Interview: Dr. Akiko Iwasaki

Vaccine efficacy, the future of COVID-19, and women in science

I follow a lot of COVID-19 experts on Twitter, but perhaps none has been so informative as Dr. Akiko Iwasaki, an immunologist at Yale. Somehow, she manages to communicate a very high volume of extremely technical information about viruses in a way that a layperson like myself can understand quite easily, but without sacrificing scientific accuracy. She also occasionally writes columns for the New York Times, Vox, and elsewhere, and appears on podcasts. Together with some other scientists, she helped create a plan to stop COVID-19. And she has done this while continuing to put out a high volume of research papers. She has also spoken out about the barriers women face in the field of biology.

Frankly, Dr. Iwasaki is pretty incredible. When I hear the word “biologist”, she is now the person who comes to mind. So it was a great honor to be able to interview her for my blog! Our unedited email exchange is below:

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N.S.: So, let me say first of all, I'm a huge fan. I follow a lot of COVID experts on Twitter, and no one has taught me as much about COVID, or about viruses in general, as you have. You're so good at figuring out exactly what information people need to know, and sending them to the best source for that information. 

A.I.: Wow. Thank you Noah. I am thrilled to know that you find my science communication efforts useful.

N.S.: So before I ask about viruses and vaccines, I just wanted to know: What made you feel the need to spend your valuable time bringing information to the masses? Was it just that COVID was such an emergency? 

A.I.: Well, before the COVID pandemic, I have always felt it is the duty of a scientist to communicate research findings to lay people in accessible manner. We are in a privileged position to pursue science thanks to large part taxes people pay. We as scientists have an obligation to explain and discuss our scientific findings to the public. When COVID hit, I felt that this was important more than ever to not only communicate our own research but to put out information on some basic mechanisms of virus infection and immunity, and to dispel myths about the virus.

N.S.: That's awesome. We'll talk about dispelling myths in a bit.

But first, I wanted to ask: How worried should we be about this new COVID strain that has appeared in the UK? I've seen some preliminary data suggesting that one of the new strain's mutations, called N501Y, which is thought to make it more infectious, doesn't affect its resistance to antibodies. But aren't there several mutations in the new strain? How worried should we be that this strain, or a descendant of it, will make our vaccines substantially less effective?

A.I.: That’s right. The N501Y mutation, which is in the receptor-binding domain of the spike protein, does not appear to evade antibody responses generated by prior infection or vaccines. There are several other mutations and deletions in both the spike and other viral genes. I do not think there is much to worry about vaccines not working against this particular variant. On average, people make multiple antibodies to different regions (called epitopes) within the spike protein alone. So even if the virus is able to evade some of them, other antibodies will still be active against the virus. In the future, a mutant virus may emerge that truly evades vaccine-induced immunity. However, at that point, the new sequence can be incorporated into a new mRNA vaccine – version 2.0. All the manufacturing and distribution infrastructure is already in place to making such a vaccine pretty rapidly.

N.S.: And, following up on that question: It seems like it will take years to vaccinate the entire world against COVID, if we even ever can do that. What are the chances that COVID will keep mutating among the unvaccinated population, and new vaccine-resistant strains will keep emerging? 

A.I.: This is theoretically possible. However, for the mutant virus to evade all possible antibody responses it will take a long time. The fact that the SARS-CoV-2 polymerase has a proofreading capability makes the mutation rate low.  Plus, we have not seen such variant arise during natural infection of 78 million people makes it very unlikely, or at least a very slow process.

N.S.: Got it. So if we get unlucky and a vaccine-resistant COVID strain does emerge, how quickly will we be able to re-vaccinate everyone? Will tweaked mRNA vaccines have to go through a long approval and testing process like the original ones did this year? Or can we quickly just swap out the spike protein and roll out the new one quickly?

AI: I am not sure how extensive such new versions of mRNA vaccines have to be tested. I bet you can just swap out the spike sequence and roll out the new vaccine relatively quickly. The new version may have to be tested in a small number of people before the roll out for safety but I am not sure. Every new vaccine will likely need regulatory approval.

N.S.: And on a related note: Suppose we do manage to vaccinate the great majority of the world against COVID. What is the endgame for this disease? Could it become endemic in some areas? Will we have to get regular vaccines against new COVID strains, like flu shots? Might the disease evolve into a less deadly form, as some predict? Or do we just not know yet?

A.I.: I think it is too early to say. If vast majority of the world is vaccinated against COVID, the virus may only cause sporadic small clusters of infection in areas that are not covered by vaccines (much like some measles outbreaks we see in some States with low vaccine uptake). However, widespread transmission of virus will be prevented by herd immunity. Even if the virus does not evolve into a less deadly form, disease will be prevented because of immune resistance.

N.S.: Got it. Well that's pretty comforting, I must say. 

Now, another scary question is: What about the next pandemic? Have globalization and humanity's increasing encroachment on animal habitats put us in higher danger of novel pandemics like this one? What can we do to limit the danger or prepare better?

