Recent research has suggested that it is more important to study expert designers than novices. Typically, however, design expertise has been seen by researchers as the accumulation and organization of domain-specific knowledge. This work, however, views design expertise not only as knowledge and skills-based, but also as directly linked to the designer’s critical and commercial success. This paper sets out to explore what makes six of the world’s most distinguished and expert designers working today both critically and commercially successful? Moreover, the paper seeks to identify if they possess uniqueness in their genetic make up? Adopting the Watson - Crick Model of living organisms as a speculative model for each of the designer’s “cultural DNA”, this paper illustrates the significant design and cultural factors which the designers possess and exploit in their work.