By Mari Hoffman, Genetics & Genomics ‘21

Author’s Note: I was interested in interviewing Dr. Linda Sonntag because of her time and dedication spent in the biotechnology field. She has been involved in multiple biotechnology companies as the Chief Executive Officer and participating as a board member. The multitude and diversity of her experiences with different companies and projects have encouraged her to get involved with bioethics. She has been a leader in bioethics and has started many of the bioethical conversations that are still being discussed today. In that capacity, she has formed multiple bioethics committees, including the very first. I was very honored to be able to interview Dr. Sonntag and ask her some of my own questions revolving around bioethics in the past and modern development of biotechnology. 

This interview has been lightly edited for clarity and brevity.

Mari Hoffman: To start off, if you would like to give a brief introduction on who you are and your background.

Dr. Linda Sonntag: My name is Linda Sonntag, and I was born, raised, and educated in South Africa. I came to the United States in 1980 and completed my post-doctoral studies at UCSF with Herbert Boyer, the founder of Genentech. I quickly realized that I was not cut out for academia in this country. I come from being a very big fish in a very small pond and now I was a Mino in the ocean. I had to find a different way of using my education and I decided to go into industry, which was right at the beginning of the formation of biotechnology. 

MH: Since you entered the field of biotechnology when it was still relatively new, when do you first remember a conversation on bioethics taking place and how has that conversation changed with the increasingly advancing technology and scientific capabilities that we have today? 

LS: The very first conversation on bioethics took place before my involvement. I think it took place around 1976 at a seminar that was led by David Baltimore, after recombinant DNA and genetic engineering were first discovered. People were concerned about what could be done with biotechnology (a term only coined in the early 1980’s) and a public conversation on bioethics up until this point had not occurred. The technology was way ahead of any conversations or agreement on how to proceed to use it for the common good and not ill. To address the concerns on the ethical issues related to recombinant DNA, a conference was organized to discuss the ethics at Asilomar, in Northern California. A moratorium was placed on all genetic engineering for academic research until the scientist could agree on what was ethical or not. The moratorium lasted several years. During this time, a number of research areas were declared ethical and others not, and the organizers also played a significant role in establishing rules and regulations as well as the creation of multiple regulatory bodies to govern the use of recombinant DNA. At that time, the scientists were able to restart their research in a robust way.  

MH: What was your first direct experience with starting a conversation on bioethics?

LS: The first company I worked with was called Agrigenetics and it was the very first agricultural biotechnology company. At the time, no regulations were in place by any federal agency to regulate genetically modified foods (GMA). The very first conversation that I had around bioethics was around whether or not the agricultural industry should be regulated. I was the lone voice who believed it should be regulated. I was very concerned that if there were no regulations, people would be very frightened by the products we wanted to commercialize if we were successful. They might view us as creating monsters that could escape into the environment. Although I had my concerns, for expediency’s sake, the industry leaders as a whole decided against being regulated because regulation adds significant costs and delays the time to reach the market.

The very first experiment that went into the field was in Davis, CA, associated with a company that was founded by academic scientists at UC Davis. It was for a strawberry plant that had been engineered to have an anti-freezing gene derived from fish inserted into its DNA  so that strawberries would not freeze and the crop would not be destroyed when there was frost. When the GMO plants were planted, local citizens in the area protested and rioted by breaking down the greenhouses and destroying the crops. That product never reached the market. 

Agricultural biotechnology eventually took off, but in a highly regulated way. You can still see the stigma today that GMO plants and seeds hold; people remain afraid of them and the business models around how they are sold.

MH: How did that experience lead to you making a change in a company’s regulations? 

LS: My next involvement was a very interesting one. Around 1985, I joined a startup where we were the first to practice precision medicine and use it to create a preventive medicine program that was designed for a circumscribed group of individuals. Historically, prevention has always been in the domain of government and consequently had been very costly to implement since governments could not be seen to discriminate and therefore all newborns were being tested for those diseases that were preventable, whether they were at risk or not. 