A.I.: Human behaviors such as deforestation, intensive animal farming, urban crowding, poor sanitation, and water storage practices have led to accelerated emergence of zoonotic infectious diseases in humans. Increase in world travel has allowed faster and wider transmission of infectious agents. I think it is time to take a hard look at our behavior and make changes where possible. For example, we should consider limiting the large indoor crowding events and make some of these virtual. If remote working is possible, encourage that over in person working. On the other hand, human interaction is absolutely important, especially for children and elderly. We need to ensure safer public and community indoor environment for schools and nursing homes.

N.S.: And why, after a long period of not worrying about coronaviruses at all, have we seen two novel coronavirus pandemics -- SARS in 2003, and now COVID-19 -- in less than two decades? Was that just a coincidence?

A.I.: You are right that these betacoronaviruses made zoonotic transmission and subsequent human to human spread in relatively short time period. This likely reflects more frequent encounter between humans and animal reservoir hosts. SARS and SARS-CoV-2 use ACE2 as entry receptor. It turns out that SARS-CoV-2 can use ACE2 expressed by a wide range of mammalian hosts including minks, cats, and other domestic and wild animals. So the evolution of the virus within and between these types of animals and jumping over to humans can lead to zoonotic transmission. Some of these viral strains capable of person to person transmission will have the pandemic potential. 

It is important to remember that during this period, other infectious agents also succeeded as emerging endemic and pandemic infections in humans, including H1N1 swine flu, Chikungunya, and Zika virus.  So the threats of future pandemics can come from multiple viral types.

N.S.: I'd love to keep asking about viruses and have you give me a whole tutorial, but I don't want to take too much of your time! Instead I'll switch to another topic I wanted to ask you about: Women in science. 

It's well known that the percent of women in bio- and life sciences has been increasing. Obviously it will take some time to reach parity at the level of tenured and senior professors, but it seems inevitable that this will also shift over time. Meanwhile, women were responsible for some of the key scientific advances involved in creating the COVID-19 vaccines. Do you think the field of bioscience is becoming more gender-equal? What are the barriers that still exist, and what are the most important steps we can take to knock them down? I know that you have struggled with sexism in biology. What can we do to fight it?

AI: While women make up more than 50% of the biomedical graduates, the percentage of women in faculty position, particularly at the professor level. There is no proportionate increase in the percentage of women faculty for decades. The percentage of women in academic positions drops most precipitously at the postdoc-to-faculty transition. In a typical open faculty search in biology, about 25% of applicants for an assistant professorship are women, whereas women comprise about 45% of the postdoctoral applicant pool. I hate it when people assign this disparity to “pipeline” problem because the pipeline is fixed, but the environment isn’t. The field of bioscience is inching towards gender equality but the pace is too slow. I will highlight some barriers women and underrepresented scientists face.

  • Bias: both explicit and implicit

  • Toxic work place experience

  • Sexual harassment/assault from colleagues and senior members

  • Lack of role models

  • Lack of confidence

  • Exclusion from the old boys club for membership, awards, prizes.

  • Women’s publications do not ‘count’ towards grant award as much as men’s.

  • Women’s publications do not receive as many citations as similar work by men’s.

  • Women don’t get to publish as much as men in high tier journals.

  • Women do not achieve promotion to leadership position at the same rate as men.

  • Lack of mentors and sponsors

  • Funding and pay gap

  • More time in parenting and domestic tasks than men, particularly during the pandemic.

How do we knock these down?

  • Infrastructure

  • Provide affordable and accessible childcare

  • Conduct couples recruitment, cluster recruitment to make it easy for families

  • Hold grant panel education to avoid implicit bias.

  • Need mind set change in recruitment

  • Change metric of success

  • Tactic:

  • Affirmation: band together preemptively to consciously support other women in discussion

  • Networking, identifying and hiring of qualified women and URM

  • Realizing this is not a woman/URM problem. Involving men (#HeforShe)

  • Mentoring and role model

  • Women/URM in leadership roles could effect change from the top

  • Leadership – change our concept of what a leader should look like.

  • Policy and institutional solutions

  • Reflective: not just have programs; change mind-set

  • Acknowledge and tackle biases

  • Leadership training and mentoring for women, boards, committees

This all sounds daunting but effort starts from one. A lot one can do on an individual level to start chipping away at the barriers.

N.S.: Wow, that is a big list. And I'm of course frustrated at how little I can personally help accomplish any of the tasks on that list!

So here's my next question: What can people like me, in the media but outside the biosciences, do to help this? What are the steps we can take, however small and modest? 

A.I.: Thank you for asking this question. People in the media can help highlight the barriers so that people can understand what problems there still are in biomedical sciences. Once we acknowledge the problems, then we can begin to tackle them. If there is no public understanding of the issues women still face in academia, we will not have the public support we need to make the change. So you are doing a lot by writing this blog!

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