Clin Chem Lab Med 2016; 54(10): e313–e314

Letter to the Editor

Eleftherios P. Diamandis* and Mario Plebani phenomenon – Part 5: Theranos’ presentation at the American Association for Clinical Chemistry Annual Conference 2016

DOI 10.1515/cclm-2016-0737 Master, two highly recognized and respected clinical Accepted for publication August 18, 2016; previously published chemists, who did a good job in asking pertinent ques- online August 30, 2016 tions to Ms. Holmes and her associates. In this respect, AACC lived up to the expectations of high standards and Keywords: diagnostics; new technologies. impartiality for this presentation. Holmes presented to a large and curious, if not To the Editor, hostile, audience. She avoided talking about Theranos’ past and the difficulties of her company [1–7]. She also The widely anticipated presentation of Theranos at the made it clear that her presentation would focus on the Annual Conference of the American Association for future, not the past, and she distanced herself from the Clinical Chemistry (AACC) was finally given on Monday, previous “Edison” instrument and introduced a new August 1st, 2016 at the Philadelphia Convention Center. analyzer named “MiniLab”. In the first part of her pres- This journal has followed the Theranos story closely over entation, Ms. Holmes described the engineering behind the last 2 years and provided frequent updates [1–4]. Eliza- the MiniLab and explained that it is a compact desktop beth Holmes, the Chief Executive of Theranos, presented device that houses a mini spectrophotometer, a mini- to an audience of over 2500 clinical chemists and other luminometer, and mini-flow-cytometer and a mini-PCR laboratory scientists, as well as to an impressive number machine, along with a centrifuge. We acknowledge the of reporters from national and international media. We difficulties of putting together all these technologies in have not seen anything like this event, at the previous 30 a very compact machine, but apart from the engineer- AACC conferences that we have attended. ing challenge, no technological breakthroughs were First, we would like to comment on the moderation described. We wonder if this machine can be manufac- of this difficult event by AACC officials. Although we tured efficiently and if it can function reliably long-term, ­disagreed with the invitation [4], we acknowledge here due to its numerous components and moving parts. Time that AACC President, Dr. Patricia Jones, made it very clear will show if this machine can perform as a robust analyti- in her opening remarks that the presentation does not cal platform using micro-volumes, and if the sensitivity mean that AACC endorses Theranos, and that no CME achieved will be adequate for demanding analytes, such credits were allocated. She also recruited an excellent as high sensitivity troponin. panel, consisting of herself, Dr. Dennis Lo and Dr. Steven The cartridge included with this system, carrying dry reagents for multiple analytes, was not described in detail. It was not clear what happens to the unused rea- *Corresponding author: Eleftherios P. Diamandis, MD, PhD, gents if cartridges with multiple analytes are used for only FRCP(C), FRSC, Head of Clinical Biochemistry, Mount Sinai Hospital and University Health Network, 60 Murray St. Box 32, Floor 6, Rm one or two analytes. We assume that the rest of the rea- L6-201, , ON M5T 3L9, , Phone: +(416) 586-8443, gents will be discarded, increasing the cost per reportable E-mail: [email protected]; Department test. Validation of some analytes by Theranos (K+, choles- of Pathology and Laboratory Medicine, Mount Sinai Hospital, terol, triglycerides, LDL-C, HDL-C, HSV-2 IgG, lymphocyte Toronto, Ontario, Canada; and Department of Laboratory Medicine subsets, ZIKA virus PCR) has shown good results but we and Pathobiology, , Toronto, Ontario, Canada Mario Plebani: Department of Laboratory Medicine, do not have independent validation or long-term perfor- University-Hospital of Padova, Padova, Italy. mance. Data on the majority of important laboratory ana- http://orcid.org/0000-0002-0270-1711 lytes were not described. e314 Diamandis and Plebani: Theranos phenomenon – Part 5

With this new machine, Ms. Holmes seems to have as current technologies for detecting the virus. This taken a step away from the direct-to-consumer laboratory remains to be seen in evaluation trials. sector (e.g. testing in pharmacies) and she is now suggest- ing that their business model includes placement of these Regarding fingerprick capillary blood testing: We have machines in hospitals and in point-of-care or doctor’s seen at the AACC exhibition smaller and less traumatic office environments. needles that permit almost painless collection of venous Ms. Holmes also spent significant time describing blood for laboratory analysis. One of us (EPD) has already Theranos’ efforts to optimize fingerpricks for high quality tested one of these new blood collection devices and capillary blood retrieval in relatively large amounts. She found out that it was totally painless and collection time has shown that her device is suitable for performing tests was less than a minute. These related technologies will on site, or for shipping to remote laboratories for further likely be preferable to patients than fingerpricks, which, analysis. as we mentioned earlier, are more painful [1]. Overall, what Ms. Holmes said was relatively straight- The video of Miss Holmes’ presentation can forward. We did not identify any disruptive technologies be found at this link: https://www.youtube.com/ or revolutionary new ways of doing what we have been watch?v=n6JRG733ReQ. doing in clinical laboratories for years but maybe, we did The future of Theranos will depend on the quality and not hear the whole story. While we appreciate that her the reliability of their products. We are looking forward to approach will save some valuable real estate, due to the see Theranos validating and publishing on their products compact size of her machine, we suspect that this benefit in the near future and having them return to the AACC may compromise quality, critical assay performance char- Conference as exhibitors and sponsors. acteristics such as sensitivity or the long-term reliability of the instrument. Author contributions: All the authors have accepted We believe that Theranos will face some challenges in responsibility for the entire content of this submitted the future, as summarized below: manuscript and approved submission. 1. Ms. Holmes admitted that her new machine is not Research funding: None declared. ready and that they are still configuring optimal pan- Employment or leadership: None declared. els for their cartridges. We do not know how much Honorarium: None declared. time it will take to do this, but being familiar with Competing interests: The funding organization(s) played in-vitro diagnostics over many years, we suspect that no role in the study design; in the collection, analysis, and it may take more time than originally thought. The interpretation of data; in the writing of the report; or in the system has to still be independently validated and decision to submit the report for publication. the results published (in progress). They also need to receive Food and Drug Administration (FDA) approv- als for their new system and assay tests, as well as References their blood collection device. 2. Based on the previous history of Theranos, we antici- 1. Diamandis EP. Theranos phenomenon: promises and fallacies. pate that they will face increased scrutiny and it may Clin Chem Lab Med 2015;53:989–93. be difficult to convince skeptics that their new tech- 2. Li M, Diamandis EP. Theranos phenomenon-part 2. Clin Chem Lab nologies are better than the old ones. Med 2015;53:1911–2. 3. Li M, Diamandis EP. Theranos phenomenon – part 3. Clin Chem 3. It remains to be seen if their system can match the Lab Med 2016;54:e145–6. performance characteristics of larger, conventional 4. Diamandis EP. Theranos phenomenon – part 4: theranos at an analyzers. international conference. Clin Chem Lab Med 2016;54:e243–4. 4. There are already many alternative machines for their 5. Li M, Diamandis EP. Theranos promises a new era of preventive targeted niche. For example, we have seen at the AACC . Clin Biochem 2015;48:1027. exhibition many other companies marketing simpler 6. Ioannidis JP. Stealth research: is biomedical innovation hap- pening outside the peer-reviewed literature? J Am Med Assoc products. The Zika virus assay was one of the most 2015;313:663–4. talked about assays at the Theranos presentation, but 7. Ioannidis JP. Stealth research and Theranos: reflections and Dr. Dennis Lo suggested that it may not be as sensitive update 1 year later. J Am Med Assoc 2016;316:389–90.