A wall-sized cabinet of small drawers; one is open showing it contains what appearto be small seeds

When you go to a Korean tra­di­tion­al med­i­cine clin­ic, you will see these med­i­cine box­es. In five thou­sand years of Korean his­to­ry, var­i­ous mix­tures of plants and ani­mals have been used to treat or pre­vent dis­eases based on actu­al tri­al and error-type clin­i­cal testing.

And this knowl­edge and expe­ri­ence has been com­piled into one book called Dongui Bogam, writ­ten about four hun­dred five years ago by a Korean doc­tor named Heo Jun. This book cov­ers over­all diag­nos­tics, inter­nal and exter­nal med­i­cine, and var­i­ous ther­a­pies includ­ing soup ther­a­py, and also acupunc­ture, which you are aware of. 

In oth­er parts of the world, when you have a headache or fever, you would not want to take aspirin, Tylenol, or Advil. These drugs have been approved and used based on the sci­en­tif­ic proven mech­a­nism of action that reduces the pre­cur­sors respon­si­ble for such a symptom. 

In Korean med­i­cine, headaches are clas­si­fied into many dif­fer­ent types. So, for exam­ple if you have a headache with back pain with­out dry mouth, you will be pre­scribed with [Korean phrase]. Never mind about the pronunciation.

If you have a headache with the severe tired­ness, you will be giv­en anoth­er mix­ture of plants to treat. And so on. When you get those mix­tures of plants, what you do is you boil them togeth­er to extract active com­pounds, you squeeze the soup out of it, and then drink it (the black soup) for a cer­tain peri­od. One major prob­lem is this black soup of course con­tains active com­pounds to cure the dis­ease, but also those unwant­ed com­pounds that cause liv­er and kid­ney toxicity. 

Several small piles of berries, seeds, barks, etc, with an arrow pointing at a piece of lab equipment, and another arrow leading from it to chemical molecule diagrams

Then, how can you iso­late only those active com­pounds out of this, and use that mix­ture as the approach to treat dis­ease in a new way, this multi-compound, multi-target approach to address this com­plex human sys­tem? So that is the con­cept of multi-compound, multi-target approach that’s use­ful for single-target, single-component approach.

You’re look­ing at all the mice with nor­mal diet, you’re look­ing at all the mice addi­tion­al­ly fed with a plant mix­ture con­tain­ing beta-lapachone. As you can see, this mouse tak­ing the plant mix­ture became much health­i­er and stronger because it increased mus­cu­lar and your brain func­tion [due to] the com­pound called beta-lapachone.

Why? Why are these nat­ur­al com­pounds bet­ter than syn­thet­ic chem­i­cals to treat dis­eases? We have inten­sive­ly ana­lyzed all those known com­pounds in the nat­ur­al prod­ucts, and found that these com­pounds have high­er sim­i­lar­i­ty, espe­cial­ly struc­tur­al sim­i­lar­i­ty, to human metabo­lites. You’re look­ing at one of the com­pounds in the mid­dle there from gin­seng, sim­i­lar to the metabo­lites in steroid metab­o­lism, for example.

One of the key philoso­phies in tra­di­tion­al Oriental med­i­cine is so-called syn­er­gis­tic com­bi­na­tion of king, min­is­ter, assis­tant, ambas­sador com­pounds. The king com­pound is the major drug, the min­is­ter increas­es the effi­ca­cy, the assis­tant reduces the side-effects, and ambas­sador deliv­ers the drug to the right site. 

This con­cept has actu­al­ly been proven by more than sys­tems biol­o­gy, because the king rep­re­sents the major drug. And then the min­is­ter rep­re­sents a com­pli­men­ta­ry drug. And then the assis­tant cor­re­sponds to neu­tral­iz­ing drug. (So reduces tox­i­c­i­ty.) And then the ambas­sador cor­re­sponds to the deliv­ery func­tion, and enhanc­ing pharmacokinetics.

So we have inten­sive­ly ana­lyzed all those known com­pounds from nat­ur­al plant extracts, and then we looked at the syn­er­gis­tic com­bi­na­tions. [Slide begins scrolling through a large num­ber of chem­i­cal dia­grams at ~3:45] And you don’t have to pay atten­tion to these com­plex chem­i­cal struc­tures, but in short, we found such syn­er­gis­tic com­bi­na­tions actu­al­ly exist to treat dis­eases bet­ter. So the old book has not only the wis­dom, but scientifically-proven mechanisms.

Now, once you iden­ti­fy these active com­pounds, what are you going to do? You need to over­pro­duce them. So, we use microor­gan­isms. So for exam­ple, we were able to engi­neer our gut bac­te­ria called E. coli, and now they are pro­duc­ing indiru­bin[?], which is a great anti-cancer agent which should have been extract­ed from plants, but now we pro­duce through E. coli.

Human life expectan­cy increased to 73 years. The num­ber of peo­ple who are over 65 years old is about 580 mil­lion. Annual health­care spend­ing around the world this year will be about eight tril­lion dol­lars. What are you going to do about it? I think it’s more impor­tant to pre­vent dis­ease, make peo­ple stay healthy rather than treat­ing dis­eases alone.

A dinner table covered with a large number of dishes ranging in size from entrees to collections of small bowls with pickles in them.

You’re look­ing at a Korean din­ner table. By the way, you don’t eat like this every day. But this rep­re­sents the best exam­ple of bal­anced diet, or bal­anced nutri­tion. It is a typ­i­cal exam­ple of a multi-compound, multi-target approach to make you stay healthy. So, med­i­cine, nutri­tion, even cos­met­ics, share the same line.

The ques­tion. Out of this knowl­edge of many dif­fer­ent plant med­i­cines, can we real­ly iden­ti­fy, or how can we more read­i­ly iden­ti­fy, those active com­pounds. Once we iden­ti­fy them, can we real­ly engi­neer microor­gan­isms to over­pro­duce these indi­vid­ual chem­i­cals that are func­tion­al. Also, the last ques­tion will be, how can we reform our cur­rent health­care sys­tem or man­age­ment sys­tem to link nutri­tion and med­i­cine togeth­er, so that we can make our life much health­i­er in this aging society? 

Thank you very much.

Further Reference

Sang Yup Lee fac­ul­ty pro­file at the KAIST web site.