23andMe and the future of DNA analysis at home

In early December 2014, it was announced that a Google-associated home DNA analysis kit developed by 23andMe was introduced to the UK market. At the same time, 23andMe products continue to be unavailable in the United States after the U.S. Food and Drug Administration (FDA) issued a decree in November 2013, according to which the company had to stop selling its genetic analysis kits in the United States. This article analyzes the current situation.

The company 23andMe was founded in 2006, when biologist Anna Wojcicki moved to California's Silicon Valley to her fiance Sergey Brin (Sergey Brin). Wojcicki has always been and remains an active critic of the US healthcare system. The biggest disappointment for her was the fact that the medical and pharmaceutical industry, the value of which is currently estimated at more than 3 billion US dollars, operates under the influence of a factor that she sees as an incentive to profit from diseases.

In an interview with the English newspaper The Guardian, Anna Wojcicki explained this by the example of obesity, which from the point of view of Wall Street is simply an excellent phenomenon, since it is not one, but a whole complex of interrelated diseases that are a potential source of income.

From this point of view, the projected 10% increase in the incidence of obesity-associated diabetes in the global population by 2030 means significant commercial growth for the industry, in which treatment brings more money than prevention.

Anna Wojcicki's move to Silicon Valley brought her together with like-minded people whose entrepreneurial experience allowed her to turn her ideas into a viable business model. Thanks to Sergey Brin, she met the TED conference staff (from the English Technology, Entertainment, Design – technology, entertainment, design): biotechnology specialist Linda Avey and her friend, management specialist Paul Cusenza.

Together, they formulated the idea of creating a company that, through DNA analysis, would directly provide patients with information about their organisms and genetic risks encoded in DNA, thereby expanding their capabilities without the participation of healthcare system employees. They proposed this idea to Google, one of the founders of which is Sergey Brin and which subsequently invested $3.9 million in a startup offering DNA analysis services.

Additional investments were subsequently received from Genentech and companies specializing in venture capital investments – New Enterprise Associates and Mohr Davidow Venture.

In 2007, 23andMe, named after the number of chromosomes in the human genome, entered the market with a DNA analysis kit in a saliva sample. The set had a very high cost, amounting to $999. However, growing pressure from competitors offering similar but less disease-focused products designed, for example, to identify risks associated with taking medications, led to the need to revise the marketing strategy.

The company began positioning its DNA analysis kit as an accessory intended for the masses and in 2012 reduced its cost to $99. This move turned out to be very popular, and over the next 9 months the number of customer profiles in the company's database doubled.

FDA puts an end to 23andMeHowever, in November 2013, 23andMe was dealt a potentially fatal blow.

The FDA announced that by selling its kit, the company violated the code of regulatory norms and regulations and demanded that the product be withdrawn from the market. According to the agency's statement, "the FDA has not received scientific evidence of the accuracy or reliability of these tests."

This event received very wide publicity and was considered excessively harsh by some supporters of direct provision of genetic testing services to the consumer, who believe that bureaucracy does not allow regulatory authorities to keep up with technological advances, access to which is provided by companies such as 23andMe.

FDA representative Jenny Haliski describes the current situation as follows. In order to return its services to the US market, 23andMe must obtain a registration certificate from the FDA, which, most likely, as indicated in the warning letter, will be subject to paragraph 510k of the Law on Food, Medicines and Perfumes and Cosmetics.

She also lists three main claims that the FDA has against 23andMe:

• In the absence of FDA approval or approval, patients may be exposed to unknown risks associated with using a device that could potentially harm them.
• The Agency found that the results obtained when applying some tests for self-use have questionable clinical value. It is not known how these results may affect people's health. In addition, there are currently no guidelines for doctors to use the results of these tests.
• Genetic tests for self-use may give inaccurate or misleading results in assessing the risk of developing diseases. The FDA has not received scientific evidence of the accuracy and reliability of the results provided by these tests.

However, Haliski confirmed that some tests of competing companies have already received FDA approval.

