As early as the mid-1960s, Merck researchers began to study male hormones, hoping to find new drugs to treat adolescent acne. There were two main steroid hormones known at that time, testosterone and dihydrotestosterone. Theoretically, if we can inhibit the 5-α reductase that converts testosterone into dihydrotestosterone, we should be able to reduce the activity of male hormones in the body, thus preventing the growth of acne.
However, with the progress of the project, the company realized that the use of steroid hormones by teenagers was difficult to be accepted by the society and the marketing was very difficult, so the research on 5-α reductase inhibitors was terminated in the early 1970s.
Almost at the same time, a little girl from a remote tribe underwent abdominal surgery in a hospital in Dominica, a Caribbean island country. The doctor unexpectedly found that "she" was a boy! This seemingly insignificant gossip brought a turn for the research project of 5a- reductase inhibitors, which eventually led to the discovery of two new drugs.
Subsequent research found that in that remote tribe, many men were born with female genitalia, so they were raised as girls. But in the process of their development, their masculine characteristics began to appear, and they grew male genitals and became men. And these men who are "transsexual" during their development will not lose their hair or go bald when they get old. Their prostate is relatively small and will not proliferate when they get old.
Further molecular genetic research shows that the content of dihydrotestosterone in these special Dominican men is much lower than that in normal people, because they all lack 5a- reductase which converts testosterone into dihydrotestosterone. This result makes Merck scientists keenly aware that 5a- reductase inhibitors can also reduce the content of dihydrotestosterone in normal people, and should also be used to prevent and treat benign prostatic hyperplasia in the elderly.
After targeting the prostate, Merck restarted the research project of 5a- reductase inhibitors. After more than ten winters and summers, Merck's research team finally put finasteride (Borrelin) on the market at 1992, becoming the first oral drug to treat benign prostatic hyperplasia.
The success of treating BPH with Borrelin gave Merck researchers the opportunity to further study the relationship between 5a- reductase and male pattern alopecia. Five years later, the second 5a- reductase inhibitor Baofa went on the market. Propafenone and Borrelin have the same active ingredients, both of which are finasteride, but the dosage form and dosage are different.
Further research on Dominican tribal men by the medical community also found that there were no patients with prostate cancer except men without hair loss and prostatic hyperplasia. Therefore, Merck cooperated with the National Cancer Institute of the United States to carry out a large-scale long-term clinical trial to study the preventive and therapeutic effects of Borrelin on prostate cancer, and there is no conclusion yet.
The discovery of Paullig and Bao Fazhi once again confirmed the famous scientist louis pasteur's famous saying: "Opportunities favor those who are prepared." In 1960s, Merck's research on androgen and 5a- reductase laid a good foundation for the future research and development of paulette, and prepared for finding the related drug targets in this metabolic pathway. Therefore, the reports on Dominican transsexuals in the middle and late 1970s and their follow-up studies immediately caught the attention of Merck researchers and seized this seemingly irrelevant and easily overlooked opportunity.
At present, the basic research of biomedicine in China is still in its infancy. Domestic elites should pay attention to accumulating pathological knowledge of common diseases and frequently-occurring diseases, pay close attention to the new trends and discoveries of basic biomedical research around the world, and be prepared.
-Excerpted from the story of new drug development