Affymetrix

In the late 1980s a team in Palo Alto had an unusual idea. Chipmakers in the valley used light shone through masks to build millions of transistors on silicon wafers. What if the same tricks could build molecules? The team, working at the Affymax Research Institute, used photolithography to make many different short chains of DNA or protein building blocks side by side on a small glass chip. That work led to the DNA microarray and to Affymetrix, the company that sold it to the world.

Affymetrix itself grew up in Santa Clara, so this is a story about Palo Alto origins rather than a Palo Alto headquarters. It also completes the family tree of Alejandro Zaffaroni, whose companies included Syntex, ALZA and DNAX.

Affymax and its Palo Alto institute

Zaffaroni cofounded Affymax in 1988. Its goal was to use combinatorial chemistry, making and testing huge numbers of related compounds at once, to cut the time and cost of finding new medicines. The European Patent Office describes Affymax as a Dutch company with a research institute in Palo Alto as a wholly owned subsidiary. Wikipedia refers to the parent as Affymax N.V.

In 1989 Affymax recruited a young scientist named Stephen P.A. Fodor to the Affymax Research Institute in Palo Alto. Both the European Patent Office and Cold Spring Harbor Laboratory's DNA Learning Center place the institute in Palo Alto. Fodor led the early research that became the gene chip. Glaxo bought Affymax in 1995, according to Stanford's obituary of Zaffaroni.

Building molecules with light

The method combined two fields. From chipmaking came photolithography: light shone through a patterned mask switches on chemistry only where the light falls. From drug discovery came combinatorial chemistry. Repeating the cycle with different masks and building blocks produced a grid in which every spot held a different, known sequence.

Fodor and colleagues published the method in the journal Science in 1991. The co-inventors named by the European Patent Office were Fodor, Michael C. Pirrung, J. Leighton Read and Lubert Stryer. Stryer was a Stanford biochemistry professor, best known to students for his biochemistry textbook. A European patent filing followed. In 2006 the European Patent Office named Fodor and his co-inventors European Inventors of the Year in the small and medium sized enterprises category.

Affymetrix spins off

Sources differ slightly on dates. Wikipedia says Affymetrix began as a unit of Affymax N.V. in 1991 under Fodor and his group. Its infobox gives a founding year of 1992. Wikipedia's article on Zaffaroni says he cofounded Affymetrix in 1991. The European Patent Office and the DNA Learning Center both say Affymax spun Affymetrix off as a separate company in 1993, to focus on making and analyzing GeneChips. Fodor and Zaffaroni are credited as cofounders.

The new company was eventually based in Santa Clara, a few miles south of Palo Alto along the chipmaking corridor. Its first product under the GeneChip trademark, an HIV genotyping chip, came out in 1994. Affymetrix went public in 1996.

Growth of the GeneChip

Gene chips arrived just as the Human Genome Project was producing sequence data. Researchers could now measure the activity of thousands of genes in one experiment, or check large numbers of genetic variants in many people. Affymetrix grew in part by buying technology from other companies:

In January 2014 the FDA cleared Affymetrix's CytoScan Dx Assay, a whole genome blood test to help find genetic causes of developmental delay and intellectual disability in children. It was described at the time as a first of its kind test.

Gene chips also shaped the local genomics business. Palo Alto's Incyte sold gene sequence data from Porter Drive in the same years. Chips and databases were two answers to the same question: how to turn the genome into something drug companies could use.

What researchers did with gene chips

Gene chips changed the scale of biology experiments. Before them, a lab might measure the activity of a handful of genes at a time. With an expression array, it could compare thousands of genes between healthy and diseased tissue in a single run. Cancer researchers used the method to sort tumors that looked alike under a microscope into groups that behaved differently.

A second use was genotyping, reading which version of a gene a person carries. Chips designed to read hundreds of thousands of single letter DNA differences, known as SNPs, made it practical to compare thousands of patients with thousands of healthy volunteers. Those genome wide association studies became one of the main tools for finding genes linked to common diseases in the 2000s. Newer sequencing machines later took over much of this work, but arrays remained a cheaper option for many tests.

Zaffaroni's other ventures

Affymetrix was one of many companies Zaffaroni started after ALZA. Wikipedia lists Symyx Technologies (1994), which applied combinatorial methods to materials science, Maxygen (1997), SurroMed and Alexza Pharmaceuticals (2000). He also helped create Perlegen. He received the National Medal of Technology in 1995 and died in Atherton in 2014, at 91.

Thermo Fisher and the brand today

On January 8, 2016, Thermo Fisher Scientific announced it would buy Affymetrix for about $1.3 billion. The deal closed on March 31, 2016. Wikipedia reports that the microarray line now sits under Thermo Fisher's Applied Biosystems brand, so Affymetrix no longer exists as a separate company.

Timeline

Tracing the story

We could not confirm the street address of the Affymax Research Institute from official sources, so we do not give one. There is no marker. To see the setting, the best stop is Stanford Research Park, where Zaffaroni's earlier companies worked and where life science startups still rent lab space today. Our biotech investors guide covers that newer generation. For the semiconductor side of the story, see Shockley, Fairchild and the semiconductor boom.

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