The difference in the views of the FDA and the United Kingdom Medicines and Healthcare Products Administration (MHRA) on 23andMe is that the MHRA considers the DNA test in saliva not as a medical device, but, according to Wojcicki's explanation, as a "predominantly informational product".

According to Beth Williams, a representative of 23andMe, one of the key factors behind the company's decision to offer its services in the UK market was the long-standing desire of several generations of the government of this country to maximize the potential of genetic testing.

Despite the victory won by the company in the UK, the third of the points listed by Khaliski, concerning the lack of convincing evidence of the accuracy of test results, leaves room for doubt.

How accurate are the results of these tests?A 2011 study comparing the genetic tests of 23andMe and two competing companies deCODEme and Navigenics (both currently defunct) was ruthless about their medical value.

The researchers said the tests provided inaccurate results and were of little value to users. The test results varied so widely that, according to the researchers, the accuracy of some predictions was comparable to a coin flip.

When asked whether 23andMe has taken measures to improve the accuracy of its tests, the lead author of the study, Professor Cecile Janssens, answered the following:

"No. However, let's be clear about the situation: I do not doubt the accuracy of their genotyping, since they work with qualified laboratories. However, the accuracy of predicting common diseases and signs has not improved since the FDA made its decision. At the present stage of the development of science, most of the diseases and signs that 23andMe tests are designed to detect cannot be predicted with a high degree of accuracy. 23andMe simply cannot affect this situation. The problem is not that they do not want to increase the predictive accuracy of their tests, but that it is impossible at this stage."

In an interview with The Guardian, 23andMe representative Brian Naughton commented on the results of the study as follows: "We know that most people are at low risk of developing most diseases. This meets our expectations and does not indicate inaccuracy."

Indeed, part of the rebranding of genetic tests carried out by the company is to shift the focus from screening to the risks of hereditary diseases to the use of personalized data to formulate "trigger points" that push users to change their lifestyle and improve their health.

Indeed, the $99 saliva DNA analysis kit is just one of 23andMe's activities.

23andMe and the "research accelerator"Despite the prominence of its main product, the company aims to make a large-scale contribution to science.

Hiding behind statements about the empowerment of patients provided by the saliva analysis kit that has become available, 23andMe suggests collecting genetic information about as many people as possible. The purpose of this is to create a huge database that researchers could use to find genetic clues when studying the causes and finding treatments for any human diseases.

To date, the company has already collected 800,000 DNA samples, while more than 80% of customers have given permission for free access to their genetic information for research purposes. This allowed the company to create one of the largest databases of genetic information in the world. However, to date, the test proposed by 23andMe analyzes only small fragments of DNA, which are only a small part of the genome.

Based on this, some critics have expressed doubts about the scientific significance of the 23andMe project to collect genetic information, which does not stand comparison with large-scale genome sequencing projects, such as the 100,000 Genomes Project launched by the UK Public Health Service (NHS), which aims to sequence 100,000 complete genomes by 2017.

Experts believe that the widespread use of genome-wide sequencing is another major revolution in medicine. At the same time, the competition of companies in providing affordable services for genome-wide sequencing has led to a significant reduction in prices for this procedure. In 2014, Illumina announced the development of a system that allows for genome-wide sequencing for US$ 1,000.

Despite the fact that the FDA has required 23andMe to withdraw saliva DNA analysis kits from the market, the company continues to provide genealogical analysis services and is replenishing its DNA database. In July, she also announced a $1.4 million grant from the U.S. National Institutes of Health (NIH).

This grant is intended to finance a two-year project aimed at expanding the database, introducing genome-wide sequencing and providing "external" researchers with access to de-identified data contained in the database, which 23andMe employees call the "Research Accelerator".

Over the past 4 years, 23andMe has published or participated in the writing of 22 scientific articles in leading peer-reviewed journals, which indicates the company's desire to deepen medical knowledge. These articles are devoted to the study of allergies, asthma, hypothyroidism, myopia, breast cancer and Parkinson's disease.

Data, privacy, patents and controversiesHowever, until now, 23andMe has not really cared about the reputation of its trademark.