I went around the country and licensed many genes that had been identified in academic labs that were linked to preventable diseases. They had the potential to be powerful predictors to identify who was at risk for certain diseases. I eventually licensed about 50 different genetic markers that could be used to identify individuals’ predispositions for developing a disease that was preventable. I was only interested in licensing genetic markers for diseases that had an environmental and/or behavioral component to them and that a patient could do something to change the outcome of the disease. After licensing these technologies, we created the very first artificial intelligence system which allowed us to circumscribe who was at risk. To test out the system we were involved with a large telephone company in Washington, DC who opted to offer our test to their employees. It quickly became very evident that with no rules in place, individuals were not protected from being discriminated against by their employers or insurance companies because they had a genetic profile that identified them as being at risk of developing diseases that could result in considerable healthcare costs or disruption to an individual’s productivity. To think through and address these issues, I created the very first bioethics committee, dedicated exclusively to problem solve and develop systems to protect individuals from discrimination. To overcome these issues, we were successfully able to identify individuals, and only we held the key to their identity and were able to preserve the patient’s anonymity from their employers and insurers. They could now get access to educational programs and support without their identity being exposed. That was the very first time that a bioethics committee was created as an institutional entity that made decisions about how businesses would be run in a more mindful and ethical manner. 

MH: That is very interesting. Would you say with ancestry tests like 23andMe where you are provided an option to give your name overrides the anonymity of genetic tests that you discussed? 

LS: Absolutely.  What we have discovered now is even if that data is anonymized, there are ways to deconstruct and identify individuals.

MH: It is very interesting that this conversation on data privacy that you started years ago is still a prevalent issue today. Are there any set laws that are currently in place today to provide protections?

LS: Laws do exist to protect genetic information from being used prejudicially, but if an individual gets refused insurance it is really hard to find out why they have been refused. If an employer has accessed that data and uses it prejudicially, for one to have any recourse, you have to prove that it was based on their knowledge of that genetic information, which is very difficult to prove.

The one law that is unfortunately currently at risk is the protections that come from the Affordable Care Act (ACA). The ACA forbids insurance companies from using pre-existing conditions to deny an individual any insurance. Due to COVID-19 and the Trump Administration’s attempt to end the ACA, a multitude of individuals who have lost their health insurance this past year due to the pandemic are now at risk of no longer being able to buy insurance that covers pre-existing conditions. All the sequelae and multitudes of long term health consequences of COVID-19 could be excluded from coverage by anyone who has lost their job as a consequence of this pandemic of epic proportions. A genetic predisposition might be included as a pre-existing condition, which might disqualify an individual for insurance. As long as the ACA is the law, nobody can be denied insurance for those reasons. Although there are these laws that exist, there are still issues around them and how to enforce them.

MH: Have there been any other experiences that you have that have led you to build a bioethics committee?

LS: The third time that I got involved in bioethics and formed a committee was when I was running a company called SyStemix, the very first stem cell company. We were using fetal tissue in our experiments which was a topic that has been controversial under Trump and prior to that during the George W. Bush administration. We were one of the first commercial companies that was openly admitting to using fetal tissue in our experiments. We knew that this might be highly controversial, so once again, I assembled a bioethics committee to opine on what we would face and how best to deal with the issues. Our committee actually included a Catholic Bishop to be a part of the conversation and eventually concluded that since we were not in any way women to choose abortion and since we were not paying for the tissue, the abortuses were simply being disposed of with no potential to benefit humankind. Even the Bishop agreed that using fetal tissue for the benefit of humankind was a worthwhile endeavor, as opposed to throwing the embryos away. 

Just this last year, Trump dismantled every single research project funded by the United States government that used fetal tissue in any way, thereby squandering hundreds of millions, if not billions of dollars worth of experiments by having all that research come to a screeching halt. 

Our company was founded on the use of a SCID-hu mouse model where any tissue from any organisms can be transplanted into the mouse since the mouse did not have an immune system of its own. It could not recognize the donor tissue as foreign and hence would not reject it. Few adult organs are capable of regeneration, whereas virtually every fetal tissue has applicability in these valuable experiments. This mouse model became the gold standard for all research on the etiology of human diseases and the potential ways to treat them.

