were discovered by serendipity - some by curious researchers who noted an accidental phenomenon, some by isolation of active ingredients form plants known for centuries to have a specific therapeutic effect. Other major drugs like statins were discovered using more advanced technologies, such as targeted screening, yet, the discoverers were looking for a different effect. In all these cases, the mechanisms of action of the drug were largely unknown at the time of their discovery, and were discovered only later.

Date: Mon, 22nd March 2010
Time: 06:00 pm to 07:30 pm
Venue: NTU Lecture Theatre 19A, North Academic Complex Level 1

Dr. Aaron Ciechanover (pronounced Chi-Kan-nover), Nobel Laureate in Chemistry (2004)

Transcribed notes:

Age is relative: we have doubled our lifespan in 100 years. This is due to improvements in sanitation, sterility, water, and antibiotics. The pursuit of longer lives is an endless quest.

Drugs intervene to stop or minimize biological aberrations. Prevention is better than cure. There are 3 types of diseases: behavioural (obesity, smoking), environmental and genetic (some diseases are recently discovered to be polygenic: more than one gene controls the expression of the disease). Behavioural and environmental diseases can be eradicated.

There are 3 revolutions in evidenced-based medicines. (Ancient medicines are not evidenced-based.)
1. 1930’s to 1960’s.
Discoveries were incidental or serendipitous. Although ancient Egyptians used willow bark (as a herb), it was not until the end of the 19th century when aspirin, the active ingredient, was found and isolated. It can prevent malignancies, inflammation, heart attacks and can reduce pain. Penicillin was discovered by Sir Alexander Fleming when he found some mould without bacteria growing on it on a discarded sample. This resulted in the first antibiotic. The mechanism for discoveries was: 1. clinical observation. 2. isolating active ingredient. 3. understand mechanism.
2. 1970’s to 2000’s
High thoroughput – brute force screening of large libraries of chemical compounds were responsible for many discoveries. Statins are cholesterol-lowering drugs and work by inhibiting a critical biological step of cholesterol formation. Such drugs, like Lipitor, are worth $25 billion. US Army soldiers from the Korean War were found to accumulate cholesterol from age 18. This drug was discovered despite it not being the main aim of the researcher.
3. 2000’s and onwards
This is an era of planning: 1. understand the mechanism first. 2. work out the active ingredients and the overall drug.

Predictions for the following years:
Currently, drugs are one-size-fit-all. In the future, there may be targeted, individualised medicine. Non-responders and responders for drugs are predicted. Responders are treated, while new drugs are developed to target non-responders. Currently Tamoxifen is used to treat oestrogen receptor positive people for breast cancer. Herceptin and Gleevec came from design.

The Human Genome Project took 20 years and $10 billion to complete for 3 billion bases from one person. Currently, to decode your genome, you have to pay $20000 and wait for one month or less. The aim is to reduce cost to less than $1000 and in 15 minutes. Ethical problems arose from the potential of this project. Who can get access to this information? The government, insurance companies, and/or ourselves? But eventually, science cannot be stopped within our borders which we define ourselves.

Question and answer session:

What kills us in a disease-free world?
The more we know, the more we know not. As we conquered infectious diseases and increased our life expectancy from 40 to 80 years, ‘old-age’ illnesses came about, such as cancer and Alzheimer’s. It makes sense that as we conquer these ‘old-age’ illnesses and increase our lifespan to above 80 years, nature will throw at us more diseases that affect only people over the age of 80.

Interdisciplinary work is a must for answering our questions about ourselves.

Why did you choose science and medicine as a career path?
There is a world below us: such as computers. There is no mystique, there are definitions, there is an end. This is a primitive world that we design. There is also a world above us that has mystique and of which we know nothing of. This world includes science and medicine.

Reflections:

This was an awe-inspiring lecture. The lecture hall itself was packed and another student and I had to sit at the steps. Dr. Ciechanover offered penetrative insights into the world of medicine and the basic modern history of it. He admitted that he could offer no answer to “whether we can cure all diseases?” but did offer his opinion that we would likely face more diseases as our lifespan grows. The question-and-answer session was engaging and that was when the audience could ask really pressing questions that were relevant to their own selves. One member of the audience, being a US citizen, wanted to hear Dr. Ciechanover’s opinion on the US healthcare system, while an undergraduate was doing her report on the role of Traditional Chinese Medicine in Singapore and wanted to hear what Dr. Ciechanover had to say. Being political hot potatoes, Dr. Ciechanover wisely chose not to answer these questions directly instead. I have learnt a lot from this lecture and am humbled and insprired by this lecture by a Nobel prize receiver.

Timothy Yap