The company reacted poorly to the FDA warning letters indicating violations of the law regarding the sale of a DNA analysis kit in saliva. Wojcicki said they misunderstood the regulatory body's requirement, and it was only in March 2014 that the FDA acknowledged that 23andMe had eliminated the violations and stopped selling the kit in question.

Wojcicki also became the subject of controversy in 2012 after she filed a patent application for a gene variant that provides protection against Parkinson's disease, according to scientific data. Despite Wojcicki's statements, according to which she tried to prevent any attempts to hinder the study of this disease, critics interpreted her act as an attempt to profit from such research, which would be a direct contradiction to the mission formulated by herself. A year later, the US Supreme Court banned the patenting of human genes.

When asked whether the negative publicity was taken into account when deciding to enter into cooperation with 23andMe, the NIH representative replied that the company received a grant under the NIH Small Business Innovative Research program, which is one of the largest sources of early funding for small companies engaged in innovative research in the United States. The application from 23andMe has successfully passed the selection process conducted on a competitive basis by a group of independent experts.

However, perhaps partly due to 23andMe's ties with Google and the accusations made by Edward Snowden, some people are suspicious of the motives that the company explains its desire to collect medical data from customers.

Kara Swisher from Wall Street Journal asked Anna Wojcicki: "Do you need all this information? I don't like the idea that Google has information about the bacteria inhabiting my gut–they might find a way to benefit from my bacteria."

Anna Wojcicki reacted to this as follows: "One of the reasons why we work directly with clients is that [in this case] you are the owner of the data. If your insurance company pays, it owns the data, and if you pay, then you own the data and if you want to share it, that's your right. Privacy is the foundation of what we do, however, as it turns out, people want to share this information – not necessarily on Facebook, but with attending physicians and family members. People are not obliged to take part in our research, but some are literally begging us to use their data, because they suffer from incurable diseases and want to do everything in their power to help the next generations."

According to Beth Williams, customer data security and privacy insurance is a prerequisite for the transaction between the customer and 23andMe. She also emphasizes that the company does not open access to individual data in the absence of an informed consent document signed by the client. Access to the system is protected by serious authentication methods. Specialized software and hardware, as well as physical means of protection, are used to protect computers in which data is stored. Personal information and genetic data are stored in physically separate computing environments, which are protected in accordance with the highest industrial standards.

How much value is "home" genomics for patients?Whether 23andMe will acquire a significant role in the context of the new era of personalized medicine is still unclear.

When asked whether, in her understanding, genetic tests for home use are of value to patients or are they just a bait, Professor Cecile Jenssens replied the following:

"It is very difficult to express an unambiguous opinion on this, since people are offered various tests, for example, tests for studying pedigree, detecting disease-causing mutations, confirming paternity, as well as predicting the risk of developing common diseases and choosing a diet and lifestyle."

However, she admits that predicting the risk of developing common diseases in general does not make sense, since "the predictive power is not high enough, and companies do not take into account the contribution of other risk factors, such as diet, amount of alcohol consumed, smoking and physical activity, which often have a more pronounced impact on the risk of developing the disease". In conclusion, she adds that "I would not call such tests 100% bait, since most of them are based on scientific data, but this is not enough to consider them useful."

At the same time, Vance Vanier, who is also president of Verinata Health and chief executive officer of Navigenics, notes that not so long ago a pregnancy test could only be taken in a doctor's office, and today you can even buy an HIV test without a prescription.

He believes that the current trend is that over time, the quality of understanding of information improves and, thanks to the emergence of more social guarantees that prevent abuse of information, the evolution of methods of its use is facilitated, eventually bringing them to the consumer market.

At the same time, Beth Williams states that 23andMe's mission is to help people get, understand and benefit from the human genome. A significant part of this mission is realized in independent research, as well as in cooperation with scientists from the academic and industrial sectors. 23andMe employees believe that the results of these studies will form the basis of new, more effective methods of treatment, diagnosis and prevention of diseases. The purpose of this work is to benefit all mankind.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru according to Medical News Today:
23andMe and the future of home DNA testing.

Portal "Eternal youth" http://vechnayamolodost.ru25.12.2014