In our case we were able to use it for AIDS and HIV research. It was the first time that we could actually create a fully functional human immune system in a mouse and infect it with HIV, to determine if different drugs could potentially cure HIV and AIDS. AZT, the very first approved HIV-antiviral drug was discovered to be effective in humans by using the SCID-hu mouse model around 1990. AZT is a pro-drug, and the only other organism that can convert it from a prodrug to an active drug is chimpanzees. By using this mouse model, it was no longer necessary to infect chimpanzees with HIV to study the disease. This year, unfortunately, for political reasons, all experiments that were using this gold standard mouse model for studying many human diseases came to a halt because President Trump decided that fetal tissue could not be used in any circumstance in any government funded research programs, for purely political reasons. 

MH: What do you think are some of the most current pressing bioethical issues?

LS: The other discussion that is very current, but I have mixed feelings on is about vaccines for COVID-19. COVID-19 trials are blinded and are conducted by splitting cohorts of individuals in a control arm and a treatment group, without the researchers or participants knowing which group is receiving the vaccine. Now that the experiments are unblinded and we can see that the vaccine is highly efficacious, the question becomes whether or not people in the control arm should be vaccinated. If they get the vaccine, it truncates our ability to see for example the longevity of the protection provided by the vaccine or long-term side effects by no longer being able to track the control group. So, what to do? The way the health care community is leaning is that the control group has to get the vaccine to protect them and then we have to figure out other ways to understand the longevity and side effects of vaccination. This is an ongoing discussion at the FDA and the NIH in order to make these important decisions around how to continue the clinical trials. Also, once the first vaccine is approved, how do you get other vaccines tested if there is already a vaccine available? There are a lot of ethical questions to consider regarding these issues.

MH: There is a lot of stigma about taking vaccines, how do you think the implementation of distributing the vaccine and getting people to take it will play out? 

LS: There are weekly conversations regarding how to distribute the vaccine and who should get it first. Clearly, they have to treat frontline workers first as they are the most at risk. Then the conversation is about who is most at risk for the virus aside from the frontline workers. People of color have a higher risk of getting sick from COVID-19 completely disproportionate to the population. The question raised asks if young children should be prioritized in getting the vaccine since they can be reservoirs of the virus and for their emotional and cognitive development must be allowed to return to school as soon as possible? There are still conversations going on around how to allocate the vaccine equally and I don’t think they have reached a complete conclusion other than the frontline workers will get it first. Who gets it next and how it rolls out is still under discussion. 

MH: Is there worry that there will not be enough people willing to get the vaccine due to stigma? 

LS: Yes, I think that is a very significant concern. I can personally tell you as a scientist that I think that vaccines and antibiotics have extended our lives dramatically. At the beginning of the 1900s, the average life span was about 40 years old due to people dying from common infectious diseases. The advantage of antibiotics and vaccines has extended our lifespan by double. I will not hesitate in getting a vaccine as soon as I can after it has been reviewed and approved by an independent, apolitical group of scientists.

MH: Are there any other major ethical topics that we missed that you would like to discuss?

LS: One critical vast ethical issue that we have not discussed is CRISPR technology. CRISPR technology is one of the most fraught technologies on the planet with the ability to do both good and bad. On the downside, scientists have found ways for example to change genes in entire populations of mice to render them infertile so that they cannot transmit Lyme disease or to eradicate entire populations of mosquitoes to prevent malaria or zika transmission or other mosquito borne diseases, of which there are many. What happens to the global ecosystem if these species are eradicated because they can no longer reproduce? The cat is out of the bag on this line of research, before a discussion on the ethics ever got started.

The first infants to have their genes in their germline modified have already been born in China. This means the germplasm (eggs and sperm) have been permanently altered and so these modifications will be transmittable to future generations. This is something that the scientific and civil community worldwide has historically completely forbidden. There are a lot more conversations surrounding ethics that need to take place in order for this technology to be broadly used. I’m afraid, it is already too late to regulate and control in a meaningful way from being used in ways that could be terribly detrimental to our planet and all its inhabitants, whether fauna, flora, microbes, or humans.