The Nobel Prize in Physiology or Medicine 1988

Figure 3.

Figure 3. Purine bases (adenine, guanine and hypoxanthine) are synthesized from simple precursors. Nucleosides are then formed by the addition of sugar moieties (deoxyribose or ribose) and subsequently converted into nucleotides by the addition of phosphate (mono-, di- and triphosphate). Nucleotides take part in cellular metabolism and are the building blocks in the synthesis of RNA and DNA. Structural analogues of the natural substances can specifically block the different metabolic steps. Some examples are given in the figure.

Already in 1948 Elion and Hitchings discovered a substance, diaminopurine, an adenine antagonist, which inhibited the growth of L. casei (Figure 3). It was also found to have an effect on experimentally induced leukemia. Clinical trials in patients were initially promising but had to be interrupted due to toxic side effects. Stimulated by this finding Elion and Hitchings continued their research which soon resulted in two new chemotherapeutic drugs, thioguanine (1950) and 6-mercaptopurine (1951). In collaboration with the Sloan-Kettering Institute 6-mercaptopurine was tried in leukemic patients who were resistant to methotrexate. About one third of the patients responded with complete remission (1953). The finding was soon confirmed, and 6-mercaptopurine (as well as thioguanine) are still used in the treatment of leukemia (Table II).

Elion and Hitchings tried to improve the therapeutic properties of 6-mercaptopurine by using sulphur-substituted compounds. The result was azathioprine (1957) which replaced mercaptopurine as an inhibitor of the immune response. For a long time azathioprine was the only drug available to prevent rejection of transplanted organs. It is still used for that purpose but also for the treatment of autoimmune diseases.

Attempts were also made to prolong the effect of 6-mercaptopurine by blocking its metabolism by xanthine oxidase which is involved in the endogenous production of uric acid (Figure 3). In 1963 this research resulted in another new drug, allopurinol, which blocks the formation of uric acid and therefore is used in the treatment of primary and secondary gout.

Hitchings and collaborators also developed pyrimethamine (1950) and trimethoprim (1956) which were found to be effective in the treatment of malaria and bacterial infections, respectively. Both drugs have a strong affinity to the enzyme dihydrofolate reductase, but pyrimethamine is 2000 times more toxic to the enzyme system in the malaria parasite than in the host. Trimethoprim has 100 000 times higher affinity to the bacterial compared to the human enzyme. An important discovery was that the chemotherapeutic effects of these two compounds were markedly enhanced by sulphonamides, drugs which inhibit the synthesis of folic acid. This pharmacotherapeutic principle is used in the combination drugs trimethoprim-sulfa and pyrimethamine-sulfa which are used in the treatment of bacterial infections and malaria, respectively.

A more recent application of Elion’s and Hitchings’ research philosophy is acyclovir, a drug used in the treatment of infections with herpes virus. Already in the 1950s they had shown that antipurines had to be transformed into nucleotides in order to become active in the cell. The herpes virus carries information which leads to the production of a new enzyme which transforms nucleosides to nucleotides (thymidine kinase) in the infected cell. This enzyme has considerably less substrate specificity than the cell’s normal enzyme. Therefore, acyclovir is transformed into its corresponding nucleotide which is the active antimetabolite and the growth of the virus is inhibited (Figure 3).

Acyclovir was described by Elion and coworkers in 1977 and is a modern example of the realization of the basic ideas from 1950. An even more recent application of these ideas is the development of azidothymidine (AZT) which was described in 1985 by other scientists from the same institute, and which is the hitherto best documented drug in the treatment of AIDS. It can be added that trimethoprim-sulfa is used in the treatment of Pneumocystis carinii, a relatively common complication to AIDS.

The clinical use of the drugs discovered by Elion and Hitchings is summarized in Table II.


G. Gahrton, B. Lundh: Blodsjukdomar. Lärobok i hematologi. Natur och Kultur, Stockholm, 1983.

Läkemedelsboken 1987/88, Apoteksbolaget, Stockholm, sid, 87-88, 150-151, 249, 625.

J.H. Shelley: Creativity in Drug Research. Trends in Pharmacological Sciences. 1983, vol. 4.

L. Stryer: Biochemistry, 3rd edition. W.H. Freeman and Company, San Francisco, 1988, chapter 25, 601-625.

To cite this section
MLA style: Press release. Nobel Media AB 2020. Wed. 23 Dec 2020. <>

Back to top

Back To TopTakes users back to the top of the page[2]


  1. ^ The Nobel Assembly at the Karolinska Institute (
  2. ^ Back to top (

Source URL: Read More
The public content above was dynamically discovered – by graded relevancy to this site’s keyword domain name. Such discovery was by systematic attempts to filter for “Creative Commons“ re-use licensing and/or by Press Release distributions. “Source URL” states the content’s owner and/or publisher. When possible, this site references the content above to generate its value-add, the dynamic sentimental analysis below, which allows us to research global sentiments across a multitude of topics related to this site’s specific keyword domain name. Additionally, when possible, this site references the content above to provide on-demand (multilingual) translations and/or to power its “Read Article to Me” feature, which reads the content aloud to visitors. Where applicable, this site also auto-generates a “References” section, which appends the content above by listing all mentioned links. Views expressed in the content above are solely those of the author(s). We do not endorse, offer to sell, promote, recommend, or, otherwise, make any statement about the content above. We reference the content above for your “reading” entertainment purposes only. Review “DMCA & Terms”, at the bottom of this site, for terms of your access and use as well as for applicable DMCA take-down request.

Acquire this Domain
You can acquire this site’s domain name! We have nurtured its online marketing value by systematically curating this site by the domain’s relevant keywords. Explore our content network – you can advertise on each or rent vs. buy the domain. | Skype: TLDtraders | +1 (475) BUY-NAME (289 – 6263). Thousands search by this site’s exact keyword domain name! Most are sent here because search engines often love the keyword. This domain can be your 24/7 lead generator! If you own it, you could capture a large amount of online traffic for your niche. Stop wasting money on ads. Instead, buy this domain to gain a long-term marketing asset. If you can’t afford to buy then you can rent the domain.

About Us
We are Internet Investors, Developers, and Franchisers – operating a content network of several thousand sites while federating 100+ eCommerce and SaaS startups. With our proprietary “inverted incubation” model, we leverage a portfolio of $100M in valued domains to impact online trends, traffic, and transactions. We use robotic process automation, machine learning, and other proprietary approaches to power our content network. Contact us to learn how we can help you with your online marketing and/or site maintenance.

